Apoptosis-inducing agents for treatment of cancer and immune and autoimmune diseases

FIELD: medicine, pharmaceitics.

SUBSTANCE: invention relates to particular derivatives of N-(phenylsulphonyl)benzamide, given in i.1 of the invention formula. The invention also relates to a pharmaceutical composition, possessing an inhibiting activity with respect to anti-apoptotic proteins Bcl-2, containing an effective quantity of one of the said compounds or a therapeutically acceptable salt of such a compound.

EFFECT: N-(phenylsulphonyl)benzamide derivatives as inhibitors of the anti-apoptotic proteins Bcl-2.

2 cl, 2 tbl, 458 ex

 

This bid is partially continuing patent application U.S. serial No. 12/631367, filed December 4, 2009, whose priority is claimed in accordance with the provisional application U.S. serial No. 61/119844, filed December 4, 2008, which are in their entirety incorporated by reference.

The SCOPE of the INVENTION

This invention relates to compounds that inhibit the activity of anti-apoptotic proteins of Bcl-2, compositions containing these compounds, and to methods of treating diseases with the flow, which is expressed anti-apoptotic proteins of Bcl-2.

BACKGROUND of the INVENTION

Anti-apoptotic proteins of Bcl-2 is associated with a number of diseases. Therefore, in the field of therapy there is a need for compounds that inhibit the activity of anti-apoptotic proteins of Bcl-2.

Overexpression of proteins of Bcl-2 correlates with resistance to chemotherapy, the outcome of disease, the development of the disease, the final forecast or their combination with different types of cancer and diseases of the immune system.

Participation proteins of Bcl-2 in diseases such as bladder cancer, brain cancer, breast cancer, cancer of the bone marrow, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, gepatotellularian, lymphoblastic leukemia, follicular lymphoma, lymphoblastic leukemia from precursor T-cells or B-cells, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, cancer of the spleen, and the like described in the joint application PCT US 2004/36770, published as WO 2005/049593, and PCT US 2004/37911, published as WO 2005/024636.

Participation proteins of Bcl-2 in immune and autoimmune diseases described in the articles, Current Allergy and Asthma Reports 2003, 3, 378-384; British Journal of Haematology 2000, 110(3), 584-90; Blood 2000, 95(4), 1283-92; and New England Journal of Medicine 2004, 351(14), 1409-1418. Participation proteins of Bcl-2 for arthritis disclosed in the joint provisional patent application U.S. serial No. 60/988479. Participation proteins of Bcl-2 in the process of transplant rejection, bone marrow disclosed in co-owned patent application U.S. serial No. 11/941196.

The INVENTION

One variant of implementation of the present invention thus relates to compounds or therapeutically acceptable salts, prodrugs or salts of prodrugs that can be used as inhibitors of anti-apoptotic proteins of Bcl-2, compounds having the formula I:

where

A1represents N or C(A2);

A2represents H, R 1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

B1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R 1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

D1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

E1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1OC(O)R 1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; and

Y1represents H, CN, NO2C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R17, OR17C(O)R17C(O)OR17, SR17, SO2R17, NH2, Other17N(R17)2, NHC(O)R17C(O)NH2C(O)other17C(O)N(R17)2NHS(O)R17or NHSO2R17; or

E1and Y1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

A2B1and D1independently selected from H, R1, OR , SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

Y1and B1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

A2D1and E1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)21C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

A2and B1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

D1E1and Y1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

A2and D1together with the atoms to which they are attached, are benzene, naphthalene, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

B1E1and Y1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3 C(O)OH, C(O)NH2or C(O)OR1A;

R1is an R2, R3, R4or R5;

R1Ais cycloalkyl, cycloalkenyl or cycloalkenyl;

R2represents phenyl, which secondinterval or fused with benzene, heteroatom or R2A; R2Ais cycloalkane or geteroseksualen;

R3is heteroaryl that secondinterval or fused with benzene, heteroatom or R3A; R3Ais cycloalkane or geteroseksualen;

R4is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R4A; R4Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R5represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R6, NC(R6A)(R6B), R7, OR7, SR7, S(O)R7, SO2R7, Other7N(R7)2C(O)R7C(O)NH2,C(O)other7C(O)N(R7)2, NHC(O)R7, NR7C(O)R7, NHSO2R7, NHC(O)OR7, SO2NH2, SO2Other7O 2N(R7)2, NHC(O)NH2, NHC(O)other7, NHC(O)CH(CH3)NHC(O)CH(CH3)NH2, NHC(O)CH(CH3)NHC(O)CH(CH3)Other1, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R6represents a C2-C5-spiralcell, each of which is unsubstituted or substituted by OH, (O), N3CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH(CH3) or N(CH3)2;

R6Aand R6Bindependently selected from alkyl or together with the N atom to which they are attached, represent R6C;

R6Cis aziridine-1-yl, azetidin-1-yl, pyrrolidin-1-yl or piperidine-1-yl, each of which contains a single CH2group, nezamenimoy or replaced with O, C(O), CNOH, CNOCH3, S, S(O), SO2or NH;

R7is an R8, R9, R10or R11;

R8represents phenyl, which secondinterval or fused with benzene, heteroatom or R8A; R8Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R9is heteroaryl that secondinterval or fused with benzene, heteroatom or R9A; R9Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R10represents C is cloaker, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R10A; R10Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R11represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R12, OR12, SR12, S(O)R12, SO2R12C(O)R12, CO(O)R12, OC(O)R12, OC(O)OR12, NH2, Other12N(R12)2, NHC(O)R12, NR12C(O)R12NHS(O)2R12, NR12S(O)2R12, NHC(O)OR12, NR12C(O)OR12, NHC(O)NH2, NHC(O)other12, NHC(O)N(R12)2, NR12C(O)other12, NR12C(O)N(R12)2C(O)NH2C(O)other12C(O)N(R12)2C(O)NHOH, C(O)NHOR12C(O)NHSO2R12C(O)NR12SO2R12, SO2NH2, SO2Other12, SO2N(R12)2C(O)H, C(O)OH, C(N)NH2C(N)other12C(N)N(R12)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R12is an R13, R14, R15or R16;

R13represents phenyl, which secondinterval or condensive is with benzene, heteroatom or R13A; R13Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R14is heteroaryl that secondinterval or fused with benzene, heteroatom or R14A; R14Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R15is cycloalkane, cycloalkene, geteroseksualen or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R15A; R15Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R16represents alkyl, alkenyl or quinil;

R17is an R18, R19, R20or R21;

R18represents phenyl, which secondinterval or fused with benzene, heteroatom or R18A; R18Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R19is heteroaryl that secondinterval or fused with benzene, heteroatom or R19A; R19Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R20is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each the second of which secondinterval or fused with benzene, heteroatom or R20A; R20Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R21represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R22, OR22, SR22, S(O)R22, SO2R22C(O)R22, CO(O)R22, OC(O)R22, OC(O)OR22, NH2, Other22N(R22)2, NHC(O)R22, NR22C(O)R22NHS(O)2R22, NR22S(O)2R22, NHC(O)OR22, NR22C(O)OR22, NHC(O)NH2, NHC(O)other22, NHC(O)N(R22)2, NR22C(O)other22, NR22C(O)N(R22)2C(O)NH2C(O)other22C(O)N(R22)2C(O)NHOH, C(O)NHOR22C(O)NHSO2R22C(O)NR22SO2R22, SO2NH2, SO2Other22, SO2N(R22)2C(O)H, C(O)OH, C(N)NH2C(N)other22C(N)N(R22)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R22is an R23, R24or R25;

R23represents phenyl, which secondinterval or fused with benzene, heteroatom or R23A; R23Ais cycloalkane, cycloalkene, geteroseksualen or heterocyclyl is n;

R24represents heteroaryl that secondinterval or fused with benzene, heteroatom or R24A; R24Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R25is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R25A; R25Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

Z1is an R26or R27;

Z2is an R28, R29or R30;

Z1Aand Z2Aboth were missing or taken together form CH2CH2CH2or Z12A;

Z12Arepresents a C2-C6-alkylene, in which one or two groups CH2replaced by NH, N(CH3), S, S(O) or SO2;

L1is an R37, OR37, SR37, S(O)R37, SO2R37C(O)R37, CO(O)R37, OC(O)R37, OC(O)OR37, Other37C(O)NH, C(O)NR37C(O)NHOR37C(O)NHSO2R37, SO2NH, SO2Other37C(N)NH, C(N)other37;

R26represents a phenylene, which secondinterval or fused with benzene or heteroatom or R26A; R26Arepresents cycloalkyl is, cycloalken, geteroseksualen or geteroseksualen;

R27represents heteroaryl that secondinterval or fused with benzene or heteroatom or R27A; R27Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R28represents a phenylene, which secondinterval or fused with benzene, heteroatom or R28A; R28Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R29represents heteroaryl that secondinterval or fused with benzene or heteroatom or R29A; R29Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R30is cycloalkyl, cycloalkenyl, heterocyclochain or heterocyclization, each of which secondinterval or fused with benzene, heteroatom or R30A; R30Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R37represents a bond, or R37A;

R37Ais alkylen, albaniles, or akinyan, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R37B, OR37B, SR37B, S(O)R37B,SO 2R37BC(O)R37B, CO(O)R37B, OC(O)R37B, OC(O)OR37B, NH2, Other37BN(R37B)2, NHC(O)R37B, NR37BC(O)R37BNHS(O)2R37B, NR37BS(O)2R37B, NHC(O)OR37B, NR37BC(O)OR37B, NHC(O)NH2, NHC(O)other37B, NHC(O)N(R37B)2, NR37BC(O)other37B, NR37BC(O)N(R37B)2C(O)NH2C(O)other37BC(O)N(R37B)2C(O)NHOH, C(O)NHOR37BC(O)NHSO2R37BC(O)NR37BSO2R37B, SO2NH2, SO2Other37B, SO2N(R37B)2C(O)H, C(O)OH, C(N)NH2C(N)other37BC(N)N(R37B)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br and I substituents;

R37Brepresents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen;

Z3is an R38, R39or R40;

R38represents phenyl, which secondinterval or fused with benzene, heteroatom or R38A; R38Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R39is heteroaryl that secondinterval or fused with benzene, heteroatom or R39A; R39Ais cycloalkane, the CEC is olken, geteroseksualen or geteroseksualen;

R40is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R40A; R40Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

where the group represented by R26and R27are substituted (i.e., if Z1Aand Z2Aare absent) or further substituted (i.e., if Z1Aand Z2Athere are one, or two, or three, or four substituents, independently selected from R41, OR41, SR41, S(O)R41, SO2R41C(O)R41, CO(O)R41, OC(O)R41, OC(O)OR41, NH2, Other41N(R41)2, NHC(O)R41, NR41C(O)R41NHS(O)2R41, NR41S(O)2R41, NHC(O)OR41, NR41C(O)OR41, NHC(O)NH2, NHC(O)other41, NHC(O)N(R41)2, NR41C(O)other41, NR41C(O)N(R41)2C(O)NH2C(O)other41C(O)N(R41)2C(O)NHOH, C(O)NHOR41C(O)NHSO2R41C(O)NR41SO2R41, SO2NH2, SO2Other41, SO2N(R41)2C(O)H, C(O)OH, C(N)NH2C(N)other41C(N)N(R41)2, CNOH, CNOCH3, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F,Cl, Br or I;

R41is an R42, R43, R44or R45;

R42represents phenyl, which secondinterval or fused with benzene, heteroatom or R42A; R42Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R43is heteroaryl that secondinterval or fused with benzene, heteroatom or R43A; R43Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R44is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R44A; R44Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R45represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R46, OR46, SR46, S(O)R46, SO2R46C(O)R46, CO(O)R46, OC(O)R46, OC(O)OR46, NH2, Other46N(R46)2, NHC(O)R46, NR46C(O)R46NHS(O)2R46, NR46S(O)2R46, NHC(O)OR46, NR46C(O)OR46, NHC(O)NH2, NHC(O)other46, NHC(O)N(R46)246C(O)other46, NR46C(O)N(R46)2C(O)NH2C(O)other46C(O)N(R46)2C(O)NHOH, C(O)NHOR46C(O)NHSO2R46C(O)NR46SO2R46, SO2NH2, SO2Other46, SO2N(R46)2C(O)H, C(O)OH, C(N)NH2C(N)other46C(N)N(R46)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R46represents alkyl, alkenyl, quinil, R47, R48or R49;

R47represents phenyl, which secondinterval or fused with benzene, heteroatom or R47A; R47Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R48is heteroaryl that secondinterval or fused with benzene, heteroatom or R48A; R48Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R49is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R49A; R49Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

where the group represented by R42, R42A, R43, R43A, R44, R44A , R47, R47A, R48, R48A, R49and R49Aindependently substituted with one, or two, or three, or four substituents, independently selected from R50, OR50, SR50, S(O)R50, SO2R50C(O)R50, CO(O)R50, OC(O)R50, OC(O)OR50, NH2, Other50N(R50)2, NHC(O)R50, NR50C(O)R50NHS(O)2R50, NR50S(O)2R50, NHC(O)OR50, NR50C(O)OR50, NHC(O)NH2, NHC(O)other50, NHC(O)N(R50)2, NR50C(O)other50, NR50C(O)N(R50)2C(O)NH2C(O)other50C(O)N(R50)2C(O)NHOH, C(O)NHOR50C(O)NHSO2R50C(O)NR50SO2R50, SO2NH2, SO2Other50, SO2N(R50)2C(O)H, C(O)OH, C(N)NH2C(N)other50C(N)N(R50)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R50is an R51, R52, R53or R54;

R51represents phenyl, which secondinterval or fused with benzene, heteroatom or R51A; R51Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R52is heteroaryl that secondinterval or fused with benzene, heteroatom or R52A ; R52Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R53is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R53A; R53Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R54represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R55, OR55, SR55, S(O)R55, SO2R55C(O)R55, CO(O)R55, OC(O)R55, OC(O)OR55, NH2, Other55N(R55)2, NHC(O)R55, NR55C(O)R55NHS(O)2R55, NR55S(O)2R55, NHC(O)OR55, NR55C(O)OR55, NHC(O)NH2, NHC(O)other55, NHC(O)N(R55)2, NR55C(O)other55, NR55C(O)N(R55)2C(O)NH2C(O)other55C(O)N(R55)2C(O)NHOH, C(O)NHOR55C(O)NHSO2R55C(O)NR55SO2R55, SO2NH2, SO2Other55, SO2N(R55)2C(O)H, C(O)OH, C(N)NH2C(N)other55C(N)N(R55)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R55pre is represents an alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen; and

where each of these following cyclic groups is independently unsubstituted, no further substitutions, substituted or optionally substituted with one, or two, or three, or four, or five substituents independently selected from R57A, R57, OR57, SR57, S(O)R57, SO2R57C(O)R57, CO(O)R57, OC(O)R57, OC(O)OR57, NH2, Other57N(R57)2, NHC(O)R57, NR57C(O)R57NHS(O)2R57, NR57S(O)2R57, NHC(O)OR57, NR57C(O)OR57, NHC(O)NH2, NHC(O)other57, NHC(O)N(R57)2, NR57C(O)other57, NR57C(O)N(R57)2C(O)NH2C(O)other57C(O)N(R57)2C(O)NHOH, C(O)NHOR57C(O)NHSO2R57C(O)NR57SO2R57, SO2NH2, SO2Other57, SO2N(R57)2C(O)H, C(O)OH, C(N)NH2C(N)other57C(N)N(R57)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R57Arepresents spirocyclic;

R57is an R58, R59, R60or R61;

R58represents phenyl, which secondinterval or condensive is with benzene, heteroatom or R58A; R58Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R59is heteroaryl that secondinterval or fused with benzene, heteroatom or R59A; R59Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R60is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R60A; R60Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R61represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R62, OR62, SR62, S(O)R62, SO2R62C(O)R62, CO(O)R62, OC(O)R62, OC(O)OR62, NH2, Other62N(R62)2, NHC(O)R62, NR62C(O)R62NHS(O)2R62, NR62S(O)2R62, NHC(O)OR62, NR62C(O)OR62, NHC(O)NH2, NHC(O)other62, NHC(O)N(R62)2, NR62C(O)other62, NR62C(O)N(R62)2C(O)NH2C(O)other62C(O)N(R62)2C(O)NHOH, C(O)NHOR62C(O)NHSO2R62C(O)NR62SO2R62, SO2 NH2, SO2Other62, SO2N(R62)2C(O)H, C(O)OH, C(N)NH2C(N)other62C(N)N(R62)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R62is an R63, R64, R65or R66;

R63represents phenyl, which secondinterval or fused with benzene, heteroatom or R63A; R63Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R64is heteroaryl that secondinterval or fused with benzene, heteroatom or R64A; R64Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R65is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R65A; R65Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R66represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R67, OR67, SR67, S(O)R67, SO2R67C(O)R67, CO(O)R67, OC(O)R67OC(O)OR 67, NH2, Other67N(R67)2, NHC(O)R67, NR67C(O)R67NHS(O)2R67, NR67S(O)2R67, NHC(O)OR67, NR67C(O)OR67, NHC(O)NH2, NHC(O)other67, NHC(O)N(R67)2, NR67C(O)other67, NR67C(O)N(R67)2C(O)NH2C(O)other67C(O)N(R67)2C(O)NHOH, C(O)NHOR67C(O)NHSO2R67C(O)NR67SO2R67, SO2NH2, SO2Other67, SO2N(R67)2C(O)H, C(O)OH, C(N)NH2C(N)other67C(N)N(R67)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I substituents;

R67represents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen;

where the group represented by R57A, R58, R59, R60, R63, R64, R65and R67are unsubstituted or substituted one, or two, or three, or four substituents, independently selected from R68, OR68, SR68, S(O)R68, SO2R68C(O)R68, CO(O)R68, OC(O)R68, OC(O)OR68, NH2, Other68N(R68)2, NHC(O)R68, NR68C(O)R68NHS(O)2R68, NR68S(O)2R68, NHC(O)OR68, NR68C(O)OR68, NHC(O)NH2, NHC(O)other68, NH(O)N(R 68)2, NR68C(O)other68, NR68C(O)N(R68)2C(O)NH2C(O)other68C(O)N(R68)2C(O)NHOH, C(O)NHOR68C(O)NHSO2R68C(O)NR68SO2R68, SO2NH2, SO2Other68, SO2N(R68)2C(O)H, C(O)OH, C(N)NH2C(N)other68C(N)N(R68)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R68is an R69, R70, R71or R72;

R69represents phenyl, which secondinterval or fused with benzene, heteroatom or R69A; R69Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R70is heteroaryl that secondinterval or fused with benzene, heteroatom or R70A; R70Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R71is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R71A; R71Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R72represents alkyl, alkenyl or alkenyl, each of which is who I am unsubstituted or substituted by one, or two, or three substituents independently selected from R73, OR73, SR73, S(O)R73, SO2R73C(O)R73, CO(O)R73, OC(O)R73, OC(O)OR73, NH2, Other73N(R73)2, NHC(O)R73, NR73C(O)R73NHS(O)2R73, NR73S(O)2R73, NHC(O)OR73, NR73C(O)OR73, NHC(O)NH2, NHC(O)other73, NHC(O)N(R73)2, NR73C(O)other73, NR73C(O)N(R73)2C(O)NH2C(O)other73C(O)N(R73)2C(O)NHOH, C(O)NHOR73C(O)NHSO2R73C(O)NR73SO2R73, SO2NH2, SO2Other73, SO2N(R73)2C(O)H, C(O)OH, C(N)NH2C(N)other73C(N)N(R73)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R73represents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen; and

groups represented by R69, R70and R71are unsubstituted or substituted one, or two, or three, or four substituents, independently selected from NH2C(O)NH2C(O)NHOH, SO2NH2, CF3, CF2CF3,C(O)H, C(O)OH, C(N)NH2, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I.

p> Another variant embodiment of the invention relates to compounds having formula (II):

or its therapeutically acceptable salts, where

R100has the same values as described for substituents on R26;

n is 0, 1, 2 or 3;

R101has the same values as described for substituents on R42;

m is 1, 2, 3, 4 or 5;

A1represents N or C(A2);

A2represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

B1represents H, R1, OR , SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

D1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)21SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

E1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; and

Y1represents H, CN, NO2C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R17OR 17C(O)R17C(O)OR17, SR17, SO2R17, NH2, Other17N(R17)2, NHC(O)R17C(O)NH2C(O)other17C(O)N(R17)2NHS(O)R17or NHSO2R17; or

E1and Y1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

A2B1and D1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

Y1and B1together with the atoms to which o is attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

A2D1and E1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

A2and B1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

D1E1and Y1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1 , OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

A2and D1together with the atoms to which they are attached, are benzene, naphthalene, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

B1E1and Y1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2N 2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

R1is an R2, R3, R4or R5;

R1Ais cycloalkyl, cycloalkenyl or cycloalkenyl;

R2represents phenyl, which secondinterval or fused with benzene, heteroatom or R2A; R2Ais cycloalkane or geteroseksualen;

R3is heteroaryl that secondinterval or fused with benzene, heteroatom or R3A; R3Ais cycloalkane or geteroseksualen;

R4is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R4A; R4Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R5depict is to place an alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R6, NC(R6A)(R6B), R7, OR7, SR7, S(O)R7, SO2R7, Other7N(R7)2C(O)R7C(O)NH2,C(O)other7C(O)N(R7)2, NHC(O)R7, NR7C(O)R7, NHSO2R7, NHC(O)OR7, SO2NH2, SO2Other7, SO2N(R7)2, NHC(O)NH2, NHC(O)other7, NHC(O)CH(CH3)NHC(O)CH(CH3)NH2, NHC(O)CH(CH3)NHC(O)CH(CH3)Other1, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R6represents a C2-C5-spiralcell, each of which is unsubstituted or substituted by OH, (O), N3CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH(CH3) or N(CH3)2;

R6Aand R6Bindependently selected from alkyl or together with the N atom to which they are attached, represent R6C;

R6Cis aziridine-1-yl, azetidin-1-yl, pyrrolidin-1-yl or piperidine-1-yl, each of which contains a single CH2group, nezamenimoy or replaced with O, C(O), CNOH, CNOCH3, S, S(O), SO2or NH;

R7is an R8, R9, R10or R11;

R8represents phenyl, to the which secondinterval or fused with benzene, heteroatom or R8A; R8Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R9is heteroaryl that secondinterval or fused with benzene, heteroatom or R9A; R9Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R10is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R10A; R10Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R11represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R12, OR12, SR12, S(O)R12, SO2R12C(O)R12, CO(O)R12, OC(O)R12, OC(O)OR12, NH2, Other12N(R12)2, NHC(O)R12, NR12C(O)R12NHS(O)2R12, NR12S(O)2R12, NHC(O)OR12, NR12C(O)OR12, NHC(O)NH2, NHC(O)other12, NHC(O)N(R12)2, NR12C(O)other12, NR12C(O)N(R12)2C(O)NH2C(O)other12C(O)N(R12)2C(O)NHOH, C(O)NHOR12C(O)NHSO2R12C(O)NR12SO2R12, SO2NH 2, SO2Other12, SO2N(R12)2C(O)H, C(O)OH, C(N)NH2C(N)other12C(N)N(R12)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R12is an R13, R14, R15or R16;

R13represents phenyl, which secondinterval or fused with benzene, heteroatom or R13A; R13Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R14is heteroaryl that secondinterval or fused with benzene, heteroatom or R14A; R14Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R15is cycloalkane, cycloalkene, geteroseksualen or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R15A; R15Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R16represents alkyl, alkenyl or quinil;

R17is an R18, R19, R20or R21;

R18represents phenyl, which secondinterval or fused with benzene, heteroatom or R18A; R18Ais Soboh cycloalkane, cycloalken, geteroseksualen or geteroseksualen;

R19is heteroaryl that secondinterval or fused with benzene, heteroatom or R19A; R19Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R20is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R20A; R20Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R21represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R22, OR22, SR22, S(O)R22, SO2R22C(O)R22, CO(O)R22, OC(O)R22, OC(O)OR22, NH2, Other22N(R22)2, NHC(O)R22, NR22C(O)R22NHS(O)2R22, NR22S(O)2R22, NHC(O)OR22, NR22C(O)OR22, NHC(O)NH2, NHC(O)other22, NHC(O)N(R22)2, NR22C(O)other22, NR22C(O)N(R22)2C(O)NH2C(O)other22C(O)N(R22)2C(O)NHOH, C(O)NHOR22C(O)NHSO2R22C(O)NR22SO2R22, SO2NH2, SO2Other22, SO2N(R22)2C(O)H, C(O)OH, CN)NH 2C(N)other22C(N)N(R22)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R22is an R23, R24or R25;

R23represents phenyl, which secondinterval or fused with benzene, heteroatom or R23A; R23Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R24represents heteroaryl that secondinterval or fused with benzene, heteroatom or R24A; R24Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R25is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R25A; R25Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

Z2is an R28, R29or R30;

Z1Aand Z2Aboth were missing or taken together form CH2CH2CH2or Z12A;

Z12Arepresents a C2-C6-alkylene, in which one or two groups CH2replaced by NH, N(CH3), S, S(O) or SO2;

L1is an R3737, SR37, S(O)R37, SO2R37C(O)R37, CO(O)R37, OC(O)R37, OC(O)OR37, Other37C(O)NH, C(O)NR37C(O)NHOR37C(O)NHSO2R37, SO2NH, SO2Other37C(N)NH, C(N)other37;

R28represents a phenylene, which secondinterval or fused with benzene, heteroatom or R28A; R28Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R29represents heteroaryl that secondinterval or fused with benzene or heteroatom or R29A; R29Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R30is cycloalkyl, cycloalkenyl, heterocyclochain or heterocyclization, each of which secondinterval or fused with benzene, heteroatom or R30A; R30Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R37represents a bond, or R37A;

R37Ais alkylen, albaniles or akinyan, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R37B, OR37B, SR37B, S(O)R37B, SO2R37BC(O)R37B, CO(O)R37B, OC(O)R37B, OC(O)OR37B , NH2, Other37BN(R37B)2, NHC(O)R37B, NR37BC(O)R37BNHS(O)2R37B, NR37BS(O)2R37B, NHC(O)OR37B, NR37BC(O)OR37B, NHC(O)NH2, NHC(O)other37B, NHC(O)N(R37B)2, NR37BC(O)other37B, NR37BC(O)N(R37B)2C(O)NH2C(O)other37BC(O)N(R37B)2C(O)NHOH, C(O)NHOR37BC(O)NHSO2R37BC(O)NR37BSO2R37B, SO2NH2, SO2Other37B, SO2N(R37B)2C(O)H, C(O)OH, C(N)NH2C(N)other37BC(N)N(R37B)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br and I substituents;

R37Brepresents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen;

Z3is an R38, R39or R40;

R38represents phenyl, which secondinterval or fused with benzene, heteroatom or R38A; R38Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R39is heteroaryl that secondinterval or fused with benzene, heteroatom or R39A; R39Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R40pre is is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R40A; R40Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

where the group represented by R42independently substituted with one, or two, or three, or four substituents, independently selected from R50, OR50, SR50, S(O)R50, SO2R50C(O)R50, CO(O)R50, OC(O)R50, OC(O)OR50, NH2, Other50N(R50)2, NHC(O)R50, NR50C(O)R50NHS(O)2R50, NR50S(O)2R50, NHC(O)OR50, NR50C(O)OR50, NHC(O)NH2, NHC(O)other50, NHC(O)N(R50)2, NR50C(O)other50, NR50C(O)N(R50)2C(O)NH2C(O)other50C(O)N(R50)2C(O)NHOH, C(O)NHOR50C(O)NHSO2R50C(O)NR50SO2R50, SO2NH2, SO2Other50, SO2N(R50)2C(O)H, C(O)OH, C(N)NH2C(N)other50C(N)N(R50)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R50is an R51, R52, R53or R54;

R51represents phenyl, which secondinterval or fused with benzene, heteroatom or R51A ; R51Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R52is heteroaryl that secondinterval or fused with benzene, heteroatom or R52A; R52Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R53is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R53A; R53Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R54represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R55, OR55, SR55, S(O)R55, SO2R55C(O)R55, CO(O)R55, OC(O)R55, OC(O)OR55, NH2, Other55N(R55)2, NHC(O)R55, NR55C(O)R55NHS(O)2R55, NR55S(O)2R55, NHC(O)OR55, NR55C(O)OR55, NHC(O)NH2, NHC(O)other55, NHC(O)N(R55)2, NR55C(O)other55, NR55C(O)N(R55)2C(O)NH2C(O)other55C(O)N(R55)2C(O)NHOH, C(O)NHOR55C(O)NHSO2R55C(O)NR55SO2R55, SO2NH2, SO2Other5 , SO2N(R55)2C(O)H, C(O)OH, C(N)NH2C(N)other55C(N)N(R55)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R55represents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen; and

where R26also, is unsubstituted or further substituted, and each of the above cyclic group is independently unsubstituted, no further substitutions, substituted or optionally substituted with one, or two, or three, or four, or five substituents independently selected from R57A, R57, OR57, SR57, S(O)R57, SO2R57C(O)R57, CO(O)R57, OC(O)R57, OC(O)OR57, NH2, Other57N(R57)2, NHC(O)R57, NR57C(O)R57NHS(O)2R57, NR57S(O)2R57, NHC(O)OR57, NR57C(O)OR57, NHC(O)NH2, NHC(O)other57, NHC(O)N(R57)2, NR57C(O)other57, NR57C(O)N(R57)2C(O)NH2C(O)other57C(O)N(R57)2C(O)NHOH, C(O)NHOR57C(O)NHSO2R57C(O)NR57SO2R57, SO2NH2, SO2Other57, SO2N(R57)2C(O)H, C(O)OH, C(N)NH2C(N)other57C(N)N(R57)2, CNOH, CNOCH3,O, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R57Arepresents spirocyclic;

R57is an R58, R59, R60or R61;

R58represents phenyl, which secondinterval or fused with benzene, heteroatom or R58A; R58Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R59is heteroaryl that secondinterval or fused with benzene, heteroatom or R59A; R59Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R60is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R60A; R60Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R61represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R62, OR62, SR62, S(O)R62, SO2R62C(O)R62, CO(O)R62, OC(O)R62, OC(O)OR62, NH2, Other62N(R62)2, NHC(O)R62, NR62C(O)R62, HS(O) 2R62, NR62S(O)2R62, NHC(O)OR62, NR62C(O)OR62, NHC(O)NH2, NHC(O)other62, NHC(O)N(R62)2, NR62C(O)other62, NR62C(O)N(R62)2C(O)NH2C(O)other62C(O)N(R62)2C(O)NHOH, C(O)NHOR62C(O)NHSO2R62C(O)NR62SO2R62, SO2NH2, SO2Other62, SO2N(R62)2C(O)H, C(O)OH, C(N)NH2C(N)other62C(N)N(R62)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R62is an R63, R64, R65or R66;

R63represents phenyl, which secondinterval or fused with benzene, heteroatom or R63A; R63Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R64is heteroaryl that secondinterval or fused with benzene, heteroatom or R64A; R64Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R65is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R65A; R65Ais cycloalkane, cycloalkene, the heterocycle is alkane or geteroseksualen;

R66represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R67, OR67, SR67, S(O)R67, SO2R67C(O)R67, CO(O)R67, OC(O)R67, OC(O)OR67, NH2, Other67N(R67)2, NHC(O)R67, NR67C(O)R67NHS(O)2R67, NR67S(O)2R67, NHC(O)OR67, NR67C(O)OR67, NHC(O)NH2, NHC(O)other67, NHC(O)N(R67)2, NR67C(O)other67, NR67C(O)N(R67)2C(O)NH2C(O)other67C(O)N(R67)2C(O)NHOH, C(O)NHOR67C(O)NHSO2R67C(O)NR67SO2R67, SO2NH2, SO2Other67, SO2N(R67)2C(O)H, C(O)OH, C(N)NH2C(N)other67C(N)N(R67)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I substituents;

R67represents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen;

where the group represented by R57A, R58, R59, R60, R63, R64, R65and R67are unsubstituted or substituted one, or two, or three, or four substituents, independently selected from R68OR 68, SR68, S(O)R68, SO2R68C(O)R68, CO(O)R68, OC(O)R68, OC(O)OR68, NH2, Other68N(R68)2, NHC(O)R68, NR68C(O)R68NHS(O)2R68, NR68S(O)2R68, NHC(O)OR68, NR68C(O)OR68, NHC(O)NH2, NHC(O)other68, NHC(O)N(R68)2, NR68C(O)other68, NR68C(O)N(R68)2C(O)NH2C(O)other68C(O)N(R68)2C(O)NHOH, C(O)NHOR68C(O)NHSO2R68C(O)NR68SO2R68, SO2NH2, SO2Other68, SO2N(R68)2C(O)H, C(O)OH, C(N)NH2C(N)other68C(N)N(R68)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R68is an R69, R70, R71or R72;

R69represents phenyl, which secondinterval or fused with benzene, heteroatom or R69A; R69Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R70is heteroaryl that secondinterval or fused with benzene, heteroatom or R70A; R70Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R71is cycloalkyl, cycloalkenyl, heteroseksualci or heterocicluri, each secondinterval or fused with benzene, heteroatom or R71A; R71Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R72represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R73, OR73, SR73, S(O)R73, SO2R73C(O)R73, CO(O)R73, OC(O)R73, OC(O)OR73, NH2, Other73N(R73)2, NHC(O)R73, NR73C(O)R73NHS(O)2R73, NR73S(O)2R73, NHC(O)OR73, NR73C(O)OR73, NHC(O)NH2, NHC(O)other73, NHC(O)N(R73)2, NR73C(O)other73, NR73C(O)N(R73)2C(O)NH2C(O)other73C(O)N(R73)2C(O)NHOH, C(O)NHOR73C(O)NHSO2R73C(O)NR73SO2R73, SO2NH2, SO2Other73, SO2N(R73)2C(O)H, C(O)OH, C(N)NH2C(N)other73C(N)N(R73)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R73represents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen; and

groups represented by R69, R70and R71are tamaseni or substituted by one, or two, or three, or four substituents, independently selected from NH2C(O)NH2C(O)NHOH, SO2NH2, CF3, CF2CF3,C(O)H, C(O)OH, C(N)NH2, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I.

Yet another variant embodiment of the invention concerns the compounds of formula I or formula II, where A1represents(A2); and A2represents H.

Yet another variant embodiment of the invention concerns the compounds of formula I or formula II, where A1represents(A2or N; A2represents H; and B1represents other1.

Yet another variant embodiment of the invention concerns the compounds of formula I or formula II, where A1represents(A2or N; A2represents H; B1represents other1; and D1represents H.

Yet another variant embodiment of the invention concerns the compounds of formula I or formula II, where A1represents(A2or N; A2represents H; B1represents other1; D1represents H; and E1represents H.

Yet another variant embodiment of the invention concerns the compounds of formula I or formula II, where A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.

Yet another variant embodiment of the invention relates to compounds having formula I, which are

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfo the Il)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(hydroxymethyl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((1-methyl-1H-indol-4-yl)oxy)benzamide;

2-(3-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-mpirun-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(3-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-methoxyphenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(dimethylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-6-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)-3-oxopropyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfo the Il)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)-2-oxoethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)propyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)-N,N-dimethylbenzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-morpholine-4-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2,4-dimethyl-1,3-thiazol-5-yl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(3,5-dichlorophenoxy)-N-((4-((methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)ethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-isopropylpiperazine-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indiso the-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-ethylpiperazin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((1,2,2,6,6-pentamethylpiperidin-4-yl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((3-nitro-4-((1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((7-fluoro-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((4'-chloro-4-(2-pyrrolidin-1-ileti-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indazol-4-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)-2-(3-(trifluoromethyl)phenoxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chloro-4-pertenece)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclo the UNT-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2-chloro-3-(trifluoromethyl)phenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-cyclopropylidene-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indol-4-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((1-methyl-1H-indol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholine-4-elfenix)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((3-(3-morpholine-4-yl-3-oxopropyl)-1H-indol-5-yl)oxy)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)Pipera the Jn-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-morpholine-4-yl-3-oxopropyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-morpholine-4-ylpropyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(1H-imidazol-1-yl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)benzyl(ethyl)carbamate;

tert-butyl 3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)benzyl(ethyl)carbamate;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((this is a melamine)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenylcarbamate;

2-(1,1'-biphenyl-2-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenylcarbamate;

2-(1,1'-biphenyl-3-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholine-4-elfenix)-N-((3-nitro-4-((then it is carbonated the ro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenyl)piperazine-1-carboxylate;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-morpholine-4-ylethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

tert-butyl 4-(4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-1-carboxylate;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-Mohali the-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-pyridin-4-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-4-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridine-3-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((1-methyl-1H-benzimidazole-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylcarbamoyl)phenoxy)-N-(4-(3-morpholinopropan)-3-nitrophenylarsonic)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-N-(4-(3-(dimethylamino)propylamino)-3-nitrophenylarsonic)-2-(3-(methylcarbamoyl)phenoxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

1064-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-(dimethylamino)propyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-(hydroxym the Teal)phenoxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((4-methoxybenzyl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

N-(4-((4-aminotetraline-2H-Piran-4-yl)methylamino)-3-nitrophenylarsonic)-2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzamide;

4-(4-(1-(4'-chlorobiphenyl-2-yl)ethyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)phenylsulfonyl)benzamide;

N-{[4-{4-[(4'-chloro-1,1'-biphenyl-2-yl)methyl]piperazine-1-yl}-2-(3,5-dichlorophenoxy)phenyl]sulfonyl}-4-[(1-methylpiperidin-4-yl)amino]-3-nitrobenzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpho is in 4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(4-pertenece)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2,3-divergence)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-pertenece)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-pertenece)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]IU the Il}piperazine-1-yl)-2-(2-pertenece)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-pertenece)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(3-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2,3-divergence)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-ylmethyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

1364-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-[(3-nitro-4-{[1-(Tien-3-ylmethyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(2-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(3-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(4-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-[(4-{[1-(2-foradil)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}Pipa is Azin-1-yl)-N-[(4-{[3-(4-methylpiperazin-1-yl)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

N-({4-[(1-arylpiperazine-4-yl)amino]-3-nitrophenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl)amino]phenyl}sulfonyl)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-6-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-6-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclo the CEN-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-[(4-{[(1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(4-fluoro-1H-indol-5-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[3-(methoxyethoxy)-2-methylphenoxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-hydroxy-2-methylphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-(3-iodinase)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorine is enyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(2-hydroxyethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[1-(2-phenylethyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3,4-dichlorophenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3,5-divergence)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-methoxyphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[3-(hydroxymethyl)phenoxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dimethylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dimethylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({1-[2-(2-methoxyethoxy)ethyl]piperidine-4-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-(2-chloro-3-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[1-(3-phenylpropyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(2-methoxyethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-ethylpiperazin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-isopropylpiperazine-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-hydroxyphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-and the]methyl}piperazine-1-yl)-2-(2-methoxyphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-methylphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-methylphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[6-(4-chlorophenyl)-1,3-benzodioxol-5-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl} is piperazin-1-yl)-N-{[4-({1-[2-(dimethylamino)-2-oxoethyl]piperidine-4-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(2-morpholine-4-retil)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

N-[(4-{[(4-aminotetraline-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-hydroxy-1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3S)-1-methylpyrrolidine-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3R)-1-methylpyrrolidine-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[3-(1H-pyrrol-2-yl)phenoxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-[(4-{[(4-hydroxy-1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)amino]carbonyl}phenoxy)-1H-indole-1-carboxylate;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-(dimethylamino)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-(diethylamino)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

TRANS-2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-{4-[1-(4'-chloro-1,1'-biphenyl-2-yl)ethyl]piperazine-1-yl}-2-(2-chlorophenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroximino the si)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-({1,3-bis[(4-methylpiperazin-1-yl)methyl]-1H-indol-4-yl}oxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-({3-[(4-methylpiperazin-1-yl)methyl]-1H-indol-4-yl}oxy)benzamide;

2-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(4-(1-methylpiperidin-4-ylamino)-3-nitrophenylacetylene)phenoxy)-N,N-dimethylbenzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-mpirun-4-reparacin-4-yl)amino]phenyl}sulfonyl)-2-{[2-(trifluoromethyl)-1H-indol-4-yl]oxy}benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-{[6-(trifluoromethyl)-1H-indol-5-yl]oxy}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)-2-{[6-(trifluoromethyl)-1H-indol-5-yl]oxy}benzamide;

2-[(2-amino-1,3-thiazol-4-yl)methoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

tert-butyl 4-[(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)amino]carbonyl}phenoxy)methyl]-1,3-thiazole-2-ylcarbamate;

2-[(2-amino-1,3-thiazol-4-yl)methoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(2-chlorophenyl)amino]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-methoxy-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(2-chlorophenyl)amino]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

tert-butyl 5-[5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]amino}carbonyl)phenoxy]-1H-indole-1-carboxylate;

2-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]-2-[(6,7-debtor-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(2-hydroc the and-1-tetrahydro-2H-Piran-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[4-({[4-(hydroxymethyl)tetrahydro-2H-Piran-4-yl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[1-(1,3-the thiazole-4-ylmethyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

N-[(4-{[(4-aminotetraline-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-ylmethyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[(3S,4R)-3-hydroxy-1-(1,3-thiazol-4-ylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[4-(hydroxymethyl)tetrahydro-2H-Piran-4-yl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[3-nitro-4-(tetrahydro-2H-Piran-4-ylamino)phenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[4-(morpholine-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(morpholine-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

2-(6-aminopyridine-3-yl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{1-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]ethyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)be semid;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3S)-tetrahydro-2H-Piran-3-ylmethyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3R)-tetrahydro-2H-Piran-3-ylmethyl]amino}phenyl)sulfonyl]benzamide;

tert-butyl 5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate;

2-[(6-aminopyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(2-methoxyethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy] - N-{[3-nitro-4-(tetrahydro-2H-Piran-4-ylethoxy)phenyl]sulfonyl}benzamide;

2-[(3-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(3-chloro-1H-indol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-({4-[(2-methoxyethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

tert-butyl 5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

tert-butyl 4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

2-[(6-aminopyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-and the]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(2-aminopyridine-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-3-ylcarbamate;

2-[(5-aminopyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-nitro-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

2-[(3-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(2-aminopyridine-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-hydroxypyridine-3-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-{[6-(benzyloxy)pyridin-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(1,4-dioxane-2-ylethoxy)-3-nitrophenyl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-[(3-chloro-1H-indol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-ACS the-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(1,4-dioxane-2-ylethoxy)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-Porterage-2H-Piran-4-yl)method is si]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-{[3-(2-amino-ethyl)-1H-indol-5-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-{[3-(2-amino-ethyl)-1H-indol-5-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-[(6-amino-5-herperidin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-chloro-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical) the Mino]-3-nitrophenyl}sulfonyl)-2-[(1-oxo-1,2,3,4-tetrahydroisoquinoline-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(1,4-dioxane-2-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-{[5-bromo-6-(1,4-dioxane-2-ylethoxy)pyridine-3-yl]sulfonyl}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-N-({5-bromo-6-[(4-morpholine-4-illlogical)amino]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-cyano-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-(3-amino-5-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(2-morpholine-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)oxy]-3-nitrophenyl}sulfonyl)benzamide;

N-({5-bromo-6-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazin-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[5-(4-chlorophenyl)-2,3,6,7-tetrahydroxy-4-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[5-(4-chlorophenyl)-2,3,6,7-tetrahydroxy-4-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-albut-2-inyl)oxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[1-(methylsulphonyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-ill logical)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(2-methoxyethyl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-ethinyl-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-{[5-ethinyl-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-cyano-6-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)oxy]pyridin-3-yl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-ethylmorpholine-3-yl)metox the]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3S)-1-tetrahydro-2H-Piran-4-reparacin-3-yl]amino}phenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,1-diocletianopolis-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydrofuran-3-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-N-({5-bromo-6-[(4-morpholine-4-illlogical)oxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-(dicyclopropyl)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(tetrahydro-2H-Piran-4-ylamino)cyclohexyl]amino}phenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(4-tetrahydro-2H-Piran-4-reparation-1-yl)cyclohexyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[(4-hydroxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({3-[3-(dimethylamino)propyl]-1H-indol-4-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({3-[3-(dimethylamino)propyl]-1H-indol-4-yl}oxy)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropyl-4-foreperiod-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[1-(4-methoxybenzyl)-1H-1,2,3-benzotriazol-4-yl]oxy}-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethyl who ekloges-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(1,4-dioxane-2-ylethoxy)-3-nitrophenyl]sulfonyl}benzamide;

TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-amino-5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}-phenoxy)nicotinamide;

2-[(6-amino-5-cyano-3-yl)oxy]-4-(4-{[2-(4-�lorgeril)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3R)-1-(2,2-dottorati)pyrrolidin-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-{[6-(acetylamino)pyridin-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({6-[(methylsulphonyl)amino]pyridine-3-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({(3R)-1-[2-fluoro-1-(permitil)ethyl]pyrrolidin-3-yl}amino)-3-nitrophenyl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-di is ethylcyclohexyl-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-methylpyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-oxetan-3-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-isopropylpyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-cyclopropylmethyl-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-cyclopropylmethyl-2-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3R)-1-cyclopropylboronic-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({4-fluoro-1-[2-fluoro-1-(permitil)ethyl]piperidine-4-yl}methoxy)-3-nitrophenyl]sulfonyl}benzamide;

tert-butyl 6-bromo-4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

tert-butyl 4-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)pyridine-2,6-childtable;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[6-(cyclopropylamino)pyridine-3-yl]oxy}-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({6-[(2,2-dottorati)amino]pyridine-3-yl}oxy)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({6-[(2,2-dottorati)amino]pyridine-3-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-{[5-chloro-6-(methylamino)pyridine-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[({4-[2-fluoro-1-(permitil)ethyl]morpholine-2-yl}methyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(2-amino-6-bromopyridin-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(2,6-diaminopyridine-4-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-(tetrahydro-2H-Piran-4-ylethoxy)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({(3R)-1-[2-fluoro-1-(permitil)ethyl]piperidine-3-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

tert-butyl 5-bromo-4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclo the Gex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(4-chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-({6-[(2,2,2-triptorelin)amino]pyridine-3-yl}oxy)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-hydroxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydrofuran-3-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({9-(4-chlorophenyl)-3-[2-fluoro-1-(permitil)ethyl]-3-azaspiro[5,5]undec-8-EN-8-yl}methyl)piperazine-1-yl]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)OK and]-4-(4-{[9-(4-chlorophenyl)-3-isopropyl-3-azaspiro[5,5]undec-8-EN-8-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[1-(N,N-dimethylphenyl)-4-foreperiod-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({(3R)-1-[2-fluoro-1-(permitil)ethyl]pyrrolidin-3-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(2-amino-5-bromopyridin-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4,4-diverticulosis)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({4'-chloro-3-[2-(dimethylamino)ethoxy]-1,1'-biphenyl-2-yl}methyl)piperazine-1-yl]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-{[5-chloro-6-({(3R)-1-[2-fluoro-1-(permitil)ethyl]pyrrolidin-3-yl}methoxy)pyridine-3-yl]sulfonyl}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[(3R)-1-(2,2-dottorati)pyrrolidin-3-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

TRANS-2-[(6-Amin is-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-cyanocyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-fluoro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[1-(2,2-dottorati)-4-foreperiod-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({3-chloro-4-[(4-Porterage-2H-Piran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[6-({4-fluoro-1-[2-fluoro-1-(permitil)ethyl]piperidine-4-yl}methoxy)-5-(trifluoromethyl)pyridine-3-yl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[2-(1H-pyrazole-4-yl)phenoxy]benzamide;

2-[2-(2-aminopyridine-3-yl)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[2-(1H-pyrazole-5-yl)phenoxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-(4,4-diverticulosis)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

N-({5-chloro-6-[(4,4-diverticulosis)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4,4-diverticulosis)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({3-chloro-4-[(4-Porterage-2H-Piran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({3-chloro-4-[(4-Porterage-2H-Piran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxycyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

tert-butyl 5-[(4-{4-[({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)carbarnoyl]-3-[(6-fluoro-1H-indol-5-yl)oxy]phenyl}piperazine-1-yl)methyl]-4-(4-chlorophenyl)-3,6-dihydropyridines-1(2H)-carboxylate;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(-{[4-(4-chlorophenyl)-1-(1,3-ditropan-2-yl)-1,2,5,6-tetrahydropyridine-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxycyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-({[4-(oxetan-3-yl)morpholine-2-yl]methyl}amino)phenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[3-nitro-4-({[4-(oxetan-3-yl)morpholine-2-yl]methyl}amino)phenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-the l)-N-{[5-chloro-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(TRANS-4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-fluoro-1-(oxetan-3-yl)piperidine-4-yl]methoxy}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimetallic ohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(TRANS-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(TRANS-4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(CIS-4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(CIS-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-chloro-4-(tetrahydro-2H-Piran-4-ylethoxy)phenyl]sulfonyl}-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-cyclopropylmethyl-2-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-(2-oxaspiro[3,5]non-7-ylethoxy)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-habiri the Jn-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[(2S)-4-cyclopropylmethyl-2-yl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(TRANS-1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(CIS-1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-N-({5-chloro-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-2-[(3-chloro-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(CIS-4-ethyl-4-hydroxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-({[(2S)-4-(oxetan-3-yl)morpholine-2-yl]methyl}amino)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-nitro-6-[(tetrahydro-2H-Piran-4-ylmethyl)amino]pyridine-3-yl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(2-oxaspiro[3,5]non-7-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[TRANS-4-(morpholine-4-yl)cyclohexyl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[CIS-4-(morpholine-4-yl)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-cyano-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[4-({[4-(methoxymethyl)cyclohexyl]methyl}amino)-3-nitrophenyl]sulfonyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[(3R)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino}phenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[(3S)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino}phenyl)sulfonyl]benzamide;

N-[4-({2-[(6-amino-5-lipiridy-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzoyl}sulfamoyl)-2-nitrophenyl]morpholine-4-carboxamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzoyl}sulfamoyl)-2-nitrophenyl]-4-cyanopiperidine-1-carboxamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[(3R)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino}phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to can-4-(4-{[2-(4-harfe who yl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(tetrahydro-2H-Piran-4-ylamino)cyclohexyl]amino}phenyl)sulfonyl]benzamide; and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3S)-tetrahydro-2H-Piran-3-ylmethyl]amino}phenyl)sulfonyl]benzamide; and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide; and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3,4-dichlorophenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and m is the metabolites.

Yet another variant embodiment of the invention relates to 2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-isopropylpiperazine-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-6-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-is)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide; and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Another variant embodiment of the invention relates to compositions for treating bladder cancer, brain cancer, breast cancer, cancer of the bone marrow, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoblastic leukemia from precursor T-cells or B-cells, melanoma, myeloid leukemia, myeloma, cancer of the oral cavity, ovarian cancer, lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small-cell lung cancer or cancer of the spleen, while this composition contains the excipient and a therapeutically effective amount of the compounds of formula (I).

Another variant embodiment of the invention relates to a method for treating bladder cancer, brain cancer, breast cancer, cancer of the bone marrow, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoblastic leukemia from precursor T-cells or B-cells, melanoma, myeloid leukemia, myeloma, cancer of the oral cavity, ovarian cancer, non-small cell lung cancer, the HRO is practical lymphoblastic myeloma, prostate cancer, small-cell lung cancer or cancer of the spleen in a patient, where the method includes the introduction to the patient a therapeutically effective amount of the compounds of formula (I).

Another variant embodiment of the invention relates to a method for treating bladder cancer, brain cancer, breast cancer, cancer of the bone marrow, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoblastic leukemia from precursor T-cells or B-cells, melanoma, myeloid leukemia, myeloma, cancer of the oral cavity, ovarian cancer, lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small-cell lung cancer or spleen in a patient, where this method includes the introduction to the patient a therapeutically effective amount of the compounds of formula (I) and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent.

DETAILED description of the INVENTION

Variable groups represented here by symbols (capital letters with numeric and/or alphabetic superscripts) and can be specifically expressed.

Note that rela is eastwoodiae valence observed for all groups and combinations thereof, what a monovalent group, having more than one atom, pictured from left to right and connected at their left ends, and that divalent group also depicted from left to right.

It should also be noted that the specific embodiments of variable groups may be the same or different, while other specific embodiments of have the same value.

The term "alkenyl", as used here, refers to a straight or branched hydrocarbon chain containing from 2 to 10 carbon atoms and having at least one carbon-carbon double bond. The term “Cx-Cyalkyl” denotes a straight or branched hydrocarbon chain containing at least one carbon-carbon double bond and having from x to y carbon atoms. The term “C2-C4alkenyl” means alkenylphenol group containing 2-4 carbon atoms. Representative examples of alkenyl include, but are not limited to, buta-2,3-dienyl, ethynyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2-heptenyl, 2-methyl-1-Heptene and 3-decenyl.

The term "albaniles" denotes a divalent group derived straight or branched hydrocarbon chain of 2-4 carbon atoms, and containing at least one carbon-carbon double bond. The term “Cx-Cy alkylene” denotes a divalent group derived straight or branched hydrocarbon chain containing at least one carbon-carbon double bond and having from x to y carbon atoms. Representative examples of Alcanena include, but are not limited to, -CH=CH - and-CH2CH=CH-.

