Nitrogen-containing heterocyclic derivatives and medicaments thereof as active ingredient

FIELD: chemistry.

SUBSTANCE: present invention refers to the new compounds of formula (I): whereat R1 is -SO2NR102R103, -NR101SO2R104 or -COOR105 whereat R101 is hydrogen atom, R102 and R103 each independently represents hydrogen atom or C1-4 alkyl, R104 is C1-4 alkyl and R105 is hydrogen atom or C1-4 alkyl ; X is bond, -CH2- or -O-; Y is -CH2-; ring A and ring B, which are same or different, each independently is benzene, pyridine, pyrazol or piperidine which can have the following substituents: C1-4 alkyl or halogen; ring D is piperidine; R2 is whereat the arrow shows the position of the bond with the ring D; R51 is (1) hydrogen atom a, (2) C1-6alkyl, which can have the following substituents: (a) hydroxy, (b) methoxy, (c) cyano, (d) carboxy, (e) halogen, (f) methyl sulphonylamino, (g) C3-8cycloalkyl or phenyl, which can have the following substituents: methyl, halogen, hydroxy or methoxy, (h) thienyl, pyrazolyl, tetrahydropyranyl, thiazolyl, isooxalyl, imidazolyl, tetraazolyl, pyridyl, pyrimidinyl which can have the following substituents: methyl, trifluoromethyl or hydroxy, (3) C2-10alkenyl, (4) C2-10alkynyl, (5) phenyl which can have the following substituents: C1-4alkyl or halogen, or (6) pyridine or tetrahydropyran; R52 is (1) hydrogen atom a, (2) C1-6alkyl which can have the following substituents: (a) hydroxy, (b) methoxy, (c) carboxy, (d) C3-8cycloalkyl, (e) phenyl or (f) oxo, (3) C3-8cycloalkyl or phenyl which can have the following substituents: C1-4alkyl, hydroxy, cyano, oxo, carbamoyl, N-methyl aminocarbonyl, carboxy, halogen, methoxy, trifluoromethoxy, methythio, methylsulphonyl, acetylamino, dimethylamino, acetyl, tetraazolyl, trifluoromethyl or methylsulphonylamino (4) C3-10cycloalkenyl, (5) adamantyl, (6) thienyl, pyrazolyl, tetrahydropyranyl, isoxaazolyl, isothiazolyl, thiadiazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, indolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, dioxaindanyl, benzodioxaindanyl which can have the following substituents: C1-4alkyl, hydroxy, oxo, halogen, azido or trifluoromethyl or (7) benzyloxy groups; and R53 is hydrogen atom or C1-6alkyl; to its salts or its solvates. The invention refers also to the regulator CCR5, to the agent of prevention and/or treatment of HIV infection, immunological or inflammatory diseases, to the pharmaceutical composition, to the medicinal preparation, to the method of disease treatment or prevention as well as to the application of compound as in claim 1.

EFFECT: obtaining of new bioactive compounds possessing anti CCR5 receptor activity.

23 cl, 41 ex

 

The technical field to which the invention relates

The present invention relates (1) to compounds represented by formula (I)

(where all the symbols have the following meaning, as described below), their salts or their solvate, or their prodrugs, and (2) treatment and/or prevention of diseases mediated by CCR5-containing compounds represented by formula (I), their salts or their solvate, or prodrug, as an active ingredient.

The level of technology

Chemokine known as the primary protein with endogenous chemotactic activating abilities against leukocytes and strong ability to bind heparin. Currently, it is believed that the chemokine is associated not only with the control of specific infiltration of leukocytes during inflammation and immune responses, but also with the development and homing of lymphocytes under physiological conditions and migration of precursor cells of hemocytes and somatic cells.

Differentiation, proliferation and cell death of hemocytes are associated with different types of cytokines. In vivo inflammation occurring locally, and differentiation, maturation, and the like lymphocytes are made in certain specific locations. That is, various necessary cells migrate into the CFP is divided into specific sites and are accumulated there, causing some inflammation and immune reactions. Accordingly, cell migration is also mandatory event in addition to differentiation, proliferation and cell death.

Migration of hemocytes in a living organism begins first of all in the development stage through the shift hematopoesis, beginning at the area AGM, permanent hematomas in the bone marrow by fetal liver tissue. In addition, precursor cells, T cells and dendritic cells of the thymus migrate from the fetal liver tissue in the bone marrow, and then, in the thymus and are cytodifferentiation in the environment of the thymus. T-cell, which receives clonal selection, migrate to the secondary lymphoid tissue and is involved in the immune response in the periphery. Cell Langerhans skin, activated and differentiated by capturing antigen, migrate to the area of T cells in local lymph node and activate uninfected T-cell in it as dendritic cells. T-cell memory performs his homing again in the lymph node via the lymphatic and blood vessels. Also B-cell, T-cell in the epithelium of the intestine, γδ T-cells, NKT-cell and dendritic cell migrate from the bone marrow without passing through the gland and differentiate to participate in the immune response.

Chemokine in IMET significant part in the migration of these different cells. Receptors chemokines are strongly linked with the control of inflammation and immune responses through a mechanism through which they are expressed during certain specific periods in different ways specific cells, and effector cells accumulate in areas where produced chemokines.

Acquired immunodeficiency syndrome (referred to as AIDS), which is induced by the human immunodeficiency virus (hereinafter referred to as "HIV"), is one of the diseases for which therapeutic methods are most desirable in recent years. After HIV infection of CD4-positive cells, which is the main the target cell, HIV reiterates its proliferation in the patient's body and, sooner or later, completely destroys the T-cell, which bears the immunological function. During this process immunological function gradually weakens, causing fever, diarrhea, enlarged lymph nodes, and the like in various States of immunodeficiency, which tend to cause complications Pneumocystis pneumonia and the like, various opportunistic infections. Such conditions represent the initial stage of AIDS, and it is known that they cause and contribute to the development of Kaposi's sarcoma and the like malignant tumors.

As the last of the JV is to get the prevention and therapeutic treatment attempts, for example, (1) to inhibit the growth of HIV by the introduction of nucleoside reverse transcriptase inhibitor or protease inhibitor and (2) to prevent or reduce opportunistic infections by administration of a medicinal product with the activity of strengthening the immune system.

Helper T-cells that bear the brunt of the immune system, mainly becoming infected with HIV. Since 1985 it is known that HIV uses a membrane protein CD4 expressed on the membrane of T-cells during infection (Cell52, 631 (1985)). The CD4 molecule consists of 433 amino acid residues, and its expression is detected in macrophages, some B-lymphocytes, cells of the vascular endothelial cells of Langerhans of skin tissues, dendritic cells of lymphoid tissues, glial cells of the Central nervous system and the like in addition to adult helper T cells. However, as there is evidence that HIV infection is not completed only by CD4 molecule, suggested the possible presence of factors other than the CD4 molecule, which is associated with HIV infection of cells.

