Method of treating arthritis

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to arthrology and therapy, and may be used for treating arthritis in a mammal A method consists in the fact that N-(4-(4-((4'-chlor(1,1'-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulphanyl)methyl)propyl)amino)-3-nitrobenzolsulphonamide is introduced into patient in need thereof.

EFFECT: invention enables reducing doses of the preparations used to the integrated therapy of arthritis ensured by lymphocytic immune suppression.

3 dwg, 2 ex

 

The technical field to which the invention relates

This invention relates to methods for treating arthritis.

Background of invention

Arthritis is a major cause of disability in people over the age of 55 years. Arthritis can be caused by trauma to the joints, autoimmune disease, or simply be the result of aging. Therefore, in therapy, there is a need in the treatment of arthritis.

Brief description of drawings

Figure 1 presents the tumor paws of mice with the introduction of 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 (EXAMPLE A).

Figure 2 presents the attenuation syndrome, macrophage activation (MAS) in mice by introduction of 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 (EXAMPLE A).

Figure 3 presents the increase in the volume of bone in mice with the introduction of 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 (EXAMPLE A).

Summary of the invention

One embodiment of the present invention relates to a method of treating arthritis in a mammalian is found, including the introduction of he compounds having the formula (I):

or its therapeutically acceptable salts, prodrugs or salts, its prodrugs, where

And1means N or(A2);

one or two or three or each of A2In1D1and E1independently selected from the group consisting of 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, NHC(O)OR1, NR1C(O)other1, NR1C(O)N(R1)2, SO2Other1, SO2N(R1)2, NHSO2R1, NHSO2Other1or N(CH3)SO2N(CH3R1and the others are independently selected from the group consisting of H, F, Cl, Br, I, CN, CF3C(O)OH, C(O)NH2or C(O)OR1A; and

Y1denotes H, CN, NO2C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R17, OR17C(O)R17C(O)OR17, SR17, NH2, Other17N(R17)2, NHC(O)R17C(O)NH2C(O)other17C(O)N(R17)2NHS(O)R17or NHSO2R17; or

In1and Y1together with the atoms to which they are attached represent an imidazole or triazole; and

one or two or each And2D1and E1independently selected from the group status is the present of 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, NHC(O)OR1, NHC(O)other1N(CH3)C(O)N(CH3R1, SO2Other1, SO2N(R1)2, NHSO2R1, NHSO2Other1or N(CH3)SO2N(CH3R1and the others are independently selected from the group consisting of H, F, Cl, Br, I, CF3, CF2CF3, CF2CF2CF3C(O)OH, C(O)NH2or C(O)OR1A;

R1means R2, R3, R4or R5;

R1Ameans alkyl, C3-C6alkenyl or3-C6-quinil;

R2means phenyl, which secondinterval or fused with benzene, heteroatom or R2A; R2Ameans cycloalkane or geteroseksualen;

R3means heteroaryl that secondinterval or fused with benzene, heteroatom or R3A; R3Ameans cycloalkane or geteroseksualen;

R4means cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R4A; R4Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R5means alkyl, alkenyl or quinil, each the of which is unsubstituted or substituted by one or two or three substituents, independently selected from the group consisting of R6, NC(R6A)(R6B), R7, OR7, SR7, S(O)R7, SO2R7, Other7N(R7)2C(O)R7C(O)NH2C(O)other7, NHC(O)R7, NHSO2R7, NHC(O)OR7, SO2NH2, SO2Other7, SO2N(R7)2, NHC(O)NH2, NHC(O)other7, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R6means C2-C5-spiralcell, which is unsubstituted or substituted, (O), N3CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH(CH3) or N(CH3)2;

R6Aand R6Bmean independently selected alkyl or, together with the nitrogen atom to which they are attached, denote R6C;

R6Cmeans aziridine-1-yl, azetidin-1-yl, pyrrolidin-1-yl or piperidine-1-yl, each of which has one CH2residue, unsubstituted or substituted by OH, C(O), CNOH, CNOCH3, S, S(O), SO2or NH;

R7means R8, R9, R10or R11;

R8means phenyl, which secondinterval or fused with benzene, heteroatom or R8A; R8Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R9means heteroaryl that secondinterval or fused with benzene, heteroatom or R9A; R9A means cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R10means3-C10-cycloalkyl,4-C10-cycloalkenyl,3-C10-heteroseksualci or4-C10-geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R10A; R10Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R11means alkyl, alkenyl or quinil, each of which is unsubstituted or substituted by one or two or three substituents, independently selected from the group consisting of R12, OR12, Other12N(R12)2C(O)NH2C(O)other12C(O)N(R12)2, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R12means R13, R14, R15or R16;

R13means phenyl, which secondinterval or fused with benzene, heteroatom or R13A; R13Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R14means heteroaryl, each of which secondinterval or fused with benzene, heteroatom or R14A; R14Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R15means cycloalkane, cycloalkene, geteroseksualen or hetero is cloaked, each secondinterval or fused with benzene, heteroatom or R15A; R15Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R16means alkyl, alkenyl or quinil;

R17means R18, R19, R20or R21;

R18means phenyl, which secondinterval or fused with benzene, heteroatom or R18A; R18Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R19means heteroaryl that secondinterval or fused with benzene, heteroatom or R19A; R19Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R20means3-C10-cycloalkyl,4-C10-cycloalkenyl,3-C10-heteroseksualci or4-C10-geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R20A; R20Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R21means alkyl, alkenyl or quinil, each of which is unsubstituted or substituted by one or two or three substituents, independently selected from the group consisting of R22, OR22, Other22N(R22)2C(O)NH2C(O)other22C(O)N(R22)2, OH, (), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R22means R23, R24or R25;

R23means phenyl, which secondinterval or fused with benzene, heteroatom or R23A; R23Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R24means heteroaryl that secondinterval or fused with benzene, heteroatom or R24A; R24Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R25means3-C6-cycloalkyl,4-C6-cycloalkenyl,3-C6-heteroseksualci or4-C6-geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R25A; R25Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

Z1means R26or R27, each of which is substituted by an R28, R29or R30, each of which is substituted by F, Cl, Br, I, CH2R37CH(R31)(R37), C(R31)(R31A)(R37), C(O)R37, OR37, SR37, S(O)R37, SO2R37, Other37or N(R32R37;

R26means phenyl, which secondinterval or fused with benzene or heteroatom;

R27means heteroaryl, which is secondinterval or fused with benzene or heteroatom;

R28means phenyl, which secondinterval or fused with benzene, heteroatom or R28A; R28Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R29means heteroaryl or R29A; R29Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R30means cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R30A; R30Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R31and R31Aindependently selected from F, Cl, Br, or independently selected from alkyl or together denote With2-C5-spiralcell;

R32means R33With(O)R33or C(O)OR33;

R33means R34or R35;

R34means phenyl, which secondinterval or condensed with aryl, heteroaryl or R34A; R34Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R35means alkyl, which is unsubstituted or substituted R36;

R36means phenyl, which secondinterval or fused with benzene, heteroatom or R36A; R36Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

Rsup> 37means R38, R39or R40, each of which is substituted by F, Cl, Br, I, R41, OR41,

Other41N(R41)2, NHC(O)OR41, SR41, S(O)R41or SO2R41;

R38means phenyl, which secondinterval or fused with benzene, heteroatom or R38A; R38Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R39means heteroaryl that secondinterval or fused with benzene, heteroatom or R39A; R39Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R40means3-C8-cycloalkyl,4-C8-cycloalkenyl,3-C8-heteroseksualci or4-C8-geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R40A; R40Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R41means R42, R43, R44or R45;

R42means phenyl, which secondinterval or fused with benzene, heteroatom or R42A; R42Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R43means heteroaryl that secondinterval or fused with benzene, heteroatom or R43A;R 43Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R44means3-C6-cycloalkyl,4-C6-cycloalkenyl,3-C6-heteroseksualci or4-C6-geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R44A; R44Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R45means alkyl, alkenyl or quinil, each of which is unsubstituted or substituted by one or two substituents, independently selected from the group consisting of R46, OR46, Other46N(R46)2C(O)NH2C(O)other46C(O)N(R46)2, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R46means R47, R48or R49;

R47means phenyl, which secondinterval or fused with benzene, heteroatom or R47A; R47Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R48means heteroaryl or R48A; R48Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R49means3-C6-cycloalkyl,4-C6-cycloalkenyl,3-C6-heteroseksualci or4-C6-geteroseksualen, each the second of which secondinterval or fused with benzene, heteroatom or R49A; R49Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

where each of the above-mentioned cyclic residue is independently unsubstituted, further unsubstituted, substituted or further substituted with one or two or three or four or five substituents, independently selected from the group consisting of R50, OR50, SR50, S(O)R50, SO2R50C(O)R50, CO(O)R50, OC(O)R50, OC(O)OR50, NH2, Other50N(R50)2C(O)NH2C(O)other50C(O)N(R50)2C(O)NHOH, C(O)NHOR50C(O)NHSO2R50C(O)NR55SO2R50, SO2NH2, SO2Other50, SO2N(R50)2, CF3, CF2CF3C(O)H, C(O)OH, C(N)NH2C(N)other50C(N)N(R50)2, OH, (O), N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;

R50means R51, R52, R53or R54;

R51means phenyl, which secondinterval or fused with benzene, heteroatom or R51A; R51Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R52means heteroaryl or R52A; R52Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R53means3-C6-cycloalkyl,4-C6/sub> -cycloalkenyl,3-C6-heteroseksualci or4-C6-geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R53A; R53Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R54means alkyl, alkenyl or quinil, each of which is unsubstituted or substituted by one or two or three substituents, independently selected from the group consisting of R55, OR55, SR55, S(O)R55, SO2R55, Other55N(R55)2C(O)R55C(O)NH2C(O)other55, NHC(O)R55, NHSO2R55, NHC(O)OR55, SO2NH2, SO2Other55, SO2N(R55)2, NHC(O)NH2, NHC(O)other55, OH, (O), C(O)OH, (O), N3, CN, NH2, CF3, OCF3, CF2CF3, OCF2CF3, F, Cl, Br or I; and

R55means alkyl, alkenyl, quinil, phenyl, heteroaryl,3-C6-cycloalkyl,4-C6-cycloalkyl,3-C6-heteroseksualci or4-C6-heteroseksualci;

the preferred embodiment are compounds having the formula (I):

and their therapeutically acceptable salts, where

R5ameans hydrogen, alkyl, alkenyl or quinil, each of which is unsubstituted or substituted by one or two or Tr is two substituents, independently selected from the group consisting of R6, NC(R6A)(R6B), R7, OR7, SR7, S(O)R7, SO2R7, Other7N(R7)2C(O)R7C(O)NH2C(O)other7, NHC(O)R7, NHSO2R7, NHC(O)OR7, SO2NH2, SO2Other7, SO2N(R7)2, NHC(O)NH2, NHC(O)other7, OH, (O), C(O)OH, (O), N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I.