The term "alkyl", as used here, refers to a straight or branched saturated hydrocarbon chain containing from 1 to 10 carbon atoms. The term “CX-Cyalkyl” denotes a straight or branched chain saturated hydrocarbon containing from x to y carbon atoms. For example, “C2-C10alkyl” denotes a straight or branched chain saturated hydrocarbon containing from 2 to 10 carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-etylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl and n-decyl.

The term "alkylene" denotes a divalent group derived straight or branched saturated hydrocarbon chain of from 1 to 10 carbon atoms, for example, from 1 to 4 carbon atoms. The term “Cx-Cyalkylene” denotes a divalent group derived straight or branched chain saturated hydrocarbon, sod is readuy from x to y carbon atoms. For example, “C2-C6alkylene” denotes a straight or branched chain saturated hydrocarbon containing from 2 to 6 carbon atoms. Examples of alkylene include, but are not limited to, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2- and-CH2CH(CH3)CH2-.

The term "quinil", as used here, refers to a straight or branched chain hydrocarbon group containing from 2 to 10 carbon atoms and having at least one carbon-carbon triple bond. The term “Cx-Cyquinil” denotes a straight or branched chain hydrocarbon groups that contain from x to y carbon atoms. Representative examples of quinil include, but are not limited to, acetylenyl, 1-PROPYNYL, 2-PROPYNYL, 3-butynyl, 2-pentenyl and 1-butynyl.

The term "akinyan", as used here, denotes a divalent radical derived straight or branched chain hydrocarbon group containing from 2 to 10 carbon atoms and having at least one carbon-carbon triple bond.

The term "aryl", as used here, refers to phenyl.

The term "cyclic group", as used here, refers to benzene, phenyl, phenylene, cycloalkane, cycloalkyl, cycloalkyl, cycloalkene, cycloalkenyl, cycloalkenyl, cycloalkyl, qi is alkinyl, cycloalkenyl, heteroaryl, heteroaryl, geteroseksualen, heteroseksualci, geteroseksualen, geteroseksualen and spiralcell.

The term "cycloalkyl", or cycloalkyl", or “cycloalkyl”, as used here, refers to monocyclic or bridged hydrocarbon ring system. Monocyclic cycloalkyl is a carbocyclic ring system containing three to eight carbon atoms, and no heteroatoms and without double bonds. Examples of monocyclic ring systems include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Monocyclic ring may contain one or two alkilinity bridge, each of which consists of one, two or three carbon atoms attached to the two non-adjacent carbon atoms of the ring system. Non-limiting examples of such bridge cycloalkyl ring systems include bicyclo[3.1.1]heptane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonan, bicyclo[3.3.1]nonan, bicyclo[4.2.1]nonan, tricyclo[3.3.1.03,7]nonan (octahydro-2,5-methanoindene or noradsanta) and tricyclo[3.3.1.13,7]decane (adamantane). Monocyclic and bridged cycloalkyl can be attached to the main molecular group via any suitable atom present in the ring system.

The term "cycloalkenyl", or "C is kloeckener", or cycloalkyl”, as used here, refers to monocyclic or bridged hydrocarbon ring system. Monocyclic cycloalkenyl contains four-, five-, six-, seven -, or eight carbon atoms and zero heteroatoms. Four-membered ring systems have one double bond, five - or six-membered ring systems have one or two double bonds, and the seven - or eight-membered ring systems have one, two or three double bonds. Representative examples of monocyclic cycloalkenyl groups include, but are not limited to, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctanol. Monocyclic cycloalkenyl ring may contain one or two alkilinity bridge, each of which consists of one, two or three carbon atoms attached to the two non-adjacent carbon atoms of the ring system. Representative examples of bicyclic cycloalkenyl groups include, but are not limited to, 4,5,6,7-tetrahydro-3aH-inden, octahydronaphthalene and 1,6-dihydroindole. Monocyclic and bicyclic cycloalkenyl can be attached to the main molecular group via any suitable atom present in the ring system.

The term "cycloalkyl", or "cycloalkenyl", or "cycloalkenyl", as used here, denotes monocyclohexyl bridged hydrocarbon ring system. Monocyclic cycloalkenyl contains eight or more carbon atoms, and zero heteroatoms and one or more triple bonds. Monocyclic cycloalkenyl ring may contain one or two alkilinity bridge, each consisting of one, two or three carbon atoms attached to the two non-adjacent carbon atoms of the ring system. Monocyclic and bridged cycloalkenyl can be attached to the main molecular group via any suitable atom contained within the ring systems.

The term "heteroaryl", or "heteroaryl", or "heteroaryl", as used here, denotes a five-membered or six-membered aromatic ring containing at least one carbon atom and one or more independently selected atoms nitrogen, oxygen or sulfur. Heteroarenes according to this invention attached via any of the adjacent atoms in the ring, provided that you meet the appropriate valence. Representative examples of heteroaryl include, but are not limited to, furanyl (including, but not limited to, furan-2-yl), imidazolyl (including, but not limited to, 1H-imidazol-1-yl), isoxazolyl, isothiazolin, oxadiazolyl, oxazolyl, pyridinyl (e.g. pyridin-4-yl, pyridine-2-yl, pyridin-3-yl), pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, tetrazolyl, thiadiazolyl,thiazolyl, thienyl (including, but not limited to, Tien-2-yl, Tien-3-yl), triazolyl and triazinyl.

The term "geteroseksualen", or "heteroseksualci", or "heterocyclochain", as used here, refers to monocyclic or bridged three-, four-, five-, six-, seven - or eight-membered ring containing at least one heteroatom independently selected from the group consisting of O, N and S, and zero double bonds. Monocyclic and bridged geteroseksualen attached to the main molecular group via any suitable carbon atom or any suitable nitrogen atom present in the ring. The heteroatoms nitrogen and sulfur heterocyclic rings optionally may be oxidized, and the nitrogen atoms may not necessarily be quaternity. Representative examples geterotsiklicheskikh groups include, but are not limited to, morpholinyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, DIOXOLANYL, tetrahydrofuranyl, thiomorpholine, dioxane, tetrahydrothieno, tetrahydrothiopyran, oxetanyl, piperazinil, imidazolidinyl, azetidin, azepane, aziridinyl, diazepan, dithiolane, dithienyl, isoxazolidine, isothiazolinones, oxadiazolidine, oxazolidinyl, pyrazolidine, tetrahydrothieno, thiadiazolidine, diazolidinyl, thiomorpholine, tritional and tritional.

The term "geteroseksualen", or "gets rocklouder", or heterocyclization", as used here, refers to monocyclic or bridged three-, four-, five-, six-, seven - or eight-membered ring containing at least one heteroatom independently selected from the group consisting of O, N and S, and one or more double bonds. Monocyclic and bridged geteroseksualen attached to the main molecular group via any suitable carbon atom or any suitable nitrogen atom present in the ring. The heteroatoms nitrogen and sulfur heterocyclic rings optionally may be oxidized, and the nitrogen atoms may not necessarily be quaternity. Representative examples geterotsiklicheskikh groups include, but are not limited to, tetrahydrocortisol, 1,4,5,6-tetrahydropyridines, 1,2,3,6-tetrahydropyridine, dihydropyran, imidazolines, isothiazolines, oxadiazolyl, isoxazolyl, oxazolyl, pyranyl, pyrazolyl, pyrrolyl, thiadiazolyl, thiazolyl and tiopronin.

The term "phenylene", as used here, denotes a divalent radical formed by removal of a hydrogen atom of the phenyl.

The term "spirooli", as used here, refers to alkylene, both ends of which are attached to the same carbon atom, and connection Examples are C2-spiralcell, C3-spiralcell, C4-spiralcell, C5/sub> -spiralcell, C6-spiralcell, C7-spiralcell, C8-spiralcell, C9-spiralcell and the like.

The term "spirolaterals", as used here, refers to spiralcell containing one or two CH2-groups are replaced with independently selected O, C(O), CNOH, CNOCH3, S, S(O), SO2or NH and one or two CH2group, nezamenennymi or replaced with N.

The term "spiroheterocyclic", as used here, denotes serialkey containing one or two CH2-groups are replaced with independently selected O, C(O), CNOH, CNOCH3, S, S(O), SO2or NH and one or two CH2group, nezamenennymi or replaced with N and also means serialkey containing one or two CH2group, nezamenennymi or replaced with independently selected O, C(O), CNOH, CNOCH3, S, S(O), SO2or NH and one or two CH2group is replaced by N.

The term "Spirito", as used here, refers to two substituents on the same carbon atom, which, together with the carbon atom to which they are attached, form cycloalkane, geteroseksualnoe, cycloalkene or geterotsyklicescoe ring.

The term "C2-C5-spiralcell", as used here, denotes a C2-spiralcell, C3-spiralcell, C4-spiralcell and C5-spiralcell.

The term "C2-Spirou the keel”, as used here, refers to al-1,2-ilen, both ends of which replace hydrogen atoms of the same CH2group.

The term "C3-spiralcell”, as used here, refers to the prop-1,3-ilen, both ends of which replace hydrogen atoms of the same CH2group.

The term "C4-spiralcell”, as used here, denotes the buta-1,4-ilen, both ends of which replace hydrogen atoms of the same CH2group.

The term "C5-spiralcell”, as used here, denotes a Penta-1,5-ilen, both ends of which replace hydrogen atoms of the same CH2group.

The term "C6-spiralcell”, as used here, denotes Gex-1,6-ilen, both ends of which replace hydrogen atoms of the same CH2group.

The term "NH protective group" as used here, refers to trichlorocyanuric, tribromoethanol, benzyloxycarbonyl, para-nitrobenzylamine, ortho-bromobenzyloxycarbonyl, chloroacetyl, dichloroacetyl, trichloroacetyl, TRIFLUOROACETYL, phenylacetyl, formyl, acetyl, benzoyl, tert-aryloxyalkyl, tert-butoxycarbonyl, para-methoxybenzeneboronic, 3,4-dimethoxyphenylacetone, 4- (phenylazo)benzyloxycarbonyl, 2-furfuryl-oxycarbonyl, diphenylcarbinol, 1,1-dimethylpropanolamine, isopropoxycarbonyl, phthaloyl, succinyl, alanyl, Laci is, 1-adamantanecarbonyl, 8-hinolincarbonova, benzyl, diphenylmethyl, triphenylmethyl, 2-nitrophenylthio, methanesulfonyl, para-toluensulfonyl, N,N-dimethylaminomethylene, benzylidene, 2-hydroxybenzylidene, 2-hydroxy-5-chlorobenzylidene, 2-hydroxy-1-naphthylmethyl, 3-hydroxy-4-pyridylmethylene, cyclohexylidene, 2-ethoxycarbonylphenyl, 2-ethoxycarbonylphenyl, 2-acetylcyclohexanone, 3,3-dimethyl-5-axillo-hexylidene, diphenylphosphoryl, dibenzoyltartaric, 5-methyl-2-oxo-2H-1,3-dioxol-4-yl-methyl, trimethylsilyl, triethylsilyl and triphenylsilane.

The term "C(O)OH protective group" as used here, denotes a methyl, ethyl, n-propyl, isopropyl, 1,1-dimethylpropyl, n-butyl, tert-butyl, phenyl, naphthyl, benzyl, diphenylmethyl, triphenylmethyl, para-nitrobenzyl, para-methoxybenzyl, bis(para-methoxyphenyl)methyl, acetylethyl, benzoylmethyl, para-nitrobenzoyl, para-bromobenzoyl, para-methanesulfonylaminoethyl, 2-tetrahydropyranyl 2-tetrahydropyranyl, 2,2,2-trichloroethyl, 2-(trimethylsilyl)ethyl, acetoxymethyl, propionylacetate, pivaloyloxymethyl, phthalimidomethyl, Succinimidyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxymethyl, methoxyethoxymethyl, 2-(trimethylsilyl)ethoxymethyl, benzoyloxymethyl, methylthiomethyl, 2-methylthioethyl, phenylthiomethyl, 1,1-dimethyl-2-propenyl, 3-methyl-3-butenyl, allyl, trimet silyl, triethylsilyl, triisopropylsilyl, diethylenediamine, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, diphenylmethylsilane and tert-butylperoxyisopropyl.

The term "OH or SH protective group" as used here, refers to benzyloxycarbonyl, 4-nitrobenzenesulfonyl, 4-bromobenzyloxycarbonyl, 4-methoxybenzenesulfonyl, 3,4-dimethoxyphenylacetone, methoxycarbonyl, etoxycarbonyl, tert-butoxycarbonyl, 1,1-dimethylpropanolamine, isopropoxycarbonyl, isobutylacetate, diphenylcarbinol, 2,2,2-trichlorocyanuric, 2,2,2-tribromoethyl, 2-(trimethylsilyl)etoxycarbonyl, 2-(phenylsulfonyl)etoxycarbonyl, 2-(triphenylphosphonio)etoxycarbonyl, 2-furfurylalcohol, 1-adamantanecarbonyl, vinyloxycarbonyl, allyloxycarbonyl, S-benzyltoluene, 4 ethoxy-1-naphthaleneboronic, 8-hinolincarbonova, acetyl, formyl, chloroacetyl, dichloroacetyl, trichloroacetyl, TRIFLUOROACETYL, methoxyacetyl, phenoxyacetyl, pivaloyl, benzoyl, methyl, tert-butyl, 2,2,2-trichloroethyl, 2-trimethylsilylmethyl, 1,1-dimethyl-2-propenyl, 3-methyl-3-butenyl, allyl, benzyl (phenylmethyl), para-methoxybenzyl, 3,4-dimethoxybenzyl, diphenylmethyl, triphenylmethyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydropyranyl, methoxymethyl, methylthiomethyl, benzoyloxymethyl, 2-methoxyethoxymethyl, 2,2,2-trichloromethyl, 2-(trimet lilil)ethoxymethyl, 1-ethoxyethyl, methanesulfonyl, para-toluensulfonyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, diethylenediamine, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, diphenylmethylsilane and tert-butylperoxyisopropyl.

Connection

These compounds can exist as geometric isomers. Compounds according to this invention may contain carbon-carbon double bond or carbon-nitrogen double bond is E or Z configuration, where the term “E” represents the order of seniority of the substituents on opposite sides of the carbon-carbon or carbon-nitrogen double bond, and the term “Z” represents the order of seniority of the substituents on the same side of the carbon-carbon or carbon-nitrogen double bond, as determined by the precedence rules of Cahn-Ingold-Prelog. Compounds according to this invention can also exist as a mixture of E and Z isomers. The substituents on cycloalkyl or heteroseksualci identified as having CIS - or TRANS-configuration. Moreover, the invention provides various isomers and mixtures thereof, formed in the different positions of the substituents in adamantanol ring system. Two substituent on one ring adamantanol ring system denoted as being of Z or E relative configuration. N instances, see C. D. Jones, M. Kaselj, R. N. Salvatore, W. J. le Noble J. Org. Chem. 1998, 63, 2758-2760 and E. L. Eliel and S. H. Wilen. (1994) Stereochemistry of Organic Compounds. New York, NY: John Wiley & Sons, Inc.

Compounds according to this invention may contain asymmetrically substituted carbon atoms of R - or S-configuration, where the terms "R" and "S" have the meanings given to IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, 13-10. Compounds having asymmetrically substituted carbon atoms with equal amounts of R and S configurations are racemic indicated carbon atoms. Atoms with an excess of one configuration relative to another are considered as having a configuration in a higher quantity, preferably an excess of about 85%-90%, more preferably with an excess of about 95%-99%, and even more preferably with an excess of more than about 99%. Accordingly, this invention includes racemic mixtures, relative and absolute stereoisomers and a mixture of relative and absolute stereoisomers.

Compounds according to this invention, the group containing NH, C(O)OH, OH or SH, can be attached forming a prodrug group. Forming a prodrug groups are removed in the process of metabolism and thereby release the compounds having a free hydroxyl, amino or carboxylate group in vivo. Prodrugs can be used to make compounds such pharmacokinet the ical properties, as the solubility and/or hydrophobicity, absorption in the gastrointestinal tract, bioavailability, danabrunetti and speed of purification. Example of connection with forming a prodrug group is [3-chloro-5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)-2-aminopyridin-1(2H)-yl]methyl dihydrophosphate (EXAMPLE 397), which is a prodrug of 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide (EXAMPLE 318).

Isotopically enriched or labeled compounds

Compounds according to the invention can exist in the isotope-labeled or isotope-enriched form, containing one or more atoms having an atomic mass or mass number different from the atomic mass or mass number most commonly found in nature. Isotopes can be radioactive or non-radioactive isotopes. Isotopes of atoms such as hydrogen, carbon, phosphorus, sulfur, fluorine, chlorine, and iodine include, but are not limited to,2H,3H,13C,14C,15N18O,32P,35S18F,36Cl125I. Compounds that contain other isotopes of these and/oráother atoms, included in the scope of this invention.

In another embodiment of the invention isotope-labeled compounds contain deuterium (2H), tritium (3H) or14C isotopes. Isotopically labeled compounds of this invention can be obtained by conventional means, well known to the ordinary person skilled in the art. Such isotope-labeled compounds of the easy way can be obtained by the methods described in these examples and Schemes, replacing on readily available isotopically labeled reagent unlabeled reagents. In some cases, the compounds may be processed isotope-labeled reagents to replace normal atom of the isotope, e.g., hydrogen by deuterium can be replaced by exposure to deuterated acid, such as D2SO4/D2O. In addition to the above, relevant ways and intermediate compounds described, for example, in the works Lizondo, J. et al., Drugs Fut, 21(11), 1116 (1996); Brickner, S. J. et al., J Med Chem, 39(3), 673 (1996); Mallesham, B. et al., Org Lett, 5(7), 963 (2003); the PCT publications WO1997010223, WO2005099353, WO1995007271, WO2006008754; US patents№№ 7538189; 7534814; 7531685; 7528131; 7521421; 7514068; 7511013; and publications of patent applications US№№ 20090137457; 20090131485; 20090131363; 20090118238; 20090111840; 20090105338; 20090105307; 20090105147; 20090093422; 20090088416 and 20090082471, methods are included here by reference.

Isotope-labeled compounds according to the invention can be used is Ana as standards to determine the effectiveness of inhibitors of Bcl-2 in the analysis of binding. Containing isotopes of the compounds used in pharmaceutical research to study the metabolic pathways of compounds in vivo by assessing the mechanism of action and metabolism nestopia labeled generic compounds (Blake et al. J. Pharm. Sci. 64, 3, 367-391 (1975)). This study metabolism is important for the development of safe, effective therapeutic drugs, because in vivo or active compound, administered to the patient, or the metabolites produced the ancestral connection, may be toxic or carcinogenic (Foster et al., Advances in Drug Research Vol. 14, pp. 2-36, Academic press, London, 1985; Kato et al., J. Labelled Comp. Radiopharmaceut., 36(10):927-932 (1995); Kushner et al., Can. J. Physiol. Pharmacol., 77, 79-88 (1999).

In addition, containing a non-radioactive isotope of the medicinal product, such as deuterated drugs called “hard drugs” can be used to treat diseases and conditions related to the activity of Bcl-2. An increased amount of the isotope present in the compounds mentioned above, with regard to their natural content is called enrichment. A number of examples of enrichment include from about 0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96 to about 100 mol.%. Replacing up to about 15% of normal atoms in the heavy isotopes is maintained for a period of from several days to weeks in mammals, including what I rodents and dogs, with the lowest observed adverse effects (Czajka D. M. and A. J. Finkel, Ann. N. Y. Acad. Sci. 1960 84:770; Thomson J. F., Ann. New York Acad. Sci 1960 84:736; Czakja D. M. et al., Am. J. Physiol. 1961 201:357). High replacement rate of 15%-23% in the liquid tissues of the human body for deuterium, as it was found that does not cause toxicity (Blagojevic N. et al., "Dosimetry &Treatment Planning for Neutron Capture Therapy", Zamenhof R, Solares, G. and O. Harling Eds. 1994. Advanced Medical Publishing, Madison Wis. pp 125-134; Diabetes Metab. 23:251 (1997)).

The labelling of the medicinal product stable isotopes can modify its physico-chemical properties such as pKa and solubility in lipids. These effects and changes can influence the pharmacodynamic response of the molecule drugs, if the isotopic substitution affects the region, including the interaction of the ligand-receptor. Although some physical properties of stable isotope-labeled molecules differ from the properties of unlabeled, chemical and biological properties are the same, with one important exception: due to the increasing mass of the heavy isotope, any relationship involving heavy isotope and the other atom is stronger than the same relationship between a light isotope and the atom. Accordingly, the introduction of isotope at the site of metabolism or enzymatic conversion will slow these reactions, significantly affecting the pharmacokinetic profile or efficacy relative to the nei is atomnogo connection.

Amides, esters and prodrugs

Prodrugs are derivatives of the active medicines to improve some of the detected unwanted physical or biological properties. Physical properties are usually solubility (too much or insufficient lipid or water solubility) or relating to the stability, at the same time problematic biological properties include too fast metabolism or poor bioavailability, which itself may be related to the physico-chemical properties.

Prodrugs are usually obtained: a) the formation of esters, popularnych esters, carbonate esters, nitrate esters, amides, hydroxamic acids, carbamates, Iminov, bases, manniche, phosphates, phosphate esters, and enamines active drugs, b) the introduction of the drug functional groups, azo, glycoside, peptide and complex ester, c) using aminolink, pollinating, polymer, salt, complex, phosphoramide, acetylenic, hemiacetals and katalinich forms of medicines. For example, see andrejus on Korolkovas's, "Essentials of Medicinal Chemistry", John Wiley-Interscience Publications, John Wiley and Sons, New York (1988), pp. 97-118, which is included here in its full by reference.

Esters can be poluchenii substrates of formula (I), containing or hydroxyl group, or carboxyl group, conventional methods known to experts in this field. Typical reactions of these compounds are the substitution of one of the heteroatoms to another atom, for example:

Amides can be obtained from the substrates of formula (I) containing or amino group, or carboxyl group, in a similar way. Esters can also be subjected to interaction with amines or ammonia with the formation of amides.

Another way of obtaining the amides of the compounds of formula (I) is heated together carboxylic acids and amines.

In schemes 2 and 3 above, R and R' are independent substrates of formula (I), the alkyl or hydrogens.

Suitable groups for A1B1D1E1, Y1L1, Z1A, Z2A, Z1, Z2and Z3in the compounds of formula (I) selected independently. Desirable embodiments of the present invention can be combined. This combination is anticipated and included in the scope of the present invention. For example, it is assumed that the variations of the implementation for any A1B1D1E1, Y1L1, Z1A, Z2A, Z1, Z2and Z3can be merge the us with options for implementation defined for any A1B1D1E1, Y1L1, Z1A, Z2A, Z1, Z2and Z3.

One variant of implementation of the present invention, therefore, pertains to compounds or therapeutically acceptable salts, prodrugs or salts of prodrugs that can be used as inhibitors of anti-apoptotic proteins of Bcl-2, where the compounds have the formula (I)

where

A1represents N or C(A2);

A2represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2N3, H, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

B1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

D1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

E1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; and

Y1p is ecstasy a H, CN, NO2C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R17, OR17C(O)R17C(O)OR17, SR17, SO2R17, NH2, Other17N(R17)2, NHC(O)R17C(O)NH2C(O)other17C(O)N(R17)2NHS(O)R17or NHSO2R17; or

E1and Y1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

A2B1and D1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF 3C(O)OH, C(O)NH2or C(O)OR1A; or

Y1and B1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

A2D1and E1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

A2and B1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

D1E1and Y 1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

A2and D1together with the atoms to which they are attached, are benzene, naphthalene, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

B1E1and Y1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1NHC(O)NH 2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

R1is an R2, R3, R4or R5;

R1Ais cycloalkyl, cycloalkenyl or cycloalkenyl;

R2represents phenyl, which secondinterval or fused with benzene, heteroatom or R2A; R2Ais cycloalkane or geteroseksualen;

R3is heteroaryl that secondinterval or fused with benzene, heteroatom or R3A; R3Ais cycloalkane or geteroseksualen;

R4is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R4A; R4A represents cycloalkyl, cycloalken, geteroseksualen or geteroseksualen;

R5represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R6, NC(R6A)(R6B), R7, OR7, SR7, S(O)R7, SO2R7, Other7N(R7)2C(O)R7C(O)NH2,C(O)other7C(O)N(R7)2, NHC(O)R7, NR7C(O)R7, NHSO2R7, NHC(O)OR7, SO2NH2, SO2Other7, SO2N(R7)2, NHC(O)NH2, NHC(O)other7, NHC(O)CH(CH3)NHC(O)CH(CH3)NH2, NHC(O)CH(CH3)NHC(O)CH(CH3)Other1, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R6represents a C2-C5-spiralcell, each of which is unsubstituted or substituted by OH, (O), N3CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH(CH3) or N(CH3)2;

R6Aand R6Bindependently selected from alkyl or together with the N atom to which they are attached, represent R6C;

R6Cis aziridine-1-yl, azetidin-1-yl, pyrrolidin-1-yl or piperidine-1-yl, each of which contains a single CH2group nezamenimoy or replaced with O, C(O), CNOH, CNOCH3, S, S(O), SO2or NH;

R7not only is em a R 8, R9, R10or R11;

R8represents phenyl, which secondinterval or fused with benzene, heteroatom or R8A; R8Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R9is heteroaryl that secondinterval or fused with benzene, heteroatom or R9A; R9Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R10is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R10A; R10Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R11represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R12, OR12, SR12, S(O)R12, SO2R12C(O)R12, CO(O)R12, OC(O)R12, OC(O)OR12, NH2, Other12N(R12)2, NHC(O)R12, NR12C(O)R12NHS(O)2R12, NR12S(O)2R12, NHC(O)OR12, NR12C(O)OR12, NHC(O)NH2, NHC(O)other12, NHC(O)N(R12)2, NR12C(O)other12, NR12C(O)N(R12) C(O)NH2C(O)other12C(O)N(R12)2C(O)NHOH, C(O)NHOR12C(O)NHSO2R12C(O)NR12SO2R12, SO2NH2, SO2Other12, SO2N(R12)2C(O)H, C(O)OH, C(N)NH2C(N)other12C(N)N(R12)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R12is an R13, R14, R15or R16;

R13represents phenyl, which secondinterval or fused with benzene, heteroatom or R13A; R13Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R14is heteroaryl that secondinterval or fused with benzene, heteroatom or R14A; R14Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R15is cycloalkane, cycloalkene, geteroseksualen or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R15A; R15Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R16represents alkyl, alkenyl or quinil;

R17is an R18, R19, R20or R21;

R18depict is to place a phenyl, which secondinterval or fused with benzene, heteroatom or R18A; R18Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R19is heteroaryl that secondinterval or fused with benzene, heteroatom or R19A; R19Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R20is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R20A; R20Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R21represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R22, OR22, SR22, S(O)R22, SO2R22C(O)R22, CO(O)R22, OC(O)R22, OC(O)OR22, NH2, Other22N(R22)2, NHC(O)R22, NR22C(O)R22NHS(O)2R22, NR22S(O)2R22, NHC(O)OR22, NR22C(O)OR22, NHC(O)NH2, NHC(O)other22, NHC(O)N(R22)2, NR22C(O)other22, NR22C(O)N(R22)2C(O)NH2C(O)other22C(O)N(R22)2C(O)NHOH, C(O)NHOR22C(O)HSO 2R22C(O)NR22SO2R22, SO2NH2, SO2Other22, SO2N(R22)2C(O)H, C(O)OH, C(N)NH2C(N)other22C(N)N(R22)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R22is an R23, R24or R25;

R23represents phenyl, which secondinterval or fused with benzene, heteroatom or R23A; R23Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R24represents heteroaryl that secondinterval or fused with benzene, heteroatom or R24A; R24Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R25is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R25A; R25Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

Z1is an R26or R27;

Z2is an R28, R29or R30;

Z1Aand Z2Aboth were missing or taken together form CH2CH2CH2or Z12A;

<> Z12Arepresents a C2-C6-alkylene, in which one or two groups CH2replaced by NH, N(CH3), S, S(O) or SO2;

L1is an R37, OR37, SR37, S(O)R37, SO2R37C(O)R37, CO(O)R37, OC(O)R37, OC(O)OR37, Other37C(O)NH, C(O)NR37C(O)NHOR37C(O)NHSO2R37, SO2NH, SO2Other37C(N)NH, C(N)other37;

R26represents a phenylene, which secondinterval or fused with benzene or heteroatom or R26A; R26Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R27represents heteroaryl that secondinterval or fused with benzene or heteroatom or R27A; R27Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R28represents a phenylene, which secondinterval or fused with benzene, heteroatom or R28A; R28Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R29represents heteroaryl that secondinterval or fused with benzene or heteroatom or R29A; R29Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R30depict is to place cycloalkyl, cycloalkenyl, heterocyclochain or heterocyclization, each of which secondinterval or fused with benzene, heteroatom or R30A; R30Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R37represents a bond, or R37A;

R37Ais alkylen, albaniles or akinyan, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R37B, OR37B, SR37B, S(O)R37B, SO2R37BC(O)R37B, CO(O)R37B, OC(O)R37B, OC(O)OR37B, NH2, Other37BN(R37B)2, NHC(O)R37B, NR37BC(O)R37BNHS(O)2R37B, NR37BS(O)2R37B, NHC(O)OR37B, NR37BC(O)OR37B, NHC(O)NH2, NHC(O)other37B, NHC(O)N(R37B)2, NR37BC(O)other37B, NR37BC(O)N(R37B)2C(O)NH2C(O)other37BC(O)N(R37B)2C(O)NHOH, C(O)NHOR37BC(O)NHSO2R37BC(O)NR37BSO2R37B, SO2NH2, SO2Other37B, SO2N(R37B)2C(O)H, C(O)OH, C(N)NH2C(N)other37BC(N)N(R37B)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br and I substituents;

R37Brepresents alkyl, alkenyl, quinil, Fe is Il, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen;

Z3is an R38, R39or R40;

R38represents phenyl, which secondinterval or fused with benzene, heteroatom or R38A; R38Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R39is heteroaryl that secondinterval or fused with benzene, heteroatom or R39A; R39Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R40is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R40A; R40Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

where the group represented by R26and R27are substituted (i.e. if Z1Aand Z2Aare absent) or further substituted (i.e., if Z1Aand Z2Athere are one, or two, or three, or four substituents, independently selected from R41, OR41, SR41, S(O)R41, SO2R41C(O)R41, CO(O)R41, OC(O)R41, OC(O)OR41, NH2, Other41N(R41)2, NHC(O)R41, NR C(O)R41NHS(O)2R41, NR41S(O)2R41, NHC(O)OR41, NR41C(O)OR41, NHC(O)NH2, NHC(O)other41, NHC(O)N(R41)2, NR41C(O)other41, NR41C(O)N(R41)2C(O)NH2C(O)other41C(O)N(R41)2C(O)NHOH, C(O)NHOR41C(O)NHSO2R41C(O)NR41SO2R41, SO2NH2, SO2Other41, SO2N(R41)2C(O)H, C(O)OH, C(N)NH2C(N)other41C(N)N(R41)2, CNOH, CNOCH3, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R41is an R42, R43, R44or R45;

R42represents phenyl, which secondinterval or fused with benzene, heteroatom or R42A; R42Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R43is heteroaryl that secondinterval or fused with benzene, heteroatom or R43A; R43Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R44is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R44A; R44Ais cycloalkane, cycloalkene,geteroseksualen or geteroseksualen;

R45represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R46, OR46, SR46, S(O)R46, SO2R46C(O)R46, CO(O)R46, OC(O)R46, OC(O)OR46, NH2, Other46N(R46)2, NHC(O)R46, NR46C(O)R46NHS(O)2R46, NR46S(O)2R46, NHC(O)OR46, NR46C(O)OR46, NHC(O)NH2, NHC(O)other46, NHC(O)N(R46)2, NR46C(O)other46, NR46C(O)N(R46)2C(O)NH2C(O)other46C(O)N(R46)2C(O)NHOH, C(O)NHOR46C(O)NHSO2R46C(O)NR46SO2R46, SO2NH2, SO2Other46, SO2N(R46)2C(O)H, C(O)OH, C(N)NH2C(N)other46C(N)N(R46)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R46represents alkyl, alkenyl, quinil, R47, R48or R49;

R47represents phenyl, which secondinterval or fused with benzene, heteroatom or R47A; R47Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R48is heteroaryl that secondinterval or condensed with Ben who I, heteroatom or R48A; R48Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R49is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R49A; R49Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

where the group represented by R42, R42A, R43, R43A, R44, R44A, R47, R47A, R48, R48A, R49and R49Aindependently substituted with one, or two, or three, or four substituents, independently selected from R50, OR50, SR50, S(O)R50, SO2R50C(O)R50, CO(O)R50, OC(O)R50, OC(O)OR50, NH2, Other50N(R50)2, NHC(O)R50, NR50C(O)R50NHS(O)2R50, NR50S(O)2R50, NHC(O)OR50, NR50C(O)OR50, NHC(O)NH2, NHC(O)other50, NHC(O)N(R50)2, NR50C(O)other50, NR50C(O)N(R50)2C(O)NH2C(O)other50C(O)N(R50)2C(O)NHOH, C(O)NHOR50C(O)NHSO2R50C(O)NR50SO2R50, SO2NH2, SO2Other50, SO2N(R50)2C(O)H, C(O)OH, C(N)NH2C(N)other50C(N)N(R50)2, CNOH, CNOCH3,OH, (O), CN, N , NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R50is an R51, R52, R53or R54;

R51represents phenyl, which secondinterval or fused with benzene, heteroatom or R51A; R51Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R52is heteroaryl that secondinterval or fused with benzene, heteroatom or R52A; R52Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R53is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R53A; R53Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R54represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R55, OR55, SR55, S(O)R55, SO2R55C(O)R55, CO(O)R55, OC(O)R55, OC(O)OR55, NH2, Other55N(R55)2, NHC(O)R55, NR55C(O)R55NHS(O)2R55, NR55S(O)2R55, NHC(O)OR55 , NR55C(O)OR55, NHC(O)NH2, NHC(O)other55, NHC(O)N(R55)2, NR55C(O)other55, NR55C(O)N(R55)2C(O)NH2C(O)other55C(O)N(R55)2C(O)NHOH, C(O)NHOR55C(O)NHSO2R55C(O)NR55SO2R55, SO2NH2, SO2Other55, SO2N(R55)2C(O)H, C(O)OH, C(N)NH2C(N)other55C(N)N(R55)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R55represents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen; and

where each of the above cyclic group is independently unsubstituted, no further substitutions, substituted or optionally substituted with one, or two, or three, or four, or five substituents independently selected from R57A, R57, OR57, SR57, S(O)R57, SO2R57C(O)R57, CO(O)R57, OC(O)R57, OC(O)OR57, NH2, Other57N(R57)2, NHC(O)R57, NR57C(O)R57NHS(O)2R57, NR57S(O)2R57, NHC(O)OR57, NR57C(O)OR57, NHC(O)NH2, NHC(O)other57, NHC(O)N(R57)2, NR57C(O)other57, NR57C(O)N(R57)2C(O)NH2C(O)other57C(O)N(R57)2C()NHOH, C(O)NHOR57C(O)NHSO2R57C(O)NR57SO2R57, SO2NH2, SO2Other57, SO2N(R57)2C(O)H, C(O)OH, C(N)NH2C(N)other57C(N)N(R57)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R57Arepresents spirocyclic;

R57is an R58, R59, R60or R61;

R58represents phenyl, which secondinterval or fused with benzene, heteroatom or R58A; R58Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R59is heteroaryl that secondinterval or fused with benzene, heteroatom or R59A; R59Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R60is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R60A; R60Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R61represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents, n is dependent selected from R 62, OR62, SR62, S(O)R62, SO2R62C(O)R62, CO(O)R62, OC(O)R62, OC(O)OR62, NH2, Other62N(R62)2, NHC(O)R62, NR62C(O)R62NHS(O)2R62, NR62S(O)2R62, NHC(O)OR62, NR62C(O)OR62, NHC(O)NH2, NHC(O)other62, NHC(O)N(R62)2, NR62C(O)other62, NR62C(O)N(R62)2C(O)NH2C(O)other62C(O)N(R62)2C(O)NHOH, C(O)NHOR62C(O)NHSO2R62C(O)NR62SO2R62, SO2NH2, SO2Other62, SO2N(R62)2C(O)H, C(O)OH, C(N)NH2C(N)other62C(N)N(R62)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R62is an R63, R64, R65or R66;

R63represents phenyl, which secondinterval or fused with benzene, heteroatom or R63A; R63Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R64is heteroaryl that secondinterval or fused with benzene, heteroatom or R64A; R64Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R65is cycloalkyl, cycloalkenyl, heterocycle lkyl or geteroseksualen, each secondinterval or fused with benzene, heteroatom or R65A; R65Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R66represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R67, OR67, SR67, S(O)R67, SO2R67C(O)R67, CO(O)R67, OC(O)R67, OC(O)OR67, NH2, Other67N(R67)2, NHC(O)R67, NR67C(O)R67NHS(O)2R67, NR67S(O)2R67, NHC(O)OR67, NR67C(O)OR67, NHC(O)NH2, NHC(O)other67, NHC(O)N(R67)2, NR67C(O)other67, NR67C(O)N(R67)2C(O)NH2C(O)other67C(O)N(R67)2C(O)NHOH, C(O)NHOR67C(O)NHSO2R67C(O)NR67SO2R67, SO2NH2, SO2Other67, SO2N(R67)2C(O)H, C(O)OH, C(N)NH2C(N)other67C(N)N(R67)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I substituents;

R67represents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen;

where the group represented by R57A, R58, R5 , R60, R63, R64, R65and R67are unsubstituted or substituted one, or two, or three, or four substituents, independently selected from R68, OR68, SR68, S(O)R68, SO2R68C(O)R68, CO(O)R68, OC(O)R68, OC(O)OR68, NH2, Other68N(R68)2, NHC(O)R68, NR68C(O)R68NHS(O)2R68, NR68S(O)2R68, NHC(O)OR68, NR68C(O)OR68, NHC(O)NH2, NHC(O)other68, NHC(O)N(R68)2, NR68C(O)other68, NR68C(O)N(R68)2C(O)NH2C(O)other68C(O)N(R68)2C(O)NHOH, C(O)NHOR68C(O)NHSO2R68C(O)NR68SO2R68, SO2NH2, SO2Other68, SO2N(R68)2C(O)H, C(O)OH, C(N)NH2C(N)other68C(N)N(R68)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R68is an R69, R70, R71or R72;

R69represents phenyl, which secondinterval or fused with benzene, heteroatom or R69A; R69Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R70is heteroaryl that secondinterval or fused with benzene, heteroatom or R 70A; R70Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R71is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R71A; R71Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R72represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R73, OR73, SR73, S(O)R73, SO2R73C(O)R73, CO(O)R73, OC(O)R73, OC(O)OR73, NH2, Other73N(R73)2, NHC(O)R73, NR73C(O)R73NHS(O)2R73, NR73S(O)2R73, NHC(O)OR73, NR73C(O)OR73, NHC(O)NH2, NHC(O)other73, NHC(O)N(R73)2, NR73C(O)other73, NR73C(O)N(R73)2C(O)NH2C(O)other73C(O)N(R73)2C(O)NHOH, C(O)NHOR73C(O)NHSO2R73C(O)NR73SO2R73, SO2NH2, SO2Other73, SO2N(R73)2C(O)H, C(O)OH, C(N)NH2C(N)other73C(N)N(R73)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R73

groups represented by R69, R70and R71are unsubstituted or substituted one, or two, or three, or four substituents, independently selected from NH2C(O)NH2C(O)NHOH, SO2NH2, CF3,CF2CF3,C(O)H, C(O)OH, C(N)NH2, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I.

Another variant of implementation of the present invention relates to compounds of formula (I), where

A1represents N or C(A2);

A2represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2NHRsup> 1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

B1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

D1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1 )2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

E1represents H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl,Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; and

Y1represents H, CN, NO2C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R17, OR17C(O)R17C(O)OR17, SR17, SO2R17, NH2, Other17N(R17)2, NHC(O)R17C(O)NH2C(O)other17C(O)N(R17)2NHS(O)R17or NHSO2R17; or

E1and Y1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

A2B1and D1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1 , NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

Y1and B1together with the atoms to which they are attached, are benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

A2D1and E1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

A2and B1together with the atoms to which they are attached, represent with the battle benzene, naftilan, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

D1E1and Y1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(R1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A; or

A2and D1together with the atoms to which they are attached, are benzene, naphthalene, heteroaryl, cycloalkyl, cycloalkene, geteroseksualen or geteroseksualen; and

B1E1and Y1independently selected from H, R1, OR1, SR1, S(O)R1, SO2R1C(O)R1C(O)OR1, OC(O)R1, Other1N(Rsup> 1)2C(O)other1C(O)N(R1)2, NHC(O)R1, NR1C(O)R1, NHC(O)OR1, NR1C(O)OR1, NHC(O)NH2, NHC(O)other1, NHC(O)N(R1)2, NR1C(O)other1, NR1C(O)N(R1)2, SO2NH2, SO2Other1, SO2N(R1)2, NHSO2R1, NR1SO2R1, NHSO2Other1, NHSO2N(R1)2, NR1SO2Other1, NR1SO2N(R1)2C(O)NHNOH, C(O)NHNOR1C(O)NHSO2R1C(NH)NH2C(NH)other1C(NH)N(R1)2NHSO2Other1, NHSO2N(CH3R1N(CH3)SO2N(CH3R1, F, Cl, Br, I, CN, NO2,N3, OH, C(O)H, CHNOH, CH(NOCH3), CF3C(O)OH, C(O)NH2or C(O)OR1A;

R1is an R2, R3, R4or R5;

R1Ais cycloalkyl, cycloalkenyl or cycloalkenyl;

R2represents phenyl, which secondinterval or fused with benzene, heteroatom or R2A; R2Ais cycloalkane or geteroseksualen;

R3is heteroaryl that secondinterval or fused with benzene, heteroatom or R3A; R3Ais cycloalkane or geteroseksualen;

R4is cycloalkyl, cycloalkenyl, heteroseksualci imagetracklabel, each secondinterval or fused with benzene, heteroatom or R4A; R4Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R5represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R6, NC(R6A)(R6B), R7, OR7, SR7, S(O)R7, SO2R7, Other7N(R7)2C(O)R7C(O)NH2,C(O)other7C(O)N(R7)2, NHC(O)R7, NR7C(O)R7, NHSO2R7, NHC(O)OR7, SO2NH2, SO2Other7, SO2N(R7)2, NHC(O)NH2, NHC(O)other7, NHC(O)CH(CH3)NHC(O)CH(CH3)NH2, NHC(O)CH(CH3)NHC(O)CH(CH3)Other1, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R6represents a C2-C5-spiralcell, each of which is unsubstituted or substituted by OH, (O), N3CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH(CH3) or N(CH3)2;

R6Aand R6Bindependently selected from alkyl or together with the N atom to which they are attached, represent R6C;

R6Cis aziridine-1-yl, azetidin-1-yl, pyrrolidin-1-yl or piperidine-1-yl, each of the which contains a single CH 2group nezamenimoy or replaced with O, C(O), CNOH, CNOCH3, S, S(O), SO2or NH;

R7is an R8, R9, R10or R11;

R8represents phenyl, which secondinterval or fused with benzene, heteroatom or R8A; R8Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R9is heteroaryl that secondinterval or fused with benzene, heteroatom or R9A; R9Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R10is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R10A; R10Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R11represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R12, OR12, SR12, S(O)R12, SO2R12C(O)R12, CO(O)R12, OC(O)R12, OC(O)OR12, NH2, Other12N(R12)2, NHC(O)R12, NR12C(O)R12NHS(O)2R12, NR12S(O)2R12, NHC(O)OR12 , NR12C(O)OR12, NHC(O)NH2, NHC(O)other12, NHC(O)N(R12)2, NR12C(O)other12, NR12C(O)N(R12)2C(O)NH2C(O)other12C(O)N(R12)2C(O)NHOH, C(O)NHOR12C(O)NHSO2R12C(O)NR12SO2R12, SO2NH2, SO2Other12, SO2N(R12)2C(O)H, C(O)OH, C(N)NH2C(N)other12C(N)N(R12)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R12is an R13, R14, R15or R16;

R13represents phenyl, which secondinterval or fused with benzene, heteroatom or R13A; R13Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R14is heteroaryl that secondinterval or fused with benzene, heteroatom or R14A; R14Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R15is cycloalkane, cycloalkene, geteroseksualen or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R15A; R15Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R16is own the th alkyl, alkenyl or quinil;

R17is an R18, R19, R20or R21;

R18represents phenyl, which secondinterval or fused with benzene, heteroatom or R18A; R18Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R19is heteroaryl that secondinterval or fused with benzene, heteroatom or R19A; R19Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R20is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R20A; R20Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R21represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R22, OR22, SR22, S(O)R22, SO2R22C(O)R22, CO(O)R22, OC(O)R22, OC(O)OR22, NH2, Other22N(R22)2, NHC(O)R22, NR22C(O)R22NHS(O)2R22, NR22S(O)2R22, NHC(O)OR22, NR22C(O)OR22, NHC(O)NH2, NHC(O)other22, NHC(O)N(R 22)2, NR22C(O)other22, NR22C(O)N(R22)2C(O)NH2C(O)other22C(O)N(R22)2C(O)NHOH, C(O)NHOR22C(O)NHSO2R22C(O)NR22SO2R22, SO2NH2, SO2Other22, SO2N(R22)2C(O)H, C(O)OH, C(N)NH2C(N)other22C(N)N(R22)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R22is an R23, R24or R25;

R23represents phenyl, which secondinterval or fused with benzene, heteroatom or R23A; R23Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R24represents heteroaryl that secondinterval or fused with benzene, heteroatom or R24A; R24Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R25is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R25A; R25Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

Z1is an R26or R27;

Z2is an R28 , R29or R30;

Z1Aand Z2Aboth were missing or taken together form CH2CH2CH2or Z12A;

Z12Arepresents a C2-C6-alkylene, in which one or two groups CH2replaced by NH, N(CH3), S, S(O) or SO2;

L1is an R37, OR37, SR37, S(O)R37, SO2R37C(O)R37, CO(O)R37, OC(O)R37, OC(O)OR37, Other37C(O)NH, C(O)NR37C(O)NHOR37C(O)NHSO2R37, SO2NH, SO2Other37C(N)NH, C(N)other37;

R26represents a phenylene, which secondinterval or fused with benzene or heteroatom or R26A; R26Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R27represents heteroaryl that secondinterval or fused with benzene or heteroatom or R27A; R27Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R28represents a phenylene, which secondinterval or fused with benzene, heteroatom or R28A; R28Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R29represents heteroaryl that secondinterval or fused with benzene or g is thereareno or R 29A; R29Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R30is cycloalkyl, cycloalkenyl, heterocyclochain or heterocyclization, each of which secondinterval or fused with benzene, heteroatom or R30A; R30Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R37represents a bond, or R37A;

R37Ais alkylen, albaniles or akinyan, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R37B, OR37B, SR37B, S(O)R37B, SO2R37BC(O)R37B, CO(O)R37B, OC(O)R37B, OC(O)OR37B, NH2, Other37BN(R37B)2, NHC(O)R37B, NR37BC(O)R37BNHS(O)2R37B, NR37BS(O)2R37B, NHC(O)OR37B, NR37BC(O)OR37B, NHC(O)NH2, NHC(O)other37B, NHC(O)N(R37B)2, NR37BC(O)other37B, NR37BC(O)N(R37B)2C(O)NH2C(O)other37BC(O)N(R37B)2C(O)NHOH, C(O)NHOR37BC(O)NHSO2R37BC(O)NR37BSO2R37B, SO2NH2, SO2Other37B, SO2N(R37B)2C(O)H, C(O)OH, C(N)NH2C(N)other37BC(N)N(R37B)2, CNOH, CNOCH3,OH, (O), CN, N3NO 2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br and I substituents;

R37Brepresents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen;

Z3is an R38, R39or R40;

R38represents phenyl, which secondinterval or fused with benzene, heteroatom or R38A; R38Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R39is heteroaryl that secondinterval or fused with benzene, heteroatom or R39A; R39Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R40is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R40A; R40Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

where the group represented by R26and R27are substituted OR41;

R41is an R42, R43, R44or R45;

R42represents phenyl, which secondinterval or fused with benzene, heteroatom or R42A; R is cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R43is heteroaryl that secondinterval or fused with benzene, heteroatom or R43A; R43Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R44is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R44A; R44Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R45represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R46, OR46, SR46, S(O)R46, SO2R46C(O)R46, CO(O)R46, OC(O)R46, OC(O)OR46, NH2, Other46N(R46)2, NHC(O)R46, NR46C(O)R46NHS(O)2R46, NR46S(O)2R46, NHC(O)OR46, NR46C(O)OR46, NHC(O)NH2, NHC(O)other46, NHC(O)N(R46)2, NR46C(O)other46, NR46C(O)N(R46)2C(O)NH2C(O)other46C(O)N(R46)2C(O)NHOH, C(O)NHOR46C(O)NHSO2R46C(O)NR46SO2R46, SO2NH2, SO2Other46, SO N(R46)2C(O)H, C(O)OH, C(N)NH2C(N)other46C(N)N(R46)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R46represents alkyl, alkenyl, quinil, R47, R48or R49;

R47represents phenyl, which secondinterval or fused with benzene, heteroatom or R47A; R47Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R48is heteroaryl that secondinterval or fused with benzene, heteroatom or R48A; R48Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R49is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R49A; R49Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

where the group represented by R42, R42A, R43, R43A, R44, R44A, R47, R47A, R48, R48A, R49and R49Aindependently substituted with one, or two, or three, or four substituents, independently selected from R50, OR50, SR50, S(O)R50, SO2 R50C(O)R50, CO(O)R50, OC(O)R50, OC(O)OR50, NH2, Other50N(R50)2, NHC(O)R50, NR50C(O)R50NHS(O)2R50, NR50S(O)2R50, NHC(O)OR50, NR50C(O)OR50, NHC(O)NH2, NHC(O)other50, NHC(O)N(R50)2, NR50C(O)other50, NR50C(O)N(R50)2C(O)NH2C(O)other50C(O)N(R50)2C(O)NHOH, C(O)NHOR50C(O)NHSO2R50C(O)NR50SO2R50, SO2NH2, SO2Other50, SO2N(R50)2C(O)H, C(O)OH, C(N)NH2C(N)other50C(N)N(R50)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R50is an R51, R52, R53or R54;

R51represents phenyl, which secondinterval or fused with benzene, heteroatom or R51A; R51Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R52is heteroaryl that secondinterval or fused with benzene, heteroatom or R52A; R52Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R53is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which is secondinterval or fused with benzene, heteroatom or R53A; R53Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R54represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R55, OR55, SR55, S(O)R55, SO2R55C(O)R55, CO(O)R55, OC(O)R55, OC(O)OR55, NH2, Other55N(R55)2, NHC(O)R55, NR55C(O)R55NHS(O)2R55, NR55S(O)2R55, NHC(O)OR55, NR55C(O)OR55, NHC(O)NH2, NHC(O)other55, NHC(O)N(R55)2, NR55C(O)other55, NR55C(O)N(R55)2C(O)NH2C(O)other55C(O)N(R55)2C(O)NHOH, C(O)NHOR55C(O)NHSO2R55C(O)NR55SO2R55, SO2NH2, SO2Other55, SO2N(R55)2C(O)H, C(O)OH, C(N)NH2C(N)other55C(N)N(R55)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R55represents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen; and

where each of the above cyclic group is independently unsubstituted, no further substitutions, substituted sludge is optionally substituted with one, or two, or three, or four, or five substituents independently selected from R57A, R57, OR57, SR57, S(O)R57, SO2R57C(O)R57, CO(O)R57, OC(O)R57, OC(O)OR57, NH2, Other57N(R57)2, NHC(O)R57, NR57C(O)R57NHS(O)2R57, NR57S(O)2R57, NHC(O)OR57, NR57C(O)OR57, NHC(O)NH2, NHC(O)other57, NHC(O)N(R57)2, NR57C(O)other57, NR57C(O)N(R57)2C(O)NH2C(O)other57C(O)N(R57)2C(O)NHOH, C(O)NHOR57C(O)NHSO2R57C(O)NR57SO2R57, SO2NH2, SO2Other57, SO2N(R57)2C(O)H, C(O)OH, C(N)NH2C(N)other57C(N)N(R57)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R57is an R58, R59, R60or R61;

R57Arepresents spirocyclic;

R58represents phenyl, which secondinterval or fused with benzene, heteroatom or R58A; R58Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R59is heteroaryl that secondinterval or fused with benzene, heteroatom or R59A; R59Apresented yet cycloalkane, cycloalken, geteroseksualen or geteroseksualen;

R60is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R60A; R60Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R61represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R62, OR62, SR62, S(O)R62, SO2R62C(O)R62, CO(O)R62, OC(O)R62, OC(O)OR62, NH2, Other62N(R62)2, NHC(O)R62, NR62C(O)R62NHS(O)2R62, NR62S(O)2R62, NHC(O)OR62, NR62C(O)OR62, NHC(O)NH2, NHC(O)other62, NHC(O)N(R62)2, NR62C(O)other62, NR62C(O)N(R62)2C(O)NH2C(O)other62C(O)N(R62)2C(O)NHOH, C(O)NHOR62C(O)NHSO2R62C(O)NR62SO2R62, SO2NH2, SO2Other62, SO2N(R62)2C(O)H, C(O)OH, C(N)NH2C(N)other62C(N)N(R62)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R62is an R63, R64, R65 or R66;

R63represents phenyl, which secondinterval or fused with benzene, heteroatom or R63A; R63Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R64is heteroaryl that secondinterval or fused with benzene, heteroatom or R64A; R64Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R65is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R65A; R65Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R66represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R67, OR67, SR67, S(O)R67, SO2R67C(O)R67, CO(O)R67, OC(O)R67, OC(O)OR67, NH2, Other67N(R67)2, NHC(O)R67, NR67C(O)R67NHS(O)2R67, NR67S(O)2R67, NHC(O)OR67, NR67C(O)OR67, NHC(O)NH2, NHC(O)other67, NHC(O)N(R67)2, NR67C(O)other67, NR67C(O)N(R67)2C(O)NH2C(ONHR 67C(O)N(R67)2C(O)NHOH, C(O)NHOR67C(O)NHSO2R67C(O)NR67SO2R67, SO2NH2, SO2Other67, SO2N(R67)2C(O)H, C(O)OH, C(N)NH2C(N)other67C(N)N(R67)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I substituents;

R67represents alkyl, alkenyl, quinil, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen;

where the group represented by R57A, R58, R59, R60, R63, R64, R65and R67are unsubstituted or substituted one, or two, or three, or four substituents, independently selected from R68, OR68, SR68, S(O)R68, SO2R68C(O)R68, CO(O)R68, OC(O)R68, OC(O)OR68, NH2, Other68N(R68)2, NHC(O)R68, NR68C(O)R68NHS(O)2R68, NR68S(O)2R68, NHC(O)OR68, NR68C(O)OR68, NHC(O)NH2, NHC(O)other68, NHC(O)N(R68)2, NR68C(O)other68, NR68C(O)N(R68)2C(O)NH2C(O)other68C(O)N(R68)2C(O)NHOH, C(O)NHOR68C(O)NHSO2R68C(O)NR68SO2R68, SO2NH2, SO2Other68, SO2N(R68)2C(O)H, C(O)OH, C(N)NH2C(N)other68 C(N)N(R68)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R68is an R69, R70, R71or R72;

R69represents phenyl, which secondinterval or fused with benzene, heteroatom or R69A; R69Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R70is heteroaryl that secondinterval or fused with benzene, heteroatom or R70A; R70Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R71is cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R71A; R71Ais cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R72represents alkyl, alkenyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R73, OR73, SR73, S(O)R73, SO2R73C(O)R73, CO(O)R73, OC(O)R73, OC(O)OR73, NH2, Other73N(R73)2, NHC(O)R73, NR73C(O)R73, NH(O) 2R73, NR73S(O)2R73, NHC(O)OR73, NR73C(O)OR73, NHC(O)NH2, NHC(O)other73, NHC(O)N(R73)2, NR73C(O)other73, NR73C(O)N(R73)2C(O)NH2C(O)other73C(O)N(R73)2C(O)NHOH, C(O)NHOR73C(O)NHSO2R73C(O)NR73SO2R73, SO2NH2, SO2Other73, SO2N(R73)2C(O)H, C(O)OH, C(N)NH2C(N)other73C(N)N(R73)2, CNOH, CNOCH3,OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R73represents alkyl, alkenyl, alkenyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen; and

groups represented by R69, R70and R71are unsubstituted or substituted one, or two, or three, or four substituents, independently selected from NH2C(O)NH2C(O)NHOH, SO2NH2, CF3,CF2CF3,C(O)H, C(O)OH, C(N)NH2, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I.