CCR5, which is the receptor for RANTES, MIP-1α and MIP-1β, also used during infection tropic (R5) HIV-macrophage (Science,272, 1955 (1996)).

Accordingly substances that can compete with CCR5 for HIV or who can connect with WEE virus is, thus making the virus is unable to communicate with CCR5 can be inhibitors of HIV infection.

Thus, it is believed that the CCR5 receptor significantly associated with inflammation, immune disease, or HIV infection. For example, it is believed that they are associated with various inflammatory diseases (asthma, nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, rhinitis, conjunctivitis, ulcerative colitis, etc.), immunological diseases (autoimmune diseases, rejection of organs in transplantation, immunosuppression, psoriasis, multiple sclerosis and the like), infection of human immunodeficiency virus (acquired immunodeficiency syndrome and the like), allergic diseases (atopic dermatitis, urticaria, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis, etc.), ischemic reperfusion injury, acute respiratory distress syndrome, shock accompanying bacterial infection, diabetes, or cancer metastasis, and the like.

It is reported that aminopiperidine derivative represented by the formula (a)

(where R1arepresents a hydrogen atom or C1-12 alkyl, R2aand R3aimagine every illegal is isimo, a hydrogen atom or C1-12 alkyl, Xarepresents a nitrogen atom or an oxygen atom, Aais

(where R4arepresents a hydrogen atom, C1-12 alkyl, C3-8 cycloalkyl, aryl, substituted aryl, aryl-C(=O)- or aryl-CH(OH)-, R5arepresents hydrogen, C1-12 alkyl, C1-4 alkoxy, halogen or COR, R6arepresents hydrogen, C1-12 alkyl or substituted C1-4 alkyl, provided that the definition of each symbol is revealed in part) are suitable for use as inhibitors of receptors chemokines (description of the application for international patent application WO02/79186).

Describes what sulfonic acid derivatives represented by the formula (b)

are selective antagonists of the CCR1 receptor (description of the application for international patent application WO02/102787).

In addition, derivatives of 1-(4-pyridyl)piperazine described as antagonists of CCR5 (description of U.S. patent No. 6391865).

On the other hand, it is reported that derivatives of diazaspiro[5.5]undecane, its salts with Quaternary ammonium or the N-oxides, or its pharmacologically acceptable salt regulate the effect of chemokine/receptor of the chemokine and used for the prevention and/or treatment of various inflammatory diseases, asthma, atopic dermatitis, urticaria, allergic diseases (allergic broncho limonadnogo aspergillosis or allergic eosinophilic gastroenteritis, etc.), nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, psoriasis, rhinitis, conjunctivitis, ischemic reperfusion disorder, multiple sclerosis, ulcerative colitis, acute respiratory distress syndrome, cytotoxic shock, diabetes, autoimmune diseases, when the reactions of rejection of transplanted organs, immune suppression, cancer metastasis and the acquired immunodeficiency syndrome (description of the application for international patent application WO01/40227).

Describes that compounds represented by formula (c)

(where mc and nc are the same or different, each is zero or an integer 1 or 2, Alk3crepresents a covalent bond or a straight or branched C1-6 alkylenes chain, R1cand R2care the same or different, represent each a hydrogen atom or a straight or branched C1-6 alkyl group, Dcrepresents an optionally substituted aromatic or heteroaromatic group, Ecrepresents optionally substituted C7-10 cycloalkyl, C7-10 cycloalkenyl or C7-10 politicalization group)are modulators of CXCR3 (description of the application for international patent application WO03/070242).

Description of the invention

Compound that regulates CCR5 receptor, the use is for the prevention and treatment of diseases, mediated CCR5 receptor. For this reason it is desirable that regulators were developed security CCR5, in particular antagonists of CCR5.

To find the compound specifically binds and regulates CCR5 receptor, the authors of the present invention have conducted intensive studies and found that the objective can be achieved by using compounds represented by formula (I), in accordance with the present invention.

The present invention relates to

1. the compound represented by formula (I):

where R1represents a hydrogen atom or an acid group which may be protected;

X and Y each independently represents a bond or a spacer containing 1 to 3 atoms as a main chain;

ring A and ring B, which are the same or different, each represents a 3-15 membered homocyclic group or heterocyclic group which may have a Deputy (deputies);

ring D is 3 to 15-membered nitrogen-containing heterocyclic group which may have a Deputy (deputies);

R2represents (1) hydrogen atom, (2) a hydrocarbon group which may have a Deputy (deputies), (3) cyano, (4) a hydroxy-group, which may be protected, (5) aminogroup is, which may have a Deputy (deputies), (6) oxoprop, (7) 3-15 membered heterocyclic group which may have a Deputy (deputies), or (8) =N-OR6where R6represents a hydrogen atom or C1-4 alkyl,

its salts or its MES, or its prodrug,

2. the connection in accordance with the above-described 1, where R1represents an acidic group which may be protected,

3. the connection in accordance with the above-described 2, where the acid group is carboxy or sulfonamidnuyu group,

4. the connection in accordance with the above-described 1, where X and Y are, each independently, a bond or a divalent group selected from (1)-CR7R8-, (2)-NR9-, (3)-CO-, (4)-O-, (5)-S-, (6)-SO-, (7)-SO2(8)-C(=N-OR10)-, where R7and R8each, independently, represents a hydrogen atom, C1-4 alkyl, -OR11or phenyl; R9represents a hydrogen atom a C1-4 alkyl, or phenyl; R10and R11each, independently, represents a hydrogen atom or C1-4 alkyl,

5. the connection in accordance with the above-described 4, where X represents a bond, -O - or-CH2-,

6. the connection in accordance with the above-described 1, where Y represents C1-3 alkylene,

7. the connection in accordance with the above-described 1, where the ring D represents a 5-to 10-membered nitrogen-containing heterocyclic group which may have a Deputy is the Deputy (deputies),

8. the connection in accordance with the above-described 1, where ring A and ring B, which are identical or different, represent, each, 5-10-membered homocyclic group or heterocyclic group which may have a Deputy (deputies),

9. the connection in accordance with the above-described 1, where ring A and ring B, which are identical or different, represent, each, a 5 - or 6-membered aromatic ring which may have a Deputy (deputies),

10. the connection in accordance with the above-described 1, where R2is

where the arrow represents a binding position to ring D; R51, R52and R53each independently represents (1) hydrogen atom, (2) a hydrocarbon group which may have a Deputy (deputies), (3) 3-15 membered heterocyclic group which may have a Deputy (deputies), (4) C1-4 alkoxygroup, which may have a Deputy (deputies), (5) fenoxaprop, which may have a Deputy (deputies), or (6) benzyloxy, which may have a Deputy (deputies),