Another embodiment relates to a method of treating arthritis in a mammal, comprising introducing him to compounds having formula (I), or therapeutically acceptable salts, where

And1means(a2);

one or two or three or each of A2In1D1and E1independently selected from the group consisting of 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, NHC(O)OR1, NR1C(O)other1, NR1C(O)N(R1)2, SO2Other1, SO2N(R1)2, NHSO2R1, NHSO2Other1or N(CH3)SO2N(CH3R1and the others are independently selected from the group consisting of H, F, Cl, Br, I, CN, CF3C(O)OH, C(O)NH2or C(O)OR1A;

Y1denotes H, CN, NO2C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF CF3, R17, OR17C(O)R17C(O)OR17, SR17, NH2, Other17N(R17)2, NHC(O)R17C(O)NH2C(O)other17C(O)N(R17)2NHS(O)R17or NHSO2R17;

R1means R2, R4or R5;

R1Ameans alkyl, C3-C6alkenyl or3-C6-quinil;

R2means phenyl, which secondinterval or fused with benzene or heteroatom;

R4means cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene or heteroatom;

R5means alkyl, alkenyl or quinil, each of which is unsubstituted or substituted by one or two or three substituents, independently selected from the group consisting of NC(R6A)(R6B), R7, OR7, SR7, S(O)R7, SO2R7, Other7N(R7)2C(O)R7C(O)NH2C(O)other7, NHC(O)R7, NHSO2R7, NHC(O)OR7, NHC(O)NH2, OH, (O), C(O)OH, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R6Aand R6Bmean independently selected alkyl or, together with the nitrogen atom to which they are attached, denote R6C;

R6Cmeans aziridine-1-yl, azetidin-1-yl, pyrrolidin-1-yl or piperidine-1-yl;

R7means R8R 9, R10or R11;

R8means phenyl, which secondinterval or fused with benzene, heteroatom or R8A; R8Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R9means heteroaryl that secondinterval or fused with benzene or heteroatom;

R10means3-C10-cycloalkyl,4-C10-cycloalkenyl,3-C10-heteroseksualci or4-C10-geteroseksualen, each of which secondinterval or fused with benzene or heteroatom;

R11means alkyl, alkenyl or quinil, each of which is unsubstituted or substituted by one or two or three substituents, independently selected from the group consisting of R12, OR12, Other12N(R12)2C(O)NH2C(O)other12C(O)N(R12)2, OH, (O), C(O)OH, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

R12means R13, R14, R15or R16;

R13means phenyl, which secondinterval or condensed with heterocyclization;

R14means heteroaryl, each of which secondinterval or fused with benzene or heteroatom;

R15means cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R16means alkyl of alkenyl or quinil;

R17means alkyl, alkenyl or quinil, each of which is unsubstituted or substituted by one or two or three substituents, independently selected from the group consisting of R22, OR22, Other22N(R22)2C(O)NH2C(O)other22C(O)N(R22)2, OH, (O), C(O)OH, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;

Z1means R26or R27, each of which is substituted by an R28, R29or R30, each of which is substituted by F, Cl, Br, I, CH2R37C(R31)(R31A)(R37), C(O)R37, OR37, SR37, S(O)R37, SO2R37, Other37or N(R32R37;

R26means phenyl, which secondinterval or fused with benzene or heteroatom;

R27means heteroaryl that secondinterval or fused with benzene or heteroatom;

R28means phenyl, which secondinterval or fused with benzene or heteroatom;

R29means heteroaryl or R29A; R29Ameans cycloalkane, cycloalkene, geteroseksualen or geteroseksualen;

R30means cycloalkyl, cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or fused with benzene, heteroatom or R30A; R30Ameans cycloalkane, cycloalkene, heterocyclic is or geteroseksualen;

R31and R31Atogether, mean2-C5-spiralcell;

R37means R38, R39or R40, each of which is substituted by F, Cl, Br, I, R41, OR41,

Other41N(R41)2, NHC(O)OR41, SR41, S(O)R41or SO2R41;

R38means phenyl, which secondinterval or fused with benzene or heteroatom;

R39means heteroaryl that secondinterval or fused with benzene or heteroatom;

R40means3-C8-cycloalkyl,4-C8-cycloalkenyl,3-C8-heteroseksualci or4-C8-geteroseksualen;

R41means R42, R43, R44or R45;

R42means phenyl, which secondinterval or fused with benzene or heteroatom;

R43means heteroaryl that secondinterval or fused with benzene or heteroatom;

R44means3-C6-cycloalkyl,4-C6-cycloalkenyl,3-C6-heteroseksualci or4-C6-geteroseksualen;

R45means alkyl;

where each of the above-mentioned cyclic residue is independently unsubstituted, further unsubstituted, substituted or further substituted with one or two or three or four or five deputies who, independently selected from the group consisting of R50, OR50, SR50, SO2R50C(O)R50, CO(O)R50, NH2, Other50N(R50)2C(O)NHOH, C(O)NHSO2R50C(O)OH, OH, (O), CF3, OCF3, F, Cl, Br or I;

R50means R51, R52, R53or R54;

R51means phenyl, which secondinterval or fused with benzene;

R52means heteroaryl;

R53means3-C6-cycloalkyl,4-C6-cycloalkenyl,3-C6-heteroseksualci or4-C6-geteroseksualen, each of which secondinterval or fused with benzene or heteroatom;

R54means alkyl, which is unsubstituted or substituted R55, OR55, SR55or N(R55)2; and

R55means alkyl, alkenyl, quinil, phenyl, heteroaryl,3-C6-cycloalkyl,4-C6-cycloalkyl,3-C6-heteroseksualci or4-C6-heteroseksualci.

Yet another embodiment relates to a method of treating arthritis in a mammal, comprising introducing him to compounds having formula (I), or therapeutically acceptable salts, where

And1means(a2);

one or two or three or each of A2In1D1and E1independently selected from the group, with Toyama of R 1, OR1, SO2R1C(O)OR1, Other1, NR1C(O)N(R1)2and the others are independently selected from the group consisting of H, F, Cl, Br, I, CF3C(O)OH, C(O)NH2or C(O)OR1A; R1Ameans alkyl;

Y1denotes H, CN, NO2, F, Cl, Br, I, CF3, R17, NH2C(O)NH2;

R1means phenyl, R4or R5;

R4means cycloalkyl or heteroseksualci;

R5means alkyl, which is unsubstituted or substituted by one or two substituents, independently selected from the group consisting of R7, OR7, SR7, SO2R7, Other7N(R7)2C(O)R7C(O)NH2C(O)other7, NHC(O)R7, NHSO2R7, NHC(O)OR7, NHC(O)NH2, (O), C(O)OH, NH2, CF3, CF2CF3, F, Cl, Br or I;

R7means R8, R9, R10or R11;

R8means phenyl, which secondinterval or condensed with heterocyclization;

R9means heteroaryl that secondinterval or fused with benzene;

R10means3-C10-cycloalkyl,3-C10-heteroseksualci or4-C10-geteroseksualen;

R11means alkyl, which is unsubstituted or substituted R12N(R12)2C(O)N(R12)2, OH, C(O) - OH, CF3, F, Cl, Br or I;

R12who appoints R 13, R14, R15or R16;

R13means phenyl, which secondinterval or condensed with heterocyclization;

R14means heteroaryl;

R15means geteroseksualen;

R16means alkyl;

R17means alkyl;

Z1means R26or R27, each of which is substituted by an R30, each of which is substituted CH2R37or C(R31)(R31A)(R37);

R26means phenyl;

R27means heteroaryl;

R30means cycloalkenyl, heteroseksualci or geteroseksualen, each of which secondinterval or condensed with heterocyclization;

R31and R31Atogether, mean2-C5-spiralcell;

R37means R38, R39or R40, each of which is substituted by F, Cl, Br, I, R41, NHC(O)OR41, SR41or SO2R41;

R38means phenyl, which secondinterval or fused with benzene;

R39means heteroaryl;

R40means4-C8-cycloalkenyl or4-C8-geteroseksualen;

R41means R42, R43, R44or R45;

R42means phenyl, which secondinterval or fused with benzene or heteroatom;

R43means heteroaryl that recondenser the van or fused with benzene;

R44means3-C6-heteroseksualci;

R45means alkyl;

where each of the above-mentioned cyclic residue is independently unsubstituted, further unsubstituted, substituted or further substituted with one or two substituents, independently selected from the group consisting of R50, OR50, SR50, SO2R50C(O)R50, CO(O)R50, NH2, Other50N(R50)2C(O)NHOH, C(O)NHSO2R50C(O)OH, OH, (O), CF3, OCF3, F, Cl, Br or I;

R50means R51, R52, R53or R54;

R51means phenyl fused with benzene;

R52means heteroaryl;

R53means3-C6-cycloalkyl or3-C6-heteroseksualci, each of which secondinterval or fused with benzene;

R54means alkyl, which is unsubstituted or substituted R55, SR55or N(R55)2; and

R55means alkyl, phenyl or3-C6-heteroseksualci.

Yet another embodiment relates to a method of treating arthritis in a mammal, comprising introducing him typical compounds having the formula (I) or formula (I), which represents:

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonic the Ministry of foreign Affairs,

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,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-methoxy(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-fluoro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-(methylsulfanyl)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-((4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)-4-(4-(4'-phenyl-1,1'-biphenyl-2-ylmethyl)piperazine-1-yl)benzamid,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((4'-phenoxy(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)be the zoilus)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-(dimethylamino)-1-((phenylsulfanyl)methyl)butyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-5-(dimethylamino)-1-((phenylsulfanyl)methyl)pentyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-fluoro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro-4-fluoro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

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-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)benzosulfimide,/p>

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(1,3-thiazol-2-ylsulphonyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((1,3-thiazol-2-ylsulphonyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((Tien-2-ylsulphonyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(2-(dimethylamino)ethoxy)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1S)-3-(dimethylamino)-1-methyl-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(methylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfonyl)butane acid,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N-isopropyl-4-(phenylsulfanyl)butanamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diisopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R-3-(azetidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((4-(phenylsulfanyl)tetrahydro-3-furanyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-4-methoxypiperidine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-4-methoxypiperidine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-hydroxy-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-(2-(2-naphthyl)benzyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-(2-(1-naphthyl)benzyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((3'-cyano(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((3'-methoxy(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((3'-chloro(1,1'-b is phenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-(2-(1,3-benzodioxol-5-yl)benzyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-(2-(3-thienyl)benzyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-(2-(pyridin-3-yl)benzyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-(2-(quinoline-8-yl)benzyl)piperazine-1-yl)benzoyl)benzosulfimide,

N-(4-(4-(2-(1-benzofuran-2-yl)benzyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2'-methyl(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-(2-(quinoline-3-yl)benzyl)piperazine-1-yl)benzoyl)benzosulfimide,

N-(4-(4-((1-(4-chlorophenyl)-2-naphthyl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1-(4-chlorophenyl)-2-naphthyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(l is methylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1-(4-chlorophenyl)-2-naphthyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)cyclopentyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)cyclopentyl)amino)benzosulfimide,

N-(4-(4-((4'-fluoro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((3',4'-dichloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((3',4'-dichloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((3',4'-dichloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)-N-(4-(4-((4'-(trifluoromethyl)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((4'-(trifluoromethyl)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((4'-(trifluoromethyl)(1,1'-fenil)-2-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)-N-(4-(4-((4'-(triptoreline)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)-N-(4-(4-((4'-(triptoreline)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((4'-(triptoreline)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

3-nitro-N-(4-(4-((4'-phenoxy(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((4'-phenoxy(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1S)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2',4'-dichloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-(2-(2-thienyl)benzyl)piperazine-1-yl)benzoyl)benzosulfimide,

N-(4-(4-((4'-chloro-2'-methyl(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2',4'-debtor(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((4-(phenylsulfanyl)tetrahydro-3-furanyl)amino)benzosulfimide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-(2-(5-methyl-2-thienyl)benzyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((4-(phenylsulfonyl)tetrahydro-3-furanyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((4-(phenylsulfonyl)tetrahydro-3-furanyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1-methyl-4-(phenylsulfanyl)pyrrolidin-3-yl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)PR who drank)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-bromo(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-(1-(4'-chloro(1,1'-biphenyl)-2-yl)cyclopropyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(dimethylamino)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(dimethylamino)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(diethylamino)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(diethylamino)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(cyclopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzophenone,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-methoxy-4-(2-(pyridin-3-yl)benzyl)piperidine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-methoxy-4-(2-(pyridin-4-yl)benzyl)piperidine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-methoxy-4-(2-(2-thienyl)benzyl)piperidine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-methoxy-4-(2-(3-thienyl)benzyl)piperidine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(azetidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-((2,2,2-triptorelin)amino)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(methyl(2,2,2-triptorelin)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-4-methoxypiperidine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-4-methoxypiperidine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(ethyl(2,2,2-triptorelin)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2-foradil)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2,2-dottorati)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-1-((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)-1H-benzimidazole-5-sulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-1-((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)-1H-1,2,3-benzotriazol-5-sulfonamide,