In one embodiment of formula (I) A1represents N. In another embodiment of formula (I) A1represents(A2). In another embodiment of formula (I) A1represents(A2); and A2represents H.

In one Varian is e of the formula (I) B 1represents NHC(O)R1, NHSO2R1, OR1or other1. In another embodiment of formula (I) A1represents(A2); A2represents H; and B1represents other1. In another embodiment of formula (I) A1represents(A2); A2represents H; and B1is a OR1. In another embodiment of formula (I) A1represents(A2); A2represents H; and B1represents NHSO2R1. In another embodiment of formula (I) A1represents(A2); A2represents H; and B1represents NHC(O)R1. In another embodiment of formula (I) A1represents(A2or N; A2represents H; and B1represents other1. In another embodiment of formula (I) A1represents(A2or N; A2represents H; and B1is a OR1. In another embodiment of formula (I) A1represents(A2or N; A2represents H; and B1represents NHSO2R1. In another embodiment of formula (I) A1represents(A2or N; A2represents H; and B1represents NHC(O)R1.

In one embodiment of formula (I) D1represents H. In another embodiment, f is rmula (I) A 1represents(A2); A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (I) A1represents(A2); A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (I) A1represents(A2); A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (I) A1represents(A2); A2represents H; B1represents NHC(O)R1; and D1represents H. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1is the Oh NHC(O)R 1; and D1represents H.

In one embodiment of formula (I) E1represents H. In another embodiment of formula (I) A1represents(A2); A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (I) A1represents(A2); A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (I) A1represents(A2); A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (I) A1represents(A2); A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (I) A 1represents(A2or N; A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H.

In one embodiment of formula (I) Y1represents H, CN, NO2, F, Cl, Br, CF3, R17or SO2R17. In another embodiment of formula (I) Y1represents NO2. In another embodiment of formula (I), Y1represents CL. In another embodiment of formula (I) Y1represents the SO2R17; where R17has the values listed above. In another embodiment of formula (I) Y1represents the SO2R17; where R17represents alkyl. In another embodiment of formula (I) Y1is an R17; where R17represents quinil. In another embodiment of formula (I) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment, forms the crystals (I) A 1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (I) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (I) A1represents(A2); A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another variant of the formula (I) A 1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (I) A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL.

In one embodiment of formula (I) R1is an R2and R2represents phenyl. In another embodiment of formula (I) R1is an R2and R2represents phenyl, which is substituted NO2and other57.

In one embodiment of formula (I) R1is an R4or R5. In one embodiment of formula (I) R1is an R4. In one embodiment of formula (I) R1is an R5. In one embodiment of formula (I) R1is an R4; and R4is cycloalkyl or heteroseksualci. In one embodiment of formula (I) R1is an R4; and R4is cycloalkyl. In one embodiment of formula (I) R1is an R4; and R4represents heterotic alkyl.

In one embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is substituted, as shown here. In another embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted R57, Other57or N(R57)2. In another embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; and R57is an R60. In another embodiment of formula (I) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; and R60is heteroseksualci. In another embodiment of formula (I) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57/sup> ; R57is an R60; R60is heteroseksualci; where cycloalkyl ring is morpholinyl or piperazinil. In another embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted N(R57)2. In another embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2.In another embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R61and R61represents alkyl, which is unsubstituted. In another embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R60and R60is cycloalkyl, which is unsubstituted. In another embodiment of formula (I) R1is an R4; and R4the submitted is cycloalkyl; where cycloalkyl ring substituted with other57. In another embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57.In another embodiment of formula (I) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57, R57is an R60and R60is heteroseksualci, which is unsubstituted.

In one embodiment of formula (I) R1is an R4; and R4is heteroseksualci; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is substituted, as shown here. In another embodiment of formula (I) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring substituted R57. In another embodiment of formula (I) R1is an R4; and R4is heteroseksualci; where cycloalkyl ring is the first piperidinyl, pyrrolidyl, morpholinyl or piperazinyl; and where geteroseksualnoe ring substituted with one, or two, or three, or four, or five substituents R57; SO2R57or OH, and R57is an R60or R61. In another embodiment of formula (I) R1is an R4; R4is heteroseksualci; where cycloalkyl ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60or R61; R60is cycloalkyl or heteroseksualci; and R61represents alkyl. In another embodiment of formula (I) R1is an R4; R4is heteroseksualci; where cycloalkyl ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is heteroseksualci where heteroseksualci is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of formula (I) R1is an R4; R4is heteroseksualci; where Ikaalinen ring is piperidinyl, pyrrolidyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is cycloalkyl where cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of formula (I) R1is an R4; R4is heteroseksualci; where cycloalkyl ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl. In another embodiment of formula (I) R1is an R4; R4is heteroseksualci; where cycloalkyl ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1- lkyl, C2-alkyl or C3-alkyl; where C1-alkyl, C2-alkyl or C3the alkyl are unsubstituted or substituted.

In one embodiment of formula (I) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted. In one embodiment of formula (I) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted R7, OR7N(R7)2or OH.

In one embodiment of formula (I) R7is an R10or R11which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R7is an R10which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R7is an R11which is unsubstituted or substituted as specified here.

In one embodiment of formula (I) R10is cycloalkyl or heteroseksualci, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R10is heteroseksualci, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R10is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxane, piperidine is, piperidinyl or pyrrolidinyl, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R10is tetrahydropyranyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R10is morpholinyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R10is cycloalkyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R10represents cyclohexyl which is unsubstituted or substituted as specified here.

In one embodiment of formula (I) R11represents alkyl, which is unsubstituted. In another embodiment of formula (I) R11represents methyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R11represents alkyl, which is substituted as described here. In another embodiment of formula (I) R11represents alkyl, which is substituted OR12, R12is an R16and R16represents alkyl.

Another variant of implementation of the present invention relates to compounds of formula (I), where

A1represents N or C(A2);

A2 represents H;

B1is a OR1, NHC(O)R1, Other1or NHSO2R1;

D1represents H;

E1represents H; and

Y1represents H, CN, NO2, F, Cl, Br, CF3, R17or SO2R17;

R1is an R2, R4or R5;

R2represents phenyl;

R4is cycloalkyl or heteroseksualci;

R5represents an alkyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R7, OR7N(R7)2, OH, F, Cl, Br or I;

R7is an R10or R11;

R10is cycloalkyl or heteroseksualci;

R11represents alkyl, each of which is unsubstituted or substituted one, or two, or three substituents, independently selected from F, Cl, Br or I;

R17is an R21;

R21represents an alkyl or quinil, each of which is unsubstituted or substituted one, or two, or three substituents, independently selected from F, Cl, Br or I;

Z1is an R26;

Z2is an R30;

Z1Aand Z2Aboth are absent;

L1before the hat is R 37;

R26represents a phenylene;

R30is heterocyclochain;

R37is an R37A;

R37Ais alkylen, albaniles or akinyan, each of which is unsubstituted or substituted one, or two, or three substituents, independently selected from F, Cl, Br and I substituents;

Z3is an R38or R40;

R38represents phenyl, which secondinterval or fused with R38A; R38Arepresents geteroseksualen;

R40represents cycloalkenyl or geteroseksualen;

where the group represented by R26and R27are substituted (i.e. if Z1Aand Z2Aare absent) or further substituted (i.e., if Z1Aand Z2Athere are one, or two, or three, or four substituents, independently selected from R41, OR41or other41;

R41is an R42, R43or R45;

R42represents phenyl, which secondinterval or condensed with heteroatom or R42A; R42Arepresents geteroseksualen;

R43is heteroaryl that secondinterval or condensed with heteroatom;

R45represents alkyl, each is which is unsubstituted or substituted one, or two, or three substituents independently selected from R46, F, Cl, Br or I;

R46is an R47or R48;

R47represents phenyl;

R48is heteroaryl;

where the group represented by R42, R42A, R43, R43A, R44, R44A, R47, R47A, R48, R48A, R49and R49Aindependently substituted with one, or two, or three, or four substituents, independently selected from R50, OR50, CO(O)R50, NH2, Other50N(R50)2, NHC(O)R50NHS(O)2R50, NHC(O)OR50C(O)NH2C(O)other50C(O)N(R50)2, OH, (O), CN, NO2, CF3, F, Cl, Br or I;

R50is an R51, R52, R53or R54;

R51represents phenyl;

R52is heteroaryl;

R53is cycloalkyl or heteroseksualci;

R54represents alkyl, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R55, OR55C(O)R55, NH2, Other55N(R55)2, NR55C(O)OR55C(O)N(R55)2, OH, F, Cl, Br or I;

R55represents alkyl, phenyl or heteroseksualci; and

where each of the above cyclizes the I group is independently unsubstituted, no further substitutions, substituted or optionally substituted with one, or two, or three, or four, or five substituents independently selected from R57A, R57, OR57, SO2R57C(O)R57, CO(O)R57, NH2, Other57N(R57)2, OH, (O), CN, NO2, F, Cl, Br or I;

R57Arepresents spirocyclic;

R57is an R58, R60or R61;

R58represents phenyl;

R60is cycloalkyl or heteroseksualci;

R61represents an alkyl or alkenyl, each of which is unsubstituted or substituted one, or two, or three substituents independently selected from R62, OR62N(R62)2C(O)N(R62)2, OH, F, Cl, Br or I;

R62is an R63, R64, R65or R66;

R63represents phenyl;

R64is heteroaryl;

R65is cycloalkyl or heteroseksualci;

R66represents alkyl, each of which is unsubstituted or substituted one, or two, or three substituents, independently selected from OR67, F, Cl, Br or I substituents;

R67represents alkyl;

where the group represented by R57A, R58, R60, R63,R 64and R65are unsubstituted or substituted one, or two, or three, or four substituents, independently selected from R68, F, Cl, Br or I;

R68is an R71or R72;

R71is heteroseksualci;

R72represents alkyl, which is unsubstituted or substituted one, or two, or three substituents, independently selected from OR73, F, Cl, Br or I; and

R73represents alkyl.

Yet another variant embodiment of the invention relates to compounds having formula (I), which are

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-the Iran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(hydroxymethyl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amine is)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((1-methyl-1H-indol-4-yl)oxy)benzamide;

2-(3-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(3-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-methoxyphenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(dimethylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-6-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-�ENT-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)-3-oxopropyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)-2-oxoethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)propyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)-N,N-dimethylbenzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-morpholine-4-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2,4-dimethyl-1,3-thiazol-5-yl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(3,5-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)ethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-isopropylpiperazine-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indazol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-ethylpiperazin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((1,2,2,6,6-pentamethylpiperidin-4-yl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((3-nitro-4-((1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((7-fluoro-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-immiscibles-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((4'-chloro-4-(2-pyrrolidin-1-retil)-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indazol-4-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)-2-(3-(trifluoromethyl)phenoxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chloro-4-pertenece)-4-(4-((2-(4-chlorophenyl)-4,4-dim testicles-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclopentene-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2-chloro-3-(trifluoromethyl)phenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-cyclopropylidene-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indol-4-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((1-methyl-1H-indol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholine-4-elfenix)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)am the but)-3-nitrophenyl)sulfonyl)-2-((3-(3-morpholine-4-yl-3-oxopropyl)-1H-indol-5-yl)oxy)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-morpholine-4-yl-3-oxopropyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-morpholine-4-ylpropyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(1H-imidazol-1-yl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)benzyl(ethyl)carbamate;

tert-butyl 3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrag the DRO-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)benzyl(ethyl)carbamate;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenylcarbamate;

2-(1,1'-biphenyl-2-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenylcarbamate;

2-(1,1'-biphenyl-3-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((those whom rehydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholine-4-elfenix)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenyl)piperazine-1-carboxylate;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-morpholine-4-ylethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

tert-butyl 4-(4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((4-((3-morpholine-4-ylpropyl) the Mino)-3-nitrophenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-1-carboxylate;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-pyridin-4-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-4-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridine-3-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((1-methyl-1H-benzimidazole-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylcarbamoyl)phenoxy)-N-(4-(3-morpholinopropan)-3-nitrophenylarsonic)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-N-(4-(3-(dimethylamino)propylamino)-3-nitrophenylarsonic)-2-(3-(methylcarbamoyl)phenoxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-(dimethylamino)propyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)Sul is of IMT)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-(hydroxymethyl)phenoxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((4-methoxybenzyl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

N-(4-((4-aminotetraline-2H-Piran-4-yl)methylamino)-3-nitrophenylarsonic)-2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzamide;

4-(4-(1-(4'-chlorobiphenyl-2-yl)ethyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)phenylsulfonyl)benzamide;

N-{[4-{4-[(4'-chloro-1,1'-biphenyl-2-yl)methyl]piperazine-1-yl}-2-(3,5-dichlorophenoxy)phenyl]sulfonyl}-4-[(1-methylpiperidin-4-yl)amino]-3-nitrobenzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-Lai is peridin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(4-pertenece)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2,3-divergence)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-pertenece)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-is)-2-(2-pertenece)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-pertenece)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-pertenece)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(3-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}PIP the Razin-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2,3-divergence)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-[(3-nitro-4-{[1-(Tien-3-ylmethyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(2-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(3-pertenece)benzamide;

1394-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(4-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-[(4-{[1-(2-foradil)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methylpiperazin-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(4-methylpiperazin-1-yl)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

N-({4-[(1-arylpiperazine-4-yl)amino]-3-nitrophenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl)amino]phenyl}sulfonyl)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-6-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethyl logex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-6-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-[(4-{[(1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(4-fluoro-1H-indol-5-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[3-(methoxyethoxy)-2-methylphenoxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-hydroxy-2-methylphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-�lorgeril)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-(3-iodinase)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(2-hydroxyethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[1-(2-phenylethyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3,4-dichlorophenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3,5-divergence)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-methoxyphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[3-(hydroxymethyl)phenoxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dimethylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dimethylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclo the KS-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({1-[2-(2-methoxyethoxy)ethyl]piperidine-4-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-(2-chloro-3-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[1-(3-phenylpropyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(2-methoxyethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-ethylpiperazin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-isopropylpiperazine-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-hydroxyphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-immiscibles-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-methoxyphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-methylphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-methylphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[6-(4-chlorophenyl)-1,3-benzodioxol-5-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({1-[2-(dimethylamino)-2-oxoethyl]piperidine-4-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(2-morpholine-4-retil)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

N-[(4-{[(4-aminotetraline-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-hydroxy-1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3S)-1-methylpyrrolidine-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3R)-1-methylpyrrolidine-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[3-(1H-pyrrol-2-yl)phenoxy]benzo the MFA;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-[(4-{[(4-hydroxy-1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)amino]carbonyl}phenoxy)-1H-indole-1-carboxylate;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-(dimethylamino)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-(diethylamino)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

TRANS-2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfo the Il)benzamide;

4-{4-[1-(4'-chloro-1,1'-biphenyl-2-yl)ethyl]piperazine-1-yl}-2-(2-chlorophenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-({1,3-bis[(4-methylpiperazin-1-yl)methyl]-1H-indol-4-yl}oxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-({3-[(4-methylpiperazin-1-the l)methyl]-1H-indol-4-yl}oxy)benzamide;

2-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(4-(1-methylpiperidin-4-ylamino)-3-nitrophenylacetylene)phenoxy)-N,N-dimethylbenzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)-2-{[2-(trifluoromethyl)-1H-indol-4-yl]oxy}benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-{[6-(trifluoromethyl)-1H-indol-5-yl]oxy}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)-2-{[6-(trifluoromethyl)-1H-indol-5-yl]oxy}benzamide;

2-[(2-amino-1,3-thiazol-4-yl)methoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-and the Dol-5-yl)oxy]-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

tert-butyl 4-[(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)amino]carbonyl}phenoxy)methyl]-1,3-thiazole-2-ylcarbamate;

2-[(2-amino-1,3-thiazol-4-yl)methoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(2-chlorophenyl)amino]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-methoxy-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(2-chlorophenyl)amino]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-�ethylpiperidine-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

tert-butyl 5-[5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]amino}carbonyl)phenoxy]-1H-indole-1-carboxylate;

2-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]-2-[(6,7-debtor-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-f the PR-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(2-hydroxy-1-tetrahydro-2H-Piran-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[4-({[4-(hydroxymethyl)tetrahydro-2H-Piran-4-yl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[1-(1,3-the thiazole-4-ylmethyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-NITR the-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

N-[(4-{[(4-aminotetraline-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[(3S,4R)-3-hydroxy-1-(1,3-thiazol-4-ylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[4-(hydroxymethyl)tetrahydro-2H-Piran-4-yl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[3-nitro-4-(tetrahydro-2H-Piran-4-ylamino)phenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[4-(morpholine-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(morpholine-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]be same;

2-(6-aminopyridine-3-yl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{1-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]ethyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3S)-tetrahydro-2H-Piran-3-ylmethyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3R)-tetrahydro-2H-Piran-3-ylmethyl]amino}phenyl)sulfonyl]benzamide;

tert-butyl 5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate;

2-[(6-aminopyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-f the PR-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(2-methoxyethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[3-nitro-4-(tetrahydro-2H-Piran-4-ylethoxy)phenyl]sulfonyl}benzamide;

2-[(3-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(3-chloro-1H-indol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-({4-[(2-methoxyethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

tert-butyl 5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)AMI is about]carbonyl}-phenoxy)pyridine-2-ylcarbamate;

tert-butyl 4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

2-[(6-aminopyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(2-aminopyridine-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2{[({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}-phenoxy)pyridine-3-ylcarbamate;

2-[(5-aminopyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

2-[(3-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(2-aminopyridine-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-hydroxypyridine-3-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-{[6-(benzyloxy)pyridin-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(1,4-dioxane-2-ylethoxy)-3-nitrophenyl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-[(3-chloro-1H-indol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-m is teleperson-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(1,4-dioxane-2-ylethoxy)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)and the Ino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-{[3-(2-amino-ethyl)-1H-indol-5-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-{[3-(2-amino-ethyl)-1H-indol-5-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-[(6-amino-5-herperidin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-NITR the-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-chloro-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)-2-[(1-oxo-1,2,3,4-tetrahydroisoquinoline-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(1,4-dioxane-2-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-{[5-bromo-6-(1,4-dioxane-2-ylethoxy)pyridine-3-yl]sulfonyl}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-N-({5-bromo-6-[(4-morpholine-4-illlogical)amino]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-cyano-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-(3-amino-5-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(2-morpholine-4-ylethoxy)pyridine-3-ylsulphonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)oxy]-3-nitrophenyl}sulfonyl)benzamide;

N-({5-bromo-6-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[5-(4-chlorophenyl)-2,3,6,7-tetrahydroxy-4-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[5-(4-chlorophenyl)-2,3,6,7-tetrahydroxy-4-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-albut-2-inyl)oxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}PI is erasin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[1-(methylsulphonyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(2-methoxyethyl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-1H-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-ethinyl-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-{[5-ethinyl-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-cyano-6-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)oxy]pyridin-3-yl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorphen the l)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-ethylmorpholine-3-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3S)-1-tetrahydro-2H-Piran-4-reparacin-3-yl]amino}phenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,1-diocletianopolis-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydrofuran-3-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-N-({5-bromo-6-[(4-morpholine-4-illlogical)oxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-(dicyclopropyl)cyclohexyl]amine is}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(tetrahydro-2H-Piran-4-ylamino)cyclohexyl]amino}phenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(4-tetrahydro-2H-Piran-4-reparation-1-yl)cyclohexyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[(4-hydroxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({3-[3-(dimethylamino)propyl]-1H-indol-4-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({3-[3-(dimethylamino)propyl]-1H-indol-4-yl}oxy)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropyl-4-foreperiod-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclo the CEN-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[1-(4-methoxybenzyl)-1H-1,2,3-benzotriazol-4-yl]oxy}-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(1,4-dioxane-2-ylethoxy)-3-nitrophenyl]sulfonyl}benzamide;

TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclo the CEN-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-amino-5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}-phenoxy)nicotinamide;

2-[(6-amino-5-cyano-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3R)-1-(2,2-dottorati)pyrrolidin-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-{[6-(acetylamino)pyridin-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({6-[(methylsulphonyl)amino]pyridine-3-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({(3R)-1-[2-fluoro-1-(permitil)ethyl]pyrrolidin-3-yl}amino)-3-nitrophenyl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-�lorgeril)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-methylpyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-oxetan-3-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-isopropylpyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-cyclopropylmethyl-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl] ethyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-cyclopropylmethyl-2-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3R)-1-cyclopropylboronic-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({4-fluoro-1-[2-fluoro-1-(permitil)ethyl]piperidine-4-yl}methoxy)-3-nitrophenyl]sulfonyl}benzamide;

tert-butyl 6-bromo-4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

tert-butyl 4-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)pyridine-2,6-childtable;

<> 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[6-(cyclopropylamino)pyridine-3-yl]oxy}-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({6-[(2,2-dottorati)amino]pyridine-3-yl}oxy)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({6-[(2,2-dottorati)amino]pyridine-3-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-{[5-chloro-6-(methylamino)pyridine-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[({4-[2-fluoro-1-(permitil)ethyl]morpholine-2-yl}methyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(2-amino-6-bromopyridin-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(2,6-diaminopyridine-4-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-(tetrahydro-2H-Piran-4-ylethoxy)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({(3R)-1-[2-fluoro-1-(permitil)ethyl]piperidine-3-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

tert-butyl 5-bromo-4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(4-chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-({6-[(2,2,2-triptorelin)amino]pyridine-3-yl}oxy)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-hydroxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-[(6-amino-5-chloropyrid the n-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydrofuran-3-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({9-(4-chlorophenyl)-3-[2-fluoro-1-(permitil)ethyl]-3-azaspiro[5,5]undec-8-EN-8-yl}methyl)piperazine-1-yl]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[9-(4-chlorophenyl)-3-isopropyl-3-azaspiro[5,5]undec-8-EN-8-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[1-(N,N-dimethylphenyl)-4-foreperiod-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({(3R)-1-[2-fluoro-1-(permitil)ethyl]pyrrolidin-3-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(2-amino-5-bromopyridin-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4,4-diverticulosis)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-AMI is about-5-chloropyridin-3-yl)oxy]-4-[4-({4'-chloro-3-[2-(dimethylamino)ethoxy]-1,1'-biphenyl-2-yl}methyl)piperazine-1-yl]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-{[5-chloro-6-({(3R)-1-[2-fluoro-1-(permitil)ethyl]pyrrolidin-3-yl}methoxy)pyridine-3-yl]sulfonyl}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[(3R)-1-(2,2-dottorati)pyrrolidin-3-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-cyanocyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-fluoro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[1-(2,2-dottorati)-4-foreperiod-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({3-chloro-4-[(4-Porterage-2H-Piran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[6-({4-fluoro-1-[2-fluoro-1-(permitil)ethyl]piperidine-4-yl}methoxy)-5-(trifluoromethyl)pyridine-3-yl]sulfonyl}benzo the MFA;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[2-(1H-pyrazole-4-yl)phenoxy]benzamide;

2-[2-(2-aminopyridine-3-yl)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[2-(1H-pyrazole-5-yl)phenoxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4,4-diverticulosis)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

N-({5-chloro-6-[(4,4-diverticulosis)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4,4-diverticulosis)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({3-chloro-4-[(4-Porterage-2H-Piran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({3-chloro-4-[(4-Porterage-2H-Piran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl] ethyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxycyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

tert-butyl 5-[(4-{4-[({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)carbarnoyl]-3-[(6-fluoro-1H-indol-5-yl)oxy]phenyl}piperazine-1-yl)methyl]-4-(4-chlorophenyl)-3,6-dihydropyridines-1(2H)-carboxylate;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-1-(1,3-ditropan-2-yl)-1,2,5,6-tetrahydropyridine-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxycyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yloxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-({[4-(oxetan-3-yl)morpholine-2-yl]methyl}amino)phenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[3-nitro-4-({[4-(oxetan-3-yl)morpholine-2-yl]methyl}amino)phenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-chloro-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(TRANS-4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(3-aminon-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-fluoro-1-(oxetan-3-yl)piperidine-4-yl]methoxy}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(TRANS-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(TRANS-4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(CIS-4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dim testicles-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(CIS-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-chloro-4-(tetrahydro-2H-Piran-4-ylethoxy)phenyl]sulfonyl}-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-cyclopropylmethyl-2-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-(2-oxaspiro[3,5]non-7-ylethoxy)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[(2S)-4-cyclopropylmethyl-2-yl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(TRANS-1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(CIS-1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-2-[(3-chloro-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(CIS-4-ethyl-4-hydroxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-({[(2S)-4-(oxetan-3-yl)morpholine-2-yl]methyl}amino)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-nitro-6-[(tetrahydro-2H-Piran-4-ylmethyl)amino]pyridine-3-yl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(2-oxaspiro[3,5]non-7-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[TRANS-4-(morpholine-4-yl)cyclohexyl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[CIS-4-(morpholine-4-yl)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex the-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-cyano-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[4-({[4-(methoxymethyl)cyclohexyl]methyl}amino)-3-nitrophenyl]sulfonyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[(3R)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino}phenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[(3S)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino}phenyl)sulfonyl]benzamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzoyl}sulfamoyl)-2-nitrophenyl]morpholine-4-carboxamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzoyl}sulfamoyl)-2-nitrophenyl]-4-cyanopiperidine-1-carboxamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

another variant embodiment of the invention relates to TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide; and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to dihydrophosphate [3-chloro-5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)-2-aminopyridin-1(2H)-yl]bromide; and therapeutically acceptable salts, and metabolites.

Yet another variant embodiment of the invention relates to 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[(3R)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino}phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(tetrahydro-2H-Piran-4-ylamino)cyclohexyl]amino}phenyl)sulfonyl]benzamide; and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3S)-tetrahydro-2H-Piran-3-ylmethyl]amino}phenyl)sulfonyl]benzamide; and his Ter is piticescu acceptable salts, the prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide; and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3,4-dichlorophenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-isopropylpiperazine-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Another variant implementation of the image is etenia refers to 4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-6-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

Yet another variant embodiment of the invention relates to 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

In another aspect, the present invention relates to compounds of the formula (II):

,

and their therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites,

where A1B1D1E1, Y1, Z2L1and Z3have the meanings as described herein for formula(I), n is 0, 1, 2 or 3; describes the number of additional substituents on R26and R100has the same values as described for substituents on R26, m is 1, 2, 3, 4 or 5; describes the number of substituents on the R42and R101has the same values as described for substituents on R42.

In one embodiment of formula (II) A1represents N. In another embodiment of formula (II) A1represents(A2). In another embodiment of formula (II) A1represents(A2); and A2represents H.

In one embodiment of formula (II) B1represents NHC(O)R1, NHSO2R1, OR1or other1. In another embodiment of formula (II) A1represents(A2); A2represents H; and B1represents other1. In another embodiment of formula (II) A1represents(A2); A2represents H; and B1is a OR1. In another embodiment of formula (II) A1represents(A2); A2represents H; and B1represents NHSO2R1. In another embodiment of formula (II) A1represents(A2); A2represents H; and B1represents NHC(O)R1. In another embodiment of formula (II) A1represents(A2or N; A2represents H; and B1p is ecstasy a other 1. In another embodiment of formula (II) A1represents(A2or N; A2represents H; and B1is a OR1. In another embodiment of formula (II) A1represents(A2or N; A2represents H; and B1represents NHSO2R1. In another embodiment of formula (II) A1represents(A2or N; A2represents H; and B1represents NHC(O)R1.

In one embodiment of formula (II) D1represents H. In another embodiment of formula (II) A1represents(A2); A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (II) A1represents(A2); A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (II) A1represents(A2); A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (II) A1represents(A2); A2represents H; B1represents NHC(O)R1; and D1represents H. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1predstavljaet a other 1; and D1represents H. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1represents NHC(O)R1; and D1represents H.

In one embodiment of formula (II) E1represents H. In another embodiment of formula (II), A1represents(A2); A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (II) A1represents(A2); A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (II) A1represents(A2); A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (II) A1represents(A2); A represents H; B1represents NHC(O)R1; D1represents H; and E1represents H. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H.

In one embodiment of formula (II) Y1represents H, CN, NO2, F, Cl, Br, CF3, R17or SO2R17. In another embodiment of formula (II) Y1represents NO2. In another embodiment of formula (II) Y1represents CL. In another embodiment of formula (II) Y1represents the SO2R17; where R17matter, the decree is installed above. In another embodiment of formula (II) Y1represents the SO2R17; where R17represents alkyl. In another embodiment of formula (II) Y1is an R17; where R17represents quinil. In another embodiment of formula (II) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (II) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (II) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (II) A1represents(A2); A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL. In other the Ohm variant of the formula (II) A 1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (II) A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL.

In one embodiment of formula (II) R1is an R2and R2represents phenyl. In another embodiment of formula (II) R1is an R2and R2represents phenyl, which is substituted NO2and other7 .

In one embodiment of formula (II) R1is an R4or R5. In one embodiment of formula (II) R1is an R4. In one embodiment of formula (II) R1is an R5. In one embodiment of formula (II) R1is an R4; and R4is cycloalkyl or heteroseksualci. In one embodiment of formula (II) R1is an R4; and R4is cycloalkyl. In one embodiment of formula (II) R1is an R4; and R4is heteroseksualci.

In one embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is substituted, as shown here. In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted R57, Other57or N(R57)2. In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring for esino R 57; and R57is an R60. In another embodiment of formula (II) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; and R60is heteroseksualci. In another embodiment of formula (II) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; R60is heteroseksualci; where cycloalkyl ring is morpholinyl or piperazinil. In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted N(R57)2. In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2.In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo Kohl is substituted on N(R 57)2, R57is an R61and R61represents alkyl, which is unsubstituted. In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R60and R60is cycloalkyl, which is unsubstituted. In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted with other57. In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57.In another embodiment of formula (II) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57, R57is an R60and R60is heteroseksualci, which is unsubstituted.

In one embodiment of formula (II) R1is an R4; and R4is heteroseksualci; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is substituted, as shown here. In another embodiment of formula (II) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring substituted R57. In another embodiment of formula (II) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where geteroseksualnoe ring substituted with one, or two, or three, or four, or five substituents R57, SO2R57or OH, and R57is an R60or R61. In another embodiment of formula (II) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60or R61; R60is cycloalkyl or heteroseksualci; and R61represents alkyl. In another embodiment of formula (II) R1depict is to place an R 4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is heteroseksualci where heteroseksualci is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of formula (II) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is cycloalkyl where cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of formula (II) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57the submitted is an R 61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl. In another embodiment of formula (II) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl; where C1-alkyl, C2-alkyl or C3the alkyl are unsubstituted or substituted.

In one embodiment of formula (II) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted. In one embodiment of formula (II) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted R7, OR7N(R7)2or OH.

In one embodiment of formula (II) R7is an R10or R11which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R7is an R10to which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R7is an R11which is unsubstituted or substituted as specified here.

In one embodiment of formula (II) R10is cycloalkyl or heteroseksualci, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R10is heteroseksualci, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R10is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxane, piperidinyl, piperazinyl or pyrrolidinyl, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R10is tetrahydropyranyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R10is morpholinyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R10is cycloalkyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R10represents cyclohexyl which is unsubstituted or substituted as specified here.

In one embodiment of formula (II) R11represents alkyl, which is th is unsubstituted. In another embodiment of formula (II) R11represents methyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (II) R11represents alkyl, which is substituted as described here. In another embodiment of formula (II) R11represents alkyl, which is substituted OR12, R12is an R16and R16represents alkyl.

In one embodiment of formula (II) n is 0 and m is 1. In another embodiment of formula (II) n is 0 and m is 2.

Yet another variant embodiment of the invention relates to compounds having formula (II), which are

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)and the Ino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(hydroxymethyl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-PI is an-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(3-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-methoxyphenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(dimethylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)-3-oxopropyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)-2-oxoethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)propyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)phenylsulfonyl carbamoyl)phenoxy)-N,N-dimethylbenzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-morpholine-4-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2,4-dimethyl-1,3-thiazol-5-yl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(3,5-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)ethoxy)phenoxy)-N-((3-nitro-4-((tet is ahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-isopropylpiperazine-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-ethylpiperazin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((1,2,2,6,6-pentamethylpiperidin-4-yl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-(3-nitro-4-((1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((4'-chloro-4-(2-pyrrolidin-1-retil)-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)-2-(3-(trifluoromethyl)phenoxy)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chloro-4-pertenece)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclo the Gex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclopentene-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2-chloro-3-(trifluoromethyl)phenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-cyclopropylidene-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholine-4-elfenix)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(1H-imidazol-1-yl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-p the RAS-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)benzyl(ethyl)carbamate;

tert-butyl 3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)benzyl(ethyl)carbamate;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenylcarbamate;

2-(1,1'-biphenyl-2-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((is, etrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenylcarbamate;

2-(1,1'-biphenyl-3-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholine-4-elfenix)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenyl)piperazine-1-carboxylate;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-morpholine-4-ylethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino-3-nitrophenyl)sulfonyl)benzamide;

tert-butyl 4-(4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-1-carboxylate;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-pyridin-4-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-4-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridine-3-elfenix)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylcarbamoyl)phenoxy)-N-(4-(3-morpholinopropan)-3-nitrophenylarsonic)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-N-(4-(3-(dimethylamino)propylamino)-3-nitrophenylarsonic)-2-(3-(methylcarbamoyl)phenoxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-(hydroxymethyl) is enocsi)benzamide;

N-(4-((4-aminotetraline-2H-Piran-4-yl)methylamino)-3-nitrophenylarsonic)-2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzamide;

4-(4-(1-(4'-chlorobiphenyl-2-yl)ethyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)phenylsulfonyl)benzamide;

N-{[4-{4-[(4'-chloro-1,1'-biphenyl-2-yl)methyl]piperazine-1-yl}-2-(3,5-dichlorophenoxy)phenyl]sulfonyl}-4-[(1-methylpiperidin-4-yl)amino]-3-nitrobenzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-C is kleintiermedizin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(4-pertenece)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2,3-divergence)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-pertenece)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-pertenece)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-pertenece)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}PI is erasin-1-yl)-2-(2-pertenece)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(3-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2,3-divergence)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopentenopyridine-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex the-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-[(3-nitro-4-{[1-(Tien-3-ylmethyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(2-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(3-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(4-pertenece)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-[(4-{[1-(2-foradil)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(4-methylpiperazin-1-yl)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl] ethyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

N-({4-[(1-arylpiperazine-4-yl)amino]-3-nitrophenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl)amino]phenyl}sulfonyl)benzamide;

2-(3-chloro-2-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(2-morpholine-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-6-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-6-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-immiscibles-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-[(4-{[(1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[3-(methoxyethoxy)-2-methylphenoxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-hydroxy-2-methylphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-(3-iodinase)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(2-hydroxyethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[1-(2-phenylethyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3,4-dichlorophenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3,5-divergence)-4-(4-{[2-(4-�lorgeril)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-methoxyphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[3-(hydroxymethyl)phenoxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dimethylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dimethylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({1-[2-(2-methoxyethoxy)ethyl]piperidine-4-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-(2-chloro-3-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[1-(3-phenylpropyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(2-methoxyethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-44-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-ethylpiperazin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-isopropylpiperazine-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-hydroxyphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3-pertenece)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-methoxyphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(2-methylphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-methylphenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[6-(4-chlorophenyl)-1,3-benzodioxol-5-yl]IU the Il}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-(2,3-divergence)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({1-[2-(dimethylamino)-2-oxoethyl]piperidine-4-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(2-morpholine-4-retil)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

N-[(4-{[(4-aminotetraline-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-(2-chlorphen the si)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-hydroxy-1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3S)-1-methylpyrrolidine-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3R)-1-methylpyrrolidine-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[3-(1H-pyrrol-2-yl)phenoxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-(3-pertenece)-N-[(4-{[(4-hydroxy-1-methylpiperidin-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-(dimethylamino)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-(diethylamino)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

TRANS-2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-{4-[1-(4'-chloro-1,1'-biphenyl-2-yl)ethyl]piperazine-yl}-2-(2-chlorophenoxy)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(4-(1-methylpiperidin-4-ylamino)-3-nitrophenylacetylene)phenoxy)-N,N-dimethylbenzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino] enyl}sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[4-(hydroxymethyl)tetrahydro-2H-Piran-4-yl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(morpholine-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

2-(3-amino-5-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[2-(1H-pyrazole-4-yl)phenoxy]benzamide;

2-[2-(2-aminopyridine-3-yl)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[2-(1H-pyrazole-5-yl)phenoxy]Ben who amide; and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

In another aspect, the present invention relates to compounds of the formula (III):

,

and their therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites,

where A1B1D1E1, Y1, Z2L1and Z3are as described herein for formula (I), n is 0, 1, 2 or 3; describes the number of additional substituents on R26and R100has the same values as described for substituents on R26and at least one R102is a Deputy, as described for substituents on R42and R42Aand the others are H.

In one embodiment of formula (III) (A1represents N. In another embodiment of formula (III) (A1represents(A2). In another embodiment of formula (III) (A1represents(A2); and A2represents H.

In one embodiment of formula (III) B1represents NHC(O)R1, NHSO2R1, OR1or other1. In another embodiment of formula (III) (A1represents(A2); A2represents H; and B1represents other1. In another embodiment of formula (III) (A1represents(A2); A2represents H; the B 1is a OR1. In another embodiment of formula (III) (A1represents(A2); A2represents H; and B1represents NHSO2R1. In another embodiment of formula (III) (A1represents(A2); A2represents H; and B1represents NHC(O)R1. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; and B1represents other1. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; and B1is a OR1. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; and B1represents NHSO2R1. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; and B1represents NHC(O)R1.

In one embodiment of formula (III), D1represents H. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1is a OR1; and D1is the fight H. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1represents NHC(O)R1; and D1represents H. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1represents NHC(O)R1; and D1represents H.

In one embodiment of formula (III) E1represents H. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1represents other1; D1represents H; and E1presented yet a H. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (III) (A1represents(A2or N; A represents H; B1represents NHC(O)R1; D1represents H; and E1represents H.

In one embodiment of formula (III) Y1represents H, CN, NO2, F, Cl, Br, CF3, R17or SO2R17. In another embodiment of formula (III) Y1represents NO2. In another embodiment of formula (III) Y1represents CL. In another embodiment of formula (III) Y1represents the SO2R17; where R17has the values listed above. In another embodiment of formula (III) Y1represents the SO2R17; where R17represents alkyl. In another embodiment of formula (III) Y1is an R17; where R17represents quinil. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (III) (A1PR is dstanley a(A 2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (III) (A1represents(A2); A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17is the th alkyl, substituted with three F. In another embodiment of formula (III) (A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL.

In one embodiment of formula (III), R1is an R2and R2represents phenyl. In another embodiment of formula (III), R1is an R2and R2represents phenyl, which is substituted NO2and other57.

In one embodiment of formula (III), R1is an R4or R5. In one embodiment of formula (III), R1is an R4. In one embodiment of formula (III), R1is an R5. In one embodiment of formula (III), R1is an R4; and R4is cycloalkyl or heteroseksualci. In one embodiment of formula (III), R1is an R4; and R4is cycloalkyl. In one embodiment of formula (III), R1is an R4; and R4is heteroseksualci.

In one embodiment of formula (III), R1is an R4; and R4is cycloalkyl; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R1is Soboh the R 4; and R4is cycloalkyl; where cycloalkyl ring is substituted, as shown here. In another embodiment of formula (III), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted R57, Other57or N(R57)2. In another embodiment of formula (III), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; and R57is an R60. In another embodiment of formula (III), R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; and R60is heteroseksualci. In another embodiment of formula (III), R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; R60is heteroseksualci; where geteroseksualnoe ring is morpholinyl or piperazinil. In another embodiment of formula (III), R1is an R4 ; and R4is cycloalkyl; where cycloalkyl ring substituted N(R57)2. In another embodiment of formula (III), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2.In another embodiment of formula (III), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R61and R61represents alkyl, which is unsubstituted. In another embodiment of formula (III), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R60and R60is cycloalkyl, which is unsubstituted. In another embodiment of formula (III), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted with other57. In another embodiment of formula (III), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring represents illogical; and where tsiklogeksilnogo ring substituted with other57.In another embodiment of formula (III), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57, R57is an R60and R60is heteroseksualci, which is unsubstituted.

In one embodiment of formula (III), R1is an R4; and R4is heteroseksualci; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is substituted, as shown here. In another embodiment of formula (III), R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring substituted R57. In another embodiment of formula (III), R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where geteroseksualnoe ring substituted with one, or two, or three, or four, or five substituents R57, SO2R57or OH; and Rsup> 57is an R60or R61. In another embodiment of formula (III), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60or R61; R60is cycloalkyl or heteroseksualci; and R61represents alkyl. In another embodiment of formula (III), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is heteroseksualci where heteroseksualci is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of formula (III), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl the Noah ring substituted R 57; R57is an R60; R60is cycloalkyl where cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of formula (III), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl. In another embodiment of formula (III), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl; where C1-alkyl, C2-alkyl or C3the alkyl are unsubstituted or C is meseni.

In one embodiment of formula (III), R1is an R5; and R5represents alkyl, which is unsubstituted or substituted. In one embodiment of formula (III), R1is an R5; and R5represents alkyl, which is unsubstituted or substituted R7, OR7N(R7)2or OH.

In one embodiment of formula (III), R7is an R10or R11which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R7is an R10which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R7is an R11which is unsubstituted or substituted as specified here.

In one embodiment of formula (III), R10is cycloalkyl or heteroseksualci, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R10is heteroseksualci, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R10is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxane, piperidinyl, piperazinyl or pyrrolidinyl, which are unsubstituted or substituted, as is indicated here. In another variant of the formula (III), R 10is tetrahydropyranyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R10is morpholinyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R10is cycloalkyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R10represents cyclohexyl which is unsubstituted or substituted as specified here.

In one embodiment of formula (III), R11represents alkyl, which is unsubstituted. In another embodiment of formula (III), R11represents methyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (III), R11represents alkyl, which is substituted as described here. In another embodiment of formula (III), R11represents alkyl, which is substituted OR12, R12is an R16and R16represents alkyl.

In one embodiment of formula (III) n is equal to 0.

Yet another variant embodiment of the invention relates to compounds having the formula (III), which are

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-the l)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((7-fluoro-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((3-(3-morpholine-4-yl-3-oxopropyl)-1H-indol-5-yl)oxy)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-morpholine-4-yl-3-oxopropyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-morpholine-4-ylpropyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-(dimethylamino)propyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(4-fluoro-1H-indol-5-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-{[6-(trifluoromethyl)-1H-indol-5-yl]oxy}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)-2-{[6-(trifluoromethyl)-1H-indol-5-yl]oxy}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-methoxy-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 5-[5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({[(4-{[3-(dimethylamino)PR who drank]amino}-3-nitrophenyl)sulfonyl]amino}carbonyl)phenoxy]-1H-indole-1-carboxylate;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[1-(cyclopropylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]-2-[(6,7-debtor-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(2-hydroc the and-1-tetrahydro-2H-Piran-4-retil)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[4-({[4-(hydroxymethyl)tetrahydro-2H-Piran-4-yl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6,7-debtor-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[1-(1,3-the thiazole-4-ylmethyl)piperidine-4-yl]amino}phenyl)sulfonyl]benzamide;

N-[(4-{[(4-aminotetraline-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[(3S,4R)-3-hydroxy-1-(1,3-thiazol-4-ylmethyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-ningal-5-yl)oxy]-N-{[3-nitro-4-(tetrahydro-2H-Piran-4-ylamino)phenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[4-(morpholine-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide;

4-(4-{1-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]ethyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3S)-tetrahydro-2H-Piran-3-ylmethyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3R)-tetrahydro-2H-Piran-3-ylmethyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(2-methoxyethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[3-nitro-4-(tetrahydro-2H-Piran-4-ylethoxy)phenyl]sulfonyl}benzamide;

2-[(3-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(3-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(1,4-dioxane-2-ylethoxy)-3-nitrophenyl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-(1,4-dioxane-2-ylethoxy)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]Bentham is d;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

2-{[3-(2-amino-ethyl)-1H-indol-5-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-{[3-(2-amino-ethyl)-1H-indol-5-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-the l)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-chloro-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(1,4-dioxane-2-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-{[5-bromo-6-(1,4-dioxane-2-ylethoxy)pyridine-3-yl]sulfonyl}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-N-({5-bromo-6-[(4-morpholine-4-illlogical)amino]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-cyano-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-cyano-6-(2-morpholine-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-illlogical)oxy]-3-neither is Ravenel}sulfonyl)benzamide;

N-({5-bromo-6-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[5-(4-chlorophenyl)-2,3,6,7-tetrahydroxy-4-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

TRANS-2-[(6-chloro-1H-indol-5-yl)oxy]-4-(4-{[5-(4-chlorophenyl)-2,3,6,7-tetrahydroxy-4-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({4-[(4-morpholine-4-albut-2-inyl)oxy]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[1-(methylsulphonyl)piperidine-4-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-ethinyl-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-{[5-ethinyl-6-(tetrahydro-mpirun-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-cyano-6-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)oxy]pyridin-3-yl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-ethylmorpholine-3-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[(3S)-1-tetrahydro-2H-Piran-4-reparacin-3-yl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,1-diocletianopolis-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydrofuran-3-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-N-({5-bromo-6-[(4-morpholine-4-illlogical)oxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-s is-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-(dicyclopropyl)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(tetrahydro-2H-Piran-4-ylamino)cyclohexyl]amino}phenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(4-tetrahydro-2H-Piran-4-reparation-1-yl)cyclohexyl]amino}phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[(4-{[(4-hydroxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropyl-4-foreperiod-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({(3R)-1-[2-fluoro-1-(permitil)ethyl]pyrrolidin-3-yl}amino)-3-nitrophenyl]sulfonyl}-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-the l)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({5-chloro-6-[(4,4-diverticulosis)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4,4-diverticulosis)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({3-chloro-4-[(4-Porterage-2H-Piran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

N-({3-chloro-4-[(4-Porterage-2H-Piran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

tert-butyl 5-[(4-{4-[({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)carbarnoyl]-3-[(6-fluoro-1H-indol-5-yl)oxy]phenyl}piperazine-1-yl)methyl]-4-(4-chlorophenyl)-3,6-dihydropyridines-1(2H)-carboxylate;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-1-(1,3-ditropan-2-yl)-1,2,5,6-tetrahydropyridine-3-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{[3-nitro-4-({[4-(oxetan-3-yl)morpholine-2-yl]methyl}amino)phenyl]sulfonyl}benzamide; and therapeutically acceptable salts, prodrugs, salts Strait is karst and metabolites.

In another aspect, the present invention relates to compounds of the formula (IV):

,

and their therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites,

where A1B1D1E1, Y1, Z2L1and Z3are as described herein for formula (I), n is 0, 1, 2 or 3; describes the number of additional substituents on R26and R100has the same values as described for substituents on R26and at least one R102is a Deputy, as described for substituents on R42and R42Aand the others are H.

In one embodiment of formula (IV), A1represents N. In another embodiment of formula (IV), A1represents(A2). In another embodiment of formula (IV), A1represents(A2); and A2represents H.

In one embodiment of formula (IV) B1represents NHC(O)R1, NHSO2R1, OR1or other1. In another embodiment of formula (IV), A1represents(A2); A2represents H; and B1represents other1. In another embodiment of formula (IV), A1represents(A2); A2represents H; and B1is a OR1. In another embodiment of formula (IV), A1you submitted the a(A 2); A2represents H; and B1represents NHSO2R1. In another embodiment of formula (IV), A1represents(A2); A2represents H; and B1represents NHC(O)R1. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; and B1represents other1. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; and B1is a OR1. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; and B1represents NHSO2R1. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; and B1represents NHC(O)R1.

In one embodiment of formula (IV) D1represents H. In another embodiment of formula (IV), A1represents(A2); A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (IV), A1represents(A2); A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (IV), A1represents(A2); A2is Cobain; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (IV), A1represents(A2); A2represents H; B1represents NHC(O)R1; and D1represents H. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1represents NHC(O)R1; and D1represents H.

In one embodiment of formula (IV) E1represents H. In another embodiment of formula (IV), A1represents(A2); A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (IV), A1represents(A2); A2isone H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (IV), A1represents(A2); A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (IV), A1represents(A2); A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1represents NHC(O)R1; D1represents H; and E1 represents H.

In one embodiment of formula (IV) Y1represents H, CN, NO2, F, Cl, Br, CF3, R17or SO2R17. In another embodiment of formula (IV) Y1represents NO2. In another embodiment of formula (IV) Y1represents CL. In another embodiment of formula (IV) Y1represents the SO2R17; where R17has the values listed above. In another embodiment of formula (IV) Y1represents the SO2R17; where R17represents alkyl. In another embodiment of formula (IV) Y1is an R17; where R17represents quinil. In another embodiment of formula (IV), A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (IV), A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (IV), A1represents(A2); A2represents H; B1represents other1; D1p is ecstasy a H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (IV), A1represents(A2); A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (IV), A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (IV), A1represents(A2or N; A2 represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL.

In one embodiment of formula (IV) R1is an R2and R2represents phenyl. In another embodiment of formula (IV) R1is an R2and R2represents phenyl, which is substituted NO2and other57.