11. the compound according to the above 1, which is represented by formula (Ia):

where ring D1arepresents piperidine or piperazine, which may have a substituent (who zamestitel), and other symbols have the same meanings as those described above 1,

12. the compound according to the above 1, which is selected from the group consisting of

(1) N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]-carbonyl}amino)-1-piperidinyl]methyl}phenoxy)-phenyl]methanesulfonamide,

(2) N-[4-(4-{[4-(butyl{[(6-methyl-3-pyridinyl)amino]-carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide,

(3) N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]-carbonyl}amino)piperidine-1-yl]methyl} - for 3,5-dimethyl-1H-pyrazole-1-yl)phenyl]methanesulfonamide,

(4) N-[4-(4-{[4-(butyl{[(1-methyl-1H-pyrazole-4-yl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide,

(5) 3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]benzamide,

(6) N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(phenyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide,

(7) 5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]-2-fermentated,

(8) 5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]-2,4-differentated,

(9) N-[4-(4-{[4-(butyl{[(3-cyano-4-forfinal)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide, and

(10) N-[4-(4-{[4-(butyl{[(3-hydroxycyclohexyl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonic the IDA, and

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(1,3-thiazol-4-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide,

13. the regulator CCR5-containing compound according to the above 1, its salt or its MES or its prodrug,

14. the CCR5 regulator according to the above 13, which is a CCR5 antagonist,

15. the CCR5 regulator according to the above 13, which is an agent for treatment and/or prevention of diseases mediated by CCR5,

16. the CCR5 regulator in accordance with above 15, where the disease is mediated by CCR5, is the infection of the human immunodeficiency virus,

17. the CCR5 regulator in accordance with the above-described 16, where the infection of the human immunodeficiency virus is acquired immunodeficiency syndrome,

18. the CCR5 regulator in accordance with above 15, where the disease is mediated CCR5 is an immunological disease,

19. the CCR5 regulator according to the above 18, where the immunological disease is the rejection of organs in transplantation

20. the CCR5 regulator in accordance with above 15, where the disease is mediated by CCR5, is an inflammatory disease,

21. the CCR5 regulator in accordance with the above-described 20, where the inflammatory disease is asthma,

<> 22. agent for prevention and/or treatment of infection with human immunodeficiency virus, sexually transmitted diseases or inflammatory diseases, which contains a compound represented by formula (I), in accordance with the above-described 1, its salt or its MES or its prodrug,

23. the pharmaceutical composition which contains a compound represented by formula (I), in accordance with the above-described 1, its salt or its MES or its prodrug,

24. medicinal product, which contains a compound represented by formula (I), in accordance with the above-described 1, its salt or its MES or its prodrug, in combination with one or at least two agents from the nucleoside reverse transferase, protease inhibitor, CCR2 antagonist, CCR3 antagonist, CCR4 antagonist, CCR5 antagonist, CXCR4 antagonist, inhibitor of fusion, antibody against surface antigen of HIV-1 vaccines in HIV-1,

25. the method of treatment or prevention of diseases mediated by CCR5, in a mammal which comprises the administration to a mammal an effective amount of the compound represented by formula (I):

where R1represents a hydrogen atom or an acid group which may be protected;

X and Y each independently represents a bond or a spacer containing 1 is about 3 atoms as a main chain;

ring A and ring B, which are the same or different, each represent a 3-15 membered homocyclic group or heterocyclic group which may have a Deputy (deputies);

ring D is 3 to 15-membered nitrogen-containing heterocyclic group which may have a Deputy (deputies);

R2represents (1) hydrogen atom, (2) a hydrocarbon group which may have a Deputy (deputies), (3) cyano, (4) a hydroxy-group, which may be protected, (5) an amino group which may have a Deputy (deputies), (6) oxoprop, (7) 3-15 membered heterocyclic group which may have a Deputy (deputies), or (8) =N-OR6where R6represents a hydrogen atom or C1-4 alkyl,

its salt or its MES or its prodrug,

26. the use of compounds represented by formula (I):

where R1represents a hydrogen atom or an acid group which may be protected;

X and Y each independently represents a bond or a spacer containing 1-3 atoms as a main chain;

ring A and ring B, which are the same or different, each independently, represent 3-15 membered homocyclic group or heterocyclic group which may have a Deputy (deputies);

R2represents (1) hydrogen atom, (2) a hydrocarbon group which may have a Deputy (deputies), (3) cyano, (4) a hydroxy-group, which may be protected, (5) an amino group which may have a Deputy (deputies), (6) oxoprop, (7) 3-15 membered heterocyclic group which may have a Deputy (deputies) or (8) =N-OR6where R6represents a hydrogen atom or C1-4 alkyl,

its salt or its MES or its prodrug

to obtain an agent for prevention and/or treatment of diseases mediated CCR5.

"Acidic group which may be protected"represented by R1is "acidic group which may be protected by a protective group". Examples of the acid group include hydroxy, alkoxy, carboxy (-COOH), sulfo (SO3H), sulfine (SO2H)sulfonamidnuyu (SO2NH2or-NR101SO3H (R101represents a hydrogen atom or a hydrocarbon group which may have a Deputy (deputies)), phosphono (-PO(OH)2), phenol (-C6H4OH), or different types of acid Bronsted, such as nitrogen-containing ring residue having a hydrogen atom that can be removed as a proton. "Acid Bronsted" refers to a substance that donates a hydrogen ion on the natives substance. Examples of the "nitrogen-containing ring residue having hydrogen, which can be removed as a proton include:

.

The preferred acid group is carboxy or a sulfonamide. More preferred is a sulfonamide.

Examples of the protective group include a hydrocarbon group which may have a Deputy (deputies), C1-6 alkoxy, amino group, which may have a Deputy (deputies),. "Hydrocarbon group" in the "hydrocarbon group which may have a Deputy (deputies)" includes, for example, C1-15 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl and the like; C3-8 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like; C2-10 alkenyl, such as vinyl, allyl, 2-methylallyl, 2-butenyl, 3-butenyl, 3-octenyl and the like; C2-10 quinil, such as ethinyl, 2-PROPYNYL, 3-hexenyl and the like; C3-10 cycloalkenyl, such as cyclopropyl, cyclopentyl, cyclohexenyl and the like; C6-14 aryl such as phenyl, naphthyl and the like, C7-16 aralkyl, such as benzyl, phenylethyl and the like; (C3-8 cycloalkyl)-(C1-4 alkyl), such as cyclohexylmethyl, cyclohexylethyl cyclohexylprop, 1-methyl-1-cyclohexylmethyl, cyclopropylethyl and the like.