5-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzamide,

N-(4-(4-((4'-(dimethylamino)(1,1'-biphenyl)-2-yl)carbonyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-(methylsulfanyl)(1,1'-biphenyl)-2-yl)carbonyl)piperazine-1-yl)benzoyl)3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-(methylsulfanyl)(1,1'-biphenyl)-2-yl)carbonyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-cyano-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(5,6-dihydro-1(4H)-pyrimidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-methyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(5,6-dihydro-1(4H)-pyrimidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-bifen the l)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-methyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

4-(((1R)-3-(bis(2-methoxyethyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(bis(2-methoxyethyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(trifluoromethyl)benzosulfimide,

4-(((1R)-5-amino-1-((phenylsulfanyl)methyl)pentyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-4-yl)methyl)-1-piperazinil)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-methyl-1-((phenylsulfanyl)methyl)pentyl)amino)-3-nitrobenzenesulfonamide,

tert-butyl(5R)-5-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-6-(phenylsulfanyl)hexylcinnamal,

4-(((1R)-5-amino-1-((phenylsulfanyl)methyl)pentyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)IU who yl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-5-((methylsulphonyl)amino)-1-((phenylsulfanyl)methyl)pentyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-5-((aminocarbonyl)amino)-1-((phenylsulfanyl)methyl)pentyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-(2-(methylsulfanyl)benzyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-(2-(methylsulphonyl)benzyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-(2-(5,5-dimethyl-2-oxo-1,3-oxazolidin-3-yl)benzyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-(2-cyclohexylmethyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-(2-(morpholine-4-yl)benzyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-(2-(isopropylphenyl)benzyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-neither is robinsonshouse,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dipropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dipropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-3-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-3-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-3-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)-3-perbenzoic)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)-3-perbenzoic)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)-3-perbenzoic)-4-(((1R)-3(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl) - for 3,5-differentail)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl) - for 3,5-differentail)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl) - for 3,5-differentail)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

3-nitro-N-(4-(4-((1-phenyl-1H-imidazol-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((1-phenyl-1H-imidazol-2-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

3-nitro-N-(4-(4-((1-phenyl-1H-pyrazole-5-yl)methyl)piperazine-1-yl)benzoyl)-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((1-phenyl-1H-pyrazole-5-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((1-phenyl-1H-pyrazole-5-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((1-phenyl-1H-imidazol-5-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

1-((3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl-2-nitroaniline)-4-(phenylsulfanyl)butyl)-3-azetidinone acid,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2-hydroxy-2-methylpropyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

(((3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfanyl)butyl)(methyl)amino)acetic acid,

(2R)-1-((3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfanyl)butyl)-2-pyrrolidinecarbonyl acid,

1-((3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfanyl)butyl)-4-piperidinylcarbonyl acid,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2-hydroxyethyl)(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

(2S)-1-((3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfanyl)butyl)-2-pyrrolidinecarbonyl acid,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(3-(2H-tetrazol-5-yl)azetidin-1-yl)propyl)amino)benzosulfimide,

(2S)-2-amino-N-((1S)-2-(((3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfanyl)butyl)amino)-1-methyl-2-oxoethyl)propanamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(2-(2H-tetrazol-5-yl)pyrrolidin-1-yl)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(4-(((methylsulphonyl)amino)carbonyl)piperidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

1-((3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfanyl)butyl)-N-hydroxy-4-piperidinecarboxylic,

2-chloro-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

2,6-dichloro-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

4-(((1R)-3-((1R,5S)-8-azabicyclo[3.2.1]Oct-8-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(7-azabicyclo[2.2.1]hept-7-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(2-(phenylsulfanyl)ethoxy)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(2-(phenylsulfanyl)ethoxy)-3-(trifluoromethyl)baselslt the amide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-3-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-3-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

4-(((1R)-3-(7-azabicyclo[2.2.1]hept-7-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2R,5S)-2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-3-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(cyclohexyloxy)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ILM is Teal)piperazine-1-yl)benzoyl)-4-(cyclohexylmethoxy)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(2-cyclohexylmethoxy)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-(tetrahydro-2H-Piran-4-ylamino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-((2-cyclohexylethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(cyclohexyl(methyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(4,4-dimethylpiperidin-1-yl)-3-nitrobenzenesulfonamide,

tert-butyl 4-(4-(((4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitrophenoxy)-1-piperidinecarboxylate,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-(piperidine-4-yloxy)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-((1-methylpiperidin-4-yl)oxy)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((cyclohexylmethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((cyclohexylmethyl)(propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1-benzylpiperidine-4-yl)methyl)amino)-N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-((cyclohexylmethyl(methyl)amino)-3-nitrobenz sulfonamid,

4-((1-benzylpiperidine-4-yl)amino)-N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-(tetrahydro-2H-sulfanilamide-4-ylamino)benzosulfimide,

ethyl-4-(4-(((4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-1-piperidinecarboxylate,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1-propylpiperidine-4-yl)methyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(isopropylamino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(1,3-thiazol-2-ylsulphonyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-((4-phenyl-1,3-thiazol-2-yl)sulfanyl)ethyl)amino)benzosulfimide,

4-((2-(1,3-benzothiazol-2-ylsulphonyl)ethyl)amino)-N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(1,3-thiazol-2-ylsulphonyl)ethyl)amino)benzosulfimide,

4-((2-(1,3-benzoxazol-2-ylsulphonyl)ethyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-((2-(1,3-benzothiazol-2-ylsulphonyl)ethyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonic the Ministry of foreign Affairs,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(pyrimidine-2-ylsulphonyl)ethyl)amino)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((1-phenyl-1H-pyrazole-5-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1-benzylpiperidine-4-yl)methyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-((2-bromacil)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((2-((4-methyl-1,3-thiazol-2-yl)sulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((4-methoxycyclohexyl)methyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(2-thienylmethyl)ethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(2-thienylmethyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((1,3-thiazol-2-ylsulphonyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N,N-dimethyl-4-(pyrimidine-2-ylsulphonyl)butanamide,

N-(4-(4-((4'-chloro(1,1'-beef the Nile)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-3-oxo-1-((2-thienylmethyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(pyrimidine-2-ylsulphonyl)ethyl)amino)-3-nitrobenzenesulfonamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N,N-dimethyl-4-(1,3-thiazol-2-ylsulphonyl)butanamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((2-thienylmethyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-(((4-(triptoreline)-phenyl)sulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-phenoxyethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-(((4-(triptoreline)phenyl)sulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-(((4-methoxyphenyl)sulfanyl)methyl)-3-(morpholine-4-yl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-(((4-(were)sulfanyl)methyl)-3-(morpholine-4-yl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((2-thienylmethyl)methyl)propyl)amino)-3-(trifluoromethyl)benzo is sulfonamid,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-(((4-chlorophenyl)sulfanyl)methyl)-3-(morpholine-4-yl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-(((4-forfinal)sulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-(((4-forfinal)sulfanyl)methyl)-3-(morpholine-4-yl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-2-perbenzoic)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-2-perbenzoic)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-((6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)pyridine-3-yl)carbonyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperidine-4-yl)benzoyl)-4-(((1R)-3-(dim is thylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperidine-4-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-((6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)pyridine-3-yl)carbonyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-((6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)pyridine-3-yl)carbonyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperidine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperidine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-((5-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)pyridin-2-yl)carbonyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-((5-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)pyridin-2-yl)carbonyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(1-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohexen-1-yl)methyl)-1,2,3,6-tetr hydropyridine-4-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(1-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(1-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(1-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohexen-1-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1-cyclohexen-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1-cyclohexen-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-((3aR,6aS)-5-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)hexahydrofuro[3,4-c]pyrrol-2(1H)-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(methyl((methyl-4-(triptoreline)of aniline)carbonyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((2-dimethylaniline)carbonyl)(methyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((4-methoxy(methylaniline)carbonyl)(methyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((4-dimethylaniline)carbonyl)(methyl)amino)-3-nitrobenzenesulfonamide,

4-(((benzhydryl(methyl)amino)carbonyl)(methyl)amino)-N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(methyl((methyl((1S)-1-phenylethyl)amino)carbonyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(methyl((methyl(2-(4-methylpiperazin-1-yl)-1-phenylethyl)amino)carbonyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(methyl((methyl(2-(morpholine-4-yl)-1-phenylethyl)amino)carbonyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-((((1,2-diphenylether)(methyl)amino)carbonyl)(methyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-((((2-(dimethylamino)-1-phenylethyl)(methyl)amino)carbonyl)(methyl)amino)-3-nitrobenzenesulfonamide,

3-amino-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-1-(2-(phenylsulfanyl)ethyl)-1H-1,2,3-benzotriazol-5-sulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-1-(2-(phenylsulfanyl)ethyl)-1H-benzimidazole-5-sulfonamide,

N-(4-(4-((,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-4-((cyclohexylmethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-4-(cyclohexylamino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((1-((phenylsulfanyl)methyl)cyclopentyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-3-nitro-4-((1-((phenylsulfanyl)methyl)cyclopentyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((1-((phenylsulfanyl)methyl)cyclopentyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1S)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-3-nitro-4-(((1S)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1S)-3-methyl-1-((phenylsulfanyl)methyl)butyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-4-(((1S)-3-methyl-1-((phenylsulfanyl)methyl)butyl)amino)-3-nitrobenzenesulfonamide,

p> N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((1-((phenylsulfanyl)methyl)cyclopropyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((1-((phenylsulfanyl)methyl)cyclohexyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-methyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1S)-1-methyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R,2S)-2-(phenylsulfonyl)cyclohexyl)amino)benzosulfimide,

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-(trifluoromethyl)benzosulfimide,

4-(((1R)-5-amino-1-((phenylsulfanyl)methyl)pentyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1S)-2-(phenylsulfanyl)-1-(pyridine-3-ylmethyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-3-nitro-4-(((1S)-2-(phenylsulfanyl)-1-(pyridine-3-ylmethyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1S,2R)-2-(phenylsulfonyl)cyclohexyl)amino)bansilal foamed,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-((1-(((2-methyl-3-furyl)sulfonyl)methyl)cyclopentyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1-(((2-methyl-3-furyl)sulfonyl)methyl)cyclopentyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1S)-2-(phenylsulfanyl)-1-(pyridine-3-ylmethyl)ethyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-3-pyridin-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)pyridine-3-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)pyridine-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

3-nitro-N-(4-(4-((2-vinylpyridin-3-yl)methyl)piperazine-1-yl)benzoyl)-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((2-vinylpyridin-3-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((2-vinylpyridin-3-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-(metals hanil)phenyl)pyridine-3-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-methoxyphenyl)pyridine-3-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-(dimethylamino)phenyl)pyridine-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-forfinal)pyridine-3-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-(methylsulphonyl)phenyl)pyridine-3-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(pyridine-4-ylsulphonyl)ethyl)amino)benzosulfimide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-(methylsulphonyl)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-(methylsulphonyl)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-(dimethylamino)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)m is Teal)propyl)amino)-3-nitrobenzenesulfonamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N,N-dimethyl-4-(phenylsulfonyl)butanamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((3S,4R)-(phenylsulfanyl)pyrrolidin-4-yl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyridine-4-ylsulphonyl)propyl)amino)benzosulfimide,