In one embodiment of formula (IV) R1is an R4or R5. In one embodiment of formula (IV) R1is an R4. In one embodiment of formula (IV) R1is an R5. In one embodiment of formula (IV) R1is an R4; and R4is cycloalkyl or heteroseksualci. In one embodiment of formula (IV) R1is an R4; and R4is cycloalkyl. In one embodiment of formula (IV) R1is an R4; and R4is heteroseksualci.

In one embodiment of formula (IV) R1is an R4; and R4is cycloalkyl; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is substituted, as ZV is camping specified. In another embodiment of formula (IV) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted R57, Other57or N(R57)2. In another embodiment of formula (IV) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; and R57is an R60. In another embodiment of formula (IV) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; and R60is heteroseksualci. In another embodiment of formula (IV) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; R60is heteroseksualci; where geteroseksualnoe ring is morpholinyl or piperazinil. In another embodiment of formula (IV) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted N(R57)2. In another Varian is e of the formula (IV) R 1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2.In another embodiment of formula (IV) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R61and R61represents alkyl, which is unsubstituted. In another embodiment of formula (IV) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R60and R60is cycloalkyl, which is unsubstituted. In another embodiment of formula (IV) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted with other57. In another embodiment of formula (IV) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57.In another embodiment of formula (IV) R1is a Rsup> 4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57, R57is an R60and R60is heteroseksualci, which is unsubstituted.

In one embodiment of formula (IV) R1is an R4; and R4is heteroseksualci; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is substituted, as shown here. In another embodiment of formula (IV) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring substituted R57. In another embodiment of formula (IV) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where geteroseksualnoe ring substituted with one, or two, or three, or four, or five substituents R57, SO2R57or OH; and R57is an R60or R61. In another embodiment of formula (IV) R1is an R4; R4/sup> is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60or R61; R60is cycloalkyl or heteroseksualci; and R61represents alkyl. In another embodiment of formula (IV) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is heteroseksualci where heteroseksualci is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of formula (IV) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is cycloalkyl where cycloalkyl represent cyclopropyl or cyclopentyl. In another embodiment of formula (IV) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl. In another embodiment of formula (IV) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl; where C1-alkyl, C2-alkyl or C3the alkyl are unsubstituted or substituted.

In one embodiment of formula (IV) R1is an R5; and R5represents alkyl, which is unsubstituted or C is substituted. In one embodiment of formula (IV) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted R7, OR7N(R7)2or OH.

In one embodiment of formula (IV) R7is an R10or R11which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R7is an R10which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R7is an R11which is unsubstituted or substituted as specified here.

In one embodiment of formula (IV) R10is cycloalkyl or heteroseksualci, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R10is heteroseksualci, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R10is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxane, piperidinyl, piperazinyl or pyrrolidinyl, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R10is tetrahydropyranyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R 10is morpholinyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R10is cycloalkyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R10represents cyclohexyl which is unsubstituted or substituted as specified here.

In one embodiment of formula (IV) R11represents alkyl, which is unsubstituted. In another embodiment of formula (IV) R11represents methyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (IV) R11represents alkyl, which is substituted as described here. In another embodiment of formula (IV) R11represents alkyl, which is substituted OR12, R12is an R16and R16represents alkyl.

In one embodiment of formula (IV) n is equal to 0.

Yet another variant embodiment of the invention relates to compounds having the formula (IV), which are

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((1-methyl-1H-indol-4-yl)oxy)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)AMI is about)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indol-4-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((1-methyl-1H-indol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)amino]carbonyl}phenoxy)-1H-indole-1-carboxylate;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-({4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-({1,3-bis[(4-methylpiperazin-1-yl)methyl]-1H-indol-4-yl}oxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-({3-[(4-methylpiperazin-1-yl)methyl]-1H-indol-4-yl}oxy)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-ipipiri the Jn-4-yl)amino]phenyl}sulfonyl)-2-{[2-(trifluoromethyl)-1H-indol-4-yl]oxy}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperidin-1-yl)propyl]amino}phenyl)sulfonyl]benzamide;

2-[(3-chloro-1H-indol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indol-4-yl)oxy]-N-({4-[(2-methoxyethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(3-chloro-1H-indol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({3-[3-(dimethylamino)propyl]-1H-indol-4-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({3-[3-(dimethylamino)propyl]-1H-indol-4-yl}oxy)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

In another aspect, the present invention relates to compounds of the formula (V):

,

and their therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites,

where A 1B1D1E1, Y1, Z2L1and Z3are as described herein for formula (I), n is 0, 1, 2 or 3; describes the number of additional substituents on R26and R100has the same values as described for substituents on R26and at least one of R103or R104is a Deputy, as described for substituents on R42and R42Aand the others are H.

In one embodiment of formula (V) A1represents N. In another embodiment of formula (V) A1represents(A2). In another embodiment of formula (V) A1represents(A2); and A2represents H.

In one embodiment of formula (V) B1represents NHC(O)R1, NHSO2R1, OR1or other1. In another embodiment of formula (V) A1represents(A2); A2represents H; and B1represents other1. In another embodiment of formula (V) A1represents(A2); A2represents H; and B1is a OR1. In another embodiment of formula (V) A1represents(A2); A2represents H; and B1represents NHSO2R1. In another embodiment of formula (V) A1represents(A2); A2represents H; and B represents NHC(O)R1. In another embodiment of formula (V) A1represents(A2or N; A2represents H; and B1represents other1. In another embodiment of formula (V) A1represents(A2or N; A2represents H; and B1is a OR1. In another embodiment of formula (V) A1represents(A2or N; A2represents H; and B1represents NHSO2R1. In another embodiment of formula (V) A1represents(A2or N; A2represents H; and B1represents NHC(O)R1.

In one embodiment of formula (V) D1represents H. In another embodiment of formula (V) A1represents(A2); A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (V) A1represents(A2); A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (V) A1represents(A2); A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (V) A1represents(A2); A2represents H; B1not only is em a NHC(O)R 1; and D1represents H. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1represents NHC(O)R1; and D1represents H.

In one embodiment of formula (V) E1represents H. In another embodiment of formula (V) A1represents(A2); A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (V) A1represents(A2); A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (V) A1represents(A2); A2represents H; B1PR is dstanley a NHSO 2R1; D1represents H; and E1represents H. In another embodiment of formula (V) A1represents(A2); A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H.

In one embodiment of formula (V) Y1represents H, CN, NO2, F, Cl, Br, CF3, R17or SO2R17. In another embodiment of formula (V) Y1represents NO2. In another embodiment, Faure the uly (V) Y 1represents CL. In another embodiment of formula (V) Y1represents the SO2R17; where R17has the values listed above. In another embodiment of formula (V) Y1represents the SO2R17; where R17represents alkyl. In another embodiment of formula (V) Y1is an R17; where R17represents quinil. In another embodiment of formula (V) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (V) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (V) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (V) A1represents(A2); A2isone H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (V) A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL.

In one embodiment of formula (V) R1is an R2and R2predstavljaet a phenyl. In another embodiment of formula (V) R1is an R2and R2represents phenyl, which is substituted NO2and other57.

In one embodiment of formula (V) R1is an R4or R5. In one embodiment of formula (V) R1is an R4. In one embodiment of formula (V) R1is an R5. In one embodiment of formula (V) R1is an R4; and R4is cycloalkyl or heteroseksualci. In one embodiment of formula (V) R1is an R4; and R4is cycloalkyl. In one embodiment of formula (V) R1is an R4; and R4is heteroseksualci.

In one embodiment of formula (V) R1is an R4; and R4is cycloalkyl; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is substituted, as shown here. In another embodiment of formula (V) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted R57, Other57or N(R57)2. In another embodiment of formula (V) R1is an R4and R 4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; and R57is an R60. In another embodiment of formula (V) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; and R60is heteroseksualci. In another embodiment of formula (V) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; R60is heteroseksualci; where geteroseksualnoe ring is morpholinyl or piperazinil. In another embodiment of formula (V) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted N(R57)2. In another embodiment of formula (V) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2.In another embodiment of formula (V) R1is the battle R 4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R61and R61represents alkyl, which is unsubstituted. In another embodiment of formula (V) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R60and R60is cycloalkyl, which is unsubstituted. In another embodiment of formula (V) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted with other57. In another embodiment of formula (V) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57.In another embodiment of formula (V) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57, R57is an R60and R60is heteroseksualci, which is one the Xia unsubstituted.

In one embodiment of formula (V) R1is an R4; and R4is heteroseksualci; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is substituted, as shown here. In another embodiment of formula (V) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring substituted R57. In another embodiment of formula (V) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where geteroseksualnoe ring substituted with one, or two, or three, or four, or five substituents R57, SO2R57or OH; and R57is an R60or R61. In another embodiment of formula (V) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is a Rsup> 60or R61; R60is cycloalkyl or heteroseksualci; and R61represents alkyl. In another embodiment of formula (V) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is heteroseksualci where heteroseksualci is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of formula (V) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is cycloalkyl where cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of formula (V), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where Pipa is edinennoe, pyrrolidinone, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl. In another embodiment of formula (V) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl; where C1-alkyl, C2-alkyl or C3the alkyl are unsubstituted or substituted.

In one embodiment of formula (V) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted. In one embodiment of formula (V) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted R7, OR7N(R7)2or OH.

In one embodiment of formula (V) R7presented yet a R 10or R11which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R7is an R10which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R7is an R11which is unsubstituted or substituted as specified here.

In one embodiment of formula (V) R10is cycloalkyl or heteroseksualci, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R10is heteroseksualci, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R10is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxane, piperidinyl, piperazinyl or pyrrolidinyl, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R10is tetrahydropyranyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R10is morpholinyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R10is cycloalkyl, which is unsubstituted or substituted, as is indicated here. In other options, the ante of the formula (V) R 10represents cyclohexyl which is unsubstituted or substituted as specified here.

In one embodiment of formula (V) R11represents alkyl, which is unsubstituted. In another embodiment of formula (V) R11represents methyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (V) R11represents alkyl, which is substituted as described here. In another embodiment of formula (V) R11represents alkyl, which is substituted OR12, R12is an R16and R16represents alkyl.

In one embodiment of formula (V) n is equal to 0. In another embodiment of formula (V) n is 0, R104represents NH2and one of R103represents CL or Br, and the others are H.

Yet another variant embodiment of the invention relates to compounds having the formula (V), which are

2-(6-aminopyridine-3-yl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(6-aminopyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 5-(5-(4-{[2-(4-chlorophenyl)-4,4-immiscibles-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

tert-butyl 4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

2-[(6-aminopyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(2-aminopyridine-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-3-ylcarbamate;

2-[(5-aminopyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

tert-butyl 4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

2-[(2-aminopyridine-4-yl)oxy]-4-(4-{[2-(4-harfe who yl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-hydroxypyridine-3-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-{[6-(benzyloxy)pyridin-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-herperidin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-morpholine-4-illlogical)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}PI is erasin-1-yl)-N-{[4-(1,4-dioxane-2-ylethoxy)-3-nitrophenyl]sulfonyl}benzamide;

TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(3-morpholine-4-ylpropyl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-amino-5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]-carbonyl}phenoxy)nicotinamide;

2-[(6-amino-5-cyano-3-yl)oxy]-4-(4-{[2-(4-�lorgeril)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3R)-1-(2,2-dottorati)pyrrolidin-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-methylpiperidin-4-yl)amino]-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide;

2-{[6-(acetylamino)pyridin-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({6-[(methylsulphonyl)amino]pyridine-3-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1-cyclopropylidene-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethy cyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(1,4-dioxane-2-ylmethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-methylpyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(1-oxetan-3-reparacin-4-yl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-isopropylpyridine-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-cyclopropylmethyl-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-cyclopropylmethyl-2-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-d is methylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(3R)-1-cyclopropylboronic-3-yl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({4-fluoro-1-[2-fluoro-1-(permitil)ethyl]piperidine-4-yl}methoxy)-3-nitrophenyl]sulfonyl}benzamide;

tert-butyl 6-bromo-4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

tert-butyl 4-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)pyridine-2,6-childtable;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[6-(cyclopropylamino)pyridine-3-yl]oxy}-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

TRANS-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({6-[(2,2-dottorati)amino]pyridine-3-yl}oxy)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-({6-[(2,2-dottorati)amino]pyridine-3-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-{[5-chloro-6-(methylamino)pyridine-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzo the ID;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[({4-[2-fluoro-1-(permitil)ethyl]morpholine-2-yl}methyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-[(2-amino-6-bromopyridin-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(2,6-diaminopyridine-4-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-(tetrahydro-2H-Piran-4-ylethoxy)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({(3R)-1-[2-fluoro-1-(permitil)ethyl]piperidine-3-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

tert-butyl 5-bromo-4-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-{[({3-the nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridine-2-ylcarbamate;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)-2-({6-[(2,2,2-triptorelin)amino]pyridine-3-yl}oxy)benzamide;

2-[(6-amino-5-chloropyridin-3-yl) is XI]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-hydroxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydrofuran-3-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({9-(4-chlorophenyl)-3-[2-fluoro-1-(permitil)ethyl]-3-azaspiro[5,5]undec-8-EN-8-yl}methyl)piperazine-1-yl]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[9-(4-chlorophenyl)-3-isopropyl-3-azaspiro[5,5]undec-8-EN-8-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[1-(N,N-dimethylphenyl)-4-foreperiod-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({(3R)-1-[2-fluoro-1-(permitil)ethyl]pyrrolidin-3-yl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(2-the Mino-5-bromopyridin-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4,4-diverticulosis)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({4'-chloro-3-[2-(dimethylamino)ethoxy]-1,1'-biphenyl-2-yl}methyl)piperazine-1-yl]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-{[5-chloro-6-({(3R)-1-[2-fluoro-1-(permitil)ethyl]pyrrolidin-3-yl}methoxy)pyridine-3-yl]sulfonyl}-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[(3R)-1-(2,2-dottorati)pyrrolidin-3-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

TRANS-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-cyanocyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-fluoro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[1-(2,2-dottorati)-4-foreperiod-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyrid the n-3-yl)oxy]-N-({3-chloro-4-[(4-Porterage-2H-Piran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[6-({4-fluoro-1-[2-fluoro-1-(permitil)ethyl]piperidine-4-yl}methoxy)-5-(trifluoromethyl)pyridine-3-yl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4,4-diverticulosis)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-({[4-(oxetan-3-yl)morpholine-2-yl]methyl}amino)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[4-fluoro-1-(oxetan-3-yl)piperidine-4-yl]methoxy}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(TRANS-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(CIS-4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(CIS-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-and the Ino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-(2-oxaspiro[3,5]non-7-ylethoxy)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[(2S)-4-cyclopropylmethyl-2-yl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(TRANS-1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(CIS-1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(CIS-4-ethyl-4-hydroxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-nitro-4-({[(2S)-4-(oxetan-3-yl)morpholine-2-yl]methyl}amino)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({5-nitro-6-[(tetrahydro-2H-Piran-4-ylmethyl)amino]pyridine-3-yl}sulfonyl)benzamide;

2-[(6-the Mino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(2-oxaspiro[3,5]non-7-ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[TRANS-4-(morpholine-4-yl)cyclohexyl]methyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[CIS-4-(morpholine-4-yl)cyclohexyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[4-({[4-({[4-(methoxymethyl)cyclohexyl]methyl}amino)-3-nitrophenyl]sulfonyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[(3R)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino}phenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[(3S)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino}phenyl)sulfonyl]benzamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzoyl}sulfamoyl)-2-nitrophenyl]morpholine-4-carboxamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzoyl}sulfamoyl)-2-nitrophenyl]-4-cyanopiperidine-1-carboxamide;

and their therapeutically acceptable salts, Pro is carstvo, salts of prodrugs and metabolites.

In another aspect, the present invention relates to compounds of the formula (VI):

,

and their therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites,

where A1B1D1E1, Y1, Z2L1and Z3are as described herein for formula (I), n is 0, 1, 2 or 3; describes the number of additional substituents on R26and R100has the same values as described for substituents on R26and at least one R102is a Deputy, as described for substituents on R42and R42Aand the others are H.

In one embodiment of formula (VI), A1represents N. In another embodiment of formula (VI), A1represents(A2). In another embodiment of formula (VI), A1represents(A2); and A2represents H.

In one embodiment of formula (VI) B1represents NHC(O)R1, NHSO2R1, OR1or other1. In another embodiment of formula (VI), A1represents(A2); A2represents H; and B1represents other1. In another embodiment of formula (VI), A1represents(A2); A2represents H; and B1is a OR1. In another variant of the formula (VI), A 1represents(A2); A2represents H; and B1represents NHSO2R1. In another embodiment of formula (VI), A1represents(A2); A2represents H; and B1represents NHC(O)R1. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; and B1represents other1. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; and B1is a OR1. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; and B1represents NHSO2R1. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; and B1represents NHC(O)R1.

In one embodiment of formula (VI) D1represents H. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1represents NHC(O)R1; and D1represents H. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1represents NHC(O)R1; and D1represents H.

In one embodiment of formula (VI) E1represents H. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (VI), A1represents(A 2); A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1represents NHC(O)R1;D 1represents H; and E1represents H.

In one embodiment of formula (VI) Y1represents H, CN, NO2, F, Cl, Br, CF3, R17or SO2R17. In another embodiment of formula (VI) Y1represents NO2. In another embodiment of formula (VI) Y1represents CL. In another embodiment of formula (VI) Y1represents the SO2R17; where R17has the values listed above. In another embodiment of formula (VI) Y1represents the SO2R17; where R17represents alkyl. In another embodiment of formula (VI) Y1is an R17; where R17represents quinil. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (VI), A1represents(A2); A2represents H; B1pre the other is a 1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (VI), A1represents(A2); A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (VI), A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (VI), A1before the hat is C(A 2or N; A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL.

In one embodiment of formula (VI), R1is an R2and R2represents phenyl. In another embodiment of formula (VI), R1is an R2and R2represents phenyl, which is substituted NO2and other57.

In one embodiment of formula (VI), R1is an R4or R5. In one embodiment of formula (VI), R1is an R4. In one embodiment of formula (VI), R1is an R5. In one embodiment of formula (VI), R1is an R4; and R4is cycloalkyl or heteroseksualci. In one embodiment of formula (VI), R1is an R4; and R4is cycloalkyl. In one embodiment of formula (VI), R1is an R4; and R4is heteroseksualci.

In one embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring assetmanagement, as is indicated here. In another embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted R57, Other57or N(R57)2. In another embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; and R57is an R60. In another embodiment of formula (VI), R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; and R60is heteroseksualci. In another embodiment of formula (VI), R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; R60is heteroseksualci; where geteroseksualnoe ring is morpholinyl or piperazinil. In another embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted N(R57)2 . In another embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2.In another embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R61and R61represents alkyl, which is unsubstituted. In another embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R60and R60is cycloalkyl, which is unsubstituted. In another embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted with other57. In another embodiment of formula (VI), R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57.In another embodiment of formula (VI) Rsup> 1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57, R57is an R60and R60is heteroseksualci, which is unsubstituted.

In one embodiment of formula (VI), R1is an R4; and R4is heteroseksualci; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is substituted, as shown here. In another embodiment of formula (VI), R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring substituted R57. In another embodiment of formula (VI), R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where geteroseksualnoe ring substituted with one, or two, or three, or four, or five substituents R57; SO2R57or OH, and R57is an R60or R61. In another embodiment of formula (VI), R1before the hat is R 4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60or R61; R60is cycloalkyl or heteroseksualci; and R61represents alkyl. In another embodiment of formula (VI), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is heteroseksualci where heteroseksualci is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of formula (VI), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is cycloalkyl, the de cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of formula (VI), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl. In another embodiment of formula (VI), R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl; where C1-alkyl, C2-alkyl or C3the alkyl are unsubstituted or substituted.

In one embodiment of formula (VI), R1is an R5; and R5represents alkyl, which is unsubstituted or C is substituted. In one embodiment of formula (VI), R1is an R5; and R5represents alkyl, which is unsubstituted or substituted R7, OR7N(R7)2or OH.

In one embodiment of formula (VI), R7is an R10or R11which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R7is an R10which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R7is an R11which is unsubstituted or substituted as specified here.

In one embodiment of formula (VI), R10is cycloalkyl or heteroseksualci, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R10is heteroseksualci, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R10is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxane, piperidinyl, piperazinyl or pyrrolidinyl, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R10is tetrahydropyranyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (I) R 10is morpholinyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R10is cycloalkyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R10represents cyclohexyl which is unsubstituted or substituted as specified here.

In one embodiment of formula (VI), R11represents alkyl, which is unsubstituted. In another embodiment of formula (VI), R11represents methyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VI), R11represents alkyl, which is substituted as described here. In another embodiment of formula (VI), R11represents alkyl, which is substituted OR12, R12is an R16and R16represents alkyl.

In one embodiment of formula (VI) n is equal to 0.

Yet another variant embodiment of the invention relates to compounds having the formula (VI), which are

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(4-chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

and its therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites

In another aspect, the present invention relates to compounds of the formula (VII):

,

and their therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites,

where A1B1D1E1, Y1, Z2L1and Z3are as described herein for formula (I), n is 0, 1, 2 or 3; describes the number of additional substituents on R26and R100has the same values as described for substituents on R26and at least one R102is a Deputy, as described for substituents on R42and R42Aand the others are H.

In one embodiment of formula (VII) A1represents N. In another embodiment of formula (VII) A1represents(A2). In another embodiment of formula (VII) A1represents(A2); and A2represents H.

In one embodiment of formula (VII) B1represents NHC(O)R1, NHSO2R1, OR1or other1. In another embodiment of formula (VII) A1represents(A2); A2represents H; and B1represents other1. In another embodiment of formula (VII) A1represents(A2); A2represents H; and B1is a OR1. In another embodiment of formula (VII) A1the present is the focus of a(A 2); A2represents H; and B1represents NHSO2R1. In another embodiment of formula (VII) A1represents(A2); A2represents H; and B1represents NHC(O)R1. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; and B1represents other1. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; and B1is a OR1. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; and B1represents NHSO2R1. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; and B1represents NHC(O)R1.

In one embodiment of formula (VII) D1represents H. In another embodiment of formula (VII) A1represents(A2); A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (VII) A1represents(A2); A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (VII) A1represents(A2); A2is the Wallpaper H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (VII) A1represents(A2); A2represents H; B1represents NHC(O)R1; and D1represents H. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1represents NHC(O)R1; and D1represents H.

In one embodiment of formula (VII) E1represents H. In another embodiment of formula (VII) A1represents(A2); A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (VII) A1represents(A2); A2presented yet a H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (VII) A1represents(A2); A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (VII), A1represents(A2); A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1represents NHC(O)R1; D1represents H; s 1represents H.

In one embodiment of formula (VII) Y1represents H, CN, NO2, F, Cl, Br, CF3, R17or SO2R17. In another embodiment of formula (VII) Y1represents NO2. In another embodiment of formula (VII) Y1represents CL. In another embodiment of formula (VII) Y1represents the SO2R17; where R17has the values listed above. In another embodiment of formula (VII) Y1represents the SO2R17; where R17represents alkyl. In another embodiment of formula (VII) Y1is an R17; where R17represents quinil. In another embodiment of formula (VII) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (VII) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (VII) A1represents(A2); A2represents H; B1represents other1; Dsup> 1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (VII) A1represents(A2); A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (VII) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (VII) A1represents the t With a(A 2or N; A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL.

In one embodiment of formula (VII) R1is an R2and R2represents phenyl. In another embodiment of formula (VII) R1is an R2and R2represents phenyl, which is substituted NO2and other57.

In one embodiment of formula (VII) R1is an R4or R5. In one embodiment of formula (VII) R1is an R4. In one embodiment of formula (VII) R1is an R5. In one embodiment of formula (VII) R1is an R4; and R4is cycloalkyl or heteroseksualci. In one embodiment of formula (VII) R1is an R4; and R4is cycloalkyl. In one embodiment of formula (VII) R1is an R4; and R4is heteroseksualci.

In one embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring t is to be replaced, as is indicated here. In another embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted R57, Other57or N(R57)2. In another embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; and R57is an R60. In another embodiment of formula (VII) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; and R60is heteroseksualci. In another embodiment of formula (VII) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; R60is heteroseksualci; where geteroseksualnoe ring is morpholinyl or piperazinil. In another embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted N(R57) . In another embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2.In another embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R61and R61represents alkyl, which is unsubstituted. In another embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R60and R60is cycloalkyl, which is unsubstituted. In another embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted with other57. In another embodiment of formula (VII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57.In another embodiment of formula (II) R 1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57, R57is an R60and R60is heteroseksualci, which is unsubstituted.

In one embodiment of formula (VII) R1is an R4; and R4is heteroseksualci; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is substituted, as shown here. In another embodiment of formula (VII) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring substituted R57. In another embodiment of formula (VII) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where geteroseksualnoe ring substituted with one, or two, or three, or four, or five substituents R57, SO2R57or OH; and R57is an R60or R61. In another embodiment of formula (VII) R1PR is dstanley a R 4; R4is heteroseksualci; where cycloalkyl ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60or R61; R60is cycloalkyl or heteroseksualci; and R61represents alkyl. In another embodiment of formula (VII) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is heteroseksualci where heteroseksualci is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of formula (VII) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is cycloalkyl, where C is cloaker is cyclopropyl or cyclopentyl. In another embodiment of formula (VII) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl. In another embodiment of formula (VII) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl; where C1-alkyl, C2-alkyl or C3the alkyl are unsubstituted or substituted.

In one embodiment of formula (VII) R1is an R5; and R5represents alkyl, which is unsubstituted elizalde. In one embodiment of formula (VII) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted R7, OR7N(R7)2or OH.

In one embodiment of formula (VII) R7is an R10or R11which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R7is an R10which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R7is an R11which is unsubstituted or substituted as specified here.

In one embodiment of formula (VII) R10is cycloalkyl or heteroseksualci, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R10is heteroseksualci, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R10is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxane, piperidinyl, piperazinyl or pyrrolidinyl, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R10is tetrahydropyranyl, which is unsubstituted or substituted, as is indicated here. In another embodiment, Faure the uly (VII) R 10is morpholinyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R10is cycloalkyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R10represents cyclohexyl which is unsubstituted or substituted as specified here.

In one embodiment of formula (VII) R11represents alkyl, which is unsubstituted. In another embodiment of formula (VII) R11represents methyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VII) R11represents alkyl, which is substituted as described here. In another embodiment of formula (VII) R11represents alkyl, which is substituted OR12, R12is an R16and R16represents alkyl.

In one embodiment of formula (VII) n is equal to 0.

Yet another variant embodiment of the invention relates to compounds having the formula (VII), which are

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indazol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indazol-4-yl)oxy)-N-(4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxycyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxycyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]benzamide;

N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclo the CEN-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-Porterage-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-N-({5-chloro-6-[(4-Porterage-2H-Piran-4-yl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(TRANS-4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-N-({5-chloro-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

N-({5-chloro-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-2-[(3-chloro-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)--({5-cyano-6-[(TRANS-4-hydroxy-4-methylcyclohexyl)methoxy]pyridine-3-yl}sulfonyl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide;

and their therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

In another aspect, the present invention relates to compounds of the formula (VIII):

and their therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites,

where A1B1D1E1, Y1, Z2L1and Z3are as described herein for formula (I), n is 0, 1, 2 or 3; describes the number of additional substituents on R26and R100has the same values as described for substituents on R26and at least one R102is a Deputy, as described for substituents on R42and R42Aand the others are H.

In one embodiment of formula (VIII) A1represents N. In another embodiment of formula (VIII) A1represents(A2). In another embodiment of formula (VIII) A1represents(A2); and A2represents H.

In one embodiment of formula (VIII) B1represents NHC(O)R1, NHSO2R1, OR1or other1. In another embodiment of formula (VIII) A1represents(A2); A2represents H; and B1represents other1. In another embodiment of formula (VIII) A1represents(A2); A2is the battle H; and B1is a OR1. In another embodiment of formula (VIII) A1represents(A2); A2represents H; and B1represents NHSO2R1. In another embodiment of formula (VIII) A1represents(A2); A2represents H; and B1represents NHC(O)R1. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; and B1represents other1. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; and B1is a OR1. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; and B1represents NHSO2R1. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; and B1represents NHC(O)R1.

In one embodiment of formula (VIII) D1represents H. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1is a OR1; and D1before the hat is H. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1represents NHC(O)R1; and D1represents H. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1represents other1; and D1represents H. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1is a OR1; and D1represents H. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1represents NHSO2R1; and D1represents H. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1represents NHC(O)R1; and D1represents H.

In one embodiment of formula (VIII) E1represents H. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1represents other1; D1represents H; and E1before the hat is H. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; and E1represents H. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; and E1represents H. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1represents NHSO2R1; D1represents H; and E1represents H. In another embodiment of formula (VIII) A1represents(A2or N; 2represents H; B1represents NHC(O)R1; D1represents H; and E1represents H.

In one embodiment of formula (VIII) Y1represents H, CN, NO2, F, Cl, Br, CF3, R17or SO2R17. In another embodiment of formula (VIII) Y1represents NO2. In another embodiment of formula (VIII) Y1represents CL. In another embodiment of formula (VIII) Y1represents the SO2R17; where R17has the values listed above. In another embodiment of formula (VIII) Y1represents the SO2R17; where R17represents alkyl. In another embodiment of formula (VIII) Y1is an R17; where R17represents quinil. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (VIII) A 1represents(A2); A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17where R17represents alkyl, substituted with three F. In another embodiment of formula (VIII) A1represents(A2); A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2or SO2R17; where R17represents an alkyl or quinil. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents NO2.In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1represents other1; D1represents H; E1represents H; and Y1represents the SO2R17 where R17represents alkyl, substituted with three F. In another embodiment of formula (VIII) A1represents(A2or N; A2represents H; B1is a OR1; D1represents H; E1represents H; and Y1represents CL.

In one embodiment of formula (VIII) R1is an R2and R2represents phenyl. In another embodiment of formula (VIII) R1is an R2and R2represents phenyl, which is substituted NO2and other57.

In one embodiment of formula (VIII) R1is an R4or R5. In one embodiment of formula (VIII) R1is an R4. In one embodiment of formula (VIII) R1is an R5. In one embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl or heteroseksualci. In one embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl. In one embodiment of formula (VIII) R1is an R4; and R4is heteroseksualci.

In one embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl; where R4is unsubstituted or substituted, as is indicated here. In another VA who ianthe formula (VIII) R 1is an R4; and R4is cycloalkyl; where cycloalkyl ring is substituted, as shown here. In another embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted R57, Other57or N(R57)2. In another embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; and R57is an R60. In another embodiment of formula (VIII) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; and R60is heteroseksualci. In another embodiment of formula (VIII) R1is an R4; R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted R57; R57is an R60; R60is heteroseksualci; where geteroseksualnoe ring is morpholinyl or piperazinil. In another embodiment of formula (VIII) R is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted N(R57)2. In another embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2.In another embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R61and R61represents alkyl, which is unsubstituted. In another embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted N(R57)2, R57is an R60and R60is cycloalkyl, which is unsubstituted. In another embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring substituted with other57. In another embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl; where cycloalkyl the second ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57.In another embodiment of formula (VIII) R1is an R4; and R4is cycloalkyl; where cycloalkyl ring is a cyclohexyl; and where tsiklogeksilnogo ring substituted with other57, R57is an R60and R60is heteroseksualci, which is unsubstituted.

In one embodiment of formula (VIII) R1is an R4; and R4is heteroseksualci; where R4is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VIII) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is substituted, as shown here. In another embodiment of formula (VIII) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring substituted R57. In another embodiment of formula (VIII) R1is an R4; and R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where geteroseksualnoe ring substituted with one, or two, or three, or four, or five substituents R57; SO2R57or OH,and R 57is an R60or R61. In another embodiment of formula (VIII) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60or R61; R60is cycloalkyl or heteroseksualci; and R61represents alkyl. In another embodiment of formula (VIII) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted R57; R57is an R60; R60is heteroseksualci where heteroseksualci is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of formula (VIII) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl; and where piperidinyl, pyrrolidine, morpholinyl or piperidin the aspects of the ring is substituted by R 57; R57is an R60; R60is cycloalkyl where cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of formula (VIII) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl. In another embodiment of formula (VIII) R1is an R4; R4is heteroseksualci; where geteroseksualnoe ring is piperidinyl, pyrrolyl, morpholinyl or piperazinyl, and where piperidinyl, pyrrolidine, morpholinyl or piperazinyl ring substituted with one, or two, or three, or four, or five substituents R57; R57is an R61; R61represents alkyl; and alkyl is a1-alkyl, C2-alkyl or C3-alkyl; where C1-alkyl, C2-alkyl or C3the alkyl are unsubstituted or is Emesene.

In one embodiment of formula (VIII) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted. In one embodiment of formula (VIII) R1is an R5; and R5represents alkyl, which is unsubstituted or substituted R7, OR7N(R7)2or OH.

In one embodiment of formula (VIII) R7is an R10or R11which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (VIII) R7is an R10which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VIII) R7is an R11which is unsubstituted or substituted as specified here.

In one embodiment of formula (VIII) R10is cycloalkyl or heteroseksualci, which are unsubstituted or substituted, as is indicated here. In another embodiment of formula (VIII) R10is heteroseksualci, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VIII) R10is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxane, piperidinyl, piperazinyl or pyrrolidinyl, which are unsubstituted or substituted, as is indicated here. In other options, the ante of the formula (VIII) R 10is tetrahydropyranyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VIII) R10is morpholinyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VIII) R10is cycloalkyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VIII) R10represents cyclohexyl which is unsubstituted or substituted as specified here.

In one embodiment of formula (VIII) R11represents alkyl, which is unsubstituted. In another embodiment of formula (VIII) R11represents methyl, which is unsubstituted or substituted, as is indicated here. In another embodiment of formula (VIII) R11represents alkyl, which is substituted as described here. In another embodiment of formula (VIII) R11represents alkyl, which is substituted OR12, R12is an R16and R16represents alkyl.

In one embodiment of formula (VIII), n is equal to 0.

Yet another variant embodiment of the invention relates to compounds having the formula (VIII), which are

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yloxy]-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[5-chloro-6-(tetrahydro-2H-Piran-4-ylethoxy)pyridine-3-yl]sulfonyl}-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-({4-[(4-Porterage-2H-Piran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(TRANS-4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-{[3-chloro-4-(tetrahydro-2H-Piran-4-ylethoxy)phenyl]sulfonyl}-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)-N-[(4-{[(4-cyclopropylmethyl-2-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-yl)oxy]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites.

The pharmaceutical compositions, combination therapy, treatment methods and the introduction

Another variant implementation of the invention encompasses pharmaceutical compositions containing the compound having the formula (I), and an inert filler.

Still have the option of carrying out the invention encompasses methods of treatment of malignant tumors in a mammal, includes introduction to him therapeutically acceptable amount of a compound having the formula (I).

Another variant implementation of the invention encompasses methods of treating autoimmune disease in a mammal, comprising introducing him therapeutically acceptable amount of a compound having the formula (I).

Yet another variant embodiment of the invention relates to compositions for treating diseases during which is expressed anti-apoptotic proteins Bcl-2, where these compositions contain the excipient and a therapeutically effective amount of the compounds having formula (I).

Yet another variant embodiment of the invention relates to a method of treating disease in a patient during which are expressed anti-apoptotic proteins Bcl-2, where these methods include the introduction to the patient a therapeutically effective amount of the compounds having formula (I).

Yet another variant embodiment of the invention relates to compositions for treating bladder cancer, brain cancer, breast cancer, cancer of the bone marrow, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoblastic leukemia from precursor T-cleto is or B-cells, melanoma, myeloid leukemia, myeloma, cancer of the oral cavity, ovarian cancer, lung cancer, prostate cancer, small-cell lung cancer or cancer of the spleen, where these compositions contain the excipient and a therapeutically effective amount of the compounds having formula (I).

Yet another variant embodiment of the invention relates to methods of treating bladder cancer, brain cancer, breast cancer, cancer of the bone marrow, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoblastic leukemia from precursor T-cells or B-cells, melanoma, myeloid leukemia, myeloma, cancer of the oral cavity, ovarian cancer, lung cancer, prostate cancer, small-cell lung cancer or cancer of the spleen in a patient, where these methods include the introduction to the patient a therapeutically effective amount of the compounds having the formula (I).

Yet another variant embodiment of the invention relates to compositions for treating diseases during which is expressed anti-apoptotic proteins Bcl-2, where these compositions contain the excipient and a therapeutically effective amount of the compounds having f is rmula (I), and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent.

Yet another variant embodiment of the invention relates to a method of treating disease in a patient during which are expressed anti-apoptotic proteins Bcl-2, where these methods include the introduction to the patient a therapeutically effective amount of the compounds having formula (I) and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent.

Yet another variant embodiment of the invention relates to compositions for treating bladder cancer, brain cancer, breast cancer, cancer of the bone marrow, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoblastic leukemia from precursor T-cells or B-cells, melanoma, myeloid leukemia, myeloma, cancer of the oral cavity, ovarian cancer, lung cancer, prostate cancer, small-cell lung cancer or cancer of the spleen, where these compositions contain the excipient and a therapeutically effective amount of the compounds having the formula (I), and therapeutic the ski effective amount of an additional therapeutic agent or more than one additional therapeutic agent.

Yet another variant embodiment of the invention relates to methods of treating bladder cancer, brain cancer, breast cancer, cancer of the bone marrow, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoblastic leukemia from precursor T-cells or B-cells, melanoma, myeloid leukemia, myeloma, cancer of the oral cavity, ovarian cancer, lung cancer, prostate cancer, small-cell lung cancer or cancer of the spleen in a patient, where these methods include the introduction to the patient a therapeutically effective amount of the compounds having the formula (I) and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent.

Metabolites of compounds having formula (I) produced during metabolic processes in vitro or in vivo, may also have utility for treating diseases associated with anti-apoptotic protein Bcl-2.

Some precursor compounds which may be metabolized in vitro or in vivo to form compounds having formula (I), may also have utility for treating diseases associated with expression of anti-apoptotic who elkow of Bcl-2.

Compounds having the formula (I) may exist as salts of addition of acids, salts add a reason or zwitterionic. Salts of the compounds formed in the process of separation or purification of compounds. Salt additions of acid compounds are salts, obtained by the interaction of compounds with the acid. For example, salts of acetate, adipate, alginate, bicarbonate, citrate, aspartate, benzoate, bansilalpet, bisulfate, butyrate, comfort, camphorsulfonate, digluconate, formate, fumarate, glycerol, glutamate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, lactobionate, lactate, maleate, mesitylenesulfonic, methanesulfonate, naphthalenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, phosphate, picrate, propionate, succinate, tartrate, thiocyanate, trichloroacetic, triptorelin, para-toluensulfonate, undecanoate compounds and their prodrugs are considered as covered by this invention. Salt add grounds compounds are salts, obtained by the interaction of compounds with hydroxide, carbonate or bicarbonate of a cation, such as the cations of lithium, sodium, potassium, calcium and magnesium.

Compounds having the formula (I) can be introduced, for example, buccal, ophthalmically, orally, osmotically, parenterally (intramuscularly, intraperitoneally, intra is termalna, intravenously, subcutaneously), rectally, topically, transdermal or vaginally.

Therapeutically effective amounts of compounds having the formula (I) depend on the patient being treated, the disease and its severity, the compositions containing the compound, time of administration, route of administration, duration of treatment, the effectiveness of the compounds, the rate of excretion and the fact that you enter whether simultaneously or not another drug. The number of compounds according to this invention having formula (I) used for the preparation of compositions intended for daily injection to the patient a single dose or divided doses is from about 0.03 to about 200 mg/kg of body weight. Composition unit doses contain the specified number or the combination of fractional units.

Compounds having the formula (I), can be introduced together with an inert filler or without him. Inert fillers include, for example, materials to encapsulate or additives, such as amplifiers, absorption, antioxidants, binders, buffers, means for coatings, dyes, diluents, disintegrating agents, emulsifiers, extenders, fiber, flavor, moisture retaining agents, lubricating agents, perfumes, preservatives, propellants, releasing agents, stabiliziruyutsya agents, sweeteners, solubilisate is s, wetting agents and mixtures thereof.

Inert fillers to obtain compositions containing the compound having the formula (I) intended for insertion in oral solid dosage forms include, for example, agar, alginic acid, aluminum hydroxide, benzyl alcohol, benzyl benzoate, 1,3-butyleneglycol, carbomer, castor oil, cellulose, cellulose acetate, cocoa butter, corn starch, corn oil, cottonseed oil, crospovidon, diglycerides, ethanol, ethylcellulose, tillaart, etiloleat, esters of fatty acids, gelatin, wheat germ oil, glucose, glycerin, oil zemanova nut, the hypromellose, isopropanol, isotonic saline, lactose, magnesium hydroxide, magnesium stearate, malt, mannitol, monoglycerides, olive oil, peanut oil, salt, potassium phosphate, potato starch, povidone, propylene glycol, ringer's solution, safflower oil, sesame oil, sodium carboxymethylcellulose, salt, sodium phosphate, sodium lauryl sulphate, sorbitol, sodium, soy oil, stearic acid, fumarate, cane sugar, surfactants, talc, tragakant, tetrahydrofurfuryl alcohol, triglycerides, water and their mixtures. Inert fillers to obtain compositions containing the compound according to this invention having formula (I, intended for the introduction of ophthalmically or orally in liquid dosage forms include, for example, 1,3-butyleneglycol, castor oil, corn oil, cottonseed oil, ethanol, esters of fatty acids and sorbitan, wheat germ oil, oil of groundnuts, glycerol, isopropanol, olive oil, polyethylene glycols, propylene glycol, sesame oil, water and mixtures thereof. Inert fillers to obtain compositions containing the compound according to this invention having formula (I) intended for the introduction of osmotically include, for example, chlorofluorocarbons, ethanol, water and mixtures thereof. Inert fillers to obtain compositions containing the compound according to this invention having formula (I) intended for the introduction of parenteral include, for example, 1,3-butanediol, castor oil, corn oil, cottonseed oil, dextrose, wheat germ oil, oil of groundnuts, liposomes, oleic acid, olive oil, peanut oil, ringer's solution, safflower oil, sesame oil, soybean oil, U. S. P. or isotonic sodium chloride solution, water and their mixtures. Inert fillers to obtain compositions containing the compound according to this invention having formula (I), designed to be inserted rectally or vaginally include, for example, oil is about, the polyethylene glycol, wax and mixtures thereof.

Compounds having the formula (I) are thought to be useful when used with alkylating agents, angiogenesis inhibitors, antibodies, antimetabolites, antimitoticheskoy agents, antiproliferative agents, antiviral agents, inhibitors of Aurora kinase, other inhibitors and promoters of apoptosis (for example, Bcl-xL, Bcl-w and Bfl-1), activators of metabolism of death receptors, kinase inhibitors, Bcr-Abl, BiTE antibodies (stimulator (engager) Bi-specific T=cells), conjugates of antibodies and drugs, biological response modifiers, inhibitors of cyclin-dependent kinases, inhibitors of cell cycle inhibitors cyclooxygenase-2, DVD, inhibitors of receptor leukemia viral oncogenic homologues (ErbB2), inhibitors of growth factor inhibitors protein (HSP)-90 heat shock, inhibitors discontiuation (HDAC), hormonal therapy, immunological agents, inhibitors of inhibitors of apoptosis proteins (IAP), built antibiotics, kinase inhibitors, inhibitors of kinesins, Jak2 inhibitors, inhibitors of the target of rapamycin mammalian microRNA, mitogen-activated inhibitors, regulated kinase extracellular signal proteins multivalent binding non-steroidal anti-inflammatory Lakers the governmental funds (NPLS), inhibitors ADP (adenosine diphosphate)-ribose polymerase (PARP), platinum chemotherapeutically agents, inhibitors of polo-like kinase (Plk) inhibitors phosphoinositide-3 kinase (PI3K) inhibitors proteasome, purine analogs, pyrimidine analogs, inhibitors of receptor tyrosine kinase, plant alkaloids echinoida/deltoid, small inhibitory ribonucleic acids (small inhibitory ribonucleic acid-siRNAs), topoisomerase inhibitors, inhibitors of ubiquitin ligase and the like, and combinations of one or more of these agents.

BiTE antibodies are bespecifically antibodies that direct T cells to attack cancer cells, simultaneously connecting two cells. T-cell then attacks the target cancer cell. Examples of BiTE antibodies include adecatumumab (Micromet MT201), blinatumomab (Micromet MT103) and the like. Without being limited to theory, one of the mechanisms of how T cells induce apoptosis in target cancer cells, is the exocytosis of cytolytic granular components, which include perforin and Grasim B. From this point of view, Bcl-2 showed attenboroughii induction of apoptosis as perforin and granzyme B. These data confirm the fact that inhibition of Bcl-2 could enhance the cytotoxic effects of T-cells, when aimed at cancer cells (V. R. Sutton, D. L. Vaux and J. A. Trapani, J. of mmunology 1997, 158 (12), 5783).

SiRNAs are molecules with endogenous RNA or chemically modified nucleotides. Modifications do not eliminate cellular activity, but rather give increased stability and/or increased cell efficiency. Examples of chemical modifications include phosphorothioate group, 2'-deoxynucleotides, 2'-OCH3-containing ribonucleotides, 2'-F-ribonucleotides, 2'-methoxyethyl the ribonucleotides, a combination thereof and the like. SiRNAs can be of different lengths (e.g., 10-200 p. N.) and patterns (e.g., loops, single/dual circuit, bumps, dents/cracks, misalignment) and processed in cells receiving the silencing of functionally active genes. Double-stranded siRNAs (ds) may have the same number of nucleotides in each chain (blunt ends) or asymmetric ends (dangling edges). The ledge 1-2 nucleotides can be represented on sensitive and/or anticholesterolemic threads, as at present at the 5' and/or 3'-ends of this chain. For example, siRNAs targeted Mcl-1 showed an increase in the activity of ABT-263, (i.e., N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide) or ABT-737 (i.e., N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide) in many tumor cell lines (Tse et al, Cancer Research 2008, 68(9), 3421 and links to work).

Multivalent binding proteins are binding proteins that contain two or more binding sites of the antigen. Multivalent binding proteins are constructed as having three or more binding sites of antigens and usually not naturally occurring antibodies. The term “multispecificity binding protein” refers to a binding protein capable of binding two or more related or unrelated purposes. Dual variable domain (DVD) binding proteins are tetravalent or multivalent binding proteins containing two or more binding sites of the antigen. These DVDs can be monospecific (i.e., capable of binding the same antigen) or multispecificity (i.e., capable of binding two or more antigens). Proteins DVDs binding DVD containing two heavy polypeptide chains and two DVD light chain polypeptide contains both DVD Ig. Each half of the DVD-Ig DVD covers polypeptide heavy chain DVD polypeptide light chain and two-binding site of the antigen. Each binding site comprises the variable domain of the heavy chain variable domain and a light chain with only 6 CDR, included in the antigen binding to the binding site of the antigen. Multispecificity DVD include the DVD-binding proteins to the that bind DLL4 and VEGF, or C-met and EFGR or ErbB3 and EGFR.

Alkylating agents include altretamine, AMD-473, AP-5280, apaziquone, bendamustine, brostallicin, busulfan, carboquone, carmustine (BCNU), chlorambucil, CLORETAZINE®(laromustine, VPN 40101M), cyclophosphamide, dacarbazine, estramustin, fotemustine, glufosfamide, ifosfamide, KW-2170, lomustin (CCNU), mafosfamide, melphalan, mitobronitol, mitolactol, nimustine, N-oxide nitrogen mustard, ranimustine, temozolomide, thiotepa, TREANDA®(very weak), treosulfan, refastened and the like.

Inhibitors of angiogenesis include endothelial-specific inhibitors of receptor tyrosine kinase (Tie-2) inhibitors of the receptor for epidermal growth factor (EGFR) inhibitors of the insulin growth factor-2 receptor (IGFR-2) inhibitors of matrix metalloproteinase-2 (MMP-2) inhibitors of matrix metalloproteinase-9 (MMP-9) inhibitors of the receptor producing plaque growth factor (DERIVED), the analogues of thrombospondin, inhibitors of receptor tyrosinekinase growth factor vasculares endothelium (VEGFR) and the like.

Antimetabolites include ALIMTA®(pemetrexed disodium, LY231514, MTA), 5-azacytidine, XELODA®(capecitabine), carmofur, LEUSTAT®(cladribine, Clofarabine, cytarabine, cytarabine ocfosfate, cytosine arabinoside, decitabine, deferoxamine, doxifluridine, eflornithine, EICAR (5-ethinyl-1-β-D-ribofuranosylthiazole-4-carboxamide), ESEC is Tabin, utilitity, fludarabine, 5-fluorouracil alone or in combination with leucovorin, GEMZAR®(gemcitabine, hydroxyurea, ALKERAN®(melphalan, mercaptopurine, 6-mercaptopurine riboside, methotrexate, mikofenolna acid, nelarabine, nolatrexed, ocfosfate, political, pentostatin, raltitrexed, ribavirin, triapin, trimetrexate, S-1, tianfuan, tegafur, TS-1, vidarabine, UFT, and the like.

Anti-virus tools include ritonavir, hydroxychloroquine, and the like.

Inhibitors of Aurora kinase include ABT-348, AZD-1152, MLN-8054, VX-680, inhibitors of A specific Aurora kinase inhibitors B-specific Aurora kinase and kinase inhibitors pan-Aurora and the like.

The inhibitor protein Bcl-2 include AT-101 ((-)hossipole), GENASENSE®(G3139 or oblimersen (Bcl-2-mechaniy antisense oligonucleotide)), IPI-194, IPI-565, N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide) (ABT-737), N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide (ABT-263), GX-070 (obatoclax) and the like.

Inhibitors of Bcr-Abl kinase include DASATINIB®(BMS-354825), GLEEVEC®(imatinib) and the like.

The CDK inhibitors include AZD-5438, BMI-1040, BMS-032, BMS-387, CVT-2584,flavopiridol, GPC-286199, MCS-5A, PD0332991, PHA-690509, seliciclib (CYC-202, R-roscovitine), ZK-304709 and the like.

COX-2 inhibitors include ABT-963, ARCOXIA®(etoricoxib), BEXTRA®(valdecoxib), BMS347070, CELEBREX®(celecoxib), a COX-189 (lumiracoxib), CT-3, DERAMAXX®(deracoxib), JTE-522, 4-methyl-2-(3,4-dimetilfenil)-1-(4-sulfamoyl-1H-pyrrole), MK-663 (etoricoxib), NS-398, parecoxib, RS-57067, SC-58125, SD-8381, SVT-2016, S-2474, T-614, VIOXX®(rofecoksib) and the like.

The EGFR inhibitors include ABX-EGF, anti-EGFR of immunoliposome, EGF-vaccine, EMD-7200, ERBITUX®(cetuximab), HR3, IgA antibodies IRESSA®(gefitinib), TARCEVA®(erlotinib or OSI-774), TP-38, EGFR hybrid protein, TYKERB®(lapatinib) and the like.

Inhibitors of ErbB2 receptor include CP-724-714, CI-1033 (canertinib), HERCEPTIN®(trastuzumab), TYKERB®(lapatinib), OMNITARG®(2C4, pertuzumab), TAK-165, GW-572016 (inferni), GW-282974, EKB-569, PI-166, dHER2 (HER2 vaccine), APC-8024 (HER2 vaccine), anti-HER/2neu bispecific antibody, B7.her2IgG3, AS HER2 trifunctional bispecific antibodies, mAB AR-209, mAB 2B-1 and the like.

Inhibitors discontiuation include depsipeptide, lunar abyss-824, MS-275, trioxin, suberoylanilide hydroxamic acid (SAHA), TSA, valproate acid and the like.

Inhibitors of HSP-90 include 17-AAG-nab, 17-AAG, CNF-101, CNF-1010, CNF-2024, 17-DMAG, geldanamycin, IPI-504, KOS-953, MYCOGRAB®(human recombinant antibody to HSP-90), NCS-683664, PU24FCl, PU-3, radicial, SNX-2112, SA-9090 VER49009 and the like.

Inhibitors of inhibitors of apoptosis proteins include HGS1029, GDC-0145, GDC-0152, LCL-161, LBW-242, and the like.

Conjugates of the antibody with the drug include anti-CD22-MC-MMAF, anti-CD22-MC-MMAE, anti-CD22-MCC-DM1, CR-011-vcMMAE, PSMA-ADC MEDI-547, SGN-19Am SGN-35, SGN-75 and the like

Metabolism activators of death receptors include TRAIL, antibodies or other agents than the target TRAIL or death receptors (e.g., DR4 and DR5), such as pomab, conatumumab, ETR2-ST01, GDC0145, (lexatumumab), HGS-1029, LBY-135, PRO-1762 and trastuzumab.

Inhibitors include kinesin Eg5 inhibitors, such as AZD4877, ARRY-520; CENPE inhibitors, such as GSK923295A and the like.

Inhibitors of JAK-2 include CEP-701 (resourcelib), XL019 and INCB018424 and the like.

The MEK inhibitors include ARRY-142886, ARRY-438162 PD-325901, PD-98059 and the like.