"Substituents" in the "hydrocarbon group which may have a Deputy (deputies)" include, for example, (1) nitro, (2) a hydroxy-group, (3) oxo-, (4) thioxo-, (5) cyano, (6) carbarnoyl, (7) aminocarbonyl, substituted C1-8 hydrocarbon and the like (for example, n-butylaminoethyl, n-cyclohexyloxycarbonyl, n-butyl-N-cyclohexyloxycarbonyl, n-cyclohexyloxycarbonyl, phenylenecarbonyl and the like), (8) carboxy, (9) C1-4 alkoxycarbonyl, such as methoxycarbonyl, etoxycarbonyl and the like, (10) sulfo, (11) a halogen, such as fluorine, chlorine, bromine or iodine, (12) C1-4 lower alkoxy which may be substituted with halogen (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, deformedarse or trifter, ethoxy), (13) phenoxy, (14) halogenfree, such as o-, m - or p-chlorophenoxy, or o-, m - or p-bromophenoxy and the like, (15) C1-4 lower alkylthio, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, tert-butylthio and the like, (16) phenylthio, (17) C1-4 lower alkylsulfonyl, such as methylsulfonyl or ethylsulfonyl and the like, (18) C1-4 lower alkylsulfonyl, such as methylsulphonyl or ethylsulfonyl and the like, (19) amino group, (20) C1-6 lower allmenalp, such as acetylamino or who propionyloksypo and the like, (21) primary or secondary amino group, substituted hydrocarbon group (for example, methylamino, ethylamino, h-propylamino, isopropylamino, h-butylamino-, dimethylamino-, diethylamino, cyclohexylamino-, 1-carbarnoyl-2-cyclohexylethylamine-, n-butyl-N-cyclohexylethylamine or phenylaminopropyl and the like), ("hydrocarbon group" has the same meanings as the above "hydrocarbon group", and can be substituted by oxo, amino group which may be substituted by the optional substituents (e.g., hydrocarbon), carbamoyl, halogen or hydroxy-group and the like), (22) C1-4 lower acyl such as formyl or acetyl, and the like, (23) benzoyl, (24) 5 - or 6-membered heterocyclic group such as 2 - or 3-thienyl, 2 - or 3-furyl, 3-, 4 - or 5-pyrazolyl, 4-tetrahydropyranyl, 2-, 4 - or 5-thiazolyl, 3-, 4 - or 5-isothiazolin, 2-, 4 - or 5-oxazolyl, 3-, 4 - or 5-isoxazolyl, 2-, 4 - or 5-imidazolyl, 1,2,3 - or 1,2,4-triazolyl, 1H or 2H-tetrazolyl, 2-, 3 - or 4-pyridyl, 2-, 4 - or 5-pyrimidinyl, 3 - or 4-pyridazinyl, hinely, ethanolic or indolyl, and the like, which contains 1-4 heteroatoms selected from oxygen, sulfur and nitrogen, together with the carbon atom, and optionally has 1-4 substituent selected from (a) halogen, such as bromine, chlorine, or fluorine, (b) hydrocarbon, such as methyl, ethyl, propyl, isopropyl, be the ZIL, cyclohexyl, cyclohexylmethyl or cyclohexylethyl and the like, optionally substituted by oxo or hydroxy-group, and the like (the"hydrocarbon group" has the same meanings as the above "hydrocarbon group"), (c) halogenfree, such as o-, m - or p-chlorophenoxy, or o-, m - or p-bromophenoxy and the like, and (d) oxo, and the like, (25) C1-10 halogenated, such as deformity, trifluoromethyl, triptorelin or trichloroethyl and the like, (26) hydroxyimino, (27) alkylenediamines, such as methoxyimino or etilendiaminova and the like, (28) alkylsulfonamides, such as methylsulfonylamino, ethylsulfonyl or benzylmethylamine and the like, or (29) arylsulfonamides, such as phenylcarbonylamino - or p-toluensulfonate and the like. "Hydrocarbon group which may have a Deputy (deputies)can be 1-10 substituents selected from the above (1)to(29). If the "hydrocarbon group" is cycloalkyl, cycloalkenyl, aryl or aralkyl, it can have from 1 to 4 C1-4 lower alkyl, such as methyl, ethyl, propyl, isopropyl or butyl and the like as substituents. When the number of substituents is two or more, each of the substituents may be the same or different.

Deputy AMI is gruppy in the "amino group, which may have a Deputy (deputies)" in "protective group"include the above-described "hydrocarbon group".

"C1-6 alkoxy" in "protective group" includes, for example, methoxy, ethoxy-, propoxy-, butoxy-, pentyloxy or hexyloxy and the like.

Preferred "protective group" in R1is a hydrocarbon group which may have a Deputy (deputies), and more preferred is C1-4 alkyl and the like.

"Acidic group which may be protected"represented by R1includes, for example, esters, such as methoxycarbonyl or etoxycarbonyl, or amide, such as carbarnoyl.

Preferably R1is-SO2NR102R103or-NR101SO2R104, -COOR105, -CONR106R107(where R102-R107represents a hydrogen atom or the above-described protective group, and other symbols have the same meanings as described above), and more preferred is-SO2NR102R103or-NR101SO2R104.

"Spacer containing 1-3 atoms in the main chain"represented by X and Y, denotes the space formed 1-3 consecutive atoms of the main chain. In this case, the number of atoms in the main chain" must be taken so that the number of such atomo is as the main chain was minimal. The "spacer having from 1 to 3 atoms as a main chain" includes, for example, a divalent group containing 1 to 3 atoms selected from-CR7R8-, -NR9-, -CO-, -O-, -S-, -SO-, -SO2and-C(=N-OR10)- (where R7and R8are each, independently, a hydrogen atom, C1-4 alkyl, -OR11or phenyl, R9represents a hydrogen atom, C1-4 alkyl or phenyl, R10and R11are each, independently, a hydrogen atom or C1-4 alkyl). In this case, the "C1-4 alkyl" includes methyl, ethyl, propyl or butyl and the like. Specifically, the "spacer having from 1 to 3 atoms as a main chain" includes, for example, -CR7R8-, -NR9-, -CO-, -O-, -S-, -C(=N-OR10)-, -NR9CO-, -CONR9-, -NR9COCR7R8- or-CONR9CR7R8- (where R7-R10has the same meanings as described above). Preferably the spacer, the term "spacer having from 1 to 3 atoms as a main chain"represented by X is-CR7R8-, -NR9-, -CO-, -O-, -S-, -SO-, -SO2- or-C(=N-OR10)- (where R7and R8are each, independently, a hydrogen atom, C1-4 alkyl, -OR11or phenyl, R9represents a hydrogen atom, C1-4 alkyl or phenyl, R10and R11are each, independently, a hydrogen atom or C1-4 alkyl) and the like.