N-(4-(4-((3-(4-chlorophenyl)pyridine-4-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((3-(4-chlorophenyl)pyridine-4-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclopenten-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-bromo-1-cyclopenten-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((2-bromo-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-methoxyphenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-forfinal)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-((2-phenyl-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-1-cycloocten-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-(methylsulfonyl)phenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohepten-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohepten-1-yl)methyl)piperazine-1-yl)benzoyl)-4-((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(morpholine-4-yl)ethoxy)piperidine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(morpholine-4-yl)ethoxy)piperidine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(pyrrolidin-1-yl)ethoxy)piperidine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(pyrrolidin-1-yl)ethoxy)piperidine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(pyrrolidin-1-yl)ethoxy)piperidine-1-yl)benzoyl)-3-nitro-4-((1-((phenylsulfanyl)methyl)cyclopentyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(dimethylamino)ethoxy)piperidine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(dimethylamino)ethoxy)piperidine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzo is a sulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(dimethylamino)ethoxy)piperidine-1-yl)benzoyl)-3-nitro-4-((1-((phenylsulfanyl)methyl)cyclopentyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(piperidine-1-yl)ethoxy)piperidine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(piperidine-1-yl)ethoxy)piperidine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-(2-(piperidine-1-yl)ethoxy)piperidine-1-yl)benzoyl)-3-nitro-4-((1-((phenylsulfanyl)methyl)cyclopentyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1S)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-(2-(dimethylamino)ethoxy)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-(2-(dimethylamino)ethoxy)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-(2-(dimethylamino)ethoxy)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-(2-(dimethylamino)ethoxy)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)b is solarpanel,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-(2-(morpholine-4-yl)ethoxy)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-(2-(morpholine-4-yl)ethoxy)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-N-(4-(4-((4'-(2-(morpholine-4-yl)ethoxy)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-(2-(morpholine-4-yl)ethoxy)(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-4-(((1R)-3-(1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-(4-methylpiperazin-1-yl)-1-((phenylsulfanyl)methyl)butyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-((2-(dimethylamino)ethyl)(methyl)amino)-1-((phenylsulfanyl the l)methyl)ethyl)amino)-3-nitrobenzenesulfonamide,

(4R)-4-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N,N-dimethyl-5-(phenylsulfanyl)pentanone,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-(dimethylamino)-1-((phenylsulfanyl)methyl)butyl)amino)-3-nitrobenzenesulfonamide,

2-(((3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfanyl)butyl)(methyl)amino)-N,N-dimethylacetamide,

(3R)-N-(tert-butyl)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfanyl)butanamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N,N-aminobutiramida 4-(phenylsulfanyl)butanamide,

(3R)-N-(tert-butyl)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N-methyl-4-(phenylsulfanyl)butanamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N-isopropyl-N-methyl-4-(phenylsulfanyl)butanamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-3-oxo-1-((phenylsulfanyl)methyl)-3-(piperidine-1-yl)propyl)amino)benzosulfimide,

N-((5R)-5-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-6-(phenylsulfanyl)hexyl)-2-(dimethylamino)acetamide", she

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N,N-dimethyl-4-(phenylsulfanyl)butanamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,1-diocletianopolis-4-yl)-3-oxo-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-4-(phenylsulfanyl)butanamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N-cyclopropyl-4-(phenylsulfanyl)butanamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N-cyclobutyl-4-(phenylsulfanyl)butanamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(4-methylpiperazin-1-yl)-3-oxo-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-3-oxo-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(azetidin-1-yl)-3-oxo-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N-(2-(morpholine-4-yl)ethyl)-4-(phenylsulfanyl)butanamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-nitroaniline)-N-methyl-4-(phenylsulfanyl)butanamide,

4-(((1R)-3-amino-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-cyano-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(tert-butylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(cyclopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(cyclobutylamine)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(tert-butyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(piperidine-1-yl)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(4-hydroxypiperidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(4-acetylpiperidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(thiomorpholine-4-yl)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2-(morpholine-4-yl)ethyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(piperazine-1-yl)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((3R)-3-hydroxypyrrolidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-((3R)-3-aminopyrrolidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(3-hydroxyazetidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(4-methylpiperazin the n-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,1-diocletianopolis-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(1,3-benzodioxol-5-ylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

4-(((1R)-3-((1,3-benzodioxol-4-ylmethyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-((pyridine-2-ylmethyl)amino)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-((2-(pyridin-2-yl)ethyl)amino)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-((pyridine-4-ylmethyl)amino)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-ylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(methyl(pyridin-4-yl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyridine-3-ylamino)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2,6-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2R,6S)-2,6-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1 ylamino)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(4-(methoxyimino)piperidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitro-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(2H-tetrazol-5-yl)propyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diisopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

4-(((1R)-3-(bis(2-hydroxyethyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(((1R)--(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-4-(triptoreline)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-amino-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-2-(trifluoromethyl)benzosulfimide,

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-forbindelsesfaneblad,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-2-(triptoreline)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-2,5-diftorbenzofenonom,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((peninsul panel)methyl)propyl)amino)-3-methylbenzenesulfonamide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diisopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2R,5R)-2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2S,5S)-2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2R,5S)-2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

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-nitro-5-(trifluoromethyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-5-(trifluoromethyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohepten-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-5-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-4-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-beef the Nile)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)for 3,5-diftorbenzofenonom,

methyl-5-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzoate,

5-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzoic acid,

5-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzoic acid,

5-(((4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzoic acid,

5-(((4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzamide,

5-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzamide,

methyl-5-(((4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzoate,

methyl-5-(((4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(triform the Teal)benzoate,

methyl-5-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzoate,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-((2R,5S)-2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)butyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-((2R,5S)-2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)butyl)amino)-3-nitrobenzenesulfonamide,

tert-butyl 3-((4-(4-((((4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)amino)carbonyl)phenyl)piperazine-1-yl)carbonyl)phenylcarbamate,

N-(4-(4-(3-(dimethylamino)benzoyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-methyl-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-(((1S)-3-(dimethylamino)-1-methyl-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-(2-(1,3-dihydro-2H-isoindole-2-yl)benzyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-(2-(cyclohexylamino)benzyl)piperazine-1-yl)-benzo is l)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-(2-(isopropylamino)benzyl)piperazine-1-yl)benzoyl)-3-nitrobenzenesulfonamide,

N-(4-(4-(2-(benzylamino)benzyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitro-N-(4-(4-(2-(piperidine-1-yl)benzyl)piperazine-1-yl)benzoyl)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)piperazine-1-yl)benzoyl)-4-((cyclohexylmethyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((1,1'-biphenyl)-2-ylmethyl)-4-methoxypiperidine-1-yl)benzoyl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1S)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)-3-(trifluoromethyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)pyridine-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)METI is)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4-(4-chlorophenyl)pyridine-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-2-fluoro-3-(trifluoromethyl)benzosulfimide,

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1,2-benzisoxazol-3-yl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1,2-benzisoxazol-3-yl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(6-(4,4-dimethylpiperidin-1-yl)-1,2-benzisoxazol-3-yl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(6-(4,4-dimethylpiperidin-1-yl)-1,2-benzisoxazol-3-yl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(6-(4-(3,3-diphenylpropane-2-yl)piperazine-1-yl)-1,2-benzisoxazol-3-yl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(6-(4-(3,3-diphenylpropane-2-yl)piperazine-1-yl)-1,2-benzisoxazol-3-yl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1,2-benzisoxazol-3-yl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

4-(((1R)-3-(dimethylamino)-1-((panels JPanel)methyl)propyl)amino)-N-(6-(4,4-dimethylpiperidin-1-yl)-1,2-benzisoxazol-3-yl)-3-nitrobenzenesulfonamide,

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1-methyl-1H-indazol-3-yl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1-methyl-1H-indazol-3-yl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrobenzenesulfonamide,

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1-methyl-1H-indazol-3-yl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1-methyl-1H-indazol-3-yl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1H-indazol-3-yl)-3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1H-indazol-3-yl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide, and

N-(6-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)-1H-indazol-3-yl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(methylsulphonyl)-4-((2-(phenylsulfanyl)ethyl)amino)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-(methylsulphonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-Biff who yl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(methylsulphonyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

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-(ethylsulfonyl)benzosulfimide,

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-(methylsulphonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diisopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diisopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2R,5S)-2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-4-(7-azabicyclo[2.2.1]hept-7-yl)-1-((phenylsulfanyl)methyl)butyl)amino)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-4-(7-azabicyclo[2.2.1]hept-7-yl)-1-((phenylsulfanyl)methyl)butyl)amino)-N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-((2R,5S)-2,5-di is ethylpyrrolidin-1-yl)-1-((phenylsulfanyl)methyl)butyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-(diisopropylamino)-1-((phenylsulfanyl)methyl)butyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-(diisopropylamino)-1-((phenylsulfanyl)methyl)butyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-(dimethylamino)-1-((phenylsulfanyl)methyl)butyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-(dimethylamino)-1-((phenylsulfanyl)methyl)butyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-((2R,5S)-2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)butyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-3-(1-azetidine)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-3-(1-azetidine)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-3-((3aR,6aS)-tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl)-1-((panels lpanel)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-3-((3aR,6aS)-tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(8-oxa-3-azabicyclo[3.2.1]Oct-3-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(8-oxa-3-azabicyclo[3.2.1]Oct-3-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)butyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-4-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)butyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-((3R,5S)-4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl) - for 3,5-dimethylpiperazine)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-((3R,5S)-4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl) - for 3,5-dimethylpiperazine)benzoyl)-3-((chloro(debtor)methyl)sulfonyl)-4-(((1R)-3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)the Mino)benzosulfimide,

4-(((1R)-3-(7-azabicyclo[2.2.1]hept-7-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)-1-cyclohepten-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-3-(7-azabicyclo[2.2.1]hept-7-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-3-((1S,4R)-2-azabicyclo[2.2.1]hept-2-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-hydroxy-1-((phenylsulfanyl)methyl)propyl)amino)-3-(methylsulphonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diisopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(methylsulphonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(IU is ylsulphonyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)benzosulfimide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(methylsulphonyl)of aniline)-N,N-aminobutiramida 4-(phenylsulfanyl)butanamide,

(3R)-3-(4-(((4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)amino)sulfonyl)-2-(methylsulphonyl)of aniline)-N-isopropyl-N-methyl-4-(phenylsulfanyl)butanamide,

4-(((1R)-3-(azetidin-1-yl)-3-oxo-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(methylsulphonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(methylsulphonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(methylsulphonyl)benzosulfimide,

4-(((1R)-3-(azetidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(methylsulphonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-(methylsulphonyl)-4-(((1R)-3-oxo-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)benzosulfimide,

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-((1,1,2,2,2-pentafluoroethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)shall ethyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((1,1,2,2,3,3,3-heptafluoropropyl)sulfonyl)benzosulfimide,