The mTOR inhibitors include AP-23573, CCI-779, everolimus, RAD-001, rapamycin, temsirolimus, ATP-competitive TORC1/TORC2 inhibitors, including PI-103, PP242, PP30, Thorin 1 and the like.

Nonsteroidal anti-inflammatory drugs include AMIGESIC®(salsalate), DOLOBID®(diflunisal), MOTRIN®(ibuprofen), ORUDIS®(Ketoprofen), RELAFEN®(nabumetone), FELDENE®(piroxicam), ibuprofen cream ALEVE®(naproxen and NAPROSYN®(naproxen), VOLTAREN®(diclofenac), INDOCIN®(indomethacin), CLINORIL®(sulindac), TOLECTIN®(tolmetin), LODINE®(etodolac), TORADOL®(etodolac), DAYPRO®(oxaprozin) and the like.

Inhibitors DERIVED include C-451, CP-673, CP-868596 and the like.

Platinum chemotherapy includes cisplatin, ELOXATIN®(oxaliplatin) heptaplatin, lobaplatin, nedaplatin, PARAPLATIN®(carboplatin), satraplatin, picoplatin and the like.

Inhibitors of polo-like kinases include BI-2536 and the like.

Inhibitors phosphoinositide-3 kinase (PI3K) include wortmannin, LY294002, XL-147, CAL-120, H-21, AEZS-127, ETP-45658, PX-866, GDC-0941, BGT226, BEZ235, XL765, and the like.

Analogues of thrombospondin include ABT-510, ABT-567, ABT-898, TSP-1 and the like.

The VEGFR inhibitors include AVASTIN®(bevacizumab), ABT-869, AEE-788, ANGIOZYME™ (ribozyme that inhibits angiogenesis (Ribozyme Pharmaceuticals (Boulder, CO.) and Chiron, (Emeryville, CA), axitinib (AG-13736), AZD-2171, CP-547,632, IM-862, MACUGEN (pegaptanib), NEXAVAR®(sorafenib, BAY43-9006), pazopanib (GW-786034), vatalanib (PTK-787, ZK-222584), SUTENT®(sunitinib, SU-11248), VEGF trap, ZACTIMA™ (vandetanib, ZD-6474), and the like.

Antibiotics include built-antibiotics aclarubicin, actinomycin D, amrubicin, annamycin, adriamycin, BLENOXANE®(bleomycin), daunorubicin, CAELYX®or MYOCET®(liposomal doxorubicin), elsamitrucin, airboren, parboil, ZAVEDOS®(idarubitsin), mitomycin C, nemorubicin, neocarzinostatin, peplomycin, pirarubicin, rebeccamycin, stimulater, streptozocin, VALSTAR®(valrubicin is n), zinostatin and the like.

The topoisomerase inhibitors include aclarubicin, 9-aminocamptothecin, amonafide, amsacrine, Ekaterin, belotecan, BN-80915, CAMPTOSAR®(irinotecan hydrochloride), camptothecin, CARDIOXANE®(dexrazoxane), diflomotecan, edotecarin, ELLENCE®or PHARMORUBICIN®(epirubicin, etoposide, exatecan, 10-hydroxycamptothecin, gimatecan, lurtotecan, mitoxantrone, oracin, parabolin, pixantrone, rubitecan, sobuzoxane, SN-38, tafluprost, topotecan, and the like.

Antibodies include AVASTIN®(bevacizumab), CD40-specific antibodies, chTNT-1/B, denosumab, ERBITUX®(cetuximab), HUMAX-CD4®(zanolimumab), IGF1R-specific antibodies, lintuzumab, PANOREX®(edrecolomab), RENCAREX®(WX G250), RITUXAN®(rituximab), ticilimumab, trastuzumab, CD20 antibodies type I and II, GA101, ofatumumab, ABT-806 (mAb-806), ErbB3 antibodies BSG2 antibodies specific DLL4 antibodies and C-met antibodies, and the like.

Hormonal therapy involves ARIMIDEX®(anastrozole), AROMASIN®(exemestane), arzoxifene, CASODEX®(bikalutamid), CETROTIDE®(cetrorelix), degarelix, deslorelin, DESOPAN®(trilostane), dexamethasone, DROGENIL®(flutamide), EVISTA®(raloxifene), AFEMA™ (fadrozole), FARESTON®(toremifene), FASLODEX®(fulvestrant), FEMARA®(letrozole), formes the Academy of Sciences, glucocorticoid, HECTOROL®(doxercalciferol), RENAGEL®(sevelamer carbonate), lasofoxifene, leuprolide acetate MEGACE®(megestrol), MIFEPREX®(mifepristone), NILANDRON™ (nilutamide), NOLVADEX®(tamoxifen citrate), PLENAXIS™ (abarelix), prednisone, PROPECIA®(finasteride), elastan, SUPREFACT®(buserelin), TRELSTAR®(luteinizing hormone vysvobojdenie hormone (LHRH)), VANTAS®(Histrelin implant), VETORYL®(trilostane or morestan), ZOLADEX®(forlin, goserelin) and the like.

Deltoid and retinoids include seocalcitol (EB1089, CB1093), lexicality (KH1060), phenetidine, PANRETIN®(alitretinoin), ATRAGEN®(liposomal tretinoin), TARGRETIN®(bexarotene), LGD-1550 and the like.

PARP inhibitors include ABT-888 (veliparib), olaparib, KU-59436, AZD-2281, AG-014699, BSI-201, BGP-15, INO-1001, ONO-2231 and the like.

Plant alkaloids include, but are not limited to, vincristine, vinblastine, vindesine, vinorelbine and the like.

Proteasome inhibitors include VELCADE®(bortezomib), MG132, NPI-0052, PR-171 and the like.

Examples of immunological tools include interferons and other strengthen the immune system agents. Interferons include alpha interferon Alfa-2a interferon Alfa-2b interferon, beta interferon, gamma-1a interferon, ACTIMMUNE®(gamma-1b interferon or gamma-n1, pegylated interferon, is Oceania and the like. Other agents include ALFAFERONE®, (IFN-α), BAM-002 (oxidized glutathione), BEROMUN®(tasonermin), BEXXAR®(tositumomab), CAMPATH®(alemtuzumab), CTLA4 (cytotoxic limfotsity antigen 4), dacarbazin, denileukin, epratuzumab, GRANOCYTE®(lenograstim), lentinan, leukocyte alpha interferon, kamod, MDX-010 (anti-CTLA-4), melanoma vaccine, mitooma, molgramostim, MYLOTARG™ (gemtuzumab ozogamicin), NEUPOGEN®(filgrastim), OncoVAC-CL, OVAREX®(oregovomab), pemtumomab (Y-muHMFG1), PROVENGE®(sipuleucel-T), sargramostim, sizofiran, tecelagem, THERACYS®(Bacillus Calmette-Guerin), ubenimex, VIRULIZIN®(immunotherapy, Lorus Pharmaceuticals), Z-100 (Specific Substance of Maruyama (SSM)), WF-10 (tetrachlorodecaoxide (TCDO)), PROLEUKIN®(aldesleukin), ZADAXIN®(thymalfasin), ZENAPAX®(daclizumab), ZEVALIN®(90Y-ibritumomab tiuxetan) and the like.

The biological response modifiers are agents that modify defense mechanisms of living organisms or biological responses, such as survival, growth or differentiation of cells in the tissue and is aimed at giving them antitumor activity and include baptisms, lentinan, sizofiran, picibanil PF-3512676 (CpG 8954), ubenimex and the like.

Analogues of pyrimidine include cytarabine (Ara C or arabinoside C), cytosine arabinoside, doxifluridine, FLUDARA®(fludarabine), 5-FU (5-fluorouracil) floxuridine, GEMZAR®(gemcitabine), TOMUDEX®(raytraced), TROXATYL™ (triacetyluridine troxacitabine) and the like.

Purine analogs include LANVIS®(tioguanin) and PURI-NETHOL®(mercaptopurine).

Antimitoticescoe agents include batubulan, epothilone D (KOS-862), N-(2-((4-hydroxyphenyl)amino)pyridine-3-yl)-4-methoxybenzenesulfonamide, ixabepilone (BMS 247550), paclitaxel, TAXOTERE®(docetaxel), PNU100940 (109881), patupilone, XRP-9881 (larotaxel), vinflunine, ZK-EPO (synthetic epothilone) and the like.

Inhibitors of ubiquitin ligase include MDM2 inhibitors, such as tested nutlins, inhibitors NEDD8, such as MLN4924, and the like.

Compounds according to this invention can also be used as radio sensibilizators that increase the effectiveness of radiotherapy. Examples of radiotherapy include external beam radiation therapy, teletherapy, brachytherapy and sealed, mesaganmesagandare radiotherapy source and the like.

Additionally, compounds having formula (I) can be combined with other chemotherapeutic agents such as ABRAXANE™ (ABI-007), ABT-100 (inhibitor farnesyl transferase), ADVEXIN®(vaccine Ad5CMV-p53), ALTOCOR®or MEVACOR®(lovastatin), AMPLIGEN®(poly I:poly C12U, a synthetic RNA), APTOSYN®(exisulind), AREDIA®(panikanova acid), Arglabin, L-asparaginase atamestane (1-methyl-3,17-Gianandrea-1,4-diene), AVAGE®(tazarotene), AVE-8062 (derived combretastatin) BEC2 (mitooma), cachectin or cachectin (tumor necrosis factor), canvaxin (vaccine), CEAVAC®(cancer vaccine), CELEUK®(celmoleukin), CEPLENE®(histamine dihydrochloride), CERVARIX®(vaccine human papillomavirus), CHOP®(C: CYTOXAN®(cyclophosphamide); H: ADRIAMYCIN®(hydroxydoxorubicin); O: vincristine (ONCOVIN®); P: prednisone), CYPAT™ (cyproterone acetate), complestatin A4P, DAB(389)EGF (catalytic and translocation domains of dipterologica, built by the linker His-Ala in human epidermal growth factor) or MID-107R™ (dipterologica), dacarbazine, dactinomycin, 5,6-dimethylxanthene-4-acetic acid (DMXAA), eniluracil, EVIZON™ (squalamine lactate), DIMERICINE®(T4N5 liposomal lotion), discodermolide, DX-8951f (exatecan mesilate), enzastaurin, EPO906 (epitalon B), GARDASIL®(recombinant vaccine quadrivalent human papillomavirus (types 6, 11, 16, 18)), GASTRIMMUNE®, GENASENSE®, GMK (ganglioside conjugate vaccine), GVAX®(a vaccine against prostate cancer), halofuginone, histrelin, hydroxycarbamide, ibandronic acid, IGN-101, IL-13-PE38, IL-13-PE38QQR (cintredekin besudotox), exotoxin IL-13-Pseudomonas, interferon-α, interferon-γ, JUNOVAN™ or MEPACT™ (mifamurtide), lonafarnib, 5,10-methylenetetrahydrofolate, mil is eosin (hexadecylphosphocholine), NEOVASTAT®(AE-941), NEUTREXIN®(trimetrexate glucuronate), NIPENT®(pentostatin), ONCONASE®(the enzyme ribonuclease), ONCOPHAGE®(the treatment of melanoma vaccine), ONCOVAX®(IL-2 vaccine), ORATHECIN™ (rubitecan), OSIDEM®(cellular drug is an antibody-based), OVAREX®MAb (murinova monoclonal antibody), paclitaxel, PANDIMEX™ (aglionby saponins from ginseng, containing 20(S)protopanaxadiol (aPPD) and 20(S)protopanaxatriol (aPPT)), panitumumab, PANVAC®-VF (investigational vaccine against cancer), pegaspargase, PEG interferon A, phenoxodiol, procarbazine, ropemaster, REMOVAB®(catumaxomab), REVLIMID®(lenalidomide), RSR13 (efaproxiral), SOMATULINE®LA (lanreotide), SORIATANE®(acitretin), staurosporine (Streptomyces staurospores), talabostat (PT100), TARGRETIN®(bexarotene), TAXOPREXIN®(DHA-paclitaxel), TELCYTA®(infospeed, TLK286), timelife, TEMODAR®(temozolomide), tesmilifene, thalidomide, THERATOPE®(STn-KLH), thymitaq (2-amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)hinzelin the dihydrochloride), TNFERADE™ (adenovector: native DNA, containing the gene for factor-α tumor necrosis), TRACLEER®or ZAVESCA®(bosentan), tretinoin (Retin-A), tetrandrine, TRISENOX®(arsenic trioxide), VIRULIZIN®, Ukrain (derivative of alkaloids from the greater celandine plant), vitaxin (antibody anti-v3), XCYIN®(motex the fin gadolinium), XINLAY™ (atrasentan), XYOTAX™ (paclitaxel poliglumex), YONDELIS®(trabectedin), ZD-6126, ZINECARD®(dexrazoxane), ZOMETA®(zolendronate acid), zorubicin and the like.

Data

The definition of the utility of compounds having formula (I) as a binder and inhibitors of anti-apoptotic proteins of Bcl-2 was performed using resonance energy transfer fluorescence time-resolved (TR-FRET). Tb-anti-GST antibody was obtained from the company Invitrogen (cat. No. PV4216).

Synthesis samples

All reagents were used as received from the supplier, unless otherwise stated. Reagents for peptide synthesis, including diisopropylethylamine (DIEA), dichloromethane (DCM), N-organic (NMP), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethylurea hexaflurophosphate (HBTU), N-hydroxybenzotriazole (HOBt) and piperidine were obtained from the company Applied Biosystems, Inc. (ABI), Foster City, CA or American Bioanalytical, Natick, MA. Pre-seasoned 9-fluorenylmethoxycarbonyl (Fmoc) amino acid cartridges (Fmoc-Ala-OH, Fmoc-Cys(Trt)-OH, Fmoc-Asp(tBu)-OH, Fmoc-Glu(tBu)-OH, Fmoc-Phe-OH, Fmoc-Gly-OH, Fmoc-His(Trt)-OH, Fmoc-Ile-OH, Fmoc-Leu-OH, Fmoc-Lys(Boc)-OH, Fmoc-Met-OH, Fmoc-Asn(Trt)-OH, Fmoc-Pro-OH, Fmor-Gln(Trt)-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Ser(tBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Val-OH, Fmoc-Trp(Boc)-OH, Fmoc-Tyr(tBu)-OH) were obtained from the firm ABI or Anaspec, San Jose, CA. Resin for peptide synthesis (Fmoc-Rink amide MBHA resin) and Fmoc-Lys(Mtt)-OH was obtained from the company Novabiochem, San Diego, CA. Separate isomer-carboxyfluorescein Succinimidyl ether (6-FAM-NHS) was obtained from the company Anaspec. Triperoxonane acid (TFU) received from the company Oakwood Products, West Columbia, SC. Thioanisole, phenol, triisopropylsilane (TIS), 3,6-dioxa-1,8-octanedithiol (DODT) and isopropanol were obtained from the firm Aldrich Chemical Co., Milwaukee, WI. Ionization mass spectrometry laser desorption using a matrix (MALDI-MS) was performed on the instrument Applied Biosystems Voyager DE-PRO MS). Electrospray mass spectroscopy (ESI-MS) was performed on a Finnigan instrument SSQ7000 (Finnigan Corp., San Jose, CA), both positive and negative ions.

A common method of solid-phase peptide synthesis (PPPS)

Peptides were synthesized, in most cases, 250 µmol pre-loaded Wang resin/vessel on the peptide sitestore ABI 433A, using 250 µmol-ing scale Fastmoc™ binding cycles. Used pre-filled cartridges containing 1 mmol standard Fmoc-amino acids, except for the provisions attaching a fluorophore, where the cartridge was placed 1 mmol Fmoc-Lys(Mtt)-OH, by monitoring the reverse conductivity. N-terminal acetylation was carried out by using 1 mmol of acetic acid per cartridge at standard conditions binding.

Remove 4-methyltricyclo (Mtt) of lysine

The pitch of the synthesizer were washed three times with dichloromethane and left wet. For about 30 minutes through the layer of resin missed 150 ml of a mixture of 95:4:1 dichloromethane:triisopropylsilane:thrift Roxanna acid. The mixture became deep yellow, then lightened to pale yellow. Within 15 min through the layer to pass 100 ml of N,N-dimethylformamide. The resin was then washed three times with N,N-dimethylformamide and filtered. Ninhydrin test showed a strong signal of the primary amine.

Tagging resin 6-carboxyfluorescein-NHS (6-FAM-NHS)

The resin was treated with 2 equivalents of 6-FAM-NHS in a mixture of 1% DIEA/N,N-dimethylformamide and stirred or shaken at room temperature overnight. After poured with resin liquid was washed three times with N,N-dimethylformamide, three times (1×DCM and 1×methanol) and dried, obtaining a resin orange color, which showed a negative ninhydrin test.

A common way to detach and remove the protection attached to the resin peptide

The peptides were tsalala from the resin by shaking for 3 hours at ambient temperature in a chip off the cocktail, consisting of 80% TFU, 5% water, 5% thioanisole, 5% phenol and 2.5% TIS and 2.5% EDT (1 ml/0.1 g resin). The resin was removed by filtration and twice washed TFU. TFU was evaporated from the filtrate, and the product precipitated with ether (10 ml/0.1 g resin), were isolated by centrifugation, washed twice with ether (10 ml/0.1 g resin) and dried, obtaining the crude peptide.

A common method of purification of peptides

Crude peptides were purified on a system preparative HPLC Gilson, using analysis Unipoit® Software (Gilson, Inc., Middleton, WI) on radial compression column containing two segments 25×100 mm, filled with particles of a Delta-Pak™ C18 15 μm with a pore size 100 Å, and suirable using one of the gradient methods listed below. Was purified from one to two milliliters of a solution of the crude peptide (10 mg/ml in a mixture of 90% DMSO/water) with the same introduction. The peaks containing the product(s) from each run were combined and liofilizovane. All preparative runs were performed at a rate of 20 ml/min using eluents in the form of buffer A: 0.1% OF TFU-water and buffer B: acetonitrile.

A General analytical method HPLC

Analytical HPLC was carried out on the system Hewlett-Packard 1200 series with a diode array detector and a fluorescence detector Hewlett-Packard 1046A, banishing software 3D HPLC ChemStation, version A. 03.04 (Hewlett-Packard Company. Palo Alto, CA), on a column of 4.6×250 mm YMC filled with particles of ODS-AQ 5 μm with a pore size 120 Å, and suirable using one of the gradient methods listed below, after pre-equilibrium with the starting conditions for 7 minutes. Suenami were buffer A: 0.1% OF TFU-water and buffer B: acetonitrile. The flow rate for all gradient was 1 ml/min

F-Bak: the Sample peptide Acetyl-(SEQ ID NO:1)GQVGRQLAIIGDK(6-FAM)-(SEQ ID NO:2)INR-NH2

Resin Fmoc-Rink amide MBHA stretched using General method for the synthesis of peptides, receiving protected joined the resin peptide (1,020 g). The Mtt group was removed, marked 6-FAM-NHS and tsalala and remove the protection as described here above, give crude product as a solid orange color (0,37 g). This product was purified using RP-HPLC. Faction around the main peak was investigated using analytical RP-HPLC and pure fractions were isolated and liofilizovane, with the main peak, giving specified in the header connection (0,0802 g) as a solid yellow; MALDI-MS m/z=2137,1 [(M+H)+].

Alternative synthesis of sample peptide F-Bak: Acetyl-(SEQ ID NO:1)GQVGRQLAIIGDK(6-FAM)-(SEQ ID NO:2)INR-NH2

The protected peptide was placed on a 0.25 mmol of resin Fmoc-Rink amide MBHA (Novabiochem) on an automated peptide synthesizer Applied Biosystems 433A, banishing Fastmoc™ binding loops using pre-seasoned 1 mmol amino acid cartridges, except for the fluorescein(6-FAM)-labeled lysine, where the cartridge is weighed 1 mmol Fmoc-Lys(4-methyldecyl). N-Terminal acetyl group is administered by placing 1 mmol of acetic acid in the cartridge and wiring, as described here above. Selective removal of 4-methyltricyclo groups was carried out using a solution of 95:4:1 DCM:TIS:TFU (about./about./vol.), passing through the resin for 15 minutes, then reduce the flow of dimethylformamide. Single isomer (6-carboxyfluorescein-NHS interact with the side chain of lysine in 1% DIEA in N,N-dimethylformamide, and the end podtverzhdalo the test with ninhydrin. The peptide was tsalala from the resin and side chain was subjected to removal of protection by treatment with a mixture of 80:5:5:5:2,5:2,5 TFU/water/phenol/thioanisole/triisopropylsilane:3,6-dioxa-1,8-octanedithiol (about./about./about./about./about./vol.), the crude peptide was isolated by precipitation from diethyl ether. The crude peptide was purified by reversed-phase high-performance liquid chromatography and the purity and identity were confirmed by analytical reversed-phase high-performance liquid chromatography and mass spectrometry laser desorption using a matrix (m/z=2137,1 ((M+H)+)).

Study of resonance energy transfer fluorescence time-resolved (TR-FRET)

Representative compounds were serially diluted in dimethyl sulfoxide (DMSO), starting with 50 μm (2× initial concentration; 10% DMSO) and 10 μl were transferred to 384-well plate. Then to each well was added 10 μl of a mixture of protein/sample/antibody to the final concentrations indicated in TABLE 1. The samples were then mixed on a shaker for 1 minute and incubated for an additional 3 hours at room temperature. For each study, the sample/antibody and protein/sample/antibody included in each study tablet as negative and positive control, respectively. Fluorescence was measured on the device Envision (Perkin Elmer), using 340/35 nm filter vozbuzhdeno and 520/525 (F-Bak peptide) and 495/510 nm (Tb-labeled anti-histidine antibody) emission filters. The inhibition constants (Ki) are shown in TABLE 2 below were determined using the equation of Wang (Wang Z.-X. An Exact Mathematical Expression For Describing Competitive Binding Of Two Different Ligands To A Protein Molecule. FEBS Lett. 1995, 360:111-4).

TABLE 1
The protein sample and the antibody used in the research TR-FRET
ProteinSampleProtein (nm)Sample (nm)AntibodyAntibody (nm)
GST-Bcl-2F-Bak peptide sample acetyl-(SEQ ID NO:1 GQVGRQLAIIGDK(6-FAM) SEQ ID NO:2 INR-amide)1100Tb-anti-GST1
6-FAM=6-carboxyfluorescein; Tb=terbium; GST=glutathione S-transferase

The samples were then mixed on a shaker for 1 minute and incubated for an additional 3 hours at room temperature. For each analysis, the sample/antibody and protein/sample/antibody were included in each plate for analysis in the form of negative and positive control, respectively. Fluorescence was measured on the spectrometer Envision (Perkin Elmer), using 340/35 nm filter who is here and 520/525 (F-Bak peptide) and 495/510 nm (Tb-labeled anti-histidine antibody) emission filters.

The inhibition constants (Kifor compounds in accordance with the invention are shown in TABLE 2 below. When Kito connect represented as “>” (more than) a certain numerical value, it is assumed that it means that the value of the affinity of binding more than the boundaries of the definitions used in the analysis. When Kito connect represented as “<” (less than) a certain numerical value, it is assumed that it means that the value of the affinity of binding is less than the boundary definitions of analysis.

319 0,000237td align="center"> <0,000010
TABLE 2
Ki TR-FRET Bcl-2 binding (μm)
Example No.Ki TR-FRET binding: Bcl-2 (µm)Example No.Ki TR-FRET binding: Bcl-2 (µm)
10,0083542320,001047
20,0314672330,000037
30,0008272340,000099
40,002474 2350,000039
50,0007462360,000071
60,0007872370,000197
70,0025922380,000124
80,0034512390,000105
90,0007542400,000912
100,000722410,000141
110,0001712420,000092
120,0003312430,000069
130,0016212440,001734
140,0000792450,00048
150,0005862460,000065
160,0030392470,000039
170,0055782480,000051
180,0024872490,000168
190,0016792500,000672
200,0039652510,000435
210,0140542520,001147
220,0054552530,00005
230,008272540,000119
240,0149842550,007013
250,001501 2560,000105
260,0005112570,000097
270,0022122580,000083
280,0013262590,000165
290,0009032600,011834
300,0000712610,000186
310,0020072620,000276
320,0015842630,00011
330,0071732640,000068
340,0000492650,000363
350,0000222660,00081
360,000072670,028426
370,0000052680,000042
380,0000132690,000469
390,000019270>1,195000
400,0000192710,001908
410,0000272720,00124
420,000032730,000516
430,0000342740,000936
440,0000362750,000081
450,0000472760,000199
460,000047 2770,000017
470,000052780,039967
480,0000532790,001703
490,0000622800,00755
500,0000622810,000111
510,0000662820,001012
520,0000722830,01721
530,0000772840,079348
540,0000822850,000037
550,000092860,003181
560,0001062870,000131
570,0001472880,000017
580,000155289<0,000010
590,0001842900,000251
600,0001872910,000273
610,000222920,000191
620,0002272930,000233
630,0004382940,000127
640,0004582950,000077
650,00052296<0,000010
660,000592297<0,000010
670,000807 2980,000054
680,0059342990,051687
690,0082463000,013659
700,0204213010,000113
710,031597302<0,000010
720,0316663030,000092
730,032263040,000822
740,189433050,000146
750,0768323060,000671
760,23953070,000524
770,450523080,00004
78>1,1950003090,00069
790,0998263100,000155
800,148723110,000185
810,0310483120,000531
820,51156313<0,000010
83>1,1950003140,003094
840,0136543150,004555
850,0056263160,000058
860,0052633170,000205
870,26427318<0,000010
88>1,1950000,000198
890,0061113200,000028
900,0106263210,000029
91>1,1950003220,00453
920,0025693230,003484
930,01683324<0,000010
940,561213250,000183
950,0004283260,000037
96>1,1950003270,000212
970,146593280,000068
980,0009593290,000108
990,071364330<0,000010
1000,112993310,000238
1010,66953320,000034
1020,0435183330,000107
1030,0067553340,000197
1040,002321335<0,000010
1050,003567336<0,000010
1060,214523370,000049
1070,000331338<0,000010
108not ODA.3390,000057
1093400,000385
1100,0000393410,000017
1110,017443420,003340
1120,0000423430,000009
1130,0000323440,000042
1140,0000363450,000005
1150,000042346<0,000010
1160,0001233470,000377
1170,0000723480,003779
1180,0001513490,000019
1190,000156350
1200,0002143510,002843
1210,0000813520,000079
122<0,0000013530,000016
1230,000113540,000114
1240,0000333550,009567
1250,0000753560,002822
1260,0000683570,000177
1270,000033580,000062
1280,0000643590,000110
1290,0001073600,000050
1300,0000673610,000015
1310,0000663620,000033
1320,000211363<0,000010
1330,0000553640,000014
1340,0001813650,004551
1350,0000683660,006052
1360,0001773670,000012
1370,000021368<0,000010
1380,0000163690,000014
1390,000125370<0,000010
1400,00023 371<0,000010
1410,0004823720,014978
1420,0000713731,195000
1430,0000533740,005337
1440,0000283750,327810
1450,0000573760,057705
1460,000043770,002323
1470,000127378<0,000010
1480,0001063790,017948
1490,000033800,008274
1500,000759381 0,000020
1510,0069353820,000114
1520,0185893830,427490
1540,0000123840,006233
1550,0000623850,049293
1560,000035386<0,000010
1570,00072387<0,000010
1580,0006193880,000020
1590,000526389<0,000010
1600,000028390<0,000010
1610,000031391<0,000010
1620,000048392<0,000010
1630,000686393<0,000010
1640,0000563940,000018
1650,000123950,000077
1660,000082396<0,000010
1670,0013453970,000137
1680,0283433980,000175
1690,000498399<0,000010
1700,0000364000,000082
1710,0000664010,000035
1720,00549 4020,000039
1730,0000194030,002136
1740,0000374040,000069
1750,0000464050,000354
1760,000244060,000166
1770,0000374070,000946
1780,0001754080,001160
1790,0000364090,000686
1800,000112410<0,000010
1810,0001194110,021291
1820,000172412 0,001125
1830,002534130,000739
1840,0001554140,000014
1850,0000834150,000013
1860,0000354160,007436
1870,0000544170,006876
1880,000073418<0,000010
1890,0000364190,000012
1900,000077420<0,000010
1910,000552421<0,000010
1920,000024422<0,000010
1930,000064423<0,000010
1940,000317424<0,000010
1950,0006844250,000013
1970,00022426<0,000010
198<0,000010427<0,000010
1990,000244428<0,000010
2000,000081429<0,000010
2010,00001430<0,000010
2020,020043431<0,000010
2030,000084432<0,000010
204 0,000075433<0,000010
2050,000153434<0,000010
2060,0000374350,000010
2070,000074436<0,000010
2080,000261437<0,000010
209<0,0000104380,000031
2100,00002439<0,000010
2110,0013384400,000022
2120,0003754410,000054
2130,000031442<0,000010
2140,0002210,000029
2150,0029544440,000018
2160,000027445<0,000010
2170,0001744460,000015
2180,0001754470,000029
2190,014857448<0,000010
2200,000127449<0,000010
2210,000227450<0,000010
222>1,195000451<0,000010
2230,0109114520,000112
2240,005603453 <0,000010
2250,0032834540,000024
2260,0075864550,000011
2270,000174456not ODA.
2290,001085457not ODA.
2300,002833458not ODA.
2310,036946

The inhibition constant (Ki) represents the dissociation constant of the complex enzyme-inhibitor or complex protein/small molecule, where the small molecule inhibits the binding of one protein with another protein. Thus, a large value of Kiindicates low affinity binding, and a small value of Kiindicates a high affinity of binding.

The data in TABLE 2 shows the inhibition constants for inhibition of Bak BH3 peptide sample protein Bcl-2 and indicates that the connection according to the accordance with the invention have a high binding affinity of anti-apoptotic protein Bcl-2. Thus, assume that the compounds may be useful in treating diseases during which expresses the anti-apoptotic protein Bcl-2.

It is expected that, as compounds having the formula I, are associated with Bcl-2, they could have utility as a binder with the anti-apoptotic protein that has close structural homology to Bcl-2, such as, for example, anti-apoptotic Bcl-XL, Bcl-w, Mcl-1 and Bfl-1/A1 proteins.

The involvement of proteins of Bcl-2 in the pathological process bladder cancer, brain cancer, breast cancer, cancer of the bone marrow, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoblastic leukemia from precursor T-cells or B-cells, melanoma, myeloid leukemia, myeloma, cancer of the oral cavity, ovarian cancer, lung cancer, prostate cancer, small-cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, cancer of the spleen, and the like described in the joint application PCT US 2004/36770, published as WO 2005/049593, and PCT US 2004/37911, published as WO 2005/024636.

The involvement of proteins of Bcl-2 in the pathological process of immune and autoimmune diseases described in Current Allergy and Asthma Reports 2003, 3, 378384; British Journal of Haematology 2000, 110(3), 584-90; Blood 2000, 95(4), 1283-92; and New England Journal of Medicine 2004, 351(14), 1409-1418.

The involvement of proteins of Bcl-2 in the pathological process of arthritis described in the joint provisional patent application U.S. serial No. 60/988479.

The involvement of proteins of Bcl-2 in the pathological process of transplant rejection, bone marrow is described in co-owned patent application U.S. serial No. 11/941196.

Overexpression of proteins of Bcl-2 correlates with resistance to chemotherapy and clinical outcome, progression zabolevaniya, full forecast or their combination in various malignant tumors and diseases of the immune system. Malignant tumors include, but are not limited to, tumors hematological and solid types, such as acoustic neuroma, acute leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia (monolithically, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute t-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer (including estrogen-receptor positive breast cancer), bronchogenic cancer, lymphoma Berkett, cervical cancer, chondrosarcoma, chordomas, horiokartsinoma, chronic leukemia, chronic is a mini-lymphocytic leukemia, chronic myelocytes (granulocyte) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, deproliferation replacement (dysplasia and metaplasia), embryonal carcinoma, endometrial cancer, endothelioma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor politely breast cancer, primary thrombocytosis, Ewing's sarcoma, fibrosarcoma, gastric carcinoma, testicular cancer, germ cells, gestazione USSR disease, glioblastoma, head and neck cancer, disease, heavy chains, hemangioblastoma, hepatoma, hepatocellular cancer, insensitive to hormone therapy for prostate cancer, leiomyosarcoma, liposarcoma, lung cancer (including small cell lung cancer and non-small cell lung cancer), lymphangiectasia sarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (lymphoma, including diffuse B-cell lymphoma, follicular lymphoma, Hodgkin's lymphoma and nehodgkinski the Hodgkin's), malignancies and hyperproliferative diseases of the blood, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoblastic leukemia from precursor T-cell or B-cell leukemia, medullary carcinoma, granulomas the WMD, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, oligodendroglioma, oral cancer, osteoliticescuu sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinoma, papillary cancer, peripheral T-cell lymphoma, pinealoma, true polycythemia, prostate cancer (including insensitive to hormonal therapy (refractory) prostate cancer), colorectal cancer, renal cell cancer, retinoblastoma, rhabdomyosarcoma, sarcoma, carcinoma of the sebaceous glands, seminoma, skin cancer, small cell lung cancer, solid tumors (carcinoma and sarcoma), stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, testicular cancer, including testicular cancer, germ cell), thyroid cancer, macroglobulinemia Mandelstam, testicular tumors, uterine cancer, Wilms tumor, and the like.

It is also expected that compounds having formula (I), will inhibit the growth of cells expressing Bcl-2, derived pediatric cancer or neoplasm, including the embryonic rhabdomyosarcoma, pediatric acute lymphoblastic leukemia, pediatric acute myelogenous leukemia, pediatric alveolar rhabdomyosarcoma, pediatric anaplastic an ependymoma, Pediatrics the Yu both anaplastic lymphoma, pediatric the anaplastic medulloblastoma, pediatric atypical teratoid-Rathenow tumor of the Central nervous system, pediatric acute biphenotypic leukemia, pediatric Burkitt's lymphoma, pediatric malignant tumors of the family of Ewing tumors such as primitive neuroectodermal tumors, pediatric diffuse anaplastic Wilms tumor, a pediatric Wilms tumor favorable histology, pediatric glioblastoma, pediatric medulloblastoma, pediatric neuroblastoma, pediatric neuroblastoma-derived of myelocytomatosis, pediatric pre-B-cell malignancies (such as leukemias), pediatric sarcoma, pediatric rhabdoid tumor of the kidney, pediatric rhabdomyosarcoma, and pediatric T-cell malignancies, such as lymphoma and skin cancer, and the like.

Autoimmune diseases include syndrome acquired immunodeficita (AIDS), autoimmune lymphoproliferative syndrome, hemolytic anemia, inflammatory diseases, and thrombocytopenia, acute or chronic immune disease associated with organ transplantation, Addison disease, allergic disease, alopecia, alopecia alopecia, atheromatous disease/arteriosclerosis, atheroscler is h, arthritis (including osteoarthritis, juvenile chronic arthritis, septic arthritis, Lyme arthritis, psoriatic arthritis and relapsing arthritis), autoimmune bullous disease, abetalipoproteinemia associated with immunoprivileged immunodeficiency diseases, acute immune disease associated with organ transplantation, acquired acrocyanosis, acute and chronic parasitic or infectious processes, acute pancreatitis, acute renal failure, acute rheumatic fever, acute transverse myelitis, adenocarcinoma, foliar ectopic ventricular systole, (acute) respiratory distress syndrome of adults, complex mental disorders, AIDS, alcoholic cirrhosis, alcohol-induced liver damage, alcohol-induced hepatitis, allergic conjunctivitis, allergic contact dermatitis, allergic rhinitis, allergies, asthma, allograft rejection, alpha-l-antitrypsin deficits, Alzheimer's disease, amyotrophic lateral sclerosis, anemia, bronchial asthma, associated with ankylosing spondylitis disease of the lung, intracellular degeneration of the anterior horn of the spinal cord antibody-mediated cytotoxicity, antiphospholipid syndrome, anti-receptor hypersensitivity reactions, aortic aneurysm and peripheral, RA is the lamination of the aorta, arterial hypertension, arteriosclerosis, arteriovenous fistula, arthropathy, fatigue, asthma, ataxia, atopic allergies, atrial fibrillation (long or paroxysmal AF), atrial flutter, atrioventricular blockade, atrophic autoimmune hypothyroidism, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune hepatitis type 1 (classical autoimmune or lupoid hepatitis), autoimmune-mediated hypoglycemia, autoimmune neutropenia, autoimmune thrombocytopenia, autoimmune disease of the thyroid gland, B-cell lymphoma, rejection, bone graft rejection of bone marrow transplant (BMT), obliterative bronchiolitis, interventricular blockade, burning, cachexia, cardiac arrhythmia syndrome cardiogenic shock, tumors of the heart, cardiomyopathy, inflammatory response to CPB, the rejection of the cartilage graft, cerebellar cortical degeneration, cerebellar disease, chaotic or multifocal trialnew tachycardia, diseases associated with chemotherapy, chlamydia, cholestasis, chronic alcoholism, chronic active hepatitis, chronic fatigue syndrome, chronic immune disease associated with organ transplantation, chronic eosinophilic pneumonia, chronic will nosplit the global pathology, chronic mucocutaneous candidiasis, chronic obstructive pulmonary disease (COPD), chronic salicylate intoxication, colorectal common variable immune deficiency (common variable hypogammaglobulinemia), conjunctivitis, disease of connective tissue associated with interstitially lung disease, contact dermatitis, hemolytic anemia with positive break of Coombs, pulmonary heart disease Creutzfeldt-Jakob disease, cryptogenic autoimmune hepatitis, cryptogenic fibrosing alveolitis, sepsis, caused by negative cultures, cystic fibrosis, diseases associated with therapy with cytokines, Crohn's disease, Boxing dementia, demyelinating diseases, dengue fever, dermatitis, dermatitic scleroderma, dermatological conditions, lung disease associated with dermatomyositis/polymyositis, diabetes, diabetic arteriosclerotic disease, diabetes, disease, diffuse Taurus Levi, dilated cardiomyopathy, dilated congestive cardiomyopathy, discoid lupus erythematosus, diseases of the basal nucleus, generalized thrombohemorrhagic syndrome, down's syndrome in adulthood induced by drugs interstitial lung disease induced Lakers the public drugs hepatitis, induced by drugs diseases of the organs of movement caused by drugs which block CNS dopamine, receptors, sensitivity to drug, eczema, encephalomyelitis, endocarditis, endocrinopathy, enteropathic synovitis, epiglottitis, infection with Epstein-Barr, erythromelalgia, extrapyramidal and cerebellar disorders, family hematopoietically lymphohistiocytic, rejection of the implant fetal thymus, hereditary ataxia, functional peripheral arterial disease, female infertility, fibrosis, fibrotic disease of the lung, fungal sepsis, gas gangrene, gastric ulcer, giant cell arteritis diagnostics, glomerular nephritis, glomerulonephritis syndrome?, autoimmune hypothyroidism the thyroid gland (Hashimoto's disease), gouty arthritis, rejection of an organ transplant or tissue, disease graft-versus-host, gram-negative sepsis, gram positive sepsis, granuloma caused by intracellular organisms, infection with Streptococcus group B (GBS), graves ' disease, hemosiderosis associated with lung disease, hairy cell leukemia, hairy cell leukemia, a disease of Hallervorden-Spitze, Hashimoto's thyroiditis, hay fever, rejection heart transpl ntata, hematochromatosis, hematopoietic malignancy (leukemia and lymphoma), hemolytic anemia, hemolytic uremic syndrome/thrombolytic thrombocytopenic purple, hemorrhage, purple, Heinlein's disease, hepatitis A, hepatitis B, hepatitis C, HIV infection/HIV neuropathy, Hodgkin's disease, hypoparathyroidism, horey Huntington, hyperkinetic motion sickness, hypersensitive reactions, hypersensitive pneumonitis, hyperthyroidism, hypokinetic motion sickness, hypothalamic-pituitary-adrenal study of the spine, idiopathic Addison disease, idiopathic leukopenia, idiopathic pulmonary fibrosis, idiopathic thrombocytopenia, idiosyncratic liver disease, infantile spinal muscular atrophy, infectious diseases, inflammation of the aorta, inflammatory bowel disease, insulin-dependent diabetes mellitus, interstitial pneumonitis, iridocyclitis/uveitis/retro-bulbar neuritis, ischemia-reperfusion lesion, ischemic stroke, juvenile pernicious anaemia, juvenile rheumatoid arthritis, juvenile spinal muscular atrophy, Kaposi's sarcoma, Kawasaki disease, kidney transplant rejection, Legionella, leishmaniasis, leprosy, lesions of corticospinal system, linear IgA dermatosis, hyperlipidemia, exclusion is their liver transplant, Lyme disease, lymphedema, lymphocytic infiltrate lung disease, malaria, male infertility idiopathic or NOS type, malignant histiocytosis, malignant melanoma, meningitis, meningococcemia, microscopic vasculitis of the kidneys, migraleve pain, mitochondrial Multisystem disorder, mixed disease of connective tissue, mixed disease of connective tissue associated with a disease of the lung, the monoclonal gammopathy, multiple myeloma, multiple system degeneration (Menzel, Dieren-Volume, Shay-Drager and Machado-Joseph), myalgic encephalitis/Royal disease Free, myasthenia gravis, microscopic vasculitis of the kidneys, Mycobacterium avium intracellular complex, the tubercle Bacillus, myelodysplastic syndrome, myocardial infarction, myocarditis ischemic disease, nasopharyngeal carcinoma, neonatal chronic lung disease, nephritis, nephrosis, nephrotic syndrome, neurodegenerative diseases, primary neurogenic muscle atrophy, neutropenias fever, non-alcoholic steatohepatitis, occlusion of the abdominal aorta and its branches, the occlusal arterial disease, rejection of transplant organs, orchitis/epididymitis, orchitis/reverse vasectomy, visceromegaly, osteoarthritis, osteoporosis, ovarian failure, rejection Tr is spuntata pancreas, parasitic diseases, graft rejection parathyroid cancer, Parkinson's disease, an inflammatory disease of the renal pelvis, common bladderwort, the leaf bladderwort, pemphigoid, persistent rhinitis, pericardial disease, peripheral atherosclerotic disease, peripheral vascular disease, peritonitis, pernicious anemia, protein-anaphylactic uveitis, Pneumocystis pneumonia due to pneumocystis SAP, pneumonia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy syndrome and replacement of the skin), postperfusion syndrome, postmoney syndrome, post-MI cardiotoniceski syndrome, post-infectious interstitial lung disease, premature ovulation, primary biliary cirrhosis, primary sclerosing hepatitis, primary myxedema, primary pulmonary hypertension, primary sclerosing cholangitis, primary vasculitis, progressive supranuclear paralysis, psoriasis, psoriasis type 1, psoriasis type 2, the psoriatic arthropathy, secondary pulmonary hypertension in the connective tissue diseases, pulmonary manifestation of polyarteritis of polyarteritis, postinflammatory interstitial lung disease, radiation fibrosis, radiation therapy, phenomenon and disease, Raynaud's disease, Raynaud's disease, a disease Reps is a, regular tachycardia with a narrow QRS, disease, Reiter, renal disease NOS, renovascular hypertension, reperfusion disturbance, restrictive cardiomyopathy, rheumatoid arthritis, associated with interstitial lung disease, rheumatoid spondylitis, sarcoidosis syndrome Schmidt, scleroderma, senile horey, senile dementia type Taurus levy syndrome, sepsis, septic shock, seronegative arthropathies, shock, sickle cell anemia, sjögren's disease, is associated with lung disease, Sjogren syndrome, rejection of the skin graft syndrome replacement skin graft rejection of the small intestine, an autoimmune response against sperm, multiple sclerosis (all subtypes), spinal ataxia, spinocerebellar degeneration, spondyloarthropathy, spondyloarthropathy sporadic sporadic polyglandular failure type I, polyglandular deficiency type II, of still's disease, streptococcal myositis, stroke, structural damage to the cerebellum, subacute sclerosing panencephalitis, metastatic ophthalmia, syncope, syphilis of the cardiovascular system, General anaphylactic reaction, the system inflammatory response syndrome, systemic juvenile rheumatoid arthritis, systemic lupus erythematosus associated with systemic lupus erythematosus disease of the lung, the system is intelligent sclerosis, associated with systemic sclerosis interstitial lung disease, T-cell or FAB ALL, Takayasu's disease/arteritis diagnostics, telangiectasia, mediated disease, Th2 type and Th1-type, obliterating thromboangiitis, thrombocytopenia, thyroiditis, toxicity, toxic shock, transplants, trauma/hemorrhage, autoimmune hepatitis type-2 (anti-LKM antibody hepatitis), insulin resistance, type B with acanthocardia, hypersensitivity reactions type III, hypersensitivity type IV, arthropathy in ulcerative colitis, ulcerative colitis, unstable angina, uremia, urosepsis, urticaria, uveitis, valvular heart disease, varicose veins, vasculitis, masculine diffuse lung disease, venous diseases, venous thrombosis, ventricular fibrillation, vitiligo acute liver disease, viral and fungal infections, vital encephalitis/aseptic meningitis, hemophagocytosis syndrome associated with viability, granulomatous's granulomatosis syndrome Wernicke-Korsakov, Wilson's disease, xenotransplantation rejection of organs or tissues, arthropathy associated with Yersinia and Salmonella, and the like.

Schemes and experimental data

The following abbreviations have the indicated values. ADDP means 1,1'-(azodicarbon)dipiperidino; AD-mix-β denotes a mixture of (DHQD)2PHAL,K 3Fe(CN)6, K2CO3and K2SO4; 9-BBN represents 9-borabicyclo(3.3.1)nonan; Vos denotes tert-butoxycarbonyl; (DHQD)2PHAL denotes diethyl ether hydrogenizing 1,4-phthalazinedione; DBU refers to 1,8-diazabicyclo[5.4.0]undec-7-ene; DIBAL denotes diisobutylaluminium; DIEA refers to diisopropylethylamine; DMAP refers to N,N-dimethylaminopyridine; DMF refers to N,N-dimethylformamide; dmpe denotes 1,2-bis(dimethylphosphino)ethane; DMSO refers to dimethylsulfoxide; dppb denotes 1,4-bis(diphenylphosphino)butane; refers to dppe is 1,2-bis(diphenylphosphino)ethane; dppf refers to 1,1'-bis(diphenylphosphino)ferrocene; dppm denotes 1,1-bis(diphenylphosphino)methane; EDAC·HCl denotes a hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide; Fm denotes fluorenylmethoxycarbonyl; HATU denotes hexaphosphate O-(7-asobancaria-1-yl)-N,N ' N ' N'-tetramethylurea; HMPA means of hexamethylphosphoramide; IPA denotes isopropyl alcohol; MP-BH3means macroporous metropolitical cyanoborohydride of triethylamine; TEA means triethylamine; TFU denotes triperoxonane acid; THF refers to tetrahydrofuran; NCS denotes the N-chlorosuccinimide; NMM denotes the N-th methylmorpholin; NMP denotes the N-th methylpyrrolidine; PPh3means triphenylphosphine.

The following schema presents to provide is considered the most easy the CSOs and easy understanding of the description of the methods and conceptual aspects of this invention. Compounds according to this invention can be obtained by synthetic chemical methods, examples of which are shown here. Note that the order of stages in the method can be changed, reagents, solvents and reaction conditions can be replaced by specially mentioned, and that unstable groups can be protected and subjected to removal of protection as necessary.

The compounds of formula (4) can be obtained as shown in SCHEME 1, and can be used as shown in SCHEME 8, to obtain the compounds of formula (I), which are representative compounds of the present invention. The compounds of formula (1), where R represents alkyl, can be converted into compounds of the formula (2), using the Z3L1MgX1where X1is a halide, in a solvent such as, but not limited to, ether or tetrahydrofuran. The compounds of formula (3) can be obtained from compounds of the formula (2) using a strong base such as NaH, and R57X2where X2is a halide and R57such as described here. The compounds of formula (3), after treatment with an aqueous solution of NaOH or LiOH, give the compounds of formula (4).

As shown in SCHEME 2, compounds of formula (5) can be subjected to mutually is deystviy with compounds of the formula (6) and regenerating agent, obtaining the compounds of formula (7). Examples of reducing agents include sodium borohydride, cyanoborohydride sodium, triacetoxyborohydride sodium, cyanoborohydride on a polymer substrate, and the like. The reaction is usually conducted in a solvent such as, but not limited to, methanol, tetrahydrofuran and dichloromethane, or a mixture thereof. The compounds of formula (8) can be obtained from compounds of formula (7), as shown in figure 1, and can be used as shown in SCHEME 8, to obtain the compounds of formula (I).

The compounds of formula (9), after the interaction of the compounds of formula (10), where X is a halide or triflate, with base to give the compound of formula (11). The base used in the reaction include triethylamine, diisopropylethylamine and the like. The compounds of formula (13), where Y such as here described for substituents on Z3can be obtained from compounds of formula (11) and compounds of formula (12) using the conditions for the combination of Suzuki, known to specialists in this area and is easily accessible from the literature. The compounds of formula (14) can be obtained from compounds of formula (13), as shown in figure 1, and can be used as shown in SCHEME 8, to obtain the compounds of formula (I).

As shown in figure 4, is connected to the I formula (17) can be obtained from compounds of formula (15) and compounds of formula (16), where R represents alkyl and R38such as described here, using the conditions for the combination of Suzuki, known to specialists in this area and is easily accessible from the literature. The compounds of formula (17) can be reduced to compounds of the formula (18), using a reducing agent such as LiAlH4in a solvent such as, but not limited to, diethyl ether or THF. The compounds of formula (19) can be obtained from compounds of formula (18) using periodinane dess-Martin or conditions of oxidation in Turn, known to specialists in this area and is easily accessible from the literature. The compounds of formula (19) can be subjected to interaction with the compound of the formula (5) and regenerating agent, obtaining the compounds of formula (20). Examples of reducing agents include sodium borohydride, cyanoborohydride sodium, triacetoxyborohydride sodium, cyanoborohydride on a polymer substrate, and the like. The reaction is usually conducted in a solvent such as, but not limited to, methanol, tetrahydrofuran, 1,2-dichloroethane and dichloromethane, or a mixture thereof. The compounds of formula (21) can be obtained from compounds of formula (20), as shown in figure 1, and can be used as shown in SCHEME 8, to obtain the compounds of formula (I).

As shown in SCHEME 5, compound f is rmula (22), where R represents alkyl, can be converted into compounds of formula (23) by reacting compounds where X1represents CL, Br, I or CF3SO3-and the compounds of formula R41-OH and catalyst, in the presence or in the absence of the first base. Examples of catalysts include complex triftoratsetata copper(I) and toluene, PdCl2Pd(OAc)2and Pd2(dba)3. The first examples of the bases include triethylamine, N,N-diisopropylethylamine, Cs2CO3, Na2CO3, K3PO4and mixtures thereof.

The compounds of formula (22) can also be converted into compounds of formula (23) by reacting compounds where X1represents CL, F or NO2and the compounds of formula R41-OH with the first base. The first examples of the bases include triethylamine, N,N-diisopropylethylamine, Cs2CO3, Na2CO3, K3PO4and mixtures thereof.

The compounds of formula (18) can be subjected to interaction with methylchloride and a base, such as, but not limited to, triethylamine, then with N-tert-butoxycarbonylamino, obtaining the compounds of formula (24). The compounds of formula (25) can be obtained by reacting compounds of the formula (24) with triethylsilane and triperoxonane acid. The compounds of formula (5) can be subjected to interaction with compounds of the formula (26) and HK 2PO4getting the compounds of formula (27) in a solvent such as, but not limited to, dimethyl sulfoxide. The compounds of formula (28) can be obtained from compounds of formula (27), as shown in figure 1, and can be used as shown in SCHEME 8, to obtain the compounds of formula (I).

As shown in SCHEME 7, compounds of formula (1) can be subjected to the interaction of the corresponding bromide triphenylphosphine formulas (29) and bases, such as, but not limited to, sodium hydride or n-utility, obtaining the compounds of formula (30). The reaction is usually conducted in a solvent such as THF or DMSO. The compounds of formula (31) can be obtained from compounds of formula (30), as shown in figure 1, and can be used as shown in SCHEME 8, to obtain the compounds of formula (I).

As shown in SCHEME 8, compounds of formula (32), which can be obtained, as described here, can be converted into compounds of formula (33) by reacting compounds with ammonia. The compounds of formula (33) can be converted into compounds of formula (I) by reacting the compounds and compounds of the formula(4), (8), (14), (21), (28), (31) or (38) and a condensing agent in the presence or in the absence of the first base. Examples condensing the agents include the hydrochloride of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide, 1,1'-carbonyldiimidazole and hexaphosphate benzotriazol-1-yl-oxtriphylline. The first examples of the bases include triethylamine, N,N-diisopropylethylamine, 4-(dimethylamino)pyridine, and mixtures thereof.

The compounds of formula (33) is obtained as shown in SCHEME 8, can also be converted into compounds of formula (I) by reacting the compounds and compounds of the formula (34) and first base. The first examples of bases include, but are not limited to, sodium hydride, triethylamine, N,N-diisopropylethylamine, 4-(dimethylamino)pyridine, and mixtures thereof.