Preferred X is a bond, -O - and-CH 2- and the like.

Preferred as the "spacer having from 1 to 3 atoms as a main chain"represented by Y is C1-3 alkylene". "C1-3 alkylene" includes methylene, ethylene or propylene, and the like. More preferably Y is methylene.

"3-15-membered gomoll" in "3-15 membered gamecycledelay group or heterocyclic group, which may have a Deputy (deputies)"represented by ring a and ring B includes, for example, "cyclic hydrocarbons" and the like. "Cyclic hydrocarbon" includes, for example, "unsaturated cyclic hydrocarbon" or "saturated cyclic hydrocarbon". "Saturated cyclic hydrocarbon" includes, for example, cycloalkane, such as cyclopropane, CYCLOBUTANE, cyclopentane, cyclohexane, Cycloheptane, cyclooctane, cyclonona, cyclodecane, cyclodecane, cyclododecane, cycletrader, collateralised or cyclopentadiene and the like; perhydroanthracene; pergerson; palikonda; peritonealis; perheravintolan; Spiro[4.4]nonan; Spiro[4.5]decane; Spiro[5.5]undecane; bicyclo[2.2.1]heptane; bicyclo[3.1.1]heptane; bicyclo[2.2.2]octane; adamantane; noradsanta and the like. "Unsaturated cyclic hydrocarbon" includes, for example, cycloalkane, such as cyclopentene, cyclohexene, cycloheptene, cyclooctene, cyclopentadiene, cyclohexadiene, C is kogeplader or cyclooctadiene and the like; benzene; pentalen; azulene; inden; indan; naphthalene; dihydronaphthalene; tetrahydronaphthalen; geptalen; biphenylene; as-indocin; second-indocin; acenaphthene; acenaphthylene; fluorene; finale; phenanthrene; anthracene; bicyclo[2.2.1]hept-2-ene; bicyclo[3.1.1]hept-2-ene; bicyclo[2.2.2]Oct-2-ene and the like.

"3-15-membered heterocycle" in "3-15 membered gamecycledelay group or heterocyclic group, which may have a Deputy (deputies)"represented by ring a and ring B includes "3-15 membered unsaturated heterocycle" or "3-15 membered saturated a heterocycle".

"3-15 membered unsaturated heterocycle" includes, for example, pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, pyrazin, pyrimidine, pyridazine, azepine, diazepine, furan, Piran, oxepin, thiophene, thiopyran, tiepin, oxazol, isoxazol, thiazole, isothiazol, furazan, oxadiazole, oxazin, oxadiazon, oxazepine, oxadiazon, thiadiazole, teasin, thiadiazin, diazepin, thiadiazin, indole, isoindole, indolizine, benzofuran, isobenzofuran, benzothiophene, isobenzofuran, ditionally, indazole, quinoline, isoquinoline, hemolysin, purine phthalazine, pteridine, naphthiridine, cinoxacin, hinzelin, cinnolin, benzoxazole, benzothiazole, benzimidazole, chrome, benzocain, benzoxazepin, benzodiazepin, benzothiophen, benzodiazepin, benzodiazepin, benzazepin, benzodiazepine, benzofurazan, benzothiadiazin is, benzotriazol, carbazole, beta carboline, acridine, fenesin, dibenzofuran, Xanten, dibenzothiophen, phenothiazines, phenoxazin, phenoxathiin, tianren, phenanthridine, phenanthroline, pyrimidin, pyrrolin, imidazolin, triazoline, tetrazolyl, pyrazoline, dihydropyridines, tetrahydropyridine, dihydropyridine, tetrahydropyridine, dihydropyrimidin, tetrahydropyrimidin, dihydropyridin, tetrahydropyridine, dehydroacetic, tetrahydroazepine, dihydrovitamin, tetrahydroazepine, dihydrofuran, dihydropyran, dehydroacetic, tetrahydroazepine, dihydrothiophene, dihydrothiophene, dihydrothiophene, tetrahydrothiophene, dihydrooxazolo, dihydroisoxazole, dihydrothiazolo, dihydroisoxazole, dihydrofuran, dihydroimidazole, dihydrooxazolo, Dihydrocodeine, dihydrooxazoles, tetrahydroazepine, dihydroxyvitamin, tetrahydroazepine, dihydroeugenol, dihydrothiazine, dihydrokavain, dihydrothiazine, tetrahydroazepine, dihydrokavain, tetrahydroazepine, indolin, isoindoline, dihydrobenzofuran, dihydroisobenzofuran, dihydrobenzofuran, dihydroisobenzofuran, dihydroindol, dihydroquinoline, tetrahydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, dihydrophenazine, tetrahydrophthalate, dihydronaphthalene, tetrahydronaphthalene, dihydroquinoxaline, tetrahydroquinoxalin, dihydroquinazolin, tetrahydro insulin, dihydroindole, tetrahydroindole, benzocain, dihydroisoxazole, dihydrobenzofuran, pyrazinamidase, dihydroisoxazole, dihydrobenzofuran, dehydrobenzperidol, digitalisation, tetrahydrobenzene, dihydrobenzofuran, tetrahydrolipstatin, benzodioxepin, dihydroisoxazole, tetrahydrobenzaldehyde, dihydrocarvone, tetrahydrocarbazol, dihydrouridine, tetrahydrouridine, dihydrobenzofuran, dihydroisobenzofuran, tetrahydroxybenzophenone, tetrahydrolipstatin, dioksiinien, benzodioxan, chroman, benzodithiol, benzodithiol and the like. "3-15 membered saturated a heterocycle" includes, for example, aziridine, azetidine, asokan, pyrrolidin, imidazolidin, thiazolidin, tetrazolium, pyrazolidine, piperidine, piperazine, targetability, targetability, peligrosa, targetrotation, oxiran, oxetane, tetrahydrofuran, tetrahydropyran, perhydroxyl, thiran, tieton, tetrahydrothiophene, tetrahydrothiopyran, pengertian, tetrahydrooxazolo (oxazolidine), tetrahydrocortisol (isoxazolidine), tetrahydrothieno (thiazolidin), tetrahydrocortisol (isothiazolin), tetrahydrofuran, tetrahydrooxazolo (oxadiazolidine), tetrahydrooxazolo, tetrahydroimidazo, perhydroxyl, perhydroanthracene, tetrahydrocortisol (thiadiazolidin), tetrahydrothiophene t is targetrotation, targetrotation, targetrotation, morpholine, thiomorpholine, Ossetian, perhydroanthracene, peligrosamente, targetobjecttype, peligrosamente, peritoneal, perhydroxyl, perhydrosqualene, PermitRootLogin, perhydroanthracene, perhydrophenanthrene, perhydrophenanthrene, permitiendoles, perhydroanthracene, perhydroanthracene, perhydroanthracene, perhydrogenized, perhydrosqualene, perhydrophenanthrene, perhydrophenanthrene, dioxolane, dioxane, ditiolan, Titianand the like.