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-((1,2,2,2-titrator-1-(trifluoromethyl)ethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(5,6-dihydro-1(4H)-pyrimidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-methyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2,5-dimethylpiperidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diisopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-3-(bis(2-methoxyethyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,4,7-dioxanonane-7-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-methylpyrrolidine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(4,4-deformability-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((3R,5S) - for 3,5-dimethoxypyridine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2S)-2-(methoxymethyl)pyrrolidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(1,3-thiazolidin-3-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-harfe the Il)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((3S)-3-methylmorpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1-hydroxy-3,7-dioxa-9-azabicyclo[3.3.1]non-9-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1S)-3-(3,7-dioxa-9-azabicyclo[3.3.1]non-9-yl)-1-(2-phenylethyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((deformity)sulfonyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((deformity)sulfonyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-(ethylsulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-3-((deformity)sulfonyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((4-(4-chlorophenyl)-5,-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-(ethylsulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-3-((deformity)sulfonyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,4-oxazepan-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,4-oxazepan-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)qi is logex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,4-oxazepan-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,4-oxazepan-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,4-oxazepan-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,4-oxazepan-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,4-oxazepan-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-((1R)-3-(7-azabicyclo[2.2.1]hept-7-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

tert-butyl 4-(4-chlorophenyl)-5-((4-(4-((((4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)amino)carbonyl)phenyl)

piperazine-1-yl)methyl)-3,6-dihydro-1(2H)-pyridinecarboxylic,

tert-butyl 4-(4-chlorophenyl)-5-((4-(4-((((4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)amino)carbonyl)phenyl)

piperazine-1-yl)methyl)-3,6-dihydro-1(2H)-pyridinecarboxylic,

N-(4-(4-((4-(4-chlorophenyl)-1,2,5,6-tetrahydro-3-pyridinyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-1,2,5,6-tetrahydro-3-pyridinyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((1-acetyl-4-(4-chlorophenyl)-1,2,5,6-tetrahydro-3-pyridinyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-1-methyl-1,2,5,6-tetrahydro-3-pyridinyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)m is Teal)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-1-(cyclohexylmethyl)-1,2,5,6-tetrahydro-3-pyridinyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((1-acetyl-4-(4-chlorophenyl)-1,2,5,6-tetrahydro-3-pyridinyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-1-methyl-1,2,5,6-tetrahydro-3-pyridinyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-(((1R,2R)-2-(4-chlorophenyl)cyclohexyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4-(4-(trifluoromethyl)phenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)benzosulfimide,

4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((4-(4-(trifluoromethyl)phenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzols lonamin,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-4,4-diethyltoluene-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(diisopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((2-(4-chlorophenyl)-1-cyclohex-1-EN-1-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((2-(4-chlorophenyl)-1-cyclohex-1-EN-1-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((2-(4-harfe who yl)-1-cyclohex-1-EN-1-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(diisopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((2-(4-chlorophenyl)-1-cyclohex-1-EN-1-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((2-(4-chlorophenyl)-1-cyclohepta-1-EN-1-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((2-(4-chlorophenyl)-1-cyclohepta-1-EN-1-yl)methyl)-1,2,3,6-tetrahydropyridine-4-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(1-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperidine-4-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperidine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1-cyclohex-1-EN-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)shall enzoyl)-4-(((1R)-2-(dimethylamino)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(dimethylamino)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(diethylamino)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(diethylamino)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-2-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)ethyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2R,6S)-2,6-dimethylmorpholine-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2,6-dimethylmorpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((2R,6S)-2,6-dimethylmorpholine-4-yl)-1-((phenyl who sulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2,6-dimethylmorpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((1-(4-chlorophenyl)piperidine-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(cyclopropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(cyclopropyl(cyclopropylmethyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(cyclopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((cyclopentylmethyl)(cyclopropyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((cyclohexylmethyl)(cyclopropyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(cyclopropyl(tetrahydrofuran-3-ylmethyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-3-(benzyl(cyclopropyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(cyclopropyl(isobutyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(cyclopropyl(tetrahydro-2H-Piran-4-yl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-4,4-diethyltoluene-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-4,4-diethyltoluene-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

(4-(cyclohexylmethoxy)-N-((4'-fluoro(1,1'-biphenyl)-4-yl)carbonyl)-3-(methylsulphonyl)benzosulfimide,

N-(4-(4-(((1R,2R)-2-(4-chlorophenyl)cyclohexyl)methyl)piperazine-1-yl)be the zoilus)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-(((1S,2S)-2-(4-chlorophenyl)cyclohexyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-(((1R,2S)-2-(4-chlorophenyl)cyclohexyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-(((1S,2S)-2-(4-chlorophenyl)cyclohexyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-(((1R,2S)-2-(4-chlorophenyl)cyclohexyl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dipropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dipropylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)PR who drank)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)piperazine-1-yl)benzoyl)-3-((chloro(debtor)methyl)sulfonyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(diethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

((((4-chlorobutyl)((3R)-3-(4-(((4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)-1-piperazinil)benzoyl)amino)sulfonyl)-2-((trifluoromethyl)sulfonyl)of aniline)-4-(phenylsulfanyl)butyl)amino)carbonyl)oxy)Metreveli,

(phosphonooxy)methyl-4-chlorobutyl-((3R)-3-(4-(((4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)-1-piperazinil)benzoyl)amino)sulfonyl)-2-((trifluoromethyl)sulfonyl)of aniline)-4-(phenylsulfanyl)butyl)carbamate,

N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohe the C-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-1-cyclohepten-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)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,

4-(((1R)-3-(7-azabicyclo[2.2.1]hept-7-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-(2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(1,4-oxazepan-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

4-(((1R)-3-(azepin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-N-(4-(4-((2-(4-chlorophenyl)-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-3-((trifluoromethyl)Sul is of IMT)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-Piran-3-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)benzosulfimide,

3-(chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohepta-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

3-((chloro(debtor)methyl)sulfonyl)-N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-1-((phenylsulfanyl)methyl)-3-(pyrrolidin-1-yl)propyl)amino)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1-piperazinil)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, or

N-(4-(4-((4'-chloro(1,1'-biphenyl)-2-yl)methyl)-1-piperazinil)benzoyl)-4-(((1R)-3-(4-morpholinyl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide,

and its therapeutically acceptable with the her prodrugs, salts of prodrugs, esters, salts, esters, amides or salts, amides,

the preferred embodiments of which are:

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 (EXAMPLE a) and

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 (EXAMPLE)

or their therapeutically acceptable salts, prodrugs, salts of prodrugs, esters, salts, esters, amides or salts of amides.

Yet another embodiment relates to a method of prevention or treatment of the body, prevent rejection of hematopoietic stem cell or bone marrow in the case of organ transplant, hematopoietic stem cell or bone marrow recipient, including the introduction of he compounds having the formula (I) or formula (I).

Yet another embodiment relates to a method of treating arthritis in a mammal, comprising introducing him 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.

Yet another embodiment relates to a method of treating arthritis in a mammal, including the surrounding introduction he 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.

Yet another embodiment relates to a method of treating arthritis in a mammal, comprising introducing him 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.

Yet another embodiment relates to a method of prevention or treatment of the body, prevent rejection of hematopoietic stem cell or bone marrow in the case of organ transplant, hematopoietic stem cell or bone marrow recipient, including the introduction he 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.

Obtaining typical compounds having formula (I) and (I)-a, and their analogues described in simultaneously considering applications for U.S. patent No. 11/491851 and 11/432937.

Detailed description of the present invention

This invention relates to the treatment of arthritis in a mammal, comprising introducing him to compounds having formula (I), in which case changing the remains represented by identifiers (capital letters with numeric and/or alphabetic Superscript) and which can be specifically implemented.

Podrazumeva is t, what should be clear that the proper valence in this context are stored for all combinations, and monovalent residues having more than one atom joined at their left ends.

Assume also that it should be clear that the specific embodiment of the changing balance may be the same or different as another specific embodiment, having the same identifier.

The term "alkenyl", as used in this context, means monovalent hydrocarbon residues with linear or branched chain having one or more than one double bond carbon-carbon bonds, such as C2alkenyl,3alkenyl,4alkenyl,5alkenyl,6alkenyl etc.

The term "alkyl", as used in this context, means a monovalent saturated hydrocarbon residues with linear or branched chain, such as C1-alkyl, C2-alkyl, C3-alkyl, C4-alkyl, C5-alkyl, C6-alkyl, etc.

The term "quinil", as used in this context, means monovalent hydrocarbon residues with linear or branched chain having one or more than one triple bond of carbon-carbon bonds, such as C2-quinil,3-quinil,4-quinil,5-quinil,6-quinil etc.

The term "cycloalkyl", as used in this context, means a saturated cyclic or bicyclic hydrocarbon residues, such as C4-cycloalkane,5-cycloalkane,6-cycloalkane,7-cycloalkane,8-cycloalkane,9-cycloalkane,10-cycloalkane,11-cycloalkane,12-cycloalken etc.

The term "cycloalkyl", as used in this context, means a monovalent saturated cyclic and bicyclic hydrocarbon residues, such as C3-cycloalkyl,4-cycloalkyl,5-cycloalkyl,6-cycloalkyl,7-cycloalkyl,8-cycloalkyl,9-cycloalkyl,10-cycloalkyl,11-cycloalkyl,12-cycloalkyl,13-cycloalkyl,14-cycloalkyl etc.

The term "cycloalkyl", as used in this context, means cyclic and bicyclic hydrocarbon residues having one or more than one double bond carbon-carbon bonds, such as C5-cycloalken,6-cycloalken,7-cycloalken,8-cycloalken,9-cycloalken,10-cycloalken,11-cycloalken,12-cycloalken,13-cycloalken,14-cycloalken etc.

The term "cycloalkenyl", as used in this context, means a monovalent cyclic hydrocarbon OST the weave having one or more than one double bond carbon-carbon bonds, such as C4-cycloalkenyl,5-cycloalkenyl,6-cycloalkenyl,7-cycloalkenyl,8-cycloalkenyl,9-cycloalkenyl,10-cycloalkenyl,11-cycloalkenyl,12-cycloalkenyl,13-cycloalkenyl,14-cycloalkenyl etc.

The term "heteroaryl", as used in this context, means furan, imidazole, isothiazol, isoxazol, 1,2,3-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, oxazole, pyrazin, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, 1,3,4-thiadiazole, thiophene, triazine and 1,2,3-triazole.

The term "heteroaryl", as used in this context, means furanyl, imidazolyl, isothiazolin, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, 1,2,3-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl.

The term "geteroseksualen", as used in this context, means cycloalkyl having one or two or three CH2-residue substituted independently selected from O, S, S(O), SO2or NH and one or two CH-residue, unsubstituted or substituted N, and means cycloalkyl having one or two or three CH2-balance, nezameshchenny the or substituted independently selected from Oh, S, S(O), SO2or NH and one or two CH-residue, substituted n

The term "geteroseksualen", as used in this context, means cycloalkene having one, two, or three CH2-residue substituted independently selected from O, S, S(O), SO2or NH and one or two CH-residue, unsubstituted or substituted N, and means cycloalkene having one or two or three CH2-residue, unsubstituted or substituted independently selected from O, S, S(O), SO2or NH and one or two CH-residue, substituted n

The term "heteroseksualci", as used in this context, means cycloalkyl having one or two or three CH2-residue substituted independently selected from O, S, S(O), SO2or NH and one or two CH-residue, unsubstituted or substituted N, and means cycloalkyl having one or two or three CH2-residue, unsubstituted or substituted independently selected from O, S, S(O), SO2or NH and one or two CH-residue, substituted n

The term "geteroseksualen", as used in this context, means cycloalkenyl having one or two or three CH2-residue substituted independently selected from O, S, S(O), SO2or NH and one or two CH-residue, unsubstituted or substituted N, and means cycloalkenyl having one or two or three CH2-residue, unsubstituted Il is substituted independently selected from Oh, S, S(O), SO2or NH and one or two CH-residue, substituted n

The term "serialkey", as used in this context, means the divalent hydrocarbon residues, both ends of which are attached to the same carbon atom, and having one or more than one double bond carbon-carbon bonds, such as C3-serialkey,4-serialkey,5-serialkey etc.