As shown in SCHEME 10, compounds of formula (35), where L is a bond, alkyl, O, S, S(O), S(O)2, NH, etc. may be subjected to interaction with compounds of the formula (36), receiving the compounds of formula (37). The reaction is usually carried out at elevated temperatures in a solvent such as, but not limited to, dimethyl sulfoxide, and may require the use of a base, such as, but not limited to, potassium phosphate, potassium carbonate and the like. The compounds of formula (38) can be obtained from compounds of formula (37), as shown in figure 1, and can be used as shown in SCHEME 8, to obtain the compounds of formula (I).

Connect four is uly (39), where Y is the same as here described for substituents on Z3can be obtained from compounds of formula (39A), where X is a halide or triflate and Y-B(OH)2using the conditions for the combination of Suzuki, known to specialists in this area and is easily accessible from the literature. The compounds of formula (39) can be subjected to interaction with tert-butyl piperazine-1-carboxylate and regenerating agent, such as triacetoxyborohydride sodium, obtaining the compounds of formula (40). The reaction is usually conducted in a solvent such as, but not limited to, methylene chloride. The compounds of formula (41) can be obtained from compounds of formula (40) by the interaction of the latter with R57X, where X is a halide, and NaH in a solvent such as N,N-dimethylformamide, and then the resulting product can be processed by triethylsilanol and triperoxonane acid in dichloromethane. The compounds of formula (41) can be used, as shown in figure 10, where L1-Z3as shown in (41).

As shown in SCHEME 12, a substituted piperazine-2-ones wherein R57represents alkyl, can be subjected to interaction with compounds of the formula (6) and regenerating agent, such as triacetoxyborohydride sodium in dichloromethane, to obtain the compounds of formula (42). is soedineniya formula (42) can be reduced to compounds of formula (43), using a reducing agent such as, but not limited to, sociallyengaged, in a solvent such as, but not limited to, tetrahydrofuran. The compounds of formula (43) can be used, as shown in figure 10, where L1-Z3as shown in (43).

The following examples are presented to provide believed to be the most convenient and easy understanding of the description of the methods and conceptual aspects of this invention. Shown in the examples, the compounds were named using ACD/ChemSketch Version 5.06 (05 June 2001, Advanced Chemistry Development Inc., Toronto, Ontario), ACD/ChemSketch Version 12.01 (13 May 2009), Advanced Chemistry Development Inc., Toronto, Ontario), or ChemDraw® Ver. 9.0.5 (CambridgeSoft, Cambridge, MA). Intermediate compounds were named using ChemDraw® Ver. 9.0.5 (CambridgeSoft, Cambridge, MA).

EXAMPLE 1

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 1A

tert-butyl 4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-carboxylate

4'-Chlorobiphenyl-2-carboxaldehyde (4.1 g), tert-butyl piperazine-1-carboxylate (to 4.23 g) and triacetoxyborohydride sodium (5,61 g) in CH2Cl2(60 ml) was stirred for 24 hours. The mixture was treated with methanol and poured into ether. The extract was washed with water and saturated saline and concentrated. Concentrate chromatographia and on silica gel using a mixture of 2-25% ethyl acetate/hexane.

EXAMPLE 1B

1-((4'-chlorobiphenyl-2-yl)methyl)piperazine

The compound of EXAMPLE 1A (3.0 g) and triethylsilane (1 ml) was stirred in dichloromethane (30 ml) and triperoxonane acid (30 ml) for 2 hours. The mixture was concentrated, treated with ether and again concentrated.

EXAMPLE 1C

methyl 2-bromo-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

Methyl 2-bromo-4-perbenzoate (3 g), the compound of EXAMPLE 1B (4,43 g) and K2CO3(of 3.56 g) was stirred in DMSO (35 ml) at 125°C for 24 hours. The mixture was cooled, treated with ethyl acetate (500 ml), washed with water and saturated saline solution, dried over Na2SO4, filtered and concentrated. The concentrate was chromatographically on silica gel using a mixture of 5-25% ethyl acetate/hexane.

EXAMPLE 1D

3-((dimethylamino)methyl)phenol

3-Hydroxybenzaldehyde (1.0 g), 2M dimethylamine in THF (5 ml) and triacetoxyborohydride sodium (2 g) in CH2Cl2(10 ml) was stirred for 24 hours. The mixture was treated with methanol and chromatographically on silica gel using a mixture of 2-25% ethyl acetate/hexane.

EXAMPLE 1E

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((dimethylamino)methyl)phenoxy)benzoate

The compound of EXAMPLE 1C (400 mg), the compound of EXAMPLE 1D (260 mg), Cs2CO3(570 mg), 1-naphthoic acid (2,96 g), triflate complex of copper(I) with toluene (245 mg), ethyl acetate (9 ml), and si is and 4Å (30 mg) in toluene (2 ml) was stirred at 105°C for 24 hours. The mixture was cooled and treated with ethyl acetate (100 ml) and water (40 ml). The layers were separated and the extract is washed twice with an aqueous solution of Na2CO3and saturated saline solution, dried and concentrated. The concentrate was chromatographically on silica gel using a mixture of 25-50% ethyl acetate/hexane.

EXAMPLE 1F

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((dimethylamino)methyl)phenoxy)benzoic acid

The compound of EXAMPLE 1E (750 mg) was stirred in 25 ml of a mixture of 2:1 dioxane/1M NaOH at a temperature of 80°C for 4 hours. The solution was cooled, was established pH = 4 with a solution of NaH2PO4and concentrated HCl and was extracted with ethyl acetate. The extract was washed with saturated saline solution, dried (Na2SO4) and concentrated.

EXAMPLE 1G

3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)benzosulfimide

4-Fluoro-3-nitrobenzenesulfonamide (2,18 g), (tetrahydropyran-4-yl)methylamine (1,14 g) and triethylamine (1 g) was stirred in THF (30 ml) for 24 hours. The solution was diluted with ethyl acetate, washed with a solution of NaH2PO4and saturated saline and dried (Na2SO4), filtered and concentrated. The product is triturated in ethyl acetate.

EXAMPLE 1H

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfo the Il)benzamid

The compound of EXAMPLE 1F (128 mg), the compound of EXAMPLE 1G (73 mg), the hydrochloride of 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide (88 mg) and 4-dimethylaminopyridine (28 mg) was stirred in CH2Cl2(3 ml) for 24 hours. The mixture was cooled and was chromatographically on silica gel using a mixture of 0-10% methanol/ethyl acetate.1H NMR (300 MHz, DMSO-d6) δ of 11.15 (user. s, 1H), 8,63 (DD, 1H), 8,49 (d, 1H), 7,80 (DD, 1H), 7,44-7,53 (m, 5H), was 7.36 (m, 3H), 7,22 (m, 3H), 7,01 (s, 1H), 6,92 (d, 1H), 6,78 (d, 1H), 6,44 (s, 1H), 4,17 (m, 2H), 3,86 (DD, 2H), 3.33 and (m, 6H), and 3.16 (m, 4H), to 2.66 (s, 6H), 2,37 (user. s, 4H), 1.91 a (m, 1H), and 1.63 (d, 2H), 1,29 (m, 2H).

EXAMPLE 2

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 2A

3-(methylamino)phenol

Ethylamine was barbotirovany in a solution of 4-hydroxybenzaldehyde (2.0 g) and triacetoxyborohydride sodium (5,2 g) in CH2Cl2(60 ml) for 1 hour and the mixture is hermetically closed and was stirred for 24 hours. Added 1M aqueous NaOH solution (10 ml) and then was added di-tert-butyl dicarbonate (3.57 g) and triethylamine (2,28 ml) and the mixture was stirred for 24 hours. The solution was cooled, was established pH = 4 with a solution of NaH2PO4and concentrated HCl and was extracted with ethyl acetate. The extract was washed with saturated saline solution, dried (Na2SO4) and concentrated. Concentrate chrome which was tographically on silica gel using a mixture of 20% ethyl acetate/hexane.

EXAMPLE 2B

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylamino)phenoxy)benzoate

The compound of EXAMPLE 1C (457 mg), the compound of EXAMPLE 2A (225 mg), cesium carbonate (595 mg), triflate complex of copper(I) with toluene (41 mg) and ethyl acetate (0,016 ml) in toluene (5 ml) was stirred at 110°C for 72 hours. The mixture was cooled and was chromatographically on silica gel using a mixture of 5-25% ethyl acetate/hexane.

EXAMPLE 2C

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylamino)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 2B for connection of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 2D

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 2C connection EXAMPLE 1F in EXAMPLE 1G.1H NMR (500 MHz, DMSO-d6) δ 11,60 (user. s, 1H), of 8.37 (s, 1H), 7,69 (d, 1H), 7,58 (d, 1H), 7,47 (m, 5H), 7,38 (m, 3H), 7,24 (m, 1H), 6,95 (d, 1H), 6.89 in (DD, 1H), is 6.61 (d, 1H), of 6.26 (s, 1H), 6,13 (d, 1H), 5,97 (s, 1H), of 5.92 (d, 1H), 5,59 (user. s, 1H), 3,84 (DD, 2H), 3,37 (m, 6H), 3,03 (m, 4H), 2,89 (m, 2H), 2,59 (user. s, 3H), 2,36 (user. s, 4H), 1.91 a (m, 1H), 1,62 (d, 2H), 1,24 (m, 2H).

EXAMPLE 3

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 3A

ethyl 4-fluoro-2-(2-methyl-H-indol-5-yloxy)benzoate

Ethyl 2,4-differentat (1,14 g), K3PO4(1.30 grams) and 2-methyl-5-indolol (0,90 g) was stirred at 110°C in diglyme (12 ml) for 24 hours. The mixture was cooled and poured into ether. The solution was washed three times with 1M aqueous NaOH solution and saturated saline and dried. The solution is then concentrated. The concentrate was chromatographically on silica gel using a mixture of 10% ethyl acetate/hexane.

EXAMPLE 3B

methyl 4,4-dimethyl-2-(tripterocalyx)cyclohex-1-enecarboxylate

In the slurry, washed with hexane NaH (17 g) in dichloromethane (700 ml) was added dropwise 5,5-dimethyl-2-methoxycarbonylamino (38,5 g) at 0°C. After stirring for 30 minutes the mixture was cooled to a temperature of -78°C was added anhydride triperoxonane acid (40 ml). The mixture was heated to room temperature and was stirred for 24 hours. The extract was washed with saturated saline solution, dried and concentrated.

EXAMPLE 3C

methyl 2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enecarboxylate

The compound of EXAMPLE 3B (62,15 g), 4-Chlorfenvinphos acid (32,24 g), CsF (64 g) and tetrakis(triphenylphosphine)palladium(0) (2 g) in a mixture of 2:1 dimethoxyethane/methanol (600 ml) was heated to a temperature of 70ºC for 24 hours. The mixture was concentrated. Added ether and the mixture was filtered and concentrated.

EXAMPLE 3D

(2-(4-chlorophenyl)-4,4-dimethylcyclohex-1st who yl)methanol

To a mixture of LiBH4(13 g), the compound of EXAMPLE 3C (53,8 g) and ether (400 ml) slowly via syringe, was added methanol (25 ml). The mixture was stirred at room temperature for 24 hours. The mixture was suppressed with the help of 1H. HCl while cooling with ice. The mixture was diluted with water and was extracted with ether (3×100 ml). The extracts were dried and concentrated. The concentrate was chromatographically on silica gel using a mixture of 0-30% ethyl acetate/hexane.

EXAMPLE 3E

tert-butyl 4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-carboxylate

Methylchloride (7.5 ml) was added via syringe to the compound of EXAMPLE 3D (29.3 g) and triethylamine (30 ml) in CH2Cl2(500 ml) at a temperature of 0ºC and the mixture was stirred for 1 minute. Was added N-tert-butoxycarbonylmethyl (25 g) and the mixture was stirred at room temperature for 24 hours. The suspension was washed with saturated saline solution, dried and concentrated. The concentrate was chromatographically on silica gel using a mixture of 10-20% ethyl acetate/hexane.

EXAMPLE 3F

1-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine

This EXAMPLE was obtained by replacing the compound of EXAMPLE 3E connection EXAMPLE 1A in EXAMPLE 1B.

EXAMPLE 3G

ethyl 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(2-methyl-1H-indol-5-yloxy)benzoate

The compound of EXAMPLE 3F (1008 mg), the compound of EXAMPLE A (900 mg) and HK 2PO4(550 mg) was stirred in DMSO (7 ml) at a temperature of 140°C for 24 hours. The mixture was diluted with ethyl acetate, washed three times with water, washed with saturated salt solution, dried and concentrated. The concentrate was chromatographically on silica gel using a mixture of 30% ethyl acetate/hexane.

EXAMPLE 3H

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(2-methyl-1H-indol-5-yloxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 3G connection EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 3I

4-(1-methylpiperidin-4-ylamino)-3-nitrobenzenesulfonamide

This EXAMPLE was obtained by replacing 4-amino-N-methylpiperidine 3-(N-morpholinyl)-1-Propylamine in EXAMPLE 4A.

EXAMPLE 3J

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 3H connection EXAMPLE 1F and the compound of EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, DMSO-d6) δ 10,98 (s, 1H), 10,50 (user. s, 1H), 8,55 (DD, 1H), 8,17 (d, 1H), 7,88 (DD, 1H), 7,51 (d, 1H), 7,34 (d, 2H), 7,24 (d, 1H), 7,14 (d, 1H), 7,05 (d, 2H), 7,00 (d, 1H), 6,72 (d, 1H), 6,55 (d, 1H), between 6.08 (d, 2H), 3,85 (m, 1H), 3.45 points (m, 4H), 2,98 (user. s, 4H), 2,85 (m, 2H), 2,71 (user. s, 2H), 2.63 in (s, 2H), 2,38 (s, 2H), 2,15 (m, 6H), of 1.95 (m, 4H), of 1.80 (m, 2H), 1,38 (m, 2H), 0,92 (s, 6H).

EXAMPLE 4

4-(4-((2-(4-chlorophenyl)-4,4-dimethyl who ekloges-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 4A

4-(3-morpholinopropan)-3-nitrobenzenesulfonamide

4-Fluoro-3-nitrobenzenesulfonamide (550 mg), 3-(N-morpholinyl)-1-Propylamine (1,00 g) and triethylamine (1 g) was stirred in THF (30 ml) for 24 hours. The mixture was diluted with ethyl acetate, washed with a solution of NaH2PO4and saturated saline and dried (Na2SO4), filtered and concentrated. The product is triturated in ethyl acetate.

EXAMPLE 4B

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((2-methyl-1H-indol-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 4A for connection of EXAMPLE 1F and the compound of EXAMPLE 3H connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, DMSO-d6) δ 10,98 (m, 2H), 8,80 (DD, 1H), 8,58 (d, 1H), 7,82 (DD, 1H), 7,50 (d, 1H), 7,34 (d, 2H), 7,27 (d, 1H), 7,05 (m, 4H), 6.75 in (d, 1H), 6,62 (d, 1H), 6,10 (d, 1H), 3,60 (m, 4H), of 3.45 (m, 2H), 3,01 (user. s, 4H), 2,71 (user. s, 3H), of 2.38 (m, 8H), 2,14 (user. s, 6H), of 1.95 (m, 2H), is 1.81 (m, 2H), 1,38 (m, 2H), 0,92 (s, 6H).

EXAMPLE 5

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 5A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)benzoate

This EXAMPLE was obtained by replacing 2-chlorophenol on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 5B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)PI is erasin-1-yl)-2-(2-chlorophenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 5A for connection of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 5C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 5B for connection of EXAMPLE 1F in EXAMPLE 1H. The crude product was purified using preparative HPLC using a 250×50 mm C18 column and elwira using 20-100% CH3CN vs. 0.1% triperoxonane acid in water, giving the product as trifenatate salt.1H NMR (300 MHz, DMSO-d6) δ 11,77 (user. s, 1H), 9,58 (PTS. Shir. s, 1H), 8,63 (t, 1H), 8,46 (d, 1H), 7,79 (DD, 1H), 7,71 (user. s, 1H), 7,52 (m, 5H), 7,35 (m, 4H), to 7.15 (d, 1H), 7,13 (m, 1H), 6,99 (m, 1H), 6,78 (DD, 1H), 6,65 (d, 1H), 6,40 (s, 1H), 4,35 (PTS. Shir. s, 1H), 3,90 (m, 2H), 3,80-2,80 (PTS. Shir. m, 7H), to 3.36 (m, 4H), of 3.27 (m, 2H), 1,90 (m, 1H), and 1.63 (m, 2H), 1.28 (in m, 2H).

EXAMPLE 6

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 6A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)benzoate

This EXAMPLE was obtained by replacing 3-chlorophenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 6B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 6A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 6C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 6B for connection of EXAMPLE 5B in EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,85 (user. s, 1H), 9,60 (PTS. Shir. s, 1H), 8,63 (t, 1H), 8,43 (d, 1H), 7,72 (DD, 1H), 7,70 (user. s, 1H), 7,50 (m, 5H), 7,40 (d, 2H), 7,35 (m, 1H), 7,19 (DD, 1H), 7,14 (d, 1H), 6,95 (m, 1H), 6,80 (DD, 1H), 6,72 (m, 1H), 6,70 (m, 1H), 6,56 (d, 1H), 4,35 (PTS. Shir. s, 1H), 3,90 (m, 2H), 3,80-2,80 (PTS. Shir. m, 7H), to 3.36 (m, 4H), of 3.27 (m, 2H), 1,90 (m, 1H), and 1.63 (m, 2H), 1.28 (in m, 2H).

EXAMPLE 7

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 7A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)benzoate

This EXAMPLE was obtained by replacing 4-chlorophenol on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 7B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 7A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 7C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 7B connection EXAMPLE 5B in EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,81 (ush the R. s, 1H), 9,58 (PTS. Shir. s, 1H), 8,63 (t, 1H), 8,46 (d, 1H), 7,73 (DD, 1H), 7,71 (user. s, 1H), 7,50 (m, 5H), 7,38 (d, 2H), 7,33 (m, 1H), 7,25 (m, 2H), 7,15 (d, 1H), 6,79 (m, 3H), of 6.50 (d, 1H), 4,35 (PTS. Shir. s, 1H), 3,90 (m, 2H), 3,80-2,80 (PTS. Shir. m, 7H), to 3.36 (m, 4H), of 3.27 (m, 2H), 1,90 (m, 1H), and 1.63 (m, 2H), 1.28 (in m, 2H).

EXAMPLE 8

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 8A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)benzoate

This EXAMPLE was obtained by replacing 3-NITROPHENOL connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 8B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 8A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 8C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 8B to the compound of EXAMPLE 5B in EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,81 (user. s, 1H), 9,59 (PTS. Shir. s, 1H), at 8.60 (t, 1H), 8,39 (d, 1H), of 7.70 (m, 3H), 7,50 (m, 6H), 7,38 (m, 4H), of 7.23 (m, 1H), 7,10 (d, 1H), 6,85 (DD, 1H), 6,63 (d,1H), 4,35 (PTS. Shir. s, 1H), 3,90 (m, 2H), 3,80-2,80 (PTS. Shir. m, 7H), to 3.36 (m, 4H), of 3.27 (m, 2H), 1,90 (m, 1H), and 1.63 (m, 2H), 1.28 (in m, 2H).

EXAMPLE 9

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(hydroxymethyl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-neither is Ravenel)sulfonyl)benzamide

EXAMPLE 9A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(hydroxymethyl)phenoxy)benzoate

This EXAMPLE was obtained by replacing 3-(hydroxymethyl)phenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 9B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(hydroxymethyl)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 9A for connection of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 9C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(hydroxymethyl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 9B connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H, except that the purification was performed using HPLC according to EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,63 (user. s, 1H), 9,60 (PTS. Shir. s, 2H), to 8.70 (t, 1H), and 8.50 (d, 1H), 7,80 (DD, 1H), to 7.67 (user. s, 1H), 7,50 (m, 5H), 7,40 (m, 2H), 7,35 (user. s, 1H), 7,20 (m, 2H), 6,95 (d, 1H), 6.75 in (m, 3H), 6,40 (s, 1H), and 4.40 (s, 2H), 4,35 is 2.80 (m, 22H), to 1.98 (m, 2H).

EXAMPLE 10

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 5B for connection of EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H, except that the purification was carried out using the HPLC according to EXAMPLE 5C. 1H NMR (300 MHz, DMSO-d6) δ 11,77 (user. s, 1H), 9,62 (PTS. Shir. s, 2H), to 8.70 (t, 1H), and 8.50 (d, 1H), 7,82 (DD, 1H), 7,71 (user. s, 1H), 7,52 (m, 5H), 7,40 (m, 3H), 7,33 (user. s, 1H), 7,16 (m, 2H), 7,02 (m, 1H), 6,79 (DD, 1H), 6,70 (d, 1H), 6,40 (s, 1H), 4,35 is 2.80 (m, 22H), to 1.98 (m, 2H).

EXAMPLE 11

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 11A

4-(3-(dimethylamino)propylamino)-3-nitrobenzenesulfonamide

This EXAMPLE was obtained by replacing 3-(dimethylamino)-1-Propylamine 3-(N-morpholinyl)-1-Propylamine in EXAMPLE 4A.

EXAMPLE 11B

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 5B for connection of EXAMPLE 1F and the compound of EXAMPLE 11A for connection of EXAMPLE 1G in EXAMPLE 1H, except that the purification was performed using HPLC according to EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,77 (user. s, 1H), 9,38 (PTS. Shir. s, 2H), to 8.70 (t, 1H), and 8.50 (d, 1H), 7,82 (DD, 1H), 7,65 (user. s, 1H), 7,52 (m, 5H), 7,40 (m, 3H), 7,33 (user. s, 1H), 7,16 (m, 2H), 7,02 (m, 1H), 6,79 (DD, 1H), 6,70 (d, 1H), 6,40 (s, 1H), 4,35 is 2.80 (m, 12H), 2,80 (s, 3H), 2,78 (s, 3H), of 1.98 (m, 2H).

EXAMPLE 12

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 6B nesoedinimye EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H, except that the purification was performed using HPLC according to EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,85 (user. s, 1H), 9,63 (PTS. Shir. s, 2H), 8,66 (t, 1H), 8,43 (d, 1H), 7,78 (DD, 1H), to 7.67 (user. s, 1H), 7,50 (m, 5H), 7,40 (d, 2H), 7,35 (m, 1H), 7,20 (DD, 1H), 7,14 (d, 1H), 6,95 (m, 1H), 6,80 (DD, 1H), 6,72 (m, 1H), 6,70 (m, 1H), 6,53 (s, 1H), 4,35 is 2.80 (m, 22H), to 1.98 (m, 2H).

EXAMPLE 13

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 7B connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H, except that the purification was performed using HPLC according to EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,81 (user. s, 1H), 9,63 (PTS. Shir. s, 2H), to 8.70 (t, 1H), and 8.50 (d, 1H), 7,80 (DD, 1H), 7,69 (user. s, 1H), 7,50 (m, 5H), 7,38 (d, 2H), 7,33 (m, 1H), 7,25 (m, 2H), 7,15 (d, 1H), 6,79 (m, 3H), of 6.50 (d, 1H), 4,35 is 2.80 (m, 22H), to 1.98 (m, 2H).

EXAMPLE 14

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 6B for connection of EXAMPLE 1F and the compound of EXAMPLE 11A for connection of EXAMPLE 1G in EXAMPLE 1H, except that the purification was performed using HPLC according to EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,85 (user. s, 1H), 9,63 (PTS. Shir. s, 2H), to 8.70 (t, 1H), 8,45 (d, 1H), 7,8 (DD, 1H), 7,70 (user. s, 1H), 7,50 (m, 5H), 7,40 (d, 2H), 7,35 (m, 1H), 7,20 (DD, 1H), 7,14 (d, 1H), 6,95 (m, 1H), 6,80 (DD, 1H), 6,72 (m, 1H), 6,70 (m, 1H), 6,56 (s, 1H), 4,35 is 2.80 (m, 12H), 2,52 (s, 3H), of 2.50 (s, 3H), 2,00 (m, 2H).

EXAMPLE 15

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-chlorophenoxy)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 7B connection EXAMPLE 1F and the compound of EXAMPLE 11A for connection of EXAMPLE 1G in EXAMPLE 1H, except that the purification was performed using HPLC according to EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,81 (user. s, 1H), 9,38 (PTS. Shir. s, 1H), 8,68 (t, 1H), and 8.50 (d, 1H), 7,80 (DD, 1H), 7,69 (user. s, 1H), 7,50 (m, 5H), 7,40 (d, 2H), 7,33 (m, 1H), 7,25 (m, 2H), 7,15 (d, 1H), to 6.80 (m, 3H), 6,46 (s, 1H), 4,35 is 2.80 (m, 12H), of 2.81 (s, 3H), and 2.79 (s, 3H), of 1.98 (m, 2H).

EXAMPLE 16

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((1-methyl-1H-indol-4-yl)oxy)benzamide

EXAMPLE 16A

1-(triisopropylsilyl)-1H-indol-4-ol

4-Benzyloxyindole (1 g) was treated with 60% NaH in oil(135 mg) and triisopropylsilane (1 g) in THF, was purified using flash chromatography (98/2 mixture ethyl acetate/hexane), then dibenzylamine in ethanol (35 ml) using a catalyst Perlman (Pearlman) (0,19 g) and hydrogen from the container.

EXAMPLE 16B

methyl 2-(1H-indol-4-yloxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

This EXAMPLE floor is Ali, replacing the compound of EXAMPLE 16A for connection of EXAMPLE 1D in EXAMPLE 1E. The crude product from the stage of formation of simple ether was removed silyl group, using tetrabutylammonium fluoride in a mixture of THF/water 95/5 for 1 hour, followed by purification.

EXAMPLE 16C

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(1-methyl-1H-indol-4-yloxy)benzoate

The compound of EXAMPLE 16B (148 mg), 60% NaH in oil (9 mg) and methyliodide (57 mg) in THF (1 ml) was stirred at room temperature overnight. The mixture was chromatographically on silica gel using 20% ethyl acetate in hexane.

EXAMPLE 16D

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(1-methyl-1H-indol-4-yloxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 16C on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 16E

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((1-methyl-1H-indol-4-yl)oxy)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 11A for connection of EXAMPLE 1G and compound of EXAMPLE 16D to the compound of EXAMPLE 1F in EXAMPLE 1H, except that the purification was performed using HPLC according to EXAMPLE 5C.1H NMR (300 MHz, DMSO-d6) δ 11,58 (user. s, 1H), 9,42 (user. s, 2H), 8,64 (t, 1H), 8,44 (d, 1H), to 7.77 (DD, 1H), 7,66 (user. s, 1H), 7,50 (m, 5H), 7,37 (d, 2H), 7,30 (m, 1H), 7,25 (d, 1H), 7,19 (d, 1H), 7,06 (d, 1H), 7,00 (DD, 1H), 6.75 in (l is, 1H), 6,40 (d, 1H), 6,38 (s, 1H), 6,23 (d, 1H), 4,35 is 2.80 (m, 12H), of 3.80 (s, 3H), and 2.79 (s, 3H), 2,77 (s, 3H), a 1.96 (m, 2H).

EXAMPLE 17

2-(3-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 17A

methyl 2-(3-acetamidophenol)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

This EXAMPLE was obtained by replacing 3-acetamidophenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 17B

2-(3-acetamidophenol)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 17A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 17C

2-(3-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 17B to the compound of EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, DMSO-d6) δ memorial plaques of $ 11.48 (s, 1H), of 9.89 (s, 1H), 8,59 (m, 1H), and 8.50 (d, 1H), 7,71 (DD, 1H), 7,47 (m, 6H), was 7.36 (d, 2H), 7,24 (m, 2H), 7,14 (m, 3H), 6.75 in (DD, 1H), 6,50 (DD, 1H), to 6.39 (d, 1H), 3,86 (DD, 2H), 3,37 (m, 2H), 3,30 (m, 6H), and 3.16 (m, 4H), 2,35 (s, 4H), from 2.00 (s, 3H), 1,89 (m, 1H), and 1.63 (DD, 2H), 1.27mm (m, 2H).

EXAMPLE 18

2-(4-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 18A

methyl 2-(4-(tert-butoxycarbonylamino)phenoxy)-4-(4-((4'-lorbit the Nile-2-yl)methyl)piperazine-1-yl)benzoate

This EXAMPLE was obtained by replacing N-tert-butoxycarbonyl-4-aminophenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 18B

2-(4-(tert-butoxycarbonylamino)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 18A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 18C

tert-butyl 4-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)phenylcarbamate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 18B to the compound of EXAMPLE 1F in EXAMPLE 1H.

EXAMPLE 18D

2-(4-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 18C on the compound of EXAMPLE 1A in EXAMPLE 1B.1H NMR (300 MHz, DMSO-d6) δ M. D. 11,41 (s, 1H), 9,54 (s, 1H), 8,66 (t, 1H), 8,59 (d, 1H), 7,86 (DD, 1H), to 7.67 (m, 1H), 7,51 (DD, 5H), 7,38 (d, 2H), 7,31 (m, 1H), 7,25 (d, 1H), PC 6.82 (m, 4H), 6,69 (DD, 1H), 6,24 (m, 1H), 4.26 deaths (, 2H), 3,85 (DD, 2H), 3,35 (m, 4H), 3,26 (dt, 4H), 3.04 from (m, 4H), of 2.81 (m, 2H), 1.91 a (m, 1H), 1,62 (DD, 2H), 1.26 in (m, 2H).

EXAMPLE 19

2-(3-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 19A

methyl 2-(3-(tert-butoxycarbonylamino)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl) who Insaat

This EXAMPLE was obtained by replacing N-tert-butoxycarbonyl-3-aminophenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 19B

2-(3-(tert-butoxycarbonylamino)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 19A to the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 19C

tert-butyl 3-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)phenylcarbamate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 19B to the compound of EXAMPLE 1F in EXAMPLE 1H.

EXAMPLE 19D

2-(3-aminophenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 19C on the compound of EXAMPLE 1A in EXAMPLE 1B.1H NMR (300 MHz, DMSO-d6) δ memorial plaques is 11.39 (s, 1H), 9,50 (s, 1H), 8,64 (t, 1H), 8,54 (d, 1H), of 7.75 (DD, 2H), 7,51 (d, 5H), 7,38 (m, 2H), 7,31 (m, 1H), 7,16 (d, 1H), 6,92 (t, 1H), 6.73 x (DD, 1H), 6,38 (d, 1H), 6,28 (m, 1H), 6,09 (m, 1H), 6,02 (d, 1H), 5,24 (m, 1H), 4,36 (m, 1H), 3,86 (DD, 2H), and 3.72 (m, 1H), or 3.28 (m, 8H), 3,20 (m, 1H), 3.04 from (m, 3H), 2,85 (m, 1H), 1,90 (m, 1H), and 1.63 (DD, 2H), 1.27mm (m, 2H).

EXAMPLE 20

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-methoxyphenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 20A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-meth is xopenex)benzoate

This EXAMPLE was obtained by replacing 3-methoxyphenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 20B

4-(4-((4'-chlorobiphenyl-yl)methyl)piperazine-1-yl)-2-(3-methoxyphenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 20A to the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 20C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-methoxyphenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 20B to the compound of EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, DMSO-d6) δ M. D. 11,57 (s, 1H), 8,63 (t, 1H), of 8.47 (d, 1H), 7,76 (DD, 1H), 7,47 (m, 6H), was 7.36 (m, 2H), 7,24 (m, 1H), 7,11 (m, 2H), 6,76 (DD, 1H), 6,53 (DDD, 1H), 6.35mm (m, 3H), 3,86 (m, 2H), 3,66 (s, 3H), of 3.32 (m, 6H), 3,17 (m, 4H), of 2.36 (m, 4H), of 1.92 (m, 1H), 1,64 (DD, 2H), 1.27mm (m, 2H).

EXAMPLE 21

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(dimethylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 21A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(dimethylamino)phenoxy)benzoate

This EXAMPLE was obtained by replacing 3-(dimethylamino)phenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 21B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(dimethylamino)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 21A for connection of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 21C

4-(4-((4'-chlorine-1.1 biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(dimethylamino)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 21B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, DMSO-d6) δ M. D. 11,36 (s, 1H), 8,63 (t, 1H), 8,51 (d, 1H), 7,79 (DD, 1H), 7,46 (m, 6H), was 7.36 (m, 2H), 7,24 (m, 1H), 7,15 (d, 1H),? 7.04 baby mortality (t, 1H), 6,72 (DD, 1H), to 6.39 (DD, 1H), 6,33 (d, 1H), 6,24 (t, 1H), 6,10 (DD, 1H), 3,86 (DD, 2H), 3,32 (m, 6H), of 3.13 (m, 4H), and 2.83 (s, 6H), was 2.34 (m, 4H), 1,90 (m, 1H), and 1.63 (DD, 2H), 1.27mm (m, 2H).

EXAMPLE 22

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 22A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-cianfrocca)benzoate

This EXAMPLE was obtained by replacing 3-cyanoprop connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 22B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-cianfrocca)benzoic acid

A mixture of compound of EXAMPLE 22A (of 0.081 g) in pyridine (2 ml) in a 10 ml vessel for microwave exposure, equipped with a magnetic stirrer, was treated with LiI (0,402 g) was purged with nitrogen and heated in a CEM microwave reactor at a temperature of 120ºC for 30 minutes. The mixture was concentrated, acidified with 1N. HCl, extracted with ethyl acetate and dried (MgSO4), filtered and concentrated. The concentrate was purified column chromatography on silica gel, using gradient elution with a mixture of 0-10% methanol in dichloromethane.

EXAMPLE 22C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)Pieper is Zin-1-yl)-2-(3-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 22B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, DMSO-d6) δ M. D. 11,78 (s, 1H), to 8.62 (t, 1H), to 8.41 (d, 1H), 7,72 (DD, 1H), of 7.48 (m, 6H), 7,34 (m, 4H), 7,25 (m, 1H), was 7.08 (m, 3H), PC 6.82 (DD, 1H), is 6.54 (d, 1H), a 3.87 (DD, 2H), 3.33 and (m, 6H), up 3.22 (m, 4H), of 2.38 (m, 4H), of 1.93 (m, 1H), 1,65 (DD, 2H), 1,29 (m, 2H).

EXAMPLE 23

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-6-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 23A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-methylbenzo[d]thiazol-6-yloxy)benzoate

This EXAMPLE was obtained by replacing 2-methylbenzothiazol-6-ol the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 23B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-methylbenzo[d]thiazol-6-yloxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 23A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 23C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-6-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 23B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, DMSO-d6) δ 11,78 (s, 1H), 8,56 (t, 1H), 8,40 (d, 1H), 7,71 (d, 2H), to 7.64 (DD, 1H), 7,51 (m, 5H), 7,37 (d, 2H), 7,32 (m, 1H), 7,28 (d, 1H), 6,98 (DD, 1H), 6,79 (DD, 1H), 6,51 (m, 1H), 4,33 (user. s, 1H), a 3.87 (DD, 2H), 3,69 (user. s, 2H), or 3.28 (m, 4H), 3.04 from (user. s, 2H), 2,84 of user. s, 1H), 2,74 (s, 3H), 2.49 USD (m, 4H), 1,90 (user. s, 1H), and 1.63 (DD, 2H), 1.28 (in m, 3H).

EXAMPLE 24

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 24A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-methylbenzo[d]thiazole-5-yloxy)benzoate

This EXAMPLE was obtained by replacing 2-methylbenzothiazol-5-ol the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 24B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-methylbenzo[d]thiazole-5-yloxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 24A for connection of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 24C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 24B and the compound of EXAMPLE 4A for connection of EXAMPLE 1F and the compound of EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, DMSO-d6) δ 11,83 (s, 1H), 9,48 (user. s, 1H), 8,64 (t, 1H), 8,45 (d, 1H), 7,88 (d, 1H), 7,76 (DD, 1H), 7,50 (m, 5H), 7,37 (m, 2H), 7,30 (m, 1H), 7,18 (m, 1H),? 7.04 baby mortality (d, 1H), 6,97 (DD, 1H), 6,78 (DD, 1H), 6.48 in (user. s, 1H), 4,35 (user. s, 1H), 3,98 (m, 3H), of 3.77 (user. s, 2H), 3,60 (t, 4H), 3,49 (m, 2H), 3.15 in (m, 4H), 3.04 from (m, 4H), to 2.75 (s, 3H), of 2.56 (m, 2H), was 1.94 (m, 2H).

EXAMPLE 25

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfon the l)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 24B and the compound of EXAMPLE 11A for connection of EXAMPLE 1F and the compound of EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, DMSO-d6) up 11,86 δ (s, 1H), 9,23 (user. s, 1H), 8,63 (t, 1H), 8,46 (d, 1H), 7,88 (d, 1H), to 7.77 (DD, 2H), 7,51 (m, 6H), 7,39 (m, 3H), 7,32 (user. s, 1H), 7,19 (m, 1H),? 7.04 baby mortality (d, 1H), 6,98 (DD, 1H), 6,79 (DD, 1H), of 6.49 (user. s, 1H), 4,37 (user. s, 1H), 3,76 (user. s, 2H), 3,49 (m, 4H), 3,11 (m, 4H), and 2.79 (s, 3H), 2,77 (s, 3H), was 2.76 (s, 3H), of 1.94 (m, 2H).

EXAMPLE 26

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)-3-oxopropyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 26A

3-(2-hydroxyphenyl)-N,N-dimethylpropanamide

The solution chroman-2-it (444 mg) in THF (1 ml) was treated with dimethylamine (7.5 ml) and stirred at room temperature for 5 hours. The solution was concentrated. The concentrate was filtered through a small layer of silica gel.

EXAMPLE 26B

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)-3-oxopropyl)phenoxy)benzoate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 26A on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE -26 C

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)-3-oxopropyl)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 26B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 26D

4-(4-((4'-chloro-1,1'-b is phenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)-3-oxopropyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE -26 C connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (500 MHz, DMSO-d6) δ 11,74 (s, 1H), 8,65 (t, 1H), 8,44 (d, 1H), 7,73 (DD, 2H), 7,52 (m, 5H), 7,35 (d, 3H), 7,13 (DD, 2H), of 6.96 (t, 1H), 6.87 in (t, 1H), 6.75 in (DD, 1H), 6,44 (d, 1H), to 6.39 (d, 1H), a 3.87 (DD, 2H), 3,67 (width, 8H), to 3.34 (t, 2H), or 3.28 (t, 2H), 3.00 and (width, 2H), 2.91 in (s, 3H), and 2.79 (s, 3H), 2,74 (t, 2H), by 2.55 (t, 2H), 1.91 a (m, 1H), 1,64 (d, 2H), 1,29 (m, 2H).

EXAMPLE 27

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)-2-oxoethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 27A

2-(2-hydroxyphenyl)-N,N-dimethylacetamide

This EXAMPLE was obtained by replacing benzofuran-2(3H)-he chroman-2-he in EXAMPLE 26A.

EXAMPLE 27B

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)-2-oxoethyl)phenoxy)benzoate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 27A on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 27C

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)-2-oxoethyl)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 27B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 27D

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)-2-oxoethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 27C at connection PR IS a MEASURE 1F in EXAMPLE 1H. 1H NMR (400 MHz, DMSO-d6) δ 8,64 (t, 1H), charged 8.52 (d, 1H), 7,82 (DD, 1H), of 7.70 (s, 1H), 7,52 (DD, 5H), 7,37 (d, 2H), 7,33 (s, 1H), 7,19 (m, 2H), 7,14 (t, 1H), 7,03 (t, 1H), 6,70 (m, 2H), 6,23 (s, 1H), 3,86 (DD, 2H), to 3.64 (s, 2H), 3,40 (width, 12H) at 3.25 (t, 2H), 2,92 (s, 3H), of 2.72 (s, 3H), 1.91 a (s, 1H), and 1.63 (d, 2H), 1.28 (in m, 2H).

EXAMPLE 28

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)propyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 28A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)propyl)phenoxy)benzoate

A solution of compound of EXAMPLE 26B (211 mg) in THF (1.7 ml) at room temperature was treated with borane (689 μl) and stirred for 24 hours. The mixture was suppressed with the help of 1H. HCl and heated at 50°C during the night. The solution was concentrated. The concentrate was purified by means of flash chromatography (0-5% 7n. NH3in a mixture of 10% methanol/dichloromethane).

EXAMPLE 28B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)propyl)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 28A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 28C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(3-(dimethylamino)propyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 28B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (00 MHz, DMSO-d6) δ 8,65 (t, 1H), 8,44 (d, 1H), of 7.75 (DD, 1H), 7,51 (m, 6H), 7,39 (d, 2H), 7,32 (s, 1H), 7,16 (m, 2H), 6,98 (m, 1H), 6.90 to (t, 1H), 6,76 (d, 1H), 6.48 in (d, 1H), 6,37 (s, 1H), a 3.87 (d, 2H), 3,35 (m, 2H), 3,29 (m, 2H), of 3.07 (s, 2H), and 2.79 (s, 6H), 2,61 (t, 2H), 1,94 (s, 2H), 1,64 (d, 2H), 1,30 (m, 2H).

EXAMPLE 29

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 29A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)benzoate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 27B connection EXAMPLE 26B in EXAMPLE 28A.

EXAMPLE 29B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 29A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 29C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 29B to the compound of EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, DMSO-d6) δ 8,64 (t, 1H), 8,44 (d, 1H), 7,72 (m, 2H), 7,53 (m, 5H), 7,38 (d, 2H), 7,32 (m, 1H), 7,19 (DD, 1H), 7,15 (d, 1H), 7,01 (TD, 1H), 6.90 to (t, 1H), 6,79 (DD, 1H), of 6.49 (d, 1H), 6.42 per (d, 1H), 3,88 (m, 2H), 3,60 (width, 10H) to 3.35 (t, 2H), 3,29 (t, 4H), of 2.97 (m, 2H), 2,81 (m, 6H), 1,92 (s, 1H), 1,65 (m, 2H), 1,30 (m, 2H).

EXAMPLE 30

2-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)-N,N-dimethylbenzamide

EXAMPLE 30A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(dimethylcarbamoyl)phenoxy)benzoate

This EXAMPLE was obtained by replacing 2-hydroxy-N,N-dimethylbenzamide connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 30B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-(dimethylcarbamoyl)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 30A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 30C

2-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)-N,N-dimethylbenzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 30B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, DMSO-d6) δ 8,63 (t, 1H), charged 8.52 (d, 1H), 7,83 (DD, 1H), 7,71 (s, 1H), 7,51 (m, 5H), 7,30 (m, 5H), 7,20 (m, 1H), 7,13 (t, 1H), PC 6.82 (d, 1H), 6,74 (m, 1H), 6,24 (d, 1H), 4,30 (s, 1H), 3,80 (width, 11H), to 3.34 (t, 2H), 3.27 to (t, 2H), and 2.79 (s, 3H), of 2.66 (s, 3H), 1,90 (s, 1H), 1,62 (d, 2H), 1.27mm (DDD, 2H).

EXAMPLE 31

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 31A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-((dimethylamino)methyl)phenoxy)benzoate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 30A connection EXAMPLE 26B in EXAMPLE 28A.

EXAMPLE 31B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-((dimethyl what Mino)methyl)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 31A for connection of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 31C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 31B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, DMSO-d6) δ to 8.62 (m, 1H), scored 8.38 (d, 1H), of 7.70 (DD, 1H), to 7.61 (d, 1H), 7,51 (d, 4H), 7,39 (m, 4H), 7,33 (s, 1H), 7,15 (m, 2H), 6,97 (t, 1H), at 6.84 (d, 1H), is 6.61 (s, 1H), gold 6.43 (d, 1H), 4,33 (s, 2H), 3,88 (d, 2H), 3,55 (width, 10H) to 3.35 (m, 2H), 3,29 (m, 2H), 2,78 (s, 6H), 1,92 (s, 1H), 1,64 (d, 2H), 1,31 (m, 2H).

EXAMPLE 32

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-morpholine-4-elfenix)benzamid

EXAMPLE 32A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholinoethoxy)benzoate

This EXAMPLE was obtained by replacing 3-morpholinothio connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 32B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholinoethoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 32A for connection of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 32C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-morpholine-4-elfenix)benzamid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 32B n the compound of EXAMPLE 1F and the compound of EXAMPLE 11A for connection of EXAMPLE 1G in EXAMPLE 1H. 1H NMR (400 MHz, DMSO-d6) δ of 11.61 (user. s, 1H), 9,50 (user. s, 1H), 8,69 (t, 1H), 8,51 (d, 1H), 7,83 (DD, 1H), 7,68 (m, 1H), 7,50 (m, 5H), 7,39 (m, 2H), 7,31 (m, 1H), 7,15 (d, 1H), was 7.08 (m, 1H), 6.75 in (DD, 1H), 6,59 (DD, 1H), 6,40 (m, 2H), 6,23 (m, 1H), 3,71 (m, 4H), 3,52 (m, 4H), 3,40 (m, 4H), of 3.13 (m, 4H), to 3.00 (m, 6H), 2,78 (s, 6H), to 1.96 (m, 2H).

EXAMPLE 33

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2,4-dimethyl-1,3-thiazol-5-yl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 33A

methyl 2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

This EXAMPLE was obtained by replacing 3-(benzyloxy)phenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 33B

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-hydroxyphenoxy)benzoate

The compound of EXAMPLE 33A (510 mg) in CH2Cl2(5 ml) was cooled to 0°C, was treated with 1M BBr3in CH2Cl2(4 ml) and stirred at room temperature for 2 hours. The mixture was suppressed with the help of a saturated aqueous solution of NaHCO3and were extracted with ethyl acetate. The extract was washed with water and saturated saline solution, dried over Na2SO4and concentrated. The concentrate was purified by flash chromatography on a column of silica gel using a mixture of 0-30% ethyl acetate in hexane.

EXAMPLE 33C

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(tripterocalyx)phenoxy)benzoate

Connected to the e of EXAMPLE 33B (180 mg) in THF (5 ml) was cooled to a temperature of -78°C was added 0.5 ml of 1M solution hexamethyldisilazide lithium in THF. The mixture was stirred for 15 minutes, then was treated with 1,1,1-Cryptor-N-phenyl-N-(trifloromethyl)methanesulfonamide (146 mg). The mixture was heated to room temperature over night, extinguished with a saturated aqueous solution of NH4Cl and extracted with ethyl acetate. The extract was washed with water and saturated saline solution, dried over Na2SO4and concentrated.

EXAMPLE 33D

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2,4-dimethylthiazol-5-yl)phenoxy)benzoate

The compound of EXAMPLE 33C (60 mg), 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (36 mg) and dichlorobis(triphenylphosphine)palladium(II) (2 mg) was dissolved in 5 ml of a mixture of dimethoxyethane:ethanol:2M aqueous solution of Na2CO3(7:2:2). The mixture was heated at a temperature of 130°C for 15 minutes in a microwave reactor and concentrated. The concentrate was purified by flash chromatography on a column using a mixture of 0-30% ethyl acetate/hexane.

EXAMPLE 33E

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2,4-dimethylthiazol-5-yl)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 33D on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 33F

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2,4-dimethyl-1,3-thiazol-5-yl)phenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing with the unity of EXAMPLE 33E connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H. 1H NMR (400 MHz, DMSO-d6) δ 11,80 (user. s, 1H), 9,67 (user. s, 1H), 8,63 (t, 1H), of 8.47 (d, 1H), 7,78 (DD, 1H), 7,68 (m, 1H), 7,52 (m, 5H), 7,35 (m, 4H), 7,10 (d, 1H), 7,05 (d, 1H), 6,77 (m, 3H), to 6.57 (m, 1H), 3,95 (m, 2H), 3,60 (m, 6H), of 3.45 (m, 6H), and 3.16 (m, 4H), of 3.07 (m, 4H), of 2.51 (s, 3H), and 2.26 (s, 3H), of 1.95 (m, 2H).

EXAMPLE 34

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 34A

ethyl 2-(2-chlorophenoxy)-4-perbenzoate

This EXAMPLE was obtained by replacing 2-chlorophenol 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 34B

ethyl 2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 34A on the compound of EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 34C

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 34B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 34D

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 34C to the compound of EXAMPLE 1F and the compound of EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) δ of 8.37 (d, 1H), 8,08 (d, 1H), 7,76 (DD, 1H), 7.62mm (d, 1H), was 7.36 (d, 2H), 7,35 (d, H), 7,07 (d, 2H), 7,07-7,03 (m, 2H), 6.90 to be (TD, 1H), of 6.71 (DD, 1H), 6,55 (DD, 1H), of 6.26 (d, 1H), 3,81 (m, 1H), 3,21 (m, 2H), is 3.08 (m, 4H), of 2.86 (m, 2H), was 2.76 (s, 2H), 2.63 in (s, 3H), 2,28-2,04 (m, 8H), of 1.97 (s, 2H), 1,76 (m, 2H), 1,40 (t, 2H), were 0.94 (s, 6H).

EXAMPLE 35

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(3,5-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 35A

ethyl 2-(3,5-dichlorophenoxy)-4-perbenzoate

This EXAMPLE was obtained by replacing 3,5-dichlorophenol 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 35B

ethyl 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3,5-dichlorophenoxy)benzoate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 35A in the compound of EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 35C

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3,5-dichlorophenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 35B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 35D

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(3,5-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 35C connection EXAMPLE 1F and the compound of EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) δ 9,14 (d, 1H), 8,53 (m, 1H), 8,31 (m, 1H), 7,95 (d, 1H), 7,46 (d, 2H), 7,11 (d, 2H), 6,99 (m, 3H), for 6.81 (m, 2H), to 3.73 (m, 1H), up 3.22 (m, 4H), 3,05 (m, 2H, to 2.85 (s, 2H), has 2.56 (m, 2H), 2,46 (s, 3H), 2,30 (m, 6H), and 2.14 (m, 2H), 1,95 (m, 4H), of 1.42 (m, 2H), 0,97 (s, 6H).

EXAMPLE 36

2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 36A

ethyl 2-(3-chlorophenoxy)-4-perbenzoate

This EXAMPLE was obtained by replacing 2-chlorophenol 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 36B

ethyl 2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 36A on the compound of EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 36C

2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 36B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 36D

2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

This EXAMPLE was obtained by replacing the compound of EXAMPLE 36C connection EXAMPLE 1F and the compound of EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) ∆ 9,12 (d, 1H), 8,51 (d, 1H), 8,31 (DD, 1H), to 7.99 (d, 1H), 7,45 (d, 1H), 7,11 (m, 3H), 7,02 (m, 2H), 6,91 (DD, 1H), PC 6.82 (DD, 1H), of 6.68 (d, 2H), 4,05 (user. s, 1H), 3,55 (user. s, 2H), and 3.31 (s, 6H), 2,99 (s, 2H), 2,85 (s, 3H), of 2.51 (user. s, 3H), 2,41 (s, 6H), 1,99 (s, 2H), 1,41 (t, 2H), 0,95 (s, 6H).

POR THE MEASURES 37

4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 37A

4'-chloro-4-hydroxybiphenyl-2-carbaldehyde

2-Bromo-5-hydroxybenzaldehyde (20 g), 4-Chlorfenvinphos acid (17.1 g) and dichlorobis(triphenylphosphine)palladium(II) (1.75 g) was dissolved in 475 ml of a mixture of dimethoxyethane:ethanol:2M aqueous solution of Na2CO3(7:2:2). The mixture was heated at the boil under reflux for 1 hour. The reaction mixture was then diluted with ethyl acetate, thoroughly washed with water and saturated saline solution, dried over MgSO4, filtered and concentrated. The obtained solid product was transferred in suspension in 500 ml of a mixture (2:1) hexane:ether. Specified in the title compound was collected by filtration.

EXAMPLE 37B

tert-butyl 4-((4'-chloro-4-hydroxybiphenyl-2-yl)methyl)piperazine-1-carboxylate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 37A 4'-chlorobiphenyl-2-carboxaldehyde in EXAMPLE 1A.

EXAMPLE 37C

tert-butyl 4-((4'-chloro-4-(2-(dimethylamino)ethoxy)biphenyl-2-yl)methyl)piperazine-1-carboxylate

The compound of EXAMPLE 37B (2 g), salt of hydrochloric acid 2-chloro-N,N-dimethylethanamine (2.15 g) and cesium carbonate (9,70 g) were combined in 10 ml of N,N-dimethylformamide. The resulting mixture was heated at the temperature of the re 80°C during the night. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and poured into water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were thoroughly washed with water and saturated saline solution, dried over MgSO4, filtered and concentrated. The crude product was transferred into a suspension in 100 ml of ether and the product was isolated by filtration.

EXAMPLE 37D

2-(4'-chloro-2-(piperazine-1-ylmethyl)biphenyl-4-yloxy)-N,N-dimethylethanamine

Specified in the title compound was obtained by replacing the compound of EXAMPLE 37C on the compound of EXAMPLE 1A in EXAMPLE 1B.

EXAMPLE 37E

ethyl 4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 36A on the compound of EXAMPLE 3A and compound of EXAMPLE 37D on the compound of EXAMPLE 3F in EXAMPLE 3G.