Preferred as a 3-15 membered gamecycledelay group or heterocyclic group"represented by ring a and ring B, is a 5-10 membered homozygocity group or heterocyclic group". Specifically "5-10-membered homozygocity group" includes, for example, C5-10 saturated cyclic hydrocarbons, such as C5-10 cycloalkane (for example, cyclopentane, cyclohexane or Cycloheptane), or C5-10 unsaturated cyclic hydrocarbons, such as C5-10 cycloalkyl (for example, cyclopentene, cyclohexene, cycloheptene, cyclooctene, cyclopentadiene, cyclohexadiene, cycloheptadiene or cyclooctadiene); benzene; naphthalene; inden, and the like. "5-10-membered heterocyclic group" include 5-to 10-membered unsaturated heterocyclic group, such as pyrrole, imides is l, triazole, tetrazole, pyrazole, pyridine, pyrazin, pyrimidine, pyridazine, azepine, diazepine, furan, Piran, oxepin, thiophene, thiopyran, tiepin, oxazol, isoxazol, thiazole, isothiazol, furazan, oxadiazole, oxazin, oxadiazon, oxazepine, oxadiazon, thiadiazole, teasin, thiadiazin, diazepin, thiadiazin, indole, isoindole, indolizine, benzofuran, isobenzofuran, benzothiophene, isobenzofuran, ditionally, indazole, quinoline, isoquinoline, hemolysin, purine, phthalazine, pteridine, naphthiridine, cinoxacin, hinzelin, cinnolin, benzoxazol, benzothiazole, benzimidazole, chrome, benzofurazan, benzothiadiazole, benzotriazole, pyrrolin, imidazolin, triazoline, tetrazolyl, pyrazoline, dihydropyridines, tetrahydropyridine, dihydropyridine, tetrahydropyridine, dihydropyrimidin, tetrahydropyrimidin, dihydropyridin, tetrahydropyridine, dehydroacetic, tetrahydroazepine, dihydrovitamin, tetrahydroazepine, dihydrofuran, dihydropyran, dehydroacetic, tetrahydroazepine, dihydrothiophene, dihydrothiophene, dihydrothiophene, tetrahydrothiophene, dihydrooxazolo, dihydroisoxazole, dihydrothiazolo, dihydroisoxazole, dihydrofuran, dihydroimidazole, dihydrooxazolo, Dihydrocodeine, dihydrooxazoles, tetrahydroazepine, dihydroxyvitamin, tetrahydroazepine, dihydroeugenol, dihydrothiazine, dihydrokavain, dihydrothiazine, tetrahed thiazepine, dihydrokavain, tetrahydroazepine, indolin, isoindoline, dihydrobenzofuran, dihydroisobenzofuran, dihydrobenzofuran, dihydroisobenzofuran, dihydroindol, dihydroquinoline, tetrahydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, dihydrophenazine, tetrahydrophthalate, dihydronaphthalene, tetrahydronaphthalene, dihydroquinoxaline, tetrahydroquinoxalin, dihydroquinazolin, tetrahydroquinazolin, dihydroindole, tetrahydroindole, benzocain, dihydroisoxazole, dihydrobenzofuran, pyrazinamidase, dihydroisoxazole, dihydrobenzofuran, dehydrobenzperidol, dioksiinien, benzodioxan, chroman, benzodithiol or benzodithiol; or 5-10-membered saturated heterocyclic group such as pyrrolidino, imidazolidin, thiazolidin, tetrazolium, pyrazolidine, piperidine, piperazine, targetability, targetability, peligrosa, targetrotation, tetrahydrofuran, tetrahydropyran, perhydroxyl, tetrahydrothiophene, tetrahydrothiopyran, pengertian, tetrahydrooxazolo (oxazolidine), tetrahydrocortisol (isoxazolidine), tetrahydrothieno (thiazolidin), tetrahydrocortisol (isothiazolin), tetrahydrofuran, tetrahydrooxazolo (oxadiazolidine), tetrahydrooxazolo, tetrahydroimidazo, perhydroxyl, perhydroanthracene, tetrahydrocortisol (thiadiazolidin), tetrahydrothiophene, tetrahedralization, targetrotation, targetrotation, morpholine, thiomorpholine, Ossetian, perhydroanthracene, peligrosamente, targetobjecttype, peligrosamente, peritoneal, perhydroxyl, perhydrosqualene, PermitRootLogin, perhydroanthracene, perhydrophenanthrene, perhydrophenanthrene, permitiendoles, perhydroanthracene, perhydroanthracene, perhydroanthracene, dioxolane, dioxane, ditiolan, Titian and the like.

and the like.

More preferably ring A or ring B represents a 5-10 membered unsaturated homocyclic group or heterocyclic group. "5-10-membered unsaturated homozygocity group or heterocyclic group" represents a 5-10 membered unsaturated cyclic hydrocarbon or 5-10-membered unsaturated heterocyclic group. More preferred is a 5 - or 6-membered aromatic ring such as a benzene, pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, pyrazin, pyrimidine, pyridazine, triazine, furan, thiophene, oxazole, isoxazol, thiazole, isothiazol, furazan, oxadiazole or thiadiazole and the like.