The term "spirooli", as used in this context, means a saturated divalent hydrocarbon residues, both ends of which are attached to the same carbon atom, such as C2-spiralcell,3-spiralcell,4-spiralcell,5-spiralcell etc.

The term "cyclic residue", as used in this context, means benzene, cycloalkane, cycloalkyl, cycloalkene, cycloalkenyl, heteroaryl, heteroaryl, geteroseksualen, heteroseksualci, geteroseksualen, geteroseksualen and phenyl, spiralcell, serialkeys, spiroheterocyclic and spiroheterocyclic.

Compounds according to this invention may contain asimmetricheskii substituted carbon atoms in the R - or S-configuration, where the designations "R" and "S" are as described in Pure Appl. Chem. (1976), 45, 13-10. Compounds having asimmetricheskii substituted carbon atoms with equal amounts of R - and S-configurations are RA is himicheskimi in the case of these atoms. Atoms with an excess of one configuration over another, attributed to redundant configurations available, preferably in excess of about 85-90%, more preferably in excess of about 95-99%, and even more preferably in excess of more than about 99%. Accordingly, assume that this invention encompasses the racemic mixture, the relative and absolute diastereoisomer and mixtures thereof.

Compounds according to this invention may also contain a double bond carbon-carbon bonds or double bonds, the carbon-nitrogen in the Z - or E-configuration, in which the symbol Z indicates that the larger two deputies are on the same side of the double bond carbon-carbon or carbon-nitrogen, and the symbol E means that the larger two deputies are on opposite sides of the double bond carbon-carbon or carbon-nitrogen. Compounds according to this invention can also exist as a mixture of Z - and E-isomers.

Compounds according to this invention, containing the remains of NH, C(O)H, C(O)OH, C(O)NH2, OH or SH may have attached thereto forming a prodrug remains. Forming prodrugs residues are removed in vivo by metabolic processes and are released compounds having free group NH, C(O)H, C(O)OH, C(O)NH2, OH or SH. Prodrugs suitable DL the regulation of such pharmacokinetic properties of the compounds, as the solubility and/or hydrophobicity, absorption in the gastrointestinal tract, bioavailability, tissue penetration, and rate of clearance.

Metabolites of compounds having formula (I)produced through metabolic processes in vitro or in vivo, can also be useful for the treatment of arthritis.

Some compounds precursor compounds having formula (I), can be metabolized in vitro or in vivo to form compounds having formula (I), and thus may also be useful for the treatment of arthritis.

Compounds having the formula (I)can exist in the form of additive salts of the acid additive salts of the bases or zwitterionic. Salts of compounds having the formula (I)receive at the time of their separation or further purification. Additive salts of acids are those obtained by introducing into the interaction of compounds having the formula (I)with acid. Respectively, imply that the salts of the compounds having formula (I), including acetate, adipate, alginate, bicarbonate, citrate, aspartate, benzoate, bansilalpet (besylate), bisulfate, butyrate, comfort, camphorsulfonate, digluconate, formate, fumarate, glycerol, glutamate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, lactobionate, lactate, maleate, mesitylenesulfonic, methanesulfonate, naftilan ulpanat, nicotinate, oxalate, pamoate, pectinate, persulfate, phosphate, picrate, propionate, succinate, tartrate, thiocyanate, trichloroacetic, triptorelin, para-toluensulfonate, undecanoate, included in the scope of this invention.

Additive salts with bases compounds are those obtained by introducing into the interaction of compounds having the formula (I), with bicarbonate, carbonate, hydroxide or phosphate of cations such as lithium, sodium, potassium, calcium and magnesium.

Compounds having the formula (I)can be entered, for example, buccal, ophthalmologist, orally, osmotically, parenterally (intramuscularly, interpreterale, intrasternally, intravenously, subcutaneously), rectally, topically, transdermal and vaginally.

Therapeutically effective amounts of compounds having the formula (I), depend on being treated recipient, treatable disease and its severity, including its composition, time of administration, route of administration, duration of treatment, efficacy, speed, clearance, and is entered whether or not together another medication. The number of compounds having formula (I)used to obtain the composition for a daily injection to a patient in a single dose or in divided doses is from about 0.001 mg/kg body weight to about 200 mg/kg of body weight. Com is osili in the case of a single dose contain these quantities, or a combination of their subsets.

Compounds having the formula (I)can be entered together with excipients or without excipient. Excipients include, for example, encapsulator and additives, such as absorption accelerators, antioxidants, binders, buffers, agents for coatings, paints, solvents, dezintegriruetsja agents, emulsifiers, diluents, fillers, flavoring agents, wetting agents, lubricants, flavorings, preservatives, propellants, secreting agents, sterilizers, sweeteners, soljubilizatory, humectants and mixtures thereof.

Compounds having the formula (I)may be labeled with radioactive isotopes, such as carbon (i.e.13C), hydrogen (i.e.3H), nitrogen (i.e.15N), phosphorus (i.e.32P), sulfur (i.e.35S), iodine (i.e.125I) and other Radioactive isotopes can be incorporated into compounds having the formula (I), by introducing them into interaction with radioactive derivatizing agent, or by introducing a radioactively labeled intermediate product during their synthesis. Radiolabelled compounds of formula (I) are suitable for both prognostic and diagnostic applications and for imaging in vivo and in vitro.

Compounds having the formula (I)can be inserted in the device, such as, but not limited to, arteriovenous grafts, biliary stents, roundabout the vascular shunts, catheters, shunts the Central nervous system, coronary stents, balloons for delivery of drugs to the site of its action, peripheral stents and urethral stents, each of which may be used in the area, such as, but not limited to, vascular network, for the introduction of compounds having the formula (I), in selected tissues or organs in the body. One measure of the effectiveness of the compounds having formula (I), is reducing or eliminating associated with the unit of blood clots and related complications.

Excipients to obtain compositions containing the compound having the formula (I), in order to introduce oral, 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, cross-povidone, diglycerides, ethanol, ethylcellulose, ailleret, etiloleat, fatty acid esters, gelatin, germ oil, glucose, glycerol, peanut oil, hypromellose, isopropanol, saturated isotonic saline, lactose, magnesium hydroxide, magnesium stearate, malt, mannitol, monoglycerides, olive oil, oil of groundnuts, potassium phosphate, potato starch, povidone, propelling icol, the ringer's solution, safflower oil, sesame oil, sodium carboxymethyl cellulose, sodium phosphate, sodium lauryl sulfate, atrisorb, soybean oil, stearic acid, fumarate, sucrose, surfactants, talc, tragakant, tetrahydrofurfuryl alcohol, triglycerides, water and their mixtures. Excipients to obtain compositions containing the compound having the formula (I), in order to introduce ophthalmicus or oral, including, for example, 1,3-butyleneglycol, castor oil, corn oil, cottonseed oil, ethanol, sorbitane esters of fatty acids, germ oil, oil of groundnuts, glycerol, isopropanol, olive oil, polyethylene glycols, propylene glycol, sesame oil, water and mixtures thereof. Excipients to obtain compositions containing the compound having the formula (I), for the introduction of osmotically include, for example, chlorofluorocarbons, ethanol, water and mixtures thereof. Excipients to obtain compositions containing the compound having the formula (I), in order to introduce parenterally include, for example, 1,3-butanediol, castor oil, corn oil, cottonseed oil, dextrose, 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 dissolve the sodium chloride, water and mixtures thereof. Excipients to obtain compositions containing the compound having the formula (I), in order to introduce rectally or vaginally include, for example, cocoa butter, polyethylene glycol, wax and mixtures thereof.

When using the standard analyses in relation to activation in vitro murine lymphocyte obtained data showed that the proliferation of activated T-lymphocytes in the case of the reaction of the mixed culture of lymphocytes (MLR) and activated b-lymphocytes due to lipopolysaccharide stimulation can be ingibirovany dependent on the concentration of the image by using the compounds of EXAMPLE A. Similar effect was observed in vivo. Mice were immunized with hemocyanin patella (KLH) and were treated with compound a or filler as a control. Restimulate KLH antigen-specific T cells ex vivo showed a significant inhibition of proliferation. It was found that the cells that have been "saved" after processing Bcl-2 inhibitor compound of EXAMPLE AND are sensitive to concavalin And that, without implying limitation theory suggests that in case some may remain normal immune function.

Also, to induce disease used the standard murine model of arthritis, in which case use mice DBA/1J(H-2q)immunized with collagen and Reiman the new simhasanam after 21 days. Mice were then treated with compound a (50 mg/kg per day), filler (without drug) and dexamethasone (1 mg/kg per day) during the first clinical symptom of the disease. Mice were then assessed in relation to the average arthritic score (MAS) and tumor feet within 3 weeks after starting treatment. As shown in figures 1 and 2, as treatment with dexamethasone and compound of EXAMPLE AND show inhibition of arthritis, as determined by MAS (p<0.5) and in case of swelling of the legs (p<0,5), when compared with the filler, used as a control.

Also determined the total volume of bone by micro-computer tomography (CT) to cut the size of 1.8 mm ankle joints mouse from the base of the tibia to the tarsal/metapragmatic joints, at a resolution of 18 μm.

These data show that the compound of EXAMPLE AND as typical examples of the compounds having formula (I), leads to specific lymphocytic immune suppression and these compounds are effective in the case of arthritis treatment.

Compounds having the formula (I), can be used individually or in combination with additional therapeutic agents. For example, the additional agent can be an agent, a recognized suitable for treatment of the disease or what Oceania, being treated using compounds according to this invention, or which gives a useful property of the tool. The agents presented in this description are for illustration purposes and are not intended to limit the scope of rights of the present invention. Combinations, which are part of the present invention may be a compound having the formula (I), and at least one additional agent selected from the list according to the given context. The combination may also include more than one additional agent. Such combinations include non-steroidal(s) anti-inflammatory(s) of drug(s) tool(s), also referred to as NSAIDS, which includes a drug (such as ibuprofen). Other combinations include corticosteroids (such as prednisone). Well-known side effects in the case of steroid use can be reduced or eliminated by reducing the required dose of steroid, when patients are treated in combination with the compounds according to this invention. Examples of agents that you can use the connection according to the invention for the treatment of rheumatoid arthritis include cytokine-suppressive(s) anti-inflammatory(s) of drug(s) means(a) (CSAID), the antibody in relation to or antagonists of other human the definition of cytokines or growth factors (such as EMAP-II, GM-CSF, FGF, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-12, IL-15, IL-16, IL-21 and IL-23), interferons, LT, PDGF, TNFα, etc.

Compounds having the formula (I), can be combined with an antibody against cell surface molecules, such as CD2, CD3, CD4, CD8, CD25, CD28, CD30, CD40, CD45, CD69, CD80 (V), CD86 (V), CD90, CTLA or their ligands (e.g., CD154 (gp39 or CD40L), etc.

Combination agents may interfere at different points in the autoimmune and subsequent inflammatory cascade. Examples of such agents include CA2 (REMICADE™), CDP 571, chimeric, D2E7 (HUMIRA™), humanitariannet or human TNF-a antibody inhibitors of IL-1 inhibitors, IL-1 converting enzyme (such as IL-1RA), IL-11, p55TNFR1gG (Lenercept), p75TNFR1gG (ENBREL™), soluble P55 or P75 TNF receptors, inhibitors of TNFα converting enzyme (TACE), etc.

Still other combinations are key participants in the case of an autoimmune response which may act parallel to, dependent on or in conjunction with the function of IL-18 (such as antagonists of IL-12, including IL-12 antibody or soluble IL-12 receptor or IL-12 binding proteins). It is shown that IL-12 and IL-18 have overlapping, but different functions, and the combination of both antagonists can be most effective. Another preferred combination are not subject to depletion of anti-CD4 inhibitors. In addition, other predpochtitel the haunted combinations include antagonists costimulating way CD80 (B7.1) or CD86 (V) (such as antagonistic ligands, antibody, soluble receptors, and the like).