EXAMPLE 37F

4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 37E on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 37G

4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained PU is eaten replacement connection EXAMPLE 37F connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,88 (user. s, 1H), 9,52 (user. s, 1H), of 9.30 (user. s, 1H), 8,45 (m, 1H), 8,21 (d, 1H), 7,78 (DD, 1H), 7,50 (m, 3H), 7,38 (m, 2H), 7,18 (m, 3H), to 6.95 (m, 1H), for 6.81 (DD, 1H), 6,72 (DD, 1H), of 6.68 (m, 1H), 6,53 (m, 1H), 4,35 (m, 2H), 3,53 (m, 2H), or 3.28 (m, 2H), 3,21 (m, 4H), is 3.08 (m, 2H), 2,88 (s, 6H), by 2.73 (m, 2H), 2,64 (m, 1H), 2,43 (s, 3H), and 2.27 (m, 4H) and 1.83 (m, 2H).

EXAMPLE 38

2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 38A

methyl 6,6-dimethyl-4-exoterica-2H-Piran-3-carboxylate

In the slurry, washed with hexane NaH (0,72 g, 60%) in tetrahydrofuran (30 ml) was added a solution of 2,2-dimethylbicyclo-2H-Piran-4(3H)-she (2.0 g) in tetrahydrofuran (20 ml). The suspension was stirred at room temperature for 30 minutes. Was added dropwise via syringe dimethylcarbonate (of 6.31 ml). The mixture was heated at the boil under reflux for 4 hours. The mixture was acidified with 5% aqueous HCl and was extracted with dichloromethane (100 ml ×3), washed with water and saturated saline and dried over Na2SO4. After filtration and concentration the crude product was placed on the column and was suirable 10% ethyl acetate in hexane to obtain the product.

EXAMPLE 38B

methyl 6,6-dimethyl-4-(tripterocalyx)-5,6-dihydro-2H-Piran-3-carboxylate

To a cooled (0°C) mix suspe the Ziya NaH (0,983 g 60% in mineral oil, three times washed with hexane) in ether (50 ml) was added the compound of EXAMPLE 38A (3.2 g). The mixture was stirred at 0°C for 30 minutes, then added the anhydride triftormetilfullerenov acid (4,2 ml). The mixture was then stirred at room temperature overnight. The mixture was diluted with ether (200 ml) and washed with 5% HCl, water and saturated salt solution. After drying over Na2SO4, evaporation of the solvent gave the crude product which was used without further purification.

EXAMPLE 38C

methyl 4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-carboxylate

To a solution of compound of EXAMPLE 38B (2,88 g), 4-Chlorfenvinphos acid (1.88 g) and tetrakis(triphenylphosphine)palladium(0) (0,578 g) in toluene (40 ml) and ethanol (10 ml) was added 2n. an aqueous solution of Na2CO3(10 ml). The mixture was stirred while boiling under reflux overnight. The mixture was diluted with ether (300 ml) and washed with water, saturated salt solution and dried over Na2SO4. After filtration and evaporation of the solvent the residue was placed on a column and suirable using a mixture of 3% ethyl acetate in hexane to obtain the product.

EXAMPLE 38D

(4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl)methanol

To a solution of compound of EXAMPLE 38C (1.6 g) in ether (20 ml) was added LiAlH4(1.2 g). The mixture was stirred at room temp is the temperature for 4 hours. The mixture was carefully acidified with 5% aqueous HCl and was extracted with ethyl acetate (100 ml ×3), combined organic layers were washed with water, saturated salt solution and dried over Na2SO4. After filtration and evaporation of the solvent the crude product was placed on the column and was suirable 10% ethyl acetate in hexane to obtain the product.

EXAMPLE 38E

4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-carbaldehyde

To a solution of oxalicacid (1.1 g) in dichloromethane (30 ml) at -78°C was added dimethyl sulfoxide (6,12 ml). The mixture was stirred at -78°C for 30 minutes and then added to the solution of compound of EXAMPLE 38D (1.2 g) in dichloromethane (10 ml). The mixture was stirred at -78°C for 2 hours, then was added triethylamine (10 ml). The mixture was stirred overnight and the temperature was given ponatshego room. The mixture was diluted with ether (300 ml) and washed with water, saturated salt solution and dried over Na2SO4. After filtration and evaporation of the solvent the crude product was placed on the column and was suirable using 5% ethyl acetate in hexane to obtain the product.

EXAMPLE 38F

methyl 2-(2-chlorophenoxy)-4-(piperazine-1-yl)benzoate

This example is received, replacing piperazine in the compound of EXAMPLE 3F and the compound of EXAMPLE 34A on the compound of EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 38G

m is Teal, 2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoate

To a solution of compound of EXAMPLE 38E (100 mg) and the compound of EXAMPLE 38F (177 mg) in dichloromethane (10 ml) was added triacetoxyborohydride sodium (154 mg). The mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (200 ml) and washed with 2 wt.% aqueous NaOH solution, water and saturated salt solution. After drying over Na2SO4and filtering the solvent was evaporated in vacuum and the residue was placed on a column and suirable using 30% ethyl acetate in hexane to obtain the product.

EXAMPLE 38H

2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoic acid

To a solution of compound of EXAMPLE 38G (254 mg) in tetrahydrofuran (4 ml), methanol (2 ml) and water (2 ml) was added LiOH·H2O (126 mg). The mixture was stirred at room temperature overnight. The mixture was then neutralized with 5% aqueous HCl and was diluted with ethyl acetate (200 ml). After washing with saturated saline solution, dried over Na2SO4. Filtration and evaporation of the solvent gave the product.

EXAMPLE 38I

2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained as described in EXAMPLE 1H by replacing the compound of EXAMPLE 1F and is soedineniya EXAMPLE 1G connection EXAMPLE 38H and the compound of EXAMPLE 3I, respectively.1H NMR (300 MHz, dimethylsulfoxide-d6) δ with 8.33 (d, 1H), of 8.06 (d, 1H), 7,71 (DD, 1H), to 7.64 (d, 1H), 7,38 (d, 2H), 7,33 (DD, 1H), 7,16 (d, 2H), 7,02 (m, 2H), 6,86 (m, 1H), 6,69 (DD, 1H), of 6.49 (DD, 1H), and 6.25 (d, 1H), 4,14 (m, 2H), to 3.73 (m, 1H), totaling 3.04 (m, 10H), 2,87 (m, 2H), 2,42 (m, 4H), 2,22 (m, 6H), 1.69 in (m, 2H), 1,21 (s, 6H).

EXAMPLE 39

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)ethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 39A

2-(3-(benzyloxy)phenoxy)-N,N-dimethylethanamine

A solution of 3-(benzyloxy)phenol (2,002 g), 2-chloro-N,N-dimethylethanamine (1,459 g) in N,N-dimethylformamide (50 ml) was treated with cesium carbonate (3,91 g) and stirred at 50°C during the night. The mixture was diluted with ethyl acetate and 1N. aqueous solution of NaOH and the layers were separated. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified using flash chromatography (5% 7n. NH3in a mixture of methanol-dichloromethane) to give the desired product.

EXAMPLE 39B

3-(2-(dimethylamino)ethoxy)phenol

The compound of EXAMPLE 39A (450 mg) was dissolved in ethyl acetate (10 ml). The flask was purged with nitrogen three times, then was added 10% Pd/C (45 mg). The reaction mixture was stirred under a pressure of 1 ATM of hydrogen at room temperature overnight. The mixture was filtered and concentrated. The residue was filtered che the ez small layer of silica gel and used in the next stage without additional purification.

EXAMPLE 39C

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)ethoxy)phenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 39B on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 39D

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)ethoxy)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 39C on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 39E

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)ethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 39D connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) of 11.69 δ (m, 1H), 9,60 (m, 1H), 8,64 (s, 1H), and 8.50 (d, 1H), 7,80 (d, 1H), 7,72 (s, 1H), 7,52 (d, 5H), 7,38 (d, 2H), 7,33 (s, 1H), 7,19 (m, 2H), 6,78 (d, 1H), 6,65 (d, 1H), 6,45 (DD, 3H), 4,24 (s, 2H), 3,86 (d, 2H), to 3.67 (s, 10H), of 3.48 (s, 2H), 3,35 (t, 2H), 3.27 to (t, 2H), 2,85 (s, 6H), 1.91 a (s, 1H), and 1.63 (d, 2H), 1.27mm (d, 2H).

EXAMPLE 40

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 40A

ethyl 2-(4-amino-3-chlorophenoxy)-4-perbenzoate

Specified in the title compound was obtained by replacing 4-amino-3-chlorophenol 2-methyl-5-indolol in the EXAMPLE 3A.

EXAMPLE 40B

ethyl 2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 40A in methyl-2-bromo-4-perbenzoate and compounds of EXAMPLE 3F on the compound of EXAMPLE 1B in EXAMPLE 1C.

EXAMPLE 40C

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 40B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 40D

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 40C connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 10,70 (user. s, 1H), at 8.60 (s, 1H), to 8.20 (DD, 1H), of 7.90 (DD, 1H), 7,45 (d, 1H), 7,35 (d, 2H), 7,24 (d, 1H), 7,06 (d, 2H), 6,91 (d, 1H), 6,78 (s, 2H), only 6.64 (d, 1H), 6,14 (d, 1H), 5,24 (s, 2H), a 4.03 (m, 1H), 3,52 (m, 2H), 3,10 (m, 6H), 2,80 (m, 4H), by 2.73 (s, 3H), 2,18 (m, 6H), of 1.99 (m, 2H), equal to 1.82 (m, 2H), 1,38 (m, 2H), were 0.94 (s, 6H).

EXAMPLE 41

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-isopropylpiperazine-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 41A

4-(1-isopropyl is peridin-4-ylamino)-3-nitrobenzenesulfonamide

A suspension of 4-chloro-3-nitrobenzenesulfonamide (kzt1.664 g), triethylamine (2 ml) and 1-isopropylpiperazine-4-amine (1 g) in dioxane (10 ml) was stirred for 16 hours at a temperature of 90°C. the Reaction mixture was cooled to room temperature and the solid product was filtered. The solid product was washed with a mixture of 20% methanol/dichloromethane and the mixture was dried in vacuum, obtaining the product.

EXAMPLE 41B

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-isopropylpiperazine-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 34C to the compound of EXAMPLE 1F and the compound of EXAMPLE 41A to the compound of EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) δ 9,18 (d, 1H), 8,51 (d, 1H), of 8.37 (DD, 1H), 8,01 (d, 1H), 7,40-7,49 (m, 3H), 7,10 (d, 2H), 7,00-7,06 (m, 2H), 6,94-6,99 (m, 1H), 6,86 (DD, 1H), 6,80 (DD, 1H), 6,54 (d, 2H), 3,90-to 3.99 (m, 1H), 3,41-3,55 (m, 3H), 3,10-is 3.21 (m, 6H), 2,87 (s, 2H), 2,24 at 2.45 (m, 10H), 1,99 (s, 2H), 1,41 (t, 2H), 1,25 (d, 6H), of 0.95 (s, 6H).

EXAMPLE 42

2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 42A

Ethyl 2-(2-bromophenoxy)-4-perbenzoate

Specified in the title compound was obtained by replacing 2-bromophenol 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 42B

Ethyl 2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethyl who ekloges-1-enyl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 42A on the compound of EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 42C

2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 42B to the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 42D

2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 42C connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,81 (s, 1H), 9,24-9,76 (m, 2H), 8,48 (d, 1H), 8,21 (d, 1H), to 7.84 (DD, 1H), 7,50-of 7.60 (m, 2H), 7,41 (d, 2H), 7,25 (d, 1H), 7,18 (t, 1H), 7,11 (d, 2H), 6,95 (t, 1H), 6,80 (DD, 1H), 6,69 (d, 1H), to 6.39 (s, 1H), 4,03 is 4.13 (m, 1H), 3,47-the 3.65 (m, 5H), 3,20-3,40 (m, 3H), 3,01-3,19 (m, 4H), 2,70-only 2.91 (m, 5H), 2,14-of 2.26 (m, 4H), 2,04 (s, 2H), 1,73-of 1.93 (m, 2H), 1,48 (t, 2H), of 0.96 (s, 6H).

EXAMPLE 43

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 43A

ethyl 2-(tripterocalyx)cyclohex-1-enecarboxylate

Specified in the title compound was obtained as described in EXAMPLE 38B, by replacing the compound of EXAMPLE 38A on ethyl 2-exotic hexanecarboxylic.

EXAMPLE 43B

ethyl 2-(4-chlorophenyl)cyclohex-1-enecarboxylate

Specified in the title compound was obtained as described in EXAMPLE 38C, by replacing the compound of EXAMPLE 38B to the compound of EXAMPLE 43A.

EXAMPLE 43C

(2-(4-chlorophenyl)cyclohex-1-enyl)methanol

Specified in the title compound was obtained as described in EXAMPLE 38D, by replacing the compound of EXAMPLE 38C on the compound of EXAMPLE 43B.

EXAMPLE 43D

2-(4-chlorophenyl)cyclohex-1-interbanded

Specified in the title compound was obtained as described in EXAMPLE 38E, by replacing the compound of EXAMPLE 38D connection EXAMPLE 43C.

EXAMPLE 43E

methyl 2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-1-enyl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained as described in EXAMPLE 38G, by replacing the compound of EXAMPLE 38E connection EXAMPLE 43D.

EXAMPLE 43F

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-1-enyl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained as described in EXAMPLE 38H, by replacing the compound of EXAMPLE 38G connection EXAMPLE 43E.

EXAMPLE 43G

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained as described in EXAMPLE 1H by replacing the compound of EXAMPLE 1F and with the organisations of EXAMPLE 1G connection EXAMPLE 43F and the compound of EXAMPLE 3I, respectively.1H NMR (300 MHz, dimethylsulfoxide-d6) δ at 8.36 (d, 1H), 8,07 (d, 1H), 7,74 (DD, 1H), 7.62mm (d, 1H), 7,35 (d, 2H), to 7.09 (d, 2H),? 7.04 baby mortality (d, 1H), 6.89 in (m, 1H), 6,70 (DD, 1H), is 6.54 (DD, 1H), and 6.25 (d, 1H), 3,80 (m, 1H), 3,11 (m, 8H), 2,77 (m, 4H), at 2.59 (m, 4H), of 2.15 (m, 8H), to 1.70 (m, 8H).

EXAMPLE 44

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indazol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 44A

4-methoxy-3-methyl-1H-indazol

A solution of 1-(2-fluoro-6-methoxyphenyl)ethanone (1 g), hydrazine (1.04 g) and sodium acetate (0,49 g) was stirred for 72 hours in toluene (10 ml). The mixture was concentrated, and treated with DMSO (8 ml) and was heated at a temperature of 135°C for 24 hours. The mixture was cooled, poured into ethyl acetate (200 ml) and washed 3× with water and saturated salt solution. The organic layer was concentrated and chromatographically on silica gel using a mixture of 10-100% ethyl acetate/hexane.

EXAMPLE 44B

3-methyl-1H-indazol-4-ol

1M solution of BBr3(6,57 ml) was added to a solution of compound of EXAMPLE 44A (0.71 g) in dichloromethane (30 ml) and the reaction mixture was stirred for 18 hours. The reaction mixture was suppressed by slow addition of methanol and the mixture was concentrated and was chromatographically on silica gel using a mixture of 10% methanol/ethyl acetate.

EXAMPLE 44C

ethyl 4-fluoro-2-(3-methyl-1H-indazol-4-yloxy)benzoate

Specified in the header soy is inania was obtained by replacing the compound of EXAMPLE 44B 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 44D

ethyl 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3-methyl-1H-indazol-4-yloxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 44C on methyl-2-bromo-4-perbenzoate and compounds of EXAMPLE 3F on the compound of EXAMPLE 1B in EXAMPLE 1C.

EXAMPLE 44E

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3-methyl-1H-indazol-4-yloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 40B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 44F

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indazol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 44E connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,95 (user. s, 2H), of 8.47 (m, 1H), 8,27 (d, 1H), 7.62mm (d, 1H), was 7.36 (d, 2H), 7,07 (d, 2H), 6,95 (m, 2H), 6,72 (m, 2H), 6,36 (s, 1H), of 5.92 (d, 1H), 3,61 (m, 4H), 3.04 from (m, 4H), to 2.75 (m, 2H), 2,39 (m, 4H), to 2.18 (m, 6H), of 1.99 (s, 3H), 1,90 (m, 6H), 1.77 in (m, 2H), 1,41 (m, 2H), were 0.94 (s, 6H).

EXAMPLE 45

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 45A

ethyl 2-(2,3-divergence)-4-CFT is benzoat

Specified in the title compound was obtained by replacing 2,3-diferena 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 45B

ethyl 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(2,3-divergence)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 45A connection EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 45C

This EXAMPLE was obtained by replacing the compound of EXAMPLE 45B to the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 45D

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 45C connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) δ 9,17 (d, 1H), 8,49 (d, 1H), scored 8.38 (DD, 1H), to 7.99 (d, 1H), 7,46 (d, 2H), 7,10 (d, 2H), 7,01 (d, 1H), 6,85 (m, 3H), 6,69 (m, 2H), 3,70 (m, 1H), 3,21 (m, 4H), 3,05 (m, 2H), 2,84 (s, 2H), 2.57 m (m, 2H), the 2.46 (s, 3H), 2,28 (m, 6H), 2,11 (m, 2H), was 1.94 (m, 4H), of 1.42 (t, 2H), of 0.96 (s, 6H).

EXAMPLE 46

2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 46A

Ethyl 2-(3-bromophenoxy)-4-perbenzoate

Specified in the title compound was obtained by replacing 3-bromophenol 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 46B

E. the Il 2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 46A connection EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 46C

2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 46B to the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 46D

2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 46C connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ of $ 11.97 (s, 1H), 9,46 (s, 1H), 9,38 (s, 1H), 8,39-8,48 (m, 1H), 8,21 (d, 1H), 7,78 (DD, 1H), 7,53 (d, 1H), 7,41 (d, 2H), 7,08-of 7.24 (m, 5H), 6.75 in-6,86 (m, 3H), return of 6.58 (d, 1H), 4,08 (s, 1H), 3,62 (s, 3H), 3,55 (d, 4H), 3,23-3,39 (m, 3H), 3,05-3,20 (m, 4H), 2,78-only 2.91 (m, 5H), 2,70-2,78 (m, 1H), 2,13-of 2.28 (m, 4H), 2.05 is (s, 2H), 1,78-of 1.92 (m, 2H), 1,48 (t, 2H), of 0.96 (s, 6H).

EXAMPLE 47

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-ethylpiperazin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 47A

4-(1-ethylpiperazin-4-ylamino)-3-nitrobenzenesulfonamide

Specified in the title compound was obtained by replacing 1-ethylpiperidine-4-amine for 1-isopropylpiperazine-4-amine in EXAMPLE 41A.

EXAMPLE 4B

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-ethylpiperazin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 34C to the compound of EXAMPLE 1F and the compound of EXAMPLE 47A connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) δ 9,18 (d, 1H), and 8.50 (d, 1H), at 8.36 (DD, 1H), 8,01 (d, 1H), 7,39-7,47 (m, 3H), 7,10 (m, 5H), 7.03 is-7,06 (m, 2H), 7,02 (DD, 1H), of 6.96 (TD, 2H), 6,85 (DD, 1H), 6,80 (DD, 1H), is 6.54 (d, 1H), 3,93-4,00 (m, 1H), 3,55 (s, 2H), 3,13-is 3.21 (m, 5H), 3,10 (kV, 2H), 2,90 (s, 2H), 2,28-is 2.37 (m, 8H), 2,22-of 2.28 (m, 2H), 1,98 (s, 2H), 1,40 (t, 2H), 1.26 in (t, 3H), of 0.95 (s, 6H).

EXAMPLE 48

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((1,2,2,6,6-pentamethylpiperidin-4-yl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 48A

4-(1,2,2,6,6-pentamethylpiperidin-4-ylamino)-3-nitrobenzenesulfonamide

Specified in the title compound was obtained by replacing 1,2,2,6,6-pentamethylpiperidin-4-ylamine for 1-isopropylpiperazine-4-amine in EXAMPLE 41A.

EXAMPLE 48B

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((1,2,2,6,6-pentamethylpiperidin-4-yl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 34C to the compound of EXAMPLE 1F and the compound of EXAMPLE 48A connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, which is iridin-d 5) δ 9,19 (d, 1H), 8,45 (d, 1H), of 8.37 (DD, 1H), 8,01 (d, 1H), 7,45 (d, 3H), to 7.09 (d, 2H), 7,06 (s, 1H), 7,02-7,05 (m, 2H), 6,99 (TD, 1H), 6,86 (DD, 2H), 6,80 (DD, 1H), 6,53 (d, 1H), 4,16-of 4.25 (m, 1H), 3,16 is 3.23 (m, 4H), 2,90 (s, 2H), 2,82 (s, 3H), 2,45-of 2.54 (m, 2H), 2,31 (d, 6H), 2,17 (DD, 2H), 1,98 (s, 2H), 1.55V (s, 6H), of 1.46 (s, 6H), 1,40 (t, 2H), 0,95 (s, 6H).

EXAMPLE 49

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((3-nitro-4-((1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 49A

tert-butyl 1-(tetrahydro-2H-Piran-4-yl)piperidine-4-ylcarbamate

A mixture of tert-butyl piperidine-4-ylcarbamate (45 g) and dihydro-2H-Piran-4(3H)-she (24,74 g) in dichloromethane (1000 ml) was treated with triacetoxyborohydride sodium (61,9 g), was stirred at room temperature for 16 hours, washed with 1M aqueous sodium hydroxide solution and dried with anhydrous sodium sulfate, filtered and concentrated. The concentrate was subjected to flash chromatography on a column of silica gel using a mixture of 10-20% methanol/dichloromethane.

EXAMPLE 49B

dihydrochloride salt 1-(tetrahydro-2H-Piran-4-yl)piperidine-4-amine

A solution of compound of EXAMPLE 49A (52,57 g) in dichloromethane (900 ml) was treated with 4M aqueous HCl (462 ml), vigorously stirred at room temperature for 16 hours and concentrated.

EXAMPLE 49C

3-nitro-4-(1-(tetrahydro-2H-Piran-4-yl)piperidine-4-ylamino)benzosulfimide

A mixture of compound of EXAMPLE 49B (22,12 g), the water (43 ml) and triethylamine (43,6 ml) in 1,4-dioxane (300 ml) was stirred at room temperature until while the compound of EXAMPLE 49B is completely dissolved. The solution was then treated with 4-chloro-3-nitrobenzenesulfonamide (20,3 g), was heated at 90°C for 16 hours, cooled and concentrated. Added 10% methanol in dichloromethane and the solution was vigorously stirred at room temperature until there was a fine suspension, and then the mixture was filtered.

EXAMPLE 49D

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((3-nitro-4-((1-tetrahydro-2H-Piran-4-reparacin-4-yl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 45C connection EXAMPLE 1F and compounds of EXAMPLE 49C connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) δ 9,18 (d, 1H), 8,53 (d, 1H), 8,40 (DD, 1H), to 7.99 (d, 1H), 7,45 (d, 2H), 7,10 (d, 2H), 7,03 (d, 1H), 6,85 (m, 3H), 6,69 (m, 2H), was 4.02 (m, 2H), and 3.72 (m, 1H), and 3.31 (t, 2H), 3,21 (m, 4H), 3,11 (m, 2H), and 2.83 (m, 3H), of 2.66 (m, 2H), 2,30 (m, 6H), of 2.16 (m, 2H), 1.93 and (m, 4H), of 1.74 (m, 4H), of 1.41 (t, 2H), of 0.96 (s, 6H).

EXAMPLE 50

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((7-fluoro-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 50A

((3-fluoro-4-nitrophenoxy)methylene)dibenzo

Bromodiphenylmethane (3.5 g) and 3-fluoro-4-NITROPHENOL was dissolved in N,N-dimethylformamide (30 ml), then added K2CO3(4,2 g) and the reaction mixture is stirred at room temperature for 60 hours. The reaction mixture was distributed between water and ethyl acetate. The organic layer washed with 2M aqueous solution of Na2CO3and saturated saline, then was dried over Na2SO4. After filtration and concentration the crude product was purified by chromatography on a column using a mixture of 1,5-2,0% ethyl acetate in hexane.

EXAMPLE 50B

5-(benzhydryl)-7-fluoro-1H-indol

The compound of EXAMPLE 50A (2.0 g) was dissolved in tetrahydrofuran (60 ml), then the solution was cooled to a temperature of -40°C. Then was added dropwise vinylmania, a 1.0 M solution in tetrahydrofuran (21 ml), keeping the temperature below -30°C. the Reaction mixture was stirred at -40°C for 90 minutes and was distributed between saturated aqueous NH4Cl and ethyl acetate. The organic layer was washed with saturated saline and dried over Na2SO4. After filtration and concentration the crude product was purified by chromatography on a column using a mixture of 2,5-3,0% ethyl acetate in hexane.

EXAMPLE 50C

7-fluoro-1H-indol-5-ol

The compound of EXAMPLE 50B (240 mg) was dissolved in ethyl acetate (1 ml) and methanol (9 ml), then was added palladium hydroxide on carbon (35 mg) and the reaction mixture was stirred at room temperature in an atmosphere of hydrogen from a cylinder within 90 minutes. The reaction mixture was filtered the via celite and concentrated, give crude product, which was used in the next stage without additional purification.

EXAMPLE 50D

ethyl 4-fluoro-2-(7-fluoro-1H-indol-5-yloxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 50C for 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 50E

ethyl 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(7-fluoro-1H-indol-5-yloxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 50D connection EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 50F

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(7-fluoro-1H-indol-5-yloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 50E on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 50G

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((7-fluoro-1H-indol-5-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide bis(2,2,2-triptorelin)

Connection EXAMPLE 50F (35 mg), the compound of EXAMPLE 3I (17 mg), the hydrochloride of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (21 mg) and 4-dimethylaminopyridine (14 mg) was stirred in CH2Cl2(1.5 ml) over night. The reaction mixture was concentrated and the crude product was purified using preparative HPLC using a 250×50 mm C18 column and elwira using 20-100% CH3CN vs. 0.1% triperoxonane sour what you're in the water, what gave the product as trifenatate salt.1H NMR (300 MHz, dimethylsulfoxide-d6) δ are 11.62 (user. s, 1H), 9,65, 9,45 (both PTS. Shir. with only 2H), 8,55 (d, 1H), 8,17 (Shir. d, 1H), to 7.84 (DD, 1H), 7,50 (d, 1H), 7,43 (t, 1H), 7,39 (d, 2H), 7,20 (m, 1H), was 7.08 (d, 2H), 6.90 to (d, 1H), 6,66 (m, 2H), 6,44 (m, 1H), 6,28 (d, 1H), was 4.02, 3,82 (both Shire. with only 2H), 3,60 (PTS. Shir. m, 4H), 3,05 (PTS. Shir. m, 5H), 2,85, 2,80 (Shir. m, Shir. with just 5H), 2,20 (Shir. m, 5H), 2.00 (evens of user. s, 3H), 1,80 (PTS. Shir. m, 2H) 1,44 (Shir. t, 2H), 0,95 (s, 6H).

EXAMPLE 51

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-divergence)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 45C connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) δ of 9.21 (d, 1H), 9,00 (m, 1H), at 8.36 (DD, 1H), of 7.97 (d, 1H), 7,45 (d, 2H), 7,10 (d, 2H), 6,97 (d, 1H), 6,85 (d, 3H), 6,69 (d, 2H), 3,82 (m, 4H), to 3.38 (q, 2H), 3,21 (m, 4H), of 2.86 (s, 2H), 2,45 (m, 6H), of 2.28 (m, 6H), 1,99 (s, 2H), 1,80 (m, 2H), 1,41 (t, 2H), of 0.96 (s, 6H).

EXAMPLE 52

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 40C connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,10 (the Shire. s, 1H), 8,80 (t, 1H), 8,56 (s, 1H), 7,82 (DD, 1H), 7,45 (d, 1H), 7,35 (d, 2H), 7,17 (d, 1H), 7,06 (d, 2H), 6.89 in (d, 1H), 6,77 (s, 2H), 6,63 (d, 1H), 6,14 (d, 1H), 5,20 (user. s, 2H), 3,61 (m, 4H), 3.46 in (m, 2H), of 3.07 (m, 4H), to 2.75 (m, 2H), 2,44 (m, 6H), of 2.20 (m, 6H), of 1.97 (m, 2H), is 1.81 (m, 2H), 1,40 (m, 2H), were 0.94 (s, 6H).

EXAMPLE 53

2-(3-chlorophenoxy)-4-(4-((4'-chloro-4-(2-pyrrolidin-1-retil)-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 53A

methyl 5-formyl-2-(tripterocalyx)benzoate

Anhydride triftormetilfullerenov acid (7,74 ml) was added to methyl 5-formyl-2-hydroxybenzoate (7.5 g) in 150 ml of CH2Cl2at 0°C and the reaction mixture was stirred and allowed to warm to room temperature for 3 hours. The reaction mixture was diluted with CH2Cl2(150 ml), washed 3× with saturated saline, dried over Na2SO4, filtered and concentrated. The product was used without further purification.

EXAMPLE 53B

methyl 4'-chloro-4-formylmethyl-2-carboxylate

The compound of EXAMPLE 53A (14.5 g), 4-Chlorfenvinphos acid (6,88 g) CsF (12.2 g) and tetrakis(triphenylphosphine)palladium(0) was stirred at 70°C for 24 hours. The reaction mixture was cooled, filtered and concentrated. The crude product was treated with ethyl acetate (250 ml), washed 3× 1M aqueous NaOH solution and saturated brine, concentrated and the crip who was tographically on silica gel using a mixture of 10% ethyl acetate/hexane.

EXAMPLE 53C

methyl 4'-chloro-4-(2-oxoethyl)biphenyl-2-carboxylate

To a solution of (methoxymethyl)diphenylphosphine oxide (1,62 g) in 40 ml of tetrahydrofuran at -78°C was added diisopropylamide lithium (2M, 3.3 ml), after stirring for 3 minutes was added the compound of EXAMPLE 53B (1,57 g) and the solution was heated to room temperature. Added NaH (230 mg) and 40 ml of N,N-dimethylformamide and the mixture was heated at 60°C for 1 hour. The reaction mixture was cooled and poured into saturated aqueous solution of NaH2PO4. The resulting solution was twice extracted with ether, the combined extracts washed twice with water and saturated saline and concentrated. The crude mixture of enol ethers was treated with 1M aqueous HCl solution (50 ml) and dioxane (50 ml) and stirred at 60°C for 3 hours. The reaction mixture was cooled and poured into an aqueous solution of NaHCO3. The resulting solution was twice extracted with ether, the combined extracts were washed with water and saturated saline and concentrated. The product was used without further purification.

EXAMPLE 53D

methyl 4'-chloro-4-(2-(pyrrolidin-1-yl)ethyl)biphenyl-2-carboxylate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 53C 4'-chlorobiphenyl-2-carboxaldehyde and pyrrolidin for tert-butyl piperazine-1-carboxylate in PR THE LEAST 1A.

EXAMPLE 53E

(4'-chloro-4-(2-(pyrrolidin-1-yl)ethyl)biphenyl-2-yl)methanol

Diisobutylaluminium (1M in hexane, and 7.8 ml) was added to a solution of compound of EXAMPLE 53D (0,89 g) in dichloromethane (30 ml) at 0°C and the reaction mixture was stirred for 20 minutes. The reaction mixture was suppressed by slow addition of methanol and then poured into 1M aqueous NaOH solution (50 ml). The mixture was twice extracted with ethyl acetate and the extracts were combined, washed with saturated saline, dried over Na2SO4, filtered and concentrated.

EXAMPLE 53F

4'-chloro-4-(2-(pyrrolidin-1-yl)ethyl)biphenyl-2-carbaldehyde

Connection EXAMPLE 53E (0.85 grams) and peridinin dess-Martin (1.26 g) was stirred in dichloromethane (40 ml) for 90 minutes. The reaction mixture was extinguished with methanol (5 ml), concentrated and chromatographically on silica gel using a mixture of 10-50% ethyl acetate/hexane.

EXAMPLE 53G

tert-butyl 4-(3-(3-chlorophenoxy)-4-(etoxycarbonyl)phenyl)piperazine-1-carboxylate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 36A for methyl 2-bromo-4-perbenzoate and tert-butyl piperazine-1-carboxylate connection EXAMPLE 1B in EXAMPLE 1C.

EXAMPLE 53H

ethyl 2-(3-chlorophenoxy)-4-(piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 53G connection EXAMPLE 1A in EXAMPLE 1B.

ethyl 4-(4-((4'-chloro-4-(2-(pyrrolidin-1-yl)ethyl)biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 53F 4'-chlorobiphenyl-2-carboxaldehyde and connection EXAMPLE 53H for tert-butyl piperazine-1-carboxylate in EXAMPLE 1A.

EXAMPLE 53J

4-(4-((4'-chloro-4-(2-(pyrrolidin-1-yl)ethyl)biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-chlorophenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 53I connection EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 53K

2-(3-chlorophenoxy)-4-(4-((4'-chloro-4-(2-pyrrolidin-1-retil)-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 53J connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,80 (user. s, 1H), 8,66 (t, 1H), 8,45 (s, 1H), 8,00 (m, 1H), 7,72 (DD, 1H), 7,52 (d, 2H), 7,35 (m, 4H), 7,16 (m, 2H), 6,94 (d, 1H), 6,80 (d, 1H), 6,66 (d, 2H), 6,55 (m, 1H), 4,32 (m, 1H), 3,85 (m, 2H), of 3.56 (m, 2H), 3.33 and (m, 8H), of 3.07 (m, 6H), 2,85 (m, 2H), 2,43 (m, 2H), 2,02 (m, 2H), 1.91 a (m, 4H), and 1.63 (m, 2H), 1.27mm (m, 2H).

EXAMPLE 54

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 54A

ethyl 2-(2,3-dichlorophenoxy)-4-perbenzoate

Specified in the header is the connection is received, substituting 2,3-dichlorophenol 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 54B

ethyl 2-(2,3-dichlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 54A connection EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 54C

2-(2,3-dichlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 54B to the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 54D

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,3-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 54C connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) δ 9,16 (d, 1H), and 8.50 (d, 1H), 8,33 (DD, 1H), to 7.99 (d, 1H), 7,45 (d, 2H), 7,11 (t, 3H),? 7.04 baby mortality (d, 1H), 6,95 (t, 1H), 6,84 (DD, 1H), 6,74 (d, 1H), of 6.68 (d, 1H), 3,90-3,98 (m, 1H), 3,51 (d, 2H), 3,20-of 3.27 (m, 4H), 3.15 in (t, 2H), 2,90 (s, 2H), 2,80 (s, 3H), 2,33 (d, 9H), 2,17-of 2.26 (m, 2H), 1,99 (s, 2H), 1,41 (t, 2H), of 0.96 (s, 6H).

EXAMPLE 55

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indazol-4-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained p is the replacement of the compound of EXAMPLE 44E connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H. 1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,95 (user. s, 2H), 8,30 (d, 1H), 8,02 (d, 1H), to 7.61 (d, 1H), was 7.36 (d, 2H), 7,07 (d, 2H), 6,94 (m, 2H), 6,69 (m, 2H), 6,36 (s, 1H), of 5.92 (d, 1H), 3.27 to (m, 4H), 3.04 from (m, 7H), to 2.75 (m, 4H), 2.49 USD (m, 4H), 2,22 (m, 8H), of 1.99 (s, 3H), 1.77 in (m, 2H), 1.39 in (m, 2H), were 0.94 (s, 6H).

EXAMPLE 56

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 56A

(Z)-methyl 2-(tripterocalyx)cyclohepta-1-enecarboxylate

Specified in the title compound was obtained as described in EXAMPLE 38B, by replacing the compound of EXAMPLE 38A on methyl 2-oxocyclopentanecarboxylate.

EXAMPLE 56B

(Z)-methyl 2-(4-chlorophenyl)cyclohepta-1-enecarboxylate

Specified in the title compound was obtained as described in EXAMPLE 38C, by replacing the compound of EXAMPLE 38B to the compound of EXAMPLE 56A.

EXAMPLE 56C

(Z)-(2-(4-chlorophenyl)cyclohepta-1-enyl)methanol

Specified in the title compound was obtained as described in EXAMPLE 38D, by replacing the compound of EXAMPLE 38C connection EXAMPLE 56B.

EXAMPLE 56D

(Z)-2-(4-chlorophenyl)cyclohepta-1-interbanded

Specified in the title compound was obtained as described in EXAMPLE 38E, by replacing the compound of EXAMPLE 38D connection EXAMPLE 56C.

EXAMPLE 56E

(Z)-methyl 2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohepta-1-enyl)methyl)piperazine-1-yl)benzoate

Specified in the header of the compounds is their received, as described in EXAMPLE 38G, by replacing the compound of EXAMPLE 38E connection EXAMPLE 56D.

EXAMPLE 56F

(Z)-2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohepta-1-enyl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained as described in EXAMPLE 38H, by replacing the compound of EXAMPLE 38G connection EXAMPLE 56E.

EXAMPLE 56G

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained as described in EXAMPLE 1H by replacing the compound of EXAMPLE 1F and the compound of EXAMPLE 1G connection EXAMPLE 56F and the compound of EXAMPLE 3I, respectively.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 8,35 (d, 1H), of 8.06 (d, 1H), 7,73 (DD, 1H), 7,63 (d, 1H), 7,35 (d, 2H),? 7.04 baby mortality (m, 4H), to 6.88 (m, 1H), 6,69 (DD, 1H), of 6.52 (DD, 1H), and 6.25 (d, 1H), 3,78 (m, 1H), 3,06 (m, 6H), 2,70 (m, 4H), of 2.38 (m, 4H), of 2.26 (m, 5H), 2,07 (m, 4H), at 1.73 (m, 5H), of 1.52 (m, 5H).

EXAMPLE 57

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)-2-(3-(trifluoromethyl)phenoxy)benzamide

EXAMPLE 57A

ethyl 4-fluoro-2-(3-(trifluoromethyl)phenoxy)benzoate

Specified in the title compound was obtained, substituting 3-(trifluoromethyl)phenol for 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 57B

ethyl 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3-(three is tormentil)phenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 57A connection EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 57C

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3-(trifluoromethyl)phenoxy)benzoic acid

This EXAMPLE was obtained by replacing the compound of EXAMPLE 57B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 57D

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)-2-(3-(trifluoromethyl)phenoxy)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 57C connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 8,32 (d, 1H), 8,04 (m, 1H), 7,66 (m, 2H), 7,35 (m, 3H), 7,16 (d, 1H), 7,06 (d, 2H), to 6.95 (m, 3H), of 6.73 (DD, 1H), 6.42 per (d, 1H), 3,80 (m, 1H), 3,11 (m, 4H), and 2.83 (m, 4H), 2.63 in (m, 3H), of 2.21 (m, 6H), of 2.08 (m, 2H), 1,97 (m, 5H), to 1.76 (m, 2H), 1,41 (t, 2H), 0,95 (s, 6H).

EXAMPLE 58

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzamide

EXAMPLE 58A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-5-yloxy)benzoate

Specified in the title compound was obtained by replacing 3,4-dihydro-5-hydroxy-1H-quinoline-2-he connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 58B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-5-yloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 58A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 58C trainers

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 58B connection EXAMPLE 1F and the compound of EXAMPLE 11A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,68 (s, 1H), 10,08 (s, 1H), 8,64 (t, 1H), 8,48 (d, 1H), 7,81 (DD, 1H), 7,50 (m, 6H), 7,39 (m, 2H), 7,29 (m, 1H), 7,14 (d, 1H), 6,93 (t, 1H), 6.75 in (DD, 1H), 6,51 (d, 1H), 6,39 (m, 1H), 6,13 (d, 1H), 4,36 (m, 1H), and 3.72 (m, 1H), 3,40 (m, 6H), of 3.13 (m, 4H), 2,80 (m, 4H), 2,78 (d, 6H), 2.40 a (t, 2H), 1,96 (m, 2H).

EXAMPLE 59

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 34C to the compound of EXAMPLE 1F and connection EXAMPLE 131D to the compound of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ to 7.99 (d, 1H), 7,88 (m, 1H), 7.62mm (d, 1H), 7,38 (m, 3H), 7,06 (d, 3H), 7,01 (d, 1H), 6,93 (t, 1H), 6,69 (m, 1H), 6,56 (d, 1H), 6,50 (s, 1H), 6,24 (d, 1H), 3,25 (m, 10H), of 3.07 (s, 2H), of 3.07 (s, 3H), 2,77 (d, 3H), 2,20 (d, 5H), 2,04 (s, 2H), 1,96 (d, 2H), and 1.63 (s, 2H), 1,40 (t, 2H), were 0.94 (s, 6H).

EXAMPLE 60

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex the-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 60A

ethyl 2-(2,5-dichlorophenoxy)-4-perbenzoate

Specified in the title compound was obtained, substituting 2,5-dichlorophenol 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 60B

ethyl 2-(2,5-dichlorophenoxy)-4-(piperazine-1-yl)benzoate

Specified in the title compound was obtained, replacing piperazine in the compound of EXAMPLE 3F and the compound of EXAMPLE 60A connection EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 60C

2-chloro-4,4-dimethylcyclohex-1-interbanded

In a 250 ml round bottom flask was added N,N-dimethylformamide (3.5 ml) in dichloromethane (30 ml) to give a colorless solution. The mixture was cooled to a temperature of -10 OC was added dropwise phosphoryl trichloride (4 ml). The solution was heated to room temperature and was slowly added 3,3-dimethylcyclohexanone (5.5 ml). The mixture was heated at the boil under reflux overnight. The reaction mixture was extinguished cooled to a temperature of 0ºC solution of sodium acetate (25 g in 50 ml water). The aqueous layer was extracted with ether (3×200 ml). The organic layers were combined, dried over Na2SO4that was filtered and dried in vacuum.

EXAMPLE 60D

2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-interbanded

In a 1-l round bottom flask was added the compound of EXAMPLE 60C (6.8 g), 4-Chlorfenvinphos acid (6.5 g) and palladium(II) acetate (0.2 g) in water (100 ml) to give a suspension. Was added potassium carbonate (15 g) and tetrabutylammonium the Omid (10 g). After degassing by using vacuum and nitrogen and the mixture was stirred at 45°C for 4 hours. After filtration through silica gel for extraction of the product used ether (4×200 ml). The combined organic layers were dried over Na2SO4and filtered. The filtrate was concentrated and purified using flash chromatography on silica gel using a mixture of 0-10% ethyl acetate in hexane, getting listed at the beginning of the connection.

EXAMPLE 60E

ethyl 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 60D 4'-chlorobiphenyl-2-carboxaldehyde and compounds of EXAMPLE 60B for tert-butyl piperazine-1-carboxylate in EXAMPLE 1A.

EXAMPLE 60F

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 60E on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 60G

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 60F connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1 H NMR (400 MHz, dimethylsulfoxide-d6) δ 12,01 (user. s, 1H), 9,92 (user. s, 1H), 9,68 (user. s, 1H), 8,43 (m, 1H), 8,19 (d, 1H), 7,80 (DD, 1H), 7,55 (d, 1H), 7,39 (m, 3H), of 7.23 (d, 1H), 7,11 (d, 2H), 6,97 (DD, 1H), 6,85 (DD, 1H), 6,55 (m, 2H), to 3.58 (m, 5H), of 3.25 (m, 6H), and 2.83 (m, 4H), of 2.21 (m, 4H), 2.05 is (s, 2H), to 1.87 (m, 2H), 1,48 (t, 2H), of 0.96 (s, 6H).

EXAMPLE 61

2-(2-chloro-4-pertenece)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 61A

ethyl 2-(2-chloro-4-pertenece)-4-perbenzoate

Specified in the title compound was obtained by replacing 2-chloro-4-terfenol 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 61B

ethyl 2-(2-chloro-4-pertenece)-4-(piperazine-1-yl)benzoate

Specified in the title compound was obtained, replacing piperazine in the compound of EXAMPLE 3F and the compound of EXAMPLE 61A on the compound of EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 61C

ethyl 2-(2-chloro-4-pertenece)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 60D 4'-chlorobiphenyl-2-carboxaldehyde and compounds of EXAMPLE 61B for tert-butyl piperazine-1-carboxylate in EXAMPLE 1A.

EXAMPLE 61D

2-(2-chloro-4-pertenece)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 61C to link the EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 61E

2-(2-chloro-4-pertenece)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 61D connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ of 8.40 (m, 1H), 8,08 (m, 1H), 7,78 (DD, 1H), to 7.59 (d, 1H), 7,33 (m, 3H), 7,07 (m, 3H), 6,92 (m, 1H), 6,69 (DD, 1H), 6,59 (m, 1H), and 6.25 (d, 1H), 3,84 (m, 1H), is 3.08 (m, 4H), 2,77 (m, 8H), of 2.16 (m, 8H), of 1.97 (s, 2H), of 1.75 (m, 2H), 1,40 (t, 2H), were 0.94 (s, 6H).

EXAMPLE 62

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclopentene-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 62A

methyl 4,4-dimethyl-2-oxocyclopentanecarboxylate

The specified connection was received in accordance with WO 2006/035061 (page 53).

EXAMPLE 62B

methyl 4,4-dimethyl-2-(tripterocalyx)cyclopent-1-enecarboxylate

Specified in the title compound was obtained as described in EXAMPLE 38B, by replacing the compound of EXAMPLE 38A on the compound of EXAMPLE 62A.

EXAMPLE 62C

ethyl 2-(4-chlorophenyl)-4,4-dimethylcyclopentene-1-enecarboxylate

Specified in the title compound was obtained as described in EXAMPLE 38C, by replacing the compound of EXAMPLE 38B to the compound of EXAMPLE 62B.

EXAMPLE 62D

(2-(4-chlorophenyl)-4,4-dimethylcyclopentene-1-the Nile)methanol

Specified in the title compound was obtained as described in EXAMPLE 38D, by replacing the compound of EXAMPLE 38C connection EXAMPLE 62C.

EXAMPLE 62E

2-(4-chlorophenyl)-4,4-dimethylcyclopentene-1-interbanded

Specified in the title compound was obtained as described in EXAMPLE 38E, by replacing the compound of EXAMPLE 38D connection EXAMPLE 62D.

EXAMPLE 62F

methyl 2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclopentene-1-enyl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained as described in EXAMPLE 38G, by replacing the compound of EXAMPLE 38E connection EXAMPLE 62E.

EXAMPLE 62G

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclopentene-1-enyl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained as described in EXAMPLE 38H, by replacing the compound of EXAMPLE 38G connection EXAMPLE 62F.

EXAMPLE 62H

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclopentene-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained as described in EXAMPLE 1H by replacing the compound of EXAMPLE 1F and the compound of EXAMPLE 1G connection EXAMPLE 62G and the compound of EXAMPLE 3I, respectively.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 8,35 (d, 1H), of 8.06 (d, 1H), 7,73 (DD, 1H), to 7.64 (d, 1H), 7,33 (m, 5H),? 7.04 baby mortality (m, 2H), to 6.88 (m, 1H), 6,72 (DD, 1H), of 6.52 (DD, 1H), 628 (d, 1H), 3,78 (d, 1H), of 3.07 (d, 4H), 2,71 (m, 6H), 2,33 (m, 8H), to 2.06 (m, 4H), of 1.74 (m, 4H), 1,10 (m, 6H).

EXAMPLE 63

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 63A

ethyl 4-fluoro-2-(3-methyl-1H-indol-4-yloxy)benzoate

Specified in the title compound was obtained by replacing 3-methyl-4-indolol 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 63B

ethyl 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3-methyl-1H-indol-4-yloxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 63A on methyl-2-bromo-4-perbenzoate and compounds of EXAMPLE 3F on the compound of EXAMPLE 1B in EXAMPLE 1C.

EXAMPLE 63C

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(3-methyl-1H-indol-4-yloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 63B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 63D

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 63C connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, d 6) δ 10,92 (user. s, 2H), 8,77 (m, 1H), to 8.57 (d, 1H), 7,82 (DD, 1H), 7,55 (d, 1H), 7,33 (d, 2H), 7,15 (m, 2H), 7,03 (d, 2H), 6,99 (m, 2H), to 6.67 (d, 1H), 6,45 (d, 1H), 6,12 (d, 1H), 3,68 (m, 4H), 3,47 (m, 2H), to 3.02 (m, 6H), by 2.73 (m, 4H), 2,43 (m, 2H), and 2.14 (m, 8H), of 1.99 (s, 3H), 1.91 a (m, 2H), 1,38 (m, 2H), 0,92 (s, 6H).

EXAMPLE 64

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2-chloro-3-(trifluoromethyl)phenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 64A

ethyl 2-(2-chloro-3-(trifluoromethyl)phenoxy)-4-perbenzoate

Specified in the title compound was obtained by replacing 2-chloro-3-(trifluoromethyl)phenol for 2-methyl-5-indolol in EXAMPLE 3A.

EXAMPLE 64B

ethyl 2-(2-chloro-3-(trifluoromethyl)phenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 64A on the compound of EXAMPLE 3A in EXAMPLE 3G.

EXAMPLE 64C

2-(2-chloro-3-(trifluoromethyl)phenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 64B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 64D

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2-chloro-3-(trifluoromethyl)phenoxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the connection EXAMPLE IS 64C connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ 12,02 (s, 1H), 9,76 (s, 1H), 9,52 (s, 1H), 8,42 (m, 1H), 8,17 (d, 1H), 7,82 (DD, 1H), 7,58 (d, 1H), 7,41 (m, 3H), 7,27 (m, 2H), 7,11 (d, 2H), 6,93 (d, 1H), 6,84 (DD, 1H), to 6.57 (d, 1H), 3.15 in (m, 6H), and 2.83 (m, 8H), 2,11 (m, 8H) and 1.83 (m, 2H), 1,47 (t, 2H), of 0.96 (s, 6H).

EXAMPLE 65

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-cyclopropylidene-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 65A

4-(1-cyclopropylidene-4-ylamino)-3-nitrobenzenesulfonamide

To a solution of 4-fluoro-3-nitrobenzenesulfonamide (1.26 g) and 1-diazocyclopentadiene-4-amine (0,802 g) in tetrahydrofuran (20 ml) was added N,N-diisopropylethylamine (2,22 g) and 4-dimethylaminopyridine (35 mg). The mixture was stirred while boiling under reflux overnight. The mixture was diluted with ethyl acetate (200 ml), washed with aqueous solution of NaHCO3, water and saturated saline and dried over Na2SO4. After filtration and concentration the residue was dissolved in dichloromethane and was placed on the column and was suirable dichloromethane (500 ml), 5% 7h. NH3in 10% methanol in dichloromethane (1.5 l), to obtain the product.

EXAMPLE 65B

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((1-cyclopropylidene-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained as described in EXAMPLE H, by replacing the compound of EXAMPLE 1F and the compound of EXAMPLE 1G connection EXAMPLE 34C and the compound of EXAMPLE 65A, respectively.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 8,46 (DD, 1H), they were 8.22 (t, 1H), 7,81 (m, 2H), 7,53 (d, 1H), 7,37 (m, 4H), 7,14 (m, 1H), 7,07 (m, 1H), 6,99 (m, 1H), 6,72 (m, 1H), 6,29 (d, 1H, in), 3.75 (m, 1H), 3,13 (s, 3H), of 2.93 (d, 3H), 2,78 (s, 1H), of 2.20 (m, 5H), of 1.97 (m, 5H), to 1.59 (m, 5H), were 0.94 (s, 6H), 0,42 (m, 5H).

EXAMPLE 66

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-((3-methyl-1H-indol-4-yl)oxy)-N-((4-((1-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 63C connection EXAMPLE 1F and connection EXAMPLE 3I connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 10,86 (user. s, 2H), 8,51 (user. s, 1H), 8,15 (d, 1H), 7,82 (DD, 1H), 7,55 (d, 1H), 7,33 (d, 2H), 7,15 (m, 2H), 7,03 (d, 2H), 6,94 (m, 2H), 6,62 (d, 1H), 6,38 (d, 1H), 6,12 (d, 1H), 3,82 (m, 1H), 3,09 (m, 2H), 2,98 (m, 6H), is 2.88 (m, 2H), 2,71 (m, 3H), of 2.66 (m, 2H), 2,11 (m, 8H), of 1.99 (s, 3H), equal to 1.82 (m, 2H), 1,38 (m, 2H), 0,92 (s, 6H).

EXAMPLE 67

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-2-(2,5-dichlorophenoxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 60D connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 8,71 (m, 1H), 8,43 (who, 1H), of 7.75 (DD, 1H), 7,54 (d, 1H), was 7.36 (m, 3H), 7,07 (m, 3H), 6,94 (DD, 1H), 6,79 (DD, 1H), 6,46 (DD, 2H), to 3.67 (m, 4H), of 3.48 (q, 2H), 3,20 (m, 4H), and 2.83 (s, 2H), 2,65 (m, 6H), 2,24 (m, 6H), to 1.98 (s, 2H), a 1.88 (m, 2H), 1,42 (t, 2H), 0,95 (s, 6H).