"Substituents" in the "3-15 membered gamecycledelay group or heterocyclic group, which may have a Deputy (deputies)"represented by ring A or ring B, on the hunger for example, (1) hydrocarbon group which may have a Deputy (deputies) (the"hydrocarbon group which may have a Deputy (deputies)"has the same meanings as the above-described "hydrocarbon group which may have a Deputy (deputies)"), (2) C1-6 alkoxygroup, which may be substituted by halogen atom (for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy or triptoreline), (3) (C1-4 alkoxy)-(C1-4 alkyl) group, such as methoxyethyl and the like, (4) fenoxaprop, (5) C1-8 alkanoyloxy group, such as formyl, acetyl, propionyl, n-butyryl, isobutyryl or cyclohexyl carbonyl and the like, (6) benzoyloxy group, (7) C1-8 alkanoyloxy, such as formyloxy, atomic charges, propionyloxy, n-butyryloxy, isobutyryloxy or cyclohexyl, carbonyloxy and the like, or benzoyloxy, (8) carboxypropyl, (9) C2-7 alkoxycarbonyl group, such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, solutionline, tert-butoxycarbonyl group and the like), (10) karbamoilnuyu group, (11) N-mono-C1-4 alkylcarboxylic group, such as N-methylcarbamoyl, N-ethylcarbamate, N-propellerblades, N-isopropylcarbamate or N-butylcarbamoyl and the like,(12) N,N-di-C1-4 alkylcarboxylic group, such as N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N,N-dipropylamino or N,N-dibutylamino and the like, (13) cyclic aminocarbonyl, such as 1-aziridinyl, 1-azetidinone, 1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, n-methylpiperazine, morpholinomethyl and the like, (14) a halogen atom, such as fluorine, chlorine, bromine or iodine, (15) mono-, di - or tri-halogen-C1-4 alkyl group such as chloromethyl dichloromethyl, trifluoromethyl or triptorelin and the like, (16) oxoprop, (17) amidinopropane, (18) aminogroup, (19) amino group, (20) mono-C1-alkylamino, such as methylamino, ethylamino, propylamino, isopropylamino or butylamino and the like, (21) di-C1-4 alkylamino, such as dimethylamino, diethylamino, dipropylamino, diisopropylamino or dibutylamino and the like, (22) 3-6-membered cyclic amino group which contains a carbon atom and 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen, along with one nitrogen atom (for example, aziridinyl, azetidin, pyrrolidinyl, pyrrolyl, pyrrolyl, imidazolyl, pyrazolyl, imidazolidinyl, piperidino, morpholino, dihydropyridin, pyridyl, n-methylpiperazine or N-ethylpiperidine and the like), (23) C1-8 alkanolamine group, such as formamide, ndimethylacetamide, triptorelin, propionamide, butyramide, isobutyramide, cyclohexene is arylamino and the like, (24) benzamido group, (25) carbamoylating, (26) N-C1-4 alkylcarboxylic, such as N-methylcarbamoyl, N-ethylcarbodiimide, N-propylenpipeline, N-isopropylcarbamate, N-butylcarbamoyl and the like, (27) N,N-di-C1-4 alkylcarboxylic, such as N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N,N-dipropylamine, N,N-dibutylethanolamine and the like, (28) C1-3 alkylenedioxy, such as methylenedioxy or Ethylenedioxy and the like, (29) -B(OH)2, (30) a hydroxy-group, (31) apachegroup, (32) the nitrogroup, (33) a cyano, (34) mercaptopropyl, (35) alphagroup, (36) salinograph, (37) phosphonopropyl, (38) sulfamoyl group, (39) C1-6 monoalkylphenol, such as N-methylcarbamoyl, N-ethylsulfonyl, N-propylsulfonyl, N-isopropylamino or N-butylsulfonyl and the like, (40) di-C1-4 alkylsulfanyl group, such as N,N-dimethylsulphamoyl, N N-diethylcarbamoyl, N,N-dipropylamino or N,N-dibutylamino and the like, (41) C1-6 allylthiourea, such as methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, sec-butylthio or tert-butylthio and the like, (42) phenylthiourea, (43) C1-6 alkylsulfonyl group, such as methylsulfinyl, ethylsulfinyl, propylsulfonyl or butylsulfonyl and the like, (44) phenylsulfinyl, (45) C1-6 alkylsulfonyl, such as methyl who sulfonyl, ethylsulfonyl, propylsulfonyl or butylsulfonyl and the like, (46) phenylsulfonyl group, or (47) azide group and the like. 1-10 described above substituents may be substituted at substitutable positions in ring A and ring B. When the number of substituents is two or more, each Deputy is the same or different. Preferred as substituents in ring A and ring B is a hydrocarbon group which may have a Deputy (deputies), alkoxygroup, carboxypropyl or alkanolamine group and the like, and more preferred is a hydrocarbon group or alkoxygroup.

"Nitrogen-containing heterocycle" in "3-15 membered nitrogen-containing heterocyclic group which may have a Deputy (deputies)"represented by ring D, refers to a heterocycle, which may contain, in addition, at least one nitrogen atom, besides carbon atom, 1 to 3 heteroatoms selected from nitrogen atoms, oxygen and sulfur. "3-15 membered nitrogen-containing heterocycle" includes "3-15 membered nitrogen-containing unsaturated heterocycle" and "3-15 membered nitrogen-containing saturated a heterocycle".

"3-15 membered nitrogen-containing unsaturated heterocycle" includes, for example, pyrrole, imidazole, triazole, tetrazole, pyrazole, indole, isoindole, indazole, purine, benzimidazole, b is saseen, benzodiazepine, benzotriazol, carbazole, beta carboline, phenothiazines, phenoxazin, pyrimidin, pyrrolin, imidazolin, triazoline, tetrazolyl, pyrazoline, dihydropyridines, tetrahydropyridine, dihydropyridine, tetrahydropyridine, dihydropyrimidin, tetrahydropyrimidin, dihydropyridin, tetrahydropyridine, dehydroacetic, tetrahydroazepine, dihydrovitamin, tetrahydroazepine, dihydrooxazolo, dihydroisoxazole, dihydrothiazolo, dihydroisoxazole, dihydrofuran, dihydroimidazole, dihydrooxazolo, Dihydrocodeine, dihydrooxazoles, tetrahydroazepine, dihydroxyvitamin, tetrahydroazepine, dihydroeugenol, dihydrothiazine, dihydrokavain, dihydrothiazine, dihydrokavain, tetrahydroazepine, indolin, isoindoline, dihydroindol, dihydroquinoline, tetrahydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, dihydrophenazine, tetrahydrophthalate, dihydronaphthalene, tetrahydronaphthalene, dihydroquinoxaline, tetrahydroquinoxalin, dihydroquinazolin, tetrahydroquinazolin, dihydroindole, tetrahydroindole, dihydroisoxazole, dihydrobenzofuran, pyrazinamidase, dihydroisoxazole, dihydrobenzofuran, dehydrobenzperidol, digitalisation, tetrahydrobenzene, dihydrobenzofuran, tetrahydrolipstatin, dihydroisoxazole, tetrahydrobenzaldehyde, dihydrocarvone is, tetrahydrocarbazol, dihydrouridine, tetrahydrouridine and the like. "3-15 membered nitrogen-containing saturated a heterocycle" includes, for example, aziridine, azetidine, asokan, pyrrolidin, imidazolidin, thiazolidin, tetrazolium, pyrazolidine, piperidine, piperazine, targetability, targetability, peligrosa, targetrotation, tetrahydrooxazolo (oxazolidine), tetrahydrocortisol (isoxazolidine), tetrahydrothieno (thiazolidin), tetrahydrocortisol (isothiazolin), tetrahydrofuran, tetrahydrooxazolo (oxadiazolidine), tetrahydrooxazolo, tetrahydroimidazo, perhydroxyl, perhydroanthracene, tetrahydrocortisol (thiadiazolidin), tetrahydrothiophene, tetrahydrolipstatin, tetrahydroazepine, targetrotation, targetrotation, morpholine, thiomorpholine, peritoneal, perhydroxyl, perhydrosqualene, PermitRootLogin, perhydroanthracene, perhydrophenanthrene, perhydrophenanthrene, permitiendoles, perhydroanthracene, perhydroanthracene, perhydroanthracene, perhydrogenized, perhydrosqualene,and the like.