Compounds having the formula (I), can be combined with therapeutic agents such as 5-aminosalicylic acid, α-immunogen NNSO3, ABR-215062, acetaminophen, agonists adenosine, adrenergic agents, agents that reduce or inactivate b-cells, agents that interfere with signaling by proinflammatory cytokines (such as TNFα), or agents that interfere with signaling by proinflammatory cytokines (such as TNFα), alemtuzumab, alendronate sodium, AMG-548, amitriptylineonline, anakinra, AnergiX.MS inhibitors angiotenzinkonvertiruyuschego enzymes antegren, antibody against family V7, antibody against the receptor of IL-6, antibody against the family of IL-12, IL-15, PD-1, an antibody against tumor necrosis factor, an antibody to the molecule of the surface of b-cells, antibody to cell surface molecules, such as CD2, CD3, CD4, CD8, CD19, CD20, antibody to CD40 ligand and CD80), anti-inflammatory cytokines (such as IL-4), antithrombotic agents, aspirin, aurothiomalate (intramuscular and oral), azathioprine, azathioprineallergic, CD25, CD28, CD30, CD40, CD45, CD69, CD80, CD86, CD90 (and other ligands), IL-1 (such as IRAK), balsalazide, BBR-2778, agonists beta-2-adrenergic receptors (such as salbutamol), BIRB-796, budenoside, CA2 (REMICADE™), calaguala, caspase inhibitors (such as inhibitory caspase-1), CDC-801, CDP 571, celecoxib, chemokine receptor antagonists, cholestyramine/sucrose, ciprofloxacin/dextrose-water, ciprofloxacinciprofloxacin, colchicine, codeinefosfaat/apap, causevalidation, inhibitors of complement, Copaxone, corticosteroids (such as prednisolone) (oral, inhaled and local injection), CPI-1189, chromoglycate, CTLA4-IG, CTLA-4-IgG, cyanocobalamin, cyanocobalamin/FA/pyridoxine, cyclophosphamide, cyclosporine, ciclosporin, D2E7, daclizumab, dexamethasone, diclofenac, diclofenac sodium, diclofenac sodium/misoprostol, Diphenoxylate/atropalpus, dronabinol, etanercept, etodolac, Fampridine, fentanyl, FK506, fluocinonide, folate, folic acid, fontolizumab (antibody against IFNg), latinamerica, glucosaminyl/chondroitin, thiomalate sodium and gold, hydrocodonebitartrat/apap, hydrocortisone, hydroxychloroquine, gosciminski, ibuprofen, IC-485, IFNα1a, IFNα1b, IKK, IL-1 (such as IRAK and TRAP), inhibitors of IL-1α-converting enzyme, IL-1ra, IL-2, agonists of IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-18 BP, IL-11, IL-13, IL-15, IL-16, IL-23, Imuran®, indomethacin, antagonists of IFN-γ, infliximab, ipratropium, interferon-α1 (AVONEX®); IFN-α1b (BETASERON®), interferon α-n3, interferon-α, interferon α1-IF, ketotifen, Leflunomide, levofloxacin, LEM (encapsulated liposome mitoxantrone), lidocaineydrocortisone, LJP 394 (AB is the thymus), loperamidesee, lymphostat (antibody against BlyS), 6-MP, 6-mercaptopurine inhibitors MAR-kinase, MBP-8298, meloxicam, piperidinylcarbonyl, mercaptopurine, mesalamine, mesalazine, mesopram, mesopram (PDE4 inhibitor), inhibitors of metalloproteinases, methotrexate, methylprednisolone, methylprednisolone, methylprednisoloneside, metronidazole, midazolam.hydrocodone, mitoxantrone, MNA-715, martinslife, MRA, multivitamins, mycophenolate mofetil, nabumeton, aproximatly, natalizumab, nedocromil, neurovax, NIK, NSAID, adoptedunanimously, olsalazine, alkalosisprices/hydroxychloroquin, omeprazole, oxaprozin oxitropium, oxycodonehydrocodone, oxycodonehydrocodone/acetaminophen, R, p55TNFRIgG (LENERCEPT™), p75TNFRIgG (ENBREL™), pencillamine, a phosphodiesterase inhibitor, perpendicular 1258 (RDP-1258), piroxicam, polycarbophil, prednisone, prednisolone, promethazineodeine, propoxyphenyl, propoxyphenyl/apap, rapamycin, rituximab (the antibody against CD20), rofecoksib, roflumilast, salmeterol, salsalate, SCIO-469, sIL-1RI, sIL-1RII, sIL-6R, sIL-6R) and antiinflammatory cytokines (such as IL-4 and TGFβ), cannabidiol, sodium phosphate, soluble cytokine receptors and derivatives thereof (such as soluble P55 or P75 TNF), soluble cytokine receptors and derivatives thereof (such as soluble receptors P55 or P75 TNF), sTNF-R1, Sul is fedyashin, sulfamethoxazole/trimethoprim, sulfasalazin, sulindac, inhibitors of signal transmission of the T-cell (such as kinase inhibitors, TACE inhibitors, talampanel, terbutaline, teriflunomide, tetracyclinetoprol, TGFβ, TGF-β2, THC.CBD (cannabinoid agonist), diplomatic, thimerosal/boric acid, design TNFR-Ig, TR-14035, tramadolhydrochlorid, triaminobenzene, tyrosine kinase inhibitors, valdecoxib, antagonists of VLA-4, VLA4 Ultrahaler, VX-702, VX-740, celebratingthe, xantina (such as theophylline and aminophylline), etc.

All of the above is intended to illustrate this invention, but not limit its scope of protection. Assume that variations and modifications obvious to a qualified specialist in this field, further included in the scope of this invention as described in the attached claims.

A method of treating arthritis in a mammal, comprising introducing him 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.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention refers to orthopaedics, namely rheumatology, and concerns treating Baker's cyst. That is ensured by cyst puncture, aspiration of its content, and introduction of the non-steroid anti-inflammatory preparation xefocam in its cavity; and then the enzymatic preparation longidaza is introduced in a paraarticular space.

EFFECT: method provides effective conservative treatment of Baker's cyst with no recurrences and side effects.

11 cl, 2 dwg, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) where values of substituents are given in description, possessing inhibiting activity with respect to cathepsin K as well as to pharmaceutical compositions for treating diseases, associated with cysteine protease activity and to methods of inhibiting cathepsin K in mammals, requiring such treatment by introduction of efficient amount of compound to mammal.

EFFECT: claimed is application of formula (I) compound or its pharmaceutically acceptable salt in manufacturing medication for application in cathepsin K inhibition in a warm-blooded animal.

10 cl, 45 ex, 5 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I) and its pharmaceutically acceptable salts possessing dihydroorotate dehydrogenase inhibitory ability, to a based pharmaceutical composition, to application thereof in preparing a drug compound and to a combined preparation containing the presented compounds and the other active compound (I) in effective amounts wherein both groups G1 mean CRC, G2 mean a nitrogen atom or group CRd, of the groups G3 and G4 mean a nitrogen atom and the other one means group CH, M means a hydrogen atom or a pharmaceutically acceptable cation, while R1, R2, Ra, Rb, Rc and Rd have the values specified in the patent claim.

EFFECT: preparing pharmaceutically acceptable salts possessing dihydroorotate dehydrogenase inhibitory ability.

25 cl, 115 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely traumatology, orthopaedics and rehabilitation, and may be used for treating inflammatory-degenerative arthropathies. The therapy is three-staged. The first stage involves at least one course of the integrated therapy aiming at inflammatory response suppression and pain syndrome arrest. The second stage involves at least one session of focused extracorporeal shock wave therapy to create microcavities buried in a interarticular cartilage. At the third stage, the created microcavities buried in the interarticular cartilage are filled with a modelling compound by interarticular electrophoresis followed by stabilising the modelling compound. The modelling compound is represented by a mixture of 15 portions of fine biopolymer gel, 65 portions of hyaluronic acid, 15 portions of animal's articular cartilage extracts and 5 portions of Dimexidum solution. The modelling compound is stabilised by non-invasive exposure to pulse high-power IR laser at wave length 785 nm and heated to 44 Celsius degree.

EFFECT: method provides high clinical effectiveness to be implemented in outpatient care that enables avoiding a surgical intervention, including joint replacement, and ensuring complete removal ensured by possibility of recovery of shape, volume and normal consistence of the interarticular cartilage.

3 ex

FIELD: medicine.

SUBSTANCE: presented group of inventions refers to medicine. What is presented is application of IL-1β binding antigen for producing a drug preparation for treating juvenile rheumatoid arthritis in a patient, containing at least one antigen-binding centre which involves a first domain having an amino acid sequence specified in SEQ ID NO:1, and a second domain having an amino acid sequence specified in SEQ ID NO:2. What is presented is a pharmaceutical composition containing said antibody in a combination with pharmaceutically acceptable excipients, solvents or carriers introduced parenterally.

EFFECT: presented group of inventions provides new application of IL-1β binding antibody for treating juvenile rheumatoid arthritis, particularly systemic idiopathtic juvenile rheumatoid arthritis in mammals, particularly in a human.

10 cl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to pharmaceutical industry, in particular to composition for prevention or therapeutic treatment of inflammatory and/or degenerative condition. Composition for local application for prevention or therapeutic treatment of inflammatory and/or degenerative condition, including (i) woundwort or obtained from woundwort compound or its analogue or derivative, and (ii) tannic acid or its analogue or derivative. Method of prevention or therapeutic treatment of inflammatory and/or degenerative condition (versions). Application of composition for local application for production of medication for prevention or therapeutic treatment of inflammatory and/or degenerative condition. Set, including in two or more containers (i) tannic acid or its analogue or derivative and (ii) woundwort or obtained from woundwort compound or its analogue or derivative or any their combination. Set, including container, which includes composition for local application.

EFFECT: composition possesses synergetic pharmacological effect.

41 cl, 17 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula (I) or to its pharmaceutically acceptable salt: formula (I) wherein; R1 represents hydrogen; R2 represents phenyl, benzothienyl, benzofuranyl or the group -CH2CH2-phenyl; wherein R2 is optionally substituted by 1 or 2 substitutes optionally specified in F, O, Br, I, -CN, -NO2, -OR8, C1-C6alkyl and -N(R9)2; R4 represents phenyl substituted by 1 or 2 substitutes optionally specified in F, CI, Br, I, -CP3, -OH, -OR8 and C1-C6alkyl; each R8 is optionally specified in C1-C6alkyl; and each R9 is optionally specified in H and C1-C6alkyl. The invention also refers to a pharmaceutical composition for activity modulation of depot-controlled calcium channels (SOC-channels) containing such compounds.

EFFECT: there are produced new compounds and based pharmaceutical compositions which can find application in medicine for treating the diseases or conditions, such as rheumatoid arthritis, psoriasis, inflammatory intestinal disease, asthma and multiple sclerosis.

12 cl, 21 dwg, 1 tbl, 14 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to diseases of locomotive apparatus and can be applied for treatment of acute or chronic tendovaginitis. Ultrasonic scanning (US) of inflamed synovial bursas is performed to patient. During examination under local anesthesia with solution of 2% lidocaine puncture of bursa and suction of content with the following inoculation on medium for verification of causative agent and sensitivity to antibiotics are performed. Synovial bursa is washed with solutions of antiseptics with following introduction into its cavity of target antibiotics, dissolved in 1% solution of novocaine. Then, after thirty minutes after achiving anesthetic effect of novocaine absorption, patient performs flexion-extention movements. Procedure is carried out two times per day with interval in twenty hours.