EXAMPLE 68

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((1-methyl-1H-indol-4-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 16D connection EXAMPLE 50F and the compound of EXAMPLE 4A connection EXAMPLE 3I in EXAMPLE 50G.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,58 (user. s, 1H), 9,78 (user. s, 1H), 8,67 (t, 1H), 8,44 (d, 1H), to 7.77 (DD, 1H), 7,66 (user. s, 1H), 7,50 (m, 5H), 7,37 (d, 2H), 7,30 (m, 1H), 7,25 (d, 1H), 7,19 (d, 1H), 7,06 (d, 1H), 7,00 (DD, 1H), 6.75 in (DD, 1H), 6,40 (d, 1H), 6,38 (s, 1H), 6,23 (d, 1H), 4,35-2,80 (series Shir. m, just 22H), of 3.80 (s, 3H), a 1.96 (m, 2H).

EXAMPLE 69

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholine-4-elfenix)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 32B connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,63 (s, 1H), 9,86 (s, 1H), 8,71 (t, 1H), and 8.50 (d, 1H), 7,83 (DD, 1H), of 7.70 (s, 1H), 7,50 (m, 5H), 7,39 (d, 2H), 7,32 (m, 1H), 7,16 (d, 1H), was 7.08 (m, 1H), 6,74 (DD, 1H), 6,59 (DD, 1H), 6,40 (m, 2H), 6,23 (DD, 1H), 4,24 (m, 2H), 3,97 (m, 2H), 3,70 (m, 4H), 3,63 (m, 4H), of 3.54 (m, 4H), 3,18 (m, 4H), of 3.07 (m, 4H), to 3.00 (m, 4H), and 2.83 (m, 2H), up to 1.98 (m, 2H).

EXAMPLE 70

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((3-(3-morpholine-4-yl-3-oxopropyl)-1H-indol-5-yl)oxy)benzamide

EXAMPLE 70A

(Z)-tert-butyl 5-(benzyloxy)-3-(3-morpholino-3-oxoprop-1-enyl)-1H-indole-1-carboxylate

A mixture of tert-butyl 5-(benzyloxy)-3-bromo-1H-indole-1-carboxylate (2,011 g), 1-morpholinopropan-2-EN-1-it (0,776 g), palladium acetate (31 mg), tri-o-tolylphosphino (187 mg) and triethylamine (1,14 ml) in N,N-dimethylformamide (14 ml) under nitrogen atmosphere was stirred at a temperature of 100°C during the night. The mixture was diluted with ethyl acetate and saturated aqueous ammonium chloride. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified using flash chromatography (80% ethyl acetate-hexane) to give the desired product.

EXAMPLE 70B

tert-butyl 5-hydroxy-3-(3-morpholino-3-oxopropyl)-1H-indole-1-carboxylate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 70A on the compound of EXAMPLE 39A in EXAMPLE 39B.

EXAMPLE 70C

tert-butyl 5-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(methoxycarbonyl)phenoxy)-3-(3-morpholino-3-oxopropyl)-1H-indole-1-carboxylate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 70B on the compound of EXAMPLE 1D in EXAMPLE 1E.

NOTE THE R 70D

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(3-morpholino-3-oxopropyl)-1H-indol-5-yloxy)benzoate

A solution of compound of EXAMPLE 70C (300 mg) in dioxane (2 ml) was treated with an aqueous solution of concentrated hydrochloric acid (0,378 ml) and stirred at room temperature overnight. The solution was concentrated and the residue used in the next stage without additional purification.

EXAMPLE 70E

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(3-morpholino-3-oxopropyl)-1H-indol-5-yloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 70D on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 70F

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((3-(3-morpholine-4-yl-3-oxopropyl)-1H-indol-5-yl)oxy)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 70E connection EXAMPLE 1F and the compound of EXAMPLE 11A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,37 (s, 1H), 10,88 (s, 1H), was 9.33 (s, 1H), 8,64 (m, 2H), 7,88 (d, 1H), 7,66 (s, 1H), 7,51 (DD, 5H), 7,35 (DD, 3H), 7,29 (s, 1H), 7,21 (s, 1H), 7,13 (d, 2H), PC 6.82 (DD, 1H), to 6.67 (d, 1H), 6,21 (s, 1H), of 3.42 (s, 20H), of 3.12 (s, 2H), 2,85 (m, 2H), 2,78 (d, 6H), 2,61 (m, 2H), 1,95 (m, 2H).

EXAMPLE 71

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-yl is ethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 71A

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 33A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 71B

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 71A to the compound of EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) of 11.69 δ (m, 1H), to 8.62 (m, 1H), 8,48 (d, 1H), 7,76 (DD, 1H), 7,65 (m, 1H), 7,50 (m, 5H), 7,38 (m, 6H), 7,32 (m, 2H), 7,11 (m, 2H), 6,77 (DD, 1H), 6,62 (DD, 1H), 6,41 (m, 2H), 6.35mm (m, 1H), to 4.98 (s, 2H), a 3.83 (m, 2H), or 3.28 (m, 12H), 3,17 (m, 2H), 1,89 (m, 1H), 1,59 (m, 2H), 1.26 in (m, 2H).

EXAMPLE 72

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 72A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-cianfrocca)benzoate

Specified in the title compound was obtained by replacing 4-cyanoprop connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 72B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-cianfrocca)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 72A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 72C

4-(4-((4'-chloro-1,1'-beef the Nile-2-yl)methyl)piperazine-1-yl)-2-(4-cianfrocca)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 72B on the compound of EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ of $ 11.97 (s, 1H), 9,54 (s, 1H), to 8.62 (t, 1H), 8,44 (d, 1H), 7,66 (m, 4H), 7,53 (m, 5H), 7,37 (m, 3H), 7,12 (d, 1H), PC 6.82 (m, 3H), only 6.64 (d, 1H), 4,37 (m, 1H), 3,86 (DD, 2H), 3,49 (m, 2H), 3,26 (m, 8H), 3,10 (m, 2H), 2,84 (s, 1H), 1,92 (m, 1H), 1,64 (DD, 2H), 1.28 (in m, 2H).

EXAMPLE 73

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-morpholine-4-yl-3-oxopropyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 70E connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,38 (s, 1H), 10,87 (s, 1H), 8,59 (m, 2H), 7,79 (DD, 1H), 7,68 (s, 1H), 7,51 (DD, 5H), 7,34 (DD, 4H), 7,20 (s, 1H), 7,10 (d, 2H), for 6.81 (DD, 1H), of 6.68 (d, 1H), 6,23 (s, 1H), 3,85 (d, 2H), 3,44 (s, 18H), of 3.28 (m, 4H), 2,84 (m, 2H), 2,60 (t, 2H), 1,89 (s, 1H), and 1.63 (m, 2H), 1.27mm (m, 2H).

EXAMPLE 74

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-morpholine-4-ylpropyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 74A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(3-morpholinopropan)-1H-indol-5-yloxy)benzoate

The compound of EXAMPLE 70C (107 mg) was dissolved in anhydrous tetrahydrofuran (0.7 ml), then was added a 1M solution of borane in tetrahydrofuran (0,57 ml). The reaction mixture was stirred at anatoy temperature during the night. The reaction mixture was extinguished with the help of 1H. aqueous HCl (1.5 ml). The resulting solution was heated at 50°C during the night. The solvent was removed in vacuum. The residue was purified by flash chromatography on a column of silica gel using 10-50% ethyl acetate in hexane and the product.

EXAMPLE 74B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(3-morpholinopropan)-1H-indol-5-yloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 74A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 74C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-morpholine-4-ylpropyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 74B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,35 (m, 1H), 10,95 (s, 1H), 9,58 (m, 1H), at 8.60 (m, 2H), 7,86 (DD, 1H), 7,63 (m, 1H), 7,50 (DD, 5H), 7,35 (m, 3H), 7,28 (s, 1H), 7,22 (DD, 2H), 7,17 (d, 1H), at 6.84 (d, 1H), 6,65 (d, 1H), 6,16 (s, 1H), 3,93 (s, 1H), 3,84 (d, 2H), 3,50 (m, 15H), of 3.32 (m, 2H), 3,26 (m, 2H), 3,13 (m, 2H), 3,03 (s, 2H), 2,68 (t, 2H), 1,97 (d, 2H), 1,89 (s, 1H), 1,61 (d, 2H), 1.27mm (m, 2H).

EXAMPLE 75

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 75A

4-((dimethylamino)methyl)phenol/p>

Specified in the title compound was obtained by replacing 4-hydroxybenzaldehyde 4'-chlorobiphenyl-2-carboxaldehyde and dimethylamine for tert-butyl piperazine-1-carboxylate in EXAMPLE 1A.

EXAMPLE 75B

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((dimethylamino)methyl)phenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 75A on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 75C

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((dimethylamino)methyl)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 75B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 75D

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 75C connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,80 (user. s, 1H), 9,60 (user. s, 1H), 8,59 (m, 1H), 8,48 (m, 1H), 7,80 (d, 1H), 7,50 (d, 2H), 7,46 (m, 2H), was 7.36 (m, 4H), from 7.24 (m, 2H), 6.90 to (d, 2H), 6,77 (d, 1H), 6,44 (d, 1H), 4,16 (m, 2H), 3,84 (DD, 2H), 3,30 (m, 8H), 3.15 in (m, 4H), 2,68 (m, 4H), to 2.35 (m, 4H), of 1.88 (m, 1H), 1,61 (DD, 2H), 1,23 (m, 2H).

EXAMPLE 76

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(1H-imidazol-1-yl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzo the ID

EXAMPLE 76A

methyl 2-(4-(1H-imidazol-1-yl)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained, substituting 4-(1H-imidazol-1-yl)phenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 76B

2-(4-(1H-imidazol-1-yl)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 76A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 76C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(1H-imidazol-1-yl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 76B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ and 8.50 (s, 1H), 8,17 (d, 1H), 7,78 (m, 1H), 7,66 (m, 1H), 7,40-7,58 (m, 8H), 7,37 (d, 2H), 7,25 (m, 1H), 7,10 (d, 2H), 6,94 (d, 1H), 6.75 in (d, 1H), 6,63 (d, 1H), gold 6.43 (d, 1H), 3,82 (m, 2H), 3,37 (m, 4H), is 3.08 3.21-in (m, 6H), to 2.35 (m, 4H), equal to 1.82 (m, 1H), 1,58 (m, 2H), 1,40 (m, 2H).

EXAMPLE 77

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 77A

4-((tetrahydro-2H-Piran-4-yl)methylamino)benzosulfimide

4-Aminobenzenesulfonamide (6,80 g), tetrahydropyran-4-carboxaldehyde (4,96 g) and triacetoxyborohydride sodium (16,74 g) in tetrahydrofuran (300 ml) and acetic acid (15 ml)was stirred at room temperature for 24 hours. The reaction mixture was concentrated and treated with ethyl acetate. The resulting solution was washed with water and saturated brine, concentrated and chromatographically on silica gel using a mixture of 50% ethyl acetate/hexane.

EXAMPLE 77B

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitrophenoxy)-N-((4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide 2,2,2-triptorelin

Specified in the title compound was obtained by replacing the compound of EXAMPLE 8B connection EXAMPLE 50F and compounds of EXAMPLE 77A connection EXAMPLE 3I in EXAMPLE 50G.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,58 (user. s, 1H), 9,58 (user. s, 1H), 7,86 (m, 1H), 7,71 (user. s, 1H), 7,52 (m, 7H), 7,40 (m, 5H), 7,30 (m, 1H), PC 6.82 (DD, 1H), of 6.71 (user. s, 1H), 6,60 (d, 1H), 6,47 (d, 2H), 4,37 (PTS. Shir. s, 1H), 3,83 (DD, 2H), 3,70 (PTS. Shir. s, 1H), 3,50-3,40 (arr., 6H), 3,26, (m, 2H,), 3,05, 2,96, 2,94, 2,85 ( all Shire. with only 4H), to 1.79 (m, 1H), 1,65 (m, 2H), 1,22 (m, 2H).

EXAMPLE 78

tert-butyl 4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)benzyl(ethyl)carbamate

EXAMPLE 78A

tert-butyl ethyl(4-hydroxybenzyl)carbamate

Gaseous diethylamine was barbotirovany in a solution of 4-hydroxybenzaldehyde (2.0 g) and triacetoxyborohydride sodium (5,2 g) in dichloromethane (60 ml) until saturation. The reaction flask was hermetically closed and the reaction mixture was stirred is within 24 hours. Then was added 1M NaOH (10 ml), then di-tert-butyl dicarbonate (3.57 g) and triethylamine (2,28 ml) and the reaction mixture was stirred for 24 hours. The reaction mixture was acidified with a saturated solution of NaH2PO4, and was twice extracted with ethyl acetate and the combined extracts were washed with saturated brine and concentrated. The crude product was chromatographically on silica gel using a mixture of 20% ethyl acetate/hexane as eluent to obtain the product.

EXAMPLE 78B

methyl 2-(4-((tert-butoxycarbonyl(ethyl)amino)methyl)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 78A on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 78C

2-(4-((tert-butoxycarbonyl(ethyl)amino)methyl)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 78B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 78D

tert-butyl 4-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)benzyl(ethyl)carbamate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 78C to the compound of EXAMPLE 1F in EXAMPLE 1H.

EXAMPLE 79

tert-butyl 3-(5-(4-((4'-chloro-1,1'-biphenyl-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)benzyl(ethyl)carbamate

EXAMPLE 79A

tert-butyl ethyl(4-hydroxybenzyl)carbamate

Specified in the title compound was obtained by replacing 3-hydroxybenzaldehyde 4-hydroxybenzaldehyde in EXAMPLE 78A.

EXAMPLE 79B

methyl 2-(3-((tert-butoxycarbonyl(ethyl)amino)methyl)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 79A connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 79 ° C

2-(3-((tert-butoxycarbonyl(ethyl)amino)methyl)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 79B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 79D

tert-butyl 3-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-nitro-4-((tetrahydro-2H-Piran-4-yl)methylamino)vinylsulfonylacetamido)phenoxy)benzyl(ethyl)carbamate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 79 ° C connection EXAMPLE 1F in EXAMPLE 1H.

EXAMPLE 80

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 78D on the compound of EXAMPLE 1A in EXAMPLE 1B.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 8,63 (user. s, 1H), charged 8.52 (the Shire. s, 1H), 8,43 (s, 1H), 7,78 (DD, 1H), 7,60 (d, 1H), 7,46 (s, 4H), 7,35 (d, 2H), 7,31 (m, 1H), 7,24 (d, 1H), 7,13 (d, 1H), at 6.84 (d, 2H), 6,72 (d, 1H), 6,36 (s, 1H), Android 4.04 (s, 2H), 3,84 (DD, 2H), 3.27 to (m, 6H), the 3.11 (m, 4H), to 2.94 (m, 2H), a 2.36 (m, 4H), 1.91 a (m, 1H), 1,62 (DD, 2H), 1,23 (m, 2H), by 1.17 (t, 3H).

EXAMPLE 81

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 79D on the compound of EXAMPLE 1A in EXAMPLE 1B.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,60 (user. s, 1H), 8,80 (user. s, 1H), 8,62 (user. s, 1H), 8,51 (s, 1H), 7,82 (DD, 1H), 7,30-of 7.55 (m, 7H), from 7.24 (m, 2H), 7,19 (d, 1H),? 7.04 baby mortality (d, 1H), 6.89 in (d, 1H), 6,77 (d, 1H), 6,36 (s, 1H), 4,06 (s, 2H), 3,86 (DD, 2H), 3.27 to (m, 6H), 3,11 (m, 4H), 2,96 (m, 2H), 2,34 (m, 4H), 1,90 (m, 1H), 1,61 (DD, 2H), 1,24 (m, 2H), 1,19 (t, 3H).

EXAMPLE 82

2-(4-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 82A

methyl 2-(4-acetamidophenol)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing 4-acetamidophenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 82B

2-(4-acetamidophenol)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 82A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 82C/p>

2-(4-(acetylamino)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 82B connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,58 (s, 1H), to 9.91 (s, 1H), to 8.62 (t, 1H), 8,54 (d, 1H), 7,76 (DD, 1H), 7,68 (m, 1H), 7,51 (m, 7H), 7,34 (m, 3H), 7,16 (d, 1H), 6,85 (d, 2H), 6,72 (DD, 1H), 6.30-in (m, 1H), 4,35 (s, 1H), 3,85 (DD, 2H), 3,68 (m, 1H), 3.27 to (m, 9H), to 3.02 (m, 2H), and 2.83 (m, 1H), 2,04 (s, 3H), 1,89 (m, 1H), 1,62 (DD, 2H), 1,24 (m, 2H).

EXAMPLE 83

tert-butyl 4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenylcarbamate

This EXAMPLE was obtained by replacing the compound of EXAMPLE 18B to the compound of EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,37 (s, 1H), to 9.32 (s, 1H), 8,61 (t, 1H), to 8.57 (d, 1H), 7,81 (DD, 1H), 7,44 (m, 8H), 7,34 (m, 2H), 7,22 (m, 2H), to 6.88 (d, 2H), 6,69 (DD, 1H), of 6.20 (d, 1H), 3,85 (m, 2H), or 3.28 (m, 6H), to 3.09 (m, 4H), of 2.33 (m, 4H), 1,90 (m, 1H), and 1.63 (m, 2H), 1,47 (m, 9H), 1.26 in (m, 2H).

EXAMPLE 84

2-(1,1'-biphenyl-2-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 84A

methyl 2-(biphenyl-2-yloxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing 2-phenylphenol connection P IS the IMER 1D in EXAMPLE 1E.

EXAMPLE 84B

2-(biphenyl-2-yloxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 84A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 84C

2,2,2-triptorelin 2-(1,1'-biphenyl-2-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 84B connection EXAMPLE 50F and the compound of EXAMPLE 1G connection EXAMPLE 3I in EXAMPLE 50G.1H NMR (300 MHz, dimethylsulfoxide-d6) to 11.56 δ (PTS. Shir. s, 1H), 9,50 (PTS. Shir. s, 1H), to 8.62 (t, 1H), 8,45 (d, 1H), 7,76 (DD, 1H), 7,70 (user. s, 1H), 7,50 (m, 7H), 7,37 (d, 2H), 7,27 (m, 5H), 7,12 (m, 2H),? 7.04 baby mortality (m, 1H), 6,70 (DD, 1H), only 6.64 (d, 1H), 6,27 (s, 1H), 4,35 (PTS. Shir. s, 1H), 3,83 (DD, 2H), 3,70 (PTS. Shir. s, 1H), 3,40 (m, 4H), 3,25, 3,20 (both m, total 4H), 3.00 and, 2,80 (both Shire. with only 4H) and 1.83 (m, 1H), 1,59 (m, 2H), 1,24 (m, 2H).

EXAMPLE 85

tert-butyl 3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenylcarbamate

Specified in the title compound was obtained as described in EXAMPLE 19C.1H NMR (300 MHz, dimethylsulfoxide-d6) δ of 11.45 (s, 1H), 9,34 (s, 1H), to 8.62 (t, 1H), charged 8.52 (d, 1H), of 7.75 (DD, 1H), 7,46 (m, 6H), was 7.36 (m, 2H), 7.23 percent (m, 1H), 7,11 (m, 4H), 6,74 (DD, 1H), 6.42 per (m, 1H), 6,36 (d, 1H), 3,86 (DD, 2H), 3,30 (m, 6H), 3.15 in (m, 4H), to 2.35 (m, 4H), 1,90 (square d, 1H), 163 (DD, 2H), 1,45 (s, 9H), 1.27mm (m, 2H).

EXAMPLE 86

2-(1,1'-biphenyl-3-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 86A

methyl 2-(biphenyl-3-yloxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing 3-phenylphenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 86B

2-(biphenyl-3-yloxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 86A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 86C

2,2,2-triptorelin 2-(1,1'-biphenyl-3-yloxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 86B connection EXAMPLE 50F and the compound of EXAMPLE 1G connection EXAMPLE 3I in EXAMPLE 50G.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,82 (PTS. Shir. s, 1H), 9,60 (PTS. Shir. s, 1H), 8,72 (t, 1H), 8,42 (d, 1H), 7,70 (user. s, 1H), 7,69 (DD, 1H), 7,55-7,20 (m, 15H), of 7.00 (d, 1H), of 6.96 (s, 1H), 6,80 (m, 2H), 6,53 (d, 1H), 4,35 (PTS. Shir. s, 1H), 3,83 (DD, 2H), 3,70 (PTS. Shir. s, 1H), 3,40 (m, 4H), 3,25, 3,20 (both m, total 4H), 3.00 and, 2,80 (both Shire. with only 4H), of 1.81 (m, 1H), 1,58 (m, 2H), 1,22 (m, 2H).

EXAMPLE 87

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)ethyl)Fenox the)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 87A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)ethyl)phenoxy)benzoate

Specified in the title compound was obtained by replacing 4-(2-(dimethylamino)ethyl)phenol connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 87B

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)ethyl)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 87A connection EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 87C

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 87B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,67 (s, 1H), 9,51 (s, 1H), 8,66 (t, 1H), charged 8.52 (d, 1H), to 7.84 (DD, 1H), of 7.70 (s, 1H), 7,51 (DD, 5H), was 7.36 (m, 3H), 7,22 (m, 3H), at 6.84 (d, 2H), 6,76 (m, 1H), 6.42 per (s, 1H), 3,85 (m, 2H), 3,52 (s, 10H), the 3.35 (m, 2H), 3,26 (DD, 4H), 2,90 (m, 2H), and 2.83 (d, 6H), 1.91 a (s, 1H), 1,61 (d, 2H), 1.27mm (dt, 2H).

EXAMPLE 88

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 88A

methyl 2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoate

Specified in the title compound was obtained by replacing 4-(benzyloxy)phenol connected to the e of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 88B

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 88A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 88C

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 88B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,50 (m, 1H), 8,63 (t, 1H), 8,55 (d, 1H), 7,82 (DD, 1H), 7,66 (m, 1H), 7,41 (m, 13H), 7,20 (m, 1H), of 6.96 (d, 2H), to 6.88 (d, 2H), 6,70 (DD, 1H), and 6.25 (m, 1H), 5,04 (m, 2H), 3.27 to (m, 10H), 2,90 (m, 6H), of 1.88 (m, 1H), 1.57 in (m, 2H), 1,23 (m, 2H).

EXAMPLE 89

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-morpholine-4-elfenix)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 32B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,58 (s, 1H), 8,63 (t, 1H), 8,49 (d, 1H), 7,78 (DD, 1H), 7,69 (m, 1H), 7,52 (m, 5H), 7,38 (d, 2H), 7,33 (m, 1H), 7,15 (d, 1H), 7,07 (m, 1H), 6,74 (DD, 1H), return of 6.58 (DD, 1H), 6,40 (m, 2H), from 6.22 (DD, 1H), the 4.29 (m, 2H), 3,86 (m, 2H), 3,70 (m, 6H), 3,30 (m, 6H), to 3.00 (m, 6H), and 2.83 (m, 2H), 1.91 a (m, 1H), and 1.63 (d, 2H), 1.28 (in m, 2H).

EXAMPLE 90

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((2-methyl-1,3-benzothiazol-5-yl)oxy)-N-((3-neither the ro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 24B for connection of EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,83 (s, 1H), 9,48 (user. s, 1H), 8,64 (t, 1H), 8,45 (d, 1H), 7,88 (d, 1H), 7,76 (DD, 1H), 7,50 (m, 5H), 7,37 (m, 2H), 7,30 (m, 1H), 7,18 (m, 1H),? 7.04 baby mortality (d, 1H), 6,97 (DD, 1H), 6,78 (DD, 1H), 6.48 in (user. s, 1H), 3,84 (DD, 2H), 3,37 (m, 6H), 3,23 (m, 4H), 2,89 (m, 2H), 2,75 (s, 3H), of 2.36 (m, 3H), of 1.62 (d, 2H), 1,24 (m, 2H).

EXAMPLE 91

tert-butyl 4-(3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenyl)piperazine-1-carboxylate

EXAMPLE 91A

tert-butyl 4-(3-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(methoxycarbonyl)phenoxy)phenyl)piperazine-1-carboxylate

Specified in the title compound was obtained by replacing tert-butyl ester 1-(3-hydroxyphenyl)piperazine-4-carboxylic acid the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 91B

2-(3-(4-(tert-butoxycarbonyl)piperazine-1-yl)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 91A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 91C

tert-butyl 4-(3-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((3-the nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)-phenoxy)phenyl)piperazine-1-carboxylate

Specified in is the head of the compound was obtained by replacing the compound of EXAMPLE 91B connection EXAMPLE 1F in EXAMPLE 1H. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,65 (s, 1H), 8,65 (t, 1H), of 8.47 (d, 1H), 7,76 (DD, 1H), 7,72 (m, 1H), 7,50 (m, 5H), 7,37 (d, 2H), 7,33 (m, 1H), 7,15 (d, 1H), 7,05 (m, 1H), 6.75 in (DD, 1H), to 6.57 (DD, 1H), 6,41 (m, 2H), 6,21 (DD, 1H), or 4.31 (m, 2H), 3,86 (DD, 2H), 3,41 (m, 6H), to 3.34 (t, 2H), 3.27 to (m, 4H), to 3.00 (m, 6H), 2,85 (m, 2H), 1.91 a (m, 1H), and 1.63 (d, 2H), 1,40 (m, 9H), 1.28 (in m, 2H).

EXAMPLE 92

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 71A to the compound of EXAMPLE 1F and the compound of EXAMPLE 11A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,72 (s, 1H), 9,52 (s, 1H), 8,69 (t, 1H), and 8.50 (d, 1H), 7,81 (DD, 1H), 7,65 (s, 1H), 7,50 (m, 5H), 7,39 (m, 6H), 7,32 (m, 2H), 7,13 (m, 2H), 6,77 (DD, 1H), only 6.64 (DD, 1H), 6.42 per (s, 2H), 6,38 (m, 1H), at 4.99 (s, 2H), 3,50 (m, 10H), 3,11 (m, 4H), 2,77 (s, 6H), of 1.95 (m, 2H).

EXAMPLE 93

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 71A to the compound of EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,74 (m, 1H), 9,78 (s, 1H), 8,71 (m, 1H), and 8.50 (d, 1H), 7,82 (DD, 1H), to 7.67 (s, 1H), 7,50 (m, 5H), 7,39 (m, 6H), 7,32 (m, 2H), 7,13 (m, 1H), 6,77 (DD, 1H), only 6.64 (DD, 1H), 6,39 (m, 3H), at 4.99 (s, 2H), of 3.96 (m, 2H), 3,60 (s, 2H), 3,51 (m, 6H), 3,17 (m, 10H) to 2.67 (m, 2H), 194 (m, 2H).

EXAMPLE 94

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-morpholine-4-ylethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 94A

4-(2-(4-(benzyloxy)phenoxy)ethyl)morpholine

Specified in the title compound was obtained by replacing 4-(2-chloroethyl)morpholine 2-chloro-N,N-dimethylethanamine and 4-(benzyloxy)phenol 3-(benzyloxy)phenol in EXAMPLE 39A.

EXAMPLE 94B

4-(2-morpholinoethoxy)phenol

Specified in the title compound was obtained by replacing the compound of EXAMPLE 94A on the compound of EXAMPLE 39A in EXAMPLE 39B.

EXAMPLE 94C

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-morpholinoethoxy)phenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 94B on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 94D

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-morpholinoethoxy)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 94C on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 94E

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-morpholine-4-ylethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 94D connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, DIMET sulfoxide-d 6) δ 11,46 (m, 1H), 9,98 (m, 1H), 8,64 (d, 1H), 8,55 (d, 1H), 7,87 (d, 1H), 7,49 (m, 5H), 7,39 (d, 2H), 7,31 (s, 1H), 7,25 (d, 1H), of 6.96 (m, 5H), of 6.71 (d, 1H), 6,29 (s, 1H), 4,30 (s, 2H), 3,98 (s, 2H), of 3.85 (d, 2H), and 3.72 (s, 2H), 3,42 (s, 16H), with 3.27 (m, 2H), 1.91 a (s, 1H), 1,62 (d, 2H), 1.28 (in m, 2H).

EXAMPLE 95

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 58B connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11,50 (s, 1H), 10,07 (s, 1H), at 8.60 (t, 1H), of 8.47 (d, 1H), 7,74 (DD, 1H), 7,46 (m, 6H), was 7.36 (m, 2H), 7,24 (m, 1H), 7,14 (d, 1H), 6,92 (t, 1H), 6,74 (DD, 1H), 6,51 (d, 1H), 6.35mm (d, 1H), 6,13 (d, 1H), 3,86 (DD, 2H), 3,36 (m, 4H), of 3.25 (m, 2H), and 3.16 (m, 4H), and 2.83 (t, 2H), 2,41 (DD, 2H), 2,35 (m, 4H), 1,90 (m, 1H), 1,64 (DD, 2H), 1.28 (in m, 2H).

EXAMPLE 96

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 88B connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,53 (s, 1H), 9,74 (s, 1H), 8,69 (m, 1H), 8,59 (d, 1H), of 7.90 (DD, 1H), to 7.67 (m, 1H), 7,41 (m, 13H), 7,21 (d, 1H), 6,99 (m, 2H), 6,91 (m, 2H), 6,70 (DD, 1H), 6,23 (s, 1H), 5,07 (s, 2H), 4,28 (m, 2H), of 3.95 (s, 2H), 3,51 (m, 6H), and 3.16 (m, 10H), 2,73 (d, 2H), up to 1.98 (m, 2H).

EXAMPLE 97

tert-butyl 4-(4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)IU who yl)piperazine-1-yl)-2-((((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-1-carboxylate

EXAMPLE 97A

tert-butyl 4-(4-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(methoxycarbonyl)phenoxy)phenyl)piperazine-1-carboxylate

Specified in the title compound was obtained by replacing tert-butyl ester 1-(4-hydroxyphenyl)piperazine-4-carboxylic acid the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 97B

2-(4-(4-(tert-butoxycarbonyl)piperazine-1-yl)phenoxy)-4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 97A on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 97C

tert-butyl 4-(4-(5-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-1-carboxylate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 97B connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,44 (m, 1H), 9,67 (s, 1H), to 8.70 (t, 1H), 8,59 (d, 1H), to $ 7.91 (DD, 1H), 7,69 (s, 1H), 7,49 (m, 7H), 7,30 (m, 1H), 7,21 (d, 1H), 6,91 (m, 4H), 6,69 (DD, 1H), 6,24 (s, 1H), 3,95 (m, 2H), to 3.67 (m, 4H), to 3.52 (m, 10H), 3,17 (s, 4H), 3.04 from (m, 10H) of 1.97 (d, 2H), USD 1.43 (s, 9H).

EXAMPLE 98

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-pyridin-4-elfenix)benzamid

EXAMPLE 98A

4-(3-(benzyloxy)phenyl)pyridine

Ukazannoi the title compound was obtained, substituting 1-(benzyloxy)-3-Brabanthal connection EXAMPLE 33C and pyridine-4-Voronovo acid 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole in EXAMPLE 33D.

EXAMPLE 98B

3-(pyridin-4-yl)phenol

Specified in the title compound was obtained by replacing the compound of EXAMPLE 98A in the connection EXAMPLE in EXAMPLE 33A 33B.

EXAMPLE 98C

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(pyridin-4-yl)phenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 98B on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 98D

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(pyridin-4-yl)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 98C on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 98E

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-pyridin-4-elfenix)benzamid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 98D connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11.87 per (m, 1H), 8,68 (d, 2H), 8,58 (m, 1H), 8,42 (d, 1H), 7,73 (m, 4H), 7,52 (m, 5H), was 7.36 (m, 6H), 7,14 (s, 1H), 7,03 (d, 1H), 6,91 (m, 1H), 6,80 (DD, 1H), 6,55 (d, 1H), 4,22 (m, 2H), 3,89 (m, 7H), to 3.41 (m, 4H), 3.15 in (m, 4H), 2.91 in (m, 4H), of 1.94 (m, 2H).

EXAMPLE 99

4-(4-((4'-chloro-1,1'-biphenyl-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-4-elfenix)benzamid

EXAMPLE 99A

4-(4-(benzyloxy)phenyl)pyridine

Specified in the title compound was obtained by replacing 1-(benzyloxy)-4-Brabanthal connection EXAMPLE 33C and pyridine-4-Voronovo acid 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole in EXAMPLE 33D.

EXAMPLE 99B

4-(pyridin-4-yl)phenol

Specified in the title compound was obtained by replacing the compound of EXAMPLE 99A connection EXAMPLE in EXAMPLE 33A 33B.

EXAMPLE 99C

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(pyridin-4-yl)phenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 99B connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 99D

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(pyridin-4-yl)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 99C on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 99E

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-4-elfenix)benzamid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 99D connection EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 8,80 (d, 2H), 8,55 (m, 1H), 8,49 (d, 1H), to 7.93 (m, 5H), 7,74 (m, 1H), 7,53 (m, 5H), was 7.36 (m, 3H), 7,13 (m, 2H), 6,93 (d, 1H), 6,83 (DD, 1H), 6,62 (d, 1H), 4,60, 4H), the 4.29 (m, 2H), to 3.67 (s, 4H), 3,42 (m, 4H), of 3.13 (m, 4H), of 2.92 (m, 4H), 1,90 (m, 2H).

EXAMPLE 100

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridine-3-elfenix)benzamid

EXAMPLE 100A

3-(4-(benzyloxy)phenyl)pyridine

Specified in the title compound was obtained by replacing 1-(benzyloxy)-4-Brabanthal connection EXAMPLE 33C and pyridine-3-Voronovo acid 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole in EXAMPLE 33D.

EXAMPLE 100B

4-(pyridin-4-yl)phenol

Specified in the title compound was obtained by replacing the compound of EXAMPLE 100A connection EXAMPLE in EXAMPLE 33A 33B.

EXAMPLE 100C

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(pyridin-4-yl)phenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 100B connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 100D

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(pyridin-4-yl)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 100C on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 100E

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridine-3-elfenix)benzamid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 100D connection PR IS a MEASURE 1F and compounds of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,84 (s, 1H), 8,95 (d, 1H), 8,66 (d, 1H), to 8.57 (m, 1H), charged 8.52 (d, 1H), 8,24 (d, 1H), 7,83 (DD, 1H), 7,72 (m, 5H), 7,53 (m, 5H), 7,35 (m, 3H), 7,11 (m, 1H), 6,93 (d, 2H), for 6.81 (DD, 1H), to 6.57 (d, 1H), or 4.31 (s, 2H), 3,80 (m, 8H), 3,42 (m, 4H), 3,14 (m, 8H), was 1.94 (m, 2H).

EXAMPLE 101

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 101A

2-(4-(benzyloxy)phenoxy)-N,N-dimethylacetamide

Specified in the title compound was obtained by replacing 2-chloro-N,N-dimethyl 2-chloro-N,N-dimethylethanamine and 4-(benzyloxy)phenol 3-(benzyloxy)phenol in EXAMPLE 39A.

EXAMPLE 101B

2-(4-hydroxyphenoxy)-N,N-dimethylacetamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 101A on the compound of EXAMPLE 39A in EXAMPLE 39B.

EXAMPLE 101C

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)-2-oksidoksi)phenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 101B on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 101D

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(4-(2-(dimethylamino)-2-oksidoksi)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 101C on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 101E

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)PIP the Razin-1-yl)-2-(4-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 101D connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 8,68 (t, 1H), to 8.57 (d, 1H), 7,87 (DD, 1H), 7,72 (s, 1H), 7,53 (DD, 4H), 7,34 (m, 4H), 7,16 (d, 1H), 6,84 (m, 4H), of 6.71 (DD, 1H), 6,34 (d, 1H), 4,60 (s, 2H), 3,84 (d, 2H), 3,51 (s, 10H) to 3.36 (m, 2H), 3,26 (m, 2H), 2,81 (d, 6H), 1.91 a (s, 1H), 1,62 (d, 2H), 1.28 (in m, 2H).

EXAMPLE 102

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((1-methyl-1H-benzimidazole-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

EXAMPLE 102A

methyl 4-bromo-2-(1-methyl-1H-benzo[d]imidazol-5-yloxy)benzoate

1-Methyl-1H-benzo[d]imidazol-5-ol (296 mg), methyl 4-bromo-2-perbenzoate (311 mg) and potassium carbonate (553 mg) were combined in dimethyl sulfoxide and heated at 90°C during the night. The reaction mixture was diluted with ethyl acetate and thoroughly washed with water and saturated saline solution, dried over MgSO4, filtered and concentrated.

EXAMPLE 102B

methyl 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(1-methyl-1H-benzo[d]imidazol-5-yloxy)benzoate

The compound of EXAMPLE 102A (480 mg) and the compound of EXAMPLE 1B (457 mg) was treated with dimethoxyethane (7.5 ml) in a vessel for microwave exposure. Added Tris(dibenzylideneacetone)dipalladium(0) (37 mg), 2-(di-tert-butylphosphino)biphenyl (48 mg) and rejonowy potassium phosphate (423 mg). The vessel Hermeticism is closed and heated in a microwave reactor CEM Discovery for 30 minutes at a temperature of 150°C. The crude reaction mixture was filtered through celite and concentrated. The product was dissolved in a mixture of 1:1 dimethylsulfoxide:methanol and purified by HPLC.

EXAMPLE 102

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)-2-(1-methyl-1H-benzo[d]imidazol-5-yloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 102B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 102D

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((1-methyl-1H-benzimidazole-5-yl)oxy)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 102 to the compound of EXAMPLE 1F and the compound of EXAMPLE 4A for connection of EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, pyridine-d5) δ 9,34 (d, 1H), 8,99 (t, 1H), 8,91 (s, 1H), 8,55 (s, 1H), 8,48 (DD, 1H), 7,94 (t, 1H), 7,50 (m, 4H), 7,42 (m, 3H), 7,35 (m, 3H), 7,05 (s, 1H), 7,02 (d, 1H), 6,70 (m, 2H), with 3.79 (t, 4H), 3,39 (s, 3H), the 3.35 (m, 2H), 3.15 in (m, 4H), of 2.36 (m, 12H), of 1.74 (m, 2H).

EXAMPLE 103

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylcarbamoyl)phenoxy)-N-(4-(3-morpholinopropan)-3-nitrophenylarsonic)benzamid

EXAMPLE 103A

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylcarbamoyl)phenoxy)benzoate

Specified in the title compound was obtained by replacing 3-hydroxy-N-methylbenzamide connection EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 103B

4-(4-(4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylcarbamoyl)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 103A to the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 103C

bis(2,2,2-triptorelin) 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(methylcarbamoyl)phenoxy)-N-(4-(3-morpholinopropan)-3-nitrophenylarsonic)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 103B connection EXAMPLE 50F and the compound of EXAMPLE 4A connection EXAMPLE 3I in EXAMPLE 50G.1H NMR (300 MHz, dimethylsulfoxide-d6) to 11.79 δ (PTS. Shir. s, 1H), 9,38 (PTS. Shir. s, 1H), 8,65 (t, 1H), 8,48 (d, 1H), of 8.37 (kV, 1H), 7,78 (DD, 1H), 7,70 (user. s, 1H), 7,50 (m, 6H), 7,35 (m, 4H), 7,26 (s, 1H), 7,11 (d, 1H), 6,98 (DD, 1H), 6,79 (DD, 1H), gold 6.43 (s, 1H), 4,35 (PTS. Shir. s, 1H), 3,99 (Shir. m, 2H), 3,70 (PTS. Shir. s, 1H), 3,60, 3,50, 3,40 (all Shire. m, total 10H), 3,20, 3,10, 2,80 (all Shire. with only 8H), 2,79, 2,77 (both s, total 3H), of 1.99 (m, 2H).

EXAMPLE 104

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-N-(4-(3-(dimethylamino)propylamino)-3-nitrophenylarsonic)-2-(3-(methylcarbamoyl)phenoxy)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 103B connection EXAMPLE 50F and the compound of EXAMPLE 11A for connection EXAMPLE 3I in EXAMPLE 50G.1H NMR (500 MHz, dimethylsulfoxide-d6) to 11.79 δ (PTS. Shir. s, 1H), 9,38 (PTS. Shir. s, 1H), 8,65 (t, 1H), 8,48 (d, 1H), of 8.37 (kV, 1H), 7,78 (DD, 1H), 7,70 (user. s, 1H), 7,50 (m, 6H), 7,39 (m, 2H), 7,31 (m, 2H), 7,26 (s, 1H), 7,11 (d, 1H), 6,98 (DD, 1H), 6,79 (DD, 1H), gold 6.43 (s, 1H), 4,35 (PTS. Shir. s, 1H), 380 (PTS. Shir. s, 1H), 3,50, (Shir. m, 8H), 3,10, was 3.05 (m, Shir. s, 4H), 2,81, 2,80 (both s, 6H), 2,78, 2,77 (both s, 3H), a 1.96 (m, 2H).

EXAMPLE 105

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 105A

2-(3-(benzyloxy)phenoxy)-N,N-dimethylacetamide

Specified in the title compound was obtained by replacing 2-chloro-N,N-dimethyl 2-chloro-N,N-dimethylethanamine in EXAMPLE 39A.

EXAMPLE 105B

2-(3-hydroxyphenoxy)-N,N-dimethylacetamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 105A to the compound of EXAMPLE 39A in EXAMPLE 39B.

EXAMPLE 105C

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)-2-oksidoksi)phenoxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 105B on the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 105D

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)-2-oksidoksi)phenoxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 105 ° C connection EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 105E

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(2-(dimethylamino)-2-oksidoksi)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the header of connection produces and by replacing the compound of EXAMPLE 105D connection EXAMPLE 1F in EXAMPLE 1H. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ 8,66 (d, 1H), 8,54 (d, 1H), to 7.84 (DD, 1H), 7,72 (s, 1H), 7,51 (m, 5H), 7,35 (m, 3H), 7,28 (m, 1H), 7,16 (DD, 2H), 6.75 in (DD, 1H), 6,46 (m, 3H), 4,60 (s, 2H), 3,83 (d, 2H), 3,48 (s, 10H) to 3.34 (m, 2H), 3,24 (m, 2H), 2,78 (s, 6H), 1,89 (s, 1H), 1,60 (d, 2H), 1.26 in (m, 2H).

EXAMPLE 106

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-(dimethylamino)propyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 106A

(Z)-tert-butyl 5-(benzyloxy)-3-(3-(dimethylamino)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate

Specified in the title compound was obtained by replacing N,N-dimethylacrylamide 1-morpholinopropan-2-EN-1-he in EXAMPLE 70A.

EXAMPLE 106B

tert-butyl 3-(3-(dimethylamino)-3-oxopropyl)-5-hydroxy-1H-indole-1-carboxylate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 106A on the compound of EXAMPLE 39A in EXAMPLE 39B.

EXAMPLE 106C

tert-butyl 5-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(methoxycarbonyl)phenoxy)-3-(3-(dimethylamino)-3-oxopropyl)-1H-indole-1-carboxylate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 106B to the compound of EXAMPLE 1D in EXAMPLE 1E.

EXAMPLE 106D

methyl 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(3-(dimethylamino)propyl)-1H-indol-5-yloxy)benzoate

Specified in the title compound was obtained by replacing the compound of EXAMPLE 106C connection EXAMPLE 70C Primera 74A.

EXAMPLE 106E

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-yl)-2-(3-(3-(dimethylamino)propyl)-1H-indol-5-yloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 106D on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 106F

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((3-(3-(dimethylamino)propyl)-1H-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 106E connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 10,97 (d, 1H), 9,34 (s, 1H), 8,61 (m, 2H), 7,86 (DD, 1H), 7,54 and 7.36 (m, 8H), 7,22 (m, 4H), 6,86 (m, 1H), to 6.67 (DD, 1H), 6,16 (d, 1H), 3,83 (m, 2H), 3,34-3,24 (m, 8H), of 3.07 (m, 6H), was 2.76 (s, 6H), to 2.67 (m, 2H), 1,95 (m, 3H), of 1.65 (m, 2H), 1,29 (m, 4H), to 0.88 (m, 2H).

EXAMPLE 107

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-(hydroxymethyl)phenoxy)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 9A for connection EXAMPLE 50F and the compound of EXAMPLE 11A for connection EXAMPLE 3I in EXAMPLE 50G.1H NMR (400 MHz, dimethylsulfoxide-d6) δ 11,60 (PTS. Shir. s, 1H), 9,40 (PTS. Shir. s, 1H), 8,76 (t, 1H), 8,51 (d, 1H), 7,80 (DD, 1H), 7,65 (user. s, 1H), 7,50 (m, 5H), 7,40 (m, 2H), 7,30 (user. s, 1H), 7,20 (DD, 1H), 7,16 (d, 1H), of 6.96 (d, 1H), PC 6.82 (s, 1H), 6,65 (d, 1H), 6,60 (d, 1H), 6,40 (s, 1H), to 4.41 (s, 2H), 3,55 (m, 4H), 3,40 (m, 6H), of 3.13 (m, 4H), 2,80, ,79, (both, total 6H), to 1.98 (m, 2H).

EXAMPLE 108

4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazine-1-yl)-2-((4-methoxybenzyl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

EXAMPLE 108A

methyl ester of 4-fluoro-2-(4-methoxybenzyloxy)benzoic acid

Methyl 4-fluoro-2-hydroxybenzoate (1661 mg) was added to N,N-dimethylformamide (50 ml). Was added sodium hydride (60% in mineral oil, 430 mg), the solution was stirred for 15 minutes at room temperature was added 1-(methyl bromide)-4-methoxybenzo (2061 mg). The solution was stirred at room temperature for three days, was added to a 0.01 M aqueous solution of HCl and was extracted with ethyl acetate. The organic phase was washed with water twice, washed with saturated saline and dried over anhydrous sodium sulfate. After filtration the solvent was removed in vacuum.

EXAMPLE 108B

Methyl ester of 4-[4-(4'-chlorobiphenyl-2-ylmethyl)piperazine-1-yl]-2-(4-methoxybenzyloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 108A on methyl 2-bromo-4-perbenzoate in EXAMPLE 1C.

EXAMPLE 108C

4-[4-(4'-chlorobiphenyl-2-ylmethyl)piperazine-1-yl]-2-(4-methoxybenzyloxy)benzoic acid

Specified in the title compound was obtained by replacing the compound of EXAMPLE 108B on the compound of EXAMPLE 1E in EXAMPLE 1F.

EXAMPLE 108D

4-(4-((4'-chloro-1,1'-bifen the l-2-yl)methyl)piperazine-1-yl)-2-((4-methoxybenzyl)oxy)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide

Specified in the title compound was obtained by replacing the compound of EXAMPLE 108C connection EXAMPLE 1F in EXAMPLE 1H.1H NMR (300 MHz, dimethylsulfoxide-d6) δ 10,79 (user. s, 1H), 8,65 (t, 1H), 8,58 (d, 1H), 7,82 (DD, 1H), 7,53-7,41 (m, 7H), 7,38 (m, 2H), 7,27-7,19 (m, 2H), 6,98 (d, 2H), 6,69 (user. s, 1H), 6,55 (DD, 1H), 5,16 (s, 2H), 3,84 (DD, 2H), of 3.78 (s, 3H), 3,40 (s, 2H), 3,37-of 3.32 (m, 8H), of 2.38 (m, 4H), 1,90 (m, 1H), 1,62 (DD, 2H), 1.26 in (m, 2H).

EXAMPLE 109

N-[(4-{[(4-aminotetraline-2H-Piran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl]methyl}piperazine-1-yl)benzamid

EXAMPLE 109A

4-((4-aminotetraline-2H-Piran-4-yl)methylamino)-3-nitrobenzenesulfonamide

A mixture of 4-chloro-3-nitrobenzenesulfonamide, 4-(aminomethyl)tetrahydro-2H-Piran-4-amine, hydrochloric acid and triethylamine in dioxane (10 ml) was heated at a temperature of 110ºC overnight. After cooling, the mixture was diluted with water (10 ml) and filtered.

EXAMPLE 109B

N-(4-((4-aminotetraline-2H-Piran-4-yl)methylamino)-3-nitrophenylarsonic)-2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine-1-yl)benzamid

This example was obtained by replacing the compound of EXAMPLE 6B for connection of EXAMPLE 1F and compounds of EXAMPLE 109A connection EXAMPLE 1G in EXAMPLE 1H.1H NMR (500 MHz, DMSO-d6) δ to 8.41 (s, 1H), 8,35 (d, J=1,83 Hz, 1H), of 7.70 (DD, J=9,0, to 1.98 Hz, 1H), to 7.64 (d, J=cent to 8.85 Hz, 1H), was 7.36 (d, J=8.54 in Hz, 2H), 7,11-to 7.18 (m, 2H), 7,07 (q, j =8,24 Hz, 2H), 6,91 (DD, J=7,93, 1,22 Hz, 1H), 6,77 (DD, J=cent to 8.85, and 2.14 Hz, 1H), 6,65 (DD, J=8,09, to 1.98 Hz, 1H), 6,61-6,62 (m, 1H), 6,38 (d, J=2,14 Hz, 1H), 3,67-3,71 (m, 6H), 3,11 (m, 3H), 2,77 (s, 2H), 2,18-of 2.24 (m, 6H), 1,97 of 1.99 (m, 2H), 1,76-to 1.79 (m, 2H), 1,65-to 1.67 (m, 2H), 1,39-of 1.42 (m, 2H), were 0.94 (s, 6H).

EXAMPLE 110

4-{4-[1-(4'-chloro-1,1'-biphenyl-2-yl)ethyl]piperazine-1-yl}-2-(2-chlorophenoxy)-N-({3-nitro-4-[(tetrahydro-2H-Piran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide

EXAMPLE 110A

1-(4'-chlorobiphenyl-2-yl)alanon

A mixture of 1-(2-bromophenyl)ethanone (3.1 g), 4-Chlorfenvinphos acid (2,92 g) dichloride bis(triphenylphosphine)palladium(II) (1,202 g) and Na2CO3(3,30 g) in a mixture of 7:2:3 dimethoxyethane/ethanol/water (50 ml) was heated at a temperature of 100ºC for 3 hours and concentrated. Concentrate suspended in dichloromethane (30 ml) and filtered. The filtrate was placed on a column of silica gel and subjected to flash chromatography using a mixture 0-50% dichloromethane/hexane.

EXAMPLE 110B

tert-butyl 4-(1-(4'-chlorobiphenyl-2-yl)ethyl)piperazine-1-carboxylate

A mixture of compound of EXAMPLE 110A (1.9 g) in dichloromethane (3 ml) was treated with 1M solution of titanium chloride(IV) in dichloromethane (9,06 ml), cooled to a temperature of 0ºC, was treated with tert-butyl piperazine-1-carboxylate (of 3.07 g), was stirred at ambient temperature for 3 hours, and treated with NaCNBH3(0.828 g) in methanol(5 ml) was stirred at room temperature overnight, neutralized with aqueous NaOH solution is concentrated. The concentrate was treated with ethyl acetate and filtered. The organic filtrate was washed with water and concentrated. The concentrate was dissolved in methanol/triperoxonane acid/dimethyl sulfoxide, was placed on a column of C18 reversed-phase and suirable using a mixture of 0-80% acetonitrile in 0.1% aqueous solution triperoxonane acid for 70 minutes.

EXAMPLE 110C

1-(1-(4'-chlorobiphenyl-2-yl)ethyl)piperazine

To a solution of compound of EXAMPLE 110B (650 mg) in dichloromethane (6 ml) at a temperature of 0ºC was added triperoxonane acid (6 ml). The mixture was stirred at a temperature of 0ºC for 50 minutes and then concentrated. The concentrate was dissolved in dichloromethane, washed with aqueous solution of NaHCO3and dried over Na2SO4, filtered and concentrated.

EXAMPLE 110D

ethyl 4-(4-(1-(4'-chlorobiphenyl-2-yl)ethyl)piperazine-1-yl)-2-(2-chlorophenoxy)benzoate

Connection EXAMPLE 110C (252 mg) and ethyl 2-(2-chlorophenoxy)-4-perbenzoate (272 mg) in dimethyl sulfoxide (15 ml) was treated with potassium phosphate (219 mg), was stirred at a temperature of 135ºC overnight, cooled, diluted with dichloromethane, washed with water and concentrated. The concentrate was dissolved in dichloromethane, was placed on a column of silica gel and was suirable using a 5% solution of 10M methanolic ammonia in dichloromethane.

EXAMPLE 110E

4-(4-(1-(4'-chlorobiphenyl-2-yl)ethyl)piperazine-1-yl-2-(2-chlorophenoxy)benzoic acid

A mixture of compound of EXAMPLE 110D (300 mg) in tetrahydrofuran (10 ml) and methanol (10 ml) at a temperature of 50ºC was treated with 10% aqueous NaOH solution (2085 μl), stirred overnight, neutralized with HCl and concentrated. The concentrate was treated with water and was extracted with dichloromethane. The organic layer was dried over Na2SO4, filtered and concentrat