EFFECT: claimed method of tendovaginitis treatment is simple in application, reduces temporary disability, has strongly pronounced cosmetic effect and can be recommend to wide range of practicing doctors of hospital or clinic.

1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to traumatology, and deals with elaboration of problems of treating traumatic affection of joints. Results, carried out in experiment, make it possible to suggest the following method of treating intraarticular fractures. Immobilisation of joint with recovery of anatomically correct interrelationship, stabilisation and further training movements in joint by means of apparatus of external fixation are performed. After recovery of anatomically correct interrelationship, not later than 3 days after trauma, joint surfaces are brought apart for the width which up to 50% exceeds the width of joint space of unaffected joint. During 4-5 days 24-hour drop-by-drop introduction of 0.9% sodium chloride solution into joint cavity is performed. Simultaneously one time per day freshly prepared solution consisting of 40% glucose solution, 5% ascorbic acid solution and autologic blood plasma, taken in volume ratio 1:2:7.

EFFECT: method ensures considerable reduction of fracture treatment terms in comparison with such treated by method of tranosseous osteosynthesis with application of apparatuses of external fixation due to enhancement of reparative regeneration processes.

3 dwg

FIELD: medicine.

SUBSTANCE: invention refers to compounds of formula (I) and their pharmaceutically acceptable salts possessing the properties of a MMP12 inhibitor, a method for preparing them, an intermediate compound of formula (III), a pharmaceutical composition, a method for preparing it, using the compounds of formula (I) and versions of methods of treating with the use of the compounds of formula (I). The compounds may be used for treating the MMP12-mediated diseases, such as chronic obstructive pulmonary disease. In formula (I) and (III) R1 represents H, CH3, CH3CH2, CF3 or cyclopropyl; and R2 represents H or CH3.

EFFECT: higher clinical effectiveness.

15 cl, 1 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound which is 7-methyl-5-(3-piperazin-1-ylmethyl-[1,2,4]oxadiazol-5-yl)-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-one, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition having potentiating activity on glutamate receptors, containing the compound described above; also described is use of the compound or a pharmaceutically acceptable salt in claim 1 in producing a medicinal agent for therapy of neurological and mental disorders associated with glutamate dysfunction.

EFFECT: novel compound which can be used in therapy of neurological and mental disorders is obtained and described.

5 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to DGAT inhibitor of formula (I), its N-oxide, pharmaceutically acceptable salt and solvate, based on it pharmaceutical composition and its application for treatment of diseases, mediated by DGAT activity, such as obesity and diabetes. In general formula (I) A represents CH or N; X represents -C (=O)-C(=O); -O-C(=O)-; -NRX-C(=O)-; -Z1-C(O)-; -Z1-NRx-C(O)-; -C(O)-Z1-; -NRx-C(O)-Z1-; -S(=O)p-; -NRX-C(=S) -; Y represents NRx-C(=O)-Z2-; -NRx-C(=O)-Z2-NRy-; -NR*-C(=O)-Z2-NRy-C(=O)-; -NRx-C(=O)-Z2-NRy-C(=O)-O-; -NRx-C(O)-Z2-O-; -NRx-C(=O)-Z2-O-C(=O)-; -NRx-C(=O)-Z2-C(=O)-O-; -NRx-C(=O)-Z2-C(=O)-NRy-; -NRx-C(=O)-Z2-NRy-C(=O)-NRy-, -C(<))-Z2-; -C(=O)-NRx-Z2-; -C(=O)-NRx-Z2-O-; R1 represents C1-12alkyl, optionally substituted with cyano, C1-4alkyloxy, C1-4alkyloxy C1-4alkyloxy, C3-6cycloalkyl or aryl; C2-6alkenyl, C2-6alkinyl; C3-6cycloalkyl; adamantanyl; aryl1; aryl1C1-6alkyl; Het1; or HetC1-6alkyl, on condition that when Y represents -NRxC(=O)-Z2-; -NRx-C(=O)-Z2-NRy; -NRx-C(=O)-Z2-C(=O)-NRy-, -C(=O)Z2-; -NRx-C(=O)-Z2-NRy-C(=O)-NRy-; -C(=O)-NRx-Z2-; -C(=O)-NRx-O-Z2- or -C(=O)-NRx-Z2-NRy-; then R1 can also represent hydrogen; R2 represents R3; R3 represents phenyl, naphthalenyl, 2,3-dihydrobenzofuranyl or 6-membered aromatic heterocycle, containing 1 or 2 N atoms, where each of said cycles can optionally be substituted with, at least, one substituent, in particular, one-five substituents, said substituents represent halogen, C1-6alkyl, optionally substituted with hydroxy, polyhalogen C1-6alkyl, C1-6alkylthio, polyhalogen-C1-6alkyloxy, carboxyl, hydroxyl, C1-6alkylcarbonyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, nitro, R5R4N-C(=O)-; R5R4N-C1-6alkyl; HetC1-4alkyl, Het-C(=O)-C1-4alkyl, Het-C(=O)-; R8 represents hydrogen, halogen, C1-4alkyl, substituted with hydroxyl Values of other radicals are given in invention formula.

EFFECT: obtaining pharmaceutical composition for treatment of diseases, mediated by DGAT activity, such as obesity and diabetes.

31 cl, 5 tbl, 352 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical composition for treating diabetes, obesity or metabolic syndrome, which includes therapeutically efficient amount of (5-hydroxyadamantan-2-yl)amide of trans-2'-tret-butyl-2'H-[1,3']bipyrazolyl-4'-carboxylic acid or its pharmaceutically acceptable salts, and pharmaceutically acceptable carrier.

EFFECT: invention also relates to application of said compound for preparation of medication, intended for treatment of said diseases.

2 cl, 1 tbl, 99 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to dihydropyrazolone derivatives or of formula (I), where R1 denotes a heteroaryl group of formulae given below, where * denotes the linkage point with the dihydropyrazolone ring, A in each individual occurrence denotes C-R4 or N, wherein at most two ring members A represent N at the same time, E denotes O or S, R2, R3 and R4 are as defined in the claim. The invention also relates to a method of producing said compounds.

EFFECT: compounds of formula (I) inhibit HIF-propylhydroxylase activity and can be used to treat and/or prevent diseases, as well as for producing medicaments for treating and/or preventing diseases, particularly cardiovascular and haematologic diseases, kidney diseases, and for promoting the healing of wounds.

10 cl, 10 tbl, 178 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to specific compounds of 1-substituted 3,4-tetrahydroisoquinoline derivative. Invention also relates to pharmaceutical composition based on claimed compounds, to blocker of N-type Ca2+- channel based on claimed compounds, to application of claimed compounds, as well as to method of prevention or treatment of some pathologic conditions.

EFFECT: obtained are novel 3,4-tetrahydroisoquinoline derivatives, having substituent in 1-position and possessing blocking action on N-type Ca2+- channels.

15 cl, 129 tbl, 17 ex

FIELD: chemistry.

SUBSTANCE: compound, represented by formula

,

or its pharmaceutically acceptable salt, where Y1 represents nitrogen atom or group, represented by CRA, Y2 represents nitrogen atom or group, represented by CRB, Y3 represents nitrogen atom or group, represented by CRC, RA, RB and RC, which can be similar or different, each represents hydrogen atom, etc. (except in the case, when Y1 is CRA, Y2 is CRB and Y3 is CRC), X represents oxygen atom, etc., R1 represents C1-C6alkyl group, etc., R3 represents optionally substituted phenyl group, etc., R4 represents hydrogen atom, etc., and R5 represents optionally substituted phenyl group, etc.), possesses inhibiting action with respect to S1P binding with its receptor Edg-1(SlP1).

EFFECT: obtaining composition, which can be used as therapeutic medication in case of autoimmune diseases, rheumatoid arthritis, asthma, atopic dermatitis, rejection after organ transplantation, cancer, retinopathy, psoriasis, osteoarthritis or age-related macula lutea degeneration, etc.

13 cl, 9 ex, 1 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: invention refers to a pharmaceutical composition for prevention and treatment of diabetes mellitus and obesity containing as active ingredients a compound inhibiting activity of dipeptidylpeptidase-IV (DPP-IV), its pharmaceutically acceptable salt, its hydrate or its solvate, and one or more other antidiabetic agents or antiobesity agents.

EFFECT: pharmaceutical composition shows excellent improvement of glucose tolerance and may be used in prevention and treatment of diabetes mellitus, obesity and similar diseases, effectively reducing blood glucose level and weight.

25 cl, 8 dwg, 17 tbl, 32 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, and may be used for the use of testosterone and 5-HT1A agonist for preparing a drug for treating sexual dysfunction. Said drug is used as required wherein testosterone is released 3.5-5.5 hours before sexual activity, and 5-HT1A agonist is introduced so that effects of the peak amounts of said substances are partially overlapped. What is also presented is the use of testosterone, PDE5 inhibitor and 5-HT1A agonist for preparing the drug for treating sexual dysfunction. There are also presented pharmaceutical compositions and kits.

EFFECT: group of inventions provides reducing the blood testosterone and 5-HT1A agonist levels to physiological values that promotes treating sexual dysfunction both in males, and in females.

17 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical combination and to its use for treating an infection caused by influenza virus. The declared composition contains a pyrazine derivative of formula wherein R1 and R2 are identical or different, and each represents a hydrogen atom or a halogen atom; and R3 represent a hydrogen atom or a protective group for amino group or its salt, and, and a neuraminidase inhibitor. The neuraminidase inhibitor is specified in oseltamivir, zanamivir, peramivir or CS-8958.

EFFECT: invention provides preparing the combination which shows strong antiviral activity, smaller side effects and applicable for treating influenza.

12 cl, 8 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted sulphamide derivatives of formula I: , in which n, m, R1, R2a-c, R3, R4, R5 and R6 are as described in claim 1, in form of a racemate, enantiomers, diastereomers, mixtures of enantiomers or diastereomers or a separate enantiomer or diastereomer, bases and/or salts of physiologically compatible acids. The invention also relates to a method of producing said compounds, a medicinal agent having antagonist action on bradykinin receptor 1 (B1R), containing such compounds, use of such compounds to produce medicinal agents, as well as sulphamide-substituted derivatives selected from a group of compounds given in claim 8.

EFFECT: providing novel compounds which are suitable as pharmacologically active substances in medicinal agents for treating disorders or diseases which are at least partially transmitted through B1R receptors.

13 cl, 581 ex

FIELD: organic chemistry, heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of heteroarylalkylpiperazine of the general formula (I):

wherein m = 1, 2 or 3; q means NH or oxygen atom (O); R1, R2, R3, R4 and R5 are taken independently among the group including hydrogen atom, (C1-C15)-alkyl, OR20 wherein R20 represents hydrogen atom; R6, R7 and R8 represent hydrogen atom; R9, R10, R11, R12, R13, R14, R15 and R16 are taken independently among the group including hydrogen atom, (C1-C4)-alkyl; or R9 and R10 in common with carbon atom to which they are joined form carbonyl group; R17 means heteroaryl that is taken among the group including indolyl, benzoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, pyridyl, benzopyrazinyl substituted optionally with 1-2 substitutes taken among the group including hydrogen atom, CF3 group, (C1-C8)-alkyl, phenyl, CON(R20)2. Compounds elicit property as a partial inhibitor of oxidation of fatty acids and can be used in therapy for protection of skeletal muscles against results of muscular or systemic diseases. Also, invention describes a pharmaceutical composition based on the claimed compounds.

EFFECT: valuable medicinal properties of compounds.

39 cl, 3 tbl, 25 ex

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