Preferred "3-15 membered nitrogen-containing heterocycle" is "5-10-membered nitrogen-containing heterocycle". "5-10-membered nitrogen-containing unsaturated heterocycle" includes, for example, pyrrole, imidazole, triazole, tetrazole, pyrazole,indole, the isoindole, indazole, purine, benzimidazole, benzotriazole, pyrrolin, imidazolin, triazoline, tetrazolyl, pyrazoline, dihydropyridines, tetrahydropyridine, dihydropyridine, tetrahydropyridine, dihydropyrimidin, tetrahydropyrimidin, dihydropyridin, tetrahydropyridine, dehydroacetic, tetrahydroazepine, dihydrovitamin, tetrahydroazepine, dihydrooxazolo, dihydroisoxazole, dihydrothiazolo, dihydroisoxazole, dihydrofuran, dihydroimidazole, dihydrooxazolo, Dihydrocodeine, dihydrooxazoles, tetrahydroazepine, dihydroxyvitamin, tetrahydroazepine, dihydroeugenol, dihydrothiazine, dihydrokavain, dihydrothiazine, tetrahydroazepine, dihydrokavain, tetrahydroazepine, indolin, isoindoline, dihydroindol, dihydroquinoline, tetrahydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, dihydrophenazine, tetrahydrophthalate, dihydronaphthalene, tetrahydronaphthalene, dihydroquinoxaline, tetrahydroquinoxalin, dihydroquinazolin, tetrahydroquinazolin, dihydroindole, tetrahydroindole, dihydroisoxazole, dihydrobenzofuran, pyrazinamidase, dihydroisoxazole, dihydrobenzofuran, dehydrobenzperidol and the like. "5-10-membered nitrogen-containing saturated a heterocycle" includes, for example, asokan, pyrrolidin, imidazolidin, thiazolidin, tetrazolium, pyrazolidine, piperidine, piperazin, targetability, targetability, peligrosa, targetrotation, tetrahydrooxazolo (oxazolidine), tetrahydrocortisol (isoxazolidine), tetrahydrothieno (thiazolidin), tetrahydrocortisol (isothiazolin), tetrahydrofuran, tetrahydrooxazolo (oxadiazolidine), tetrahydrooxazolo, tetrahydroimidazo, perhydroxyl, perhydroanthracene, tetrahydrocortisol (thiadiazolidin), tetrahydrothiophene, tetrahydrolipstatin, targetrotation, targetrotation, morpholine, thiomorpholine, peritoneal, perhydroxyl, perhydrosqualene, PermitRootLogin, perhydroanthracene, perhydrophenanthrene, perhydrophenanthrene, permitiendoles, perhydroanthracene, perhydroanthracene, perhydroanthracene,and the like.

In addition, the preferred "nitrogen-containing heterocycle" is mentioned piperidine or piperazine. More preferred is piperidine.

"Substituents" in the "3 to 15-membered nitrogen-containing heterocyclic group which may have a Deputy (deputies)"represented by ring D have the same meanings as described above, the "substituents" in the "3-15 membered gamecycledelay group or heterocyclic group which may have substituents"represented by ring a and ring B.

Preferably the ring D has no substituents or I which is substituted hydrocarbon group, having a Deputy (deputies), mono-C1-4 alkylamino or di-C1-4 alkylamino and the like. More preferably the D ring does not have a Deputy.

"Hydrocarbon group" in the "hydrocarbon group which may have a Deputy (deputies)"represented by R2has the same value as the "hydrocarbon group which may have a Deputy (deputies)"defined in "protective group" "acidic group which may be protected"represented by R1. Preferred "hydrocarbon group which may have a Deputy (deputies)"represented by R2is an alkyl group substituted by oxopropoxy or (C3-8 cycloalkyl)-(C1-4 alkyl) group substituted by exography.

Among R2"the hydroxy-group, which may be protected" represents a hydroxy-group, which may be protected by a protective group". "Protective group of the hydroxy-group includes, for example, (1) C1-6 alkyl group (e.g. methyl, ethyl or n-propyl and the like), which may have 1-4 substituent selected from halogen atoms such as chlorine, bromine or fluorine and the like; C6-10 aryl, such as phenyl or naphthyl and the like; C7-12 aracelio group, such as benzyl or phenylethyl etc.; and the nitro group and the like, (2) C6-10 aryl (e.g. phenyl or naphthyl and tomopterna), which may have 1-4 substituent selected from halogen atoms such as chlorine, bromine or fluorine etc.; C1-6 alkyl group such as methyl, ethyl or n-propyl and the like; C6-10 aryl, such as phenyl or naphthyl and the like; C7-12 aracelio group, such as benzyl or phenylethyl etc.; and the nitro group and the like, (3) C7-12 aracelio group (for example, benzyl, phenylethyl or naphthylmethyl and the like), which may have 1-4 substituent selected from a halogen atom, such as chlorine, bromine or fluorine etc.; C1-6 alkyl group such as methyl, ethyl or n-propyl and the like; C6-10 aryl, such as phenyl or naphthyl and the like; C7-12 aracelio group, such as benzyl or phenylethyl etc.; and the nitro-group and the like, (4) formyl, (5) C1-6 alkyl-carbonyl group (e.g. acetyl or propionyl and the like), which may have 1-4 substituent selected from a halogen atom, such as chlorine, bromine or fluorine etc.; C1-6 alkyl group such as methyl, ethyl or n-propyl and the like; C6-10 aryl, such as phenyl or naphthyl and the like; C7-12 aracelio group, such as benzyl or phenylethyl etc.; and the nitro group and the like, (6) C6-10 aryl-oxycarbonyl group (for example, vinyloxycarbonyl or naphthalocyanines and the like), which can be 14 Deputy selected from a halogen atom, such as chlorine, bromine or fluorine etc.; C1-6 alkyl group such as methyl, ethyl or n-propyl and the like; C6-10 aryl, such as phenyl or naphthyl and the like; C7-12 aracelio group, such as benzyl or phenylethyl etc.; and the nitro group and the like, (7) C6-10 arylcarbamoyl group (for example, benzoyl or afterburner and the like), which may have 1-4 substituent selected from a halogen atom, such as chlorine, bromine or fluorine etc.; C1-6 alkyl group such as methyl, ethyl or n-propyl and the like; C6-10 aryl, such as phenyl or naphthyl and the like; C7-12 aracelio group, such as benzyl or phenylethyl etc.; and the nitro group and the like, (8) C7-12 aralkyl-carbonyl group (e.g., benzylcarbamoyl or ventilkappen and the like), which may have 1-4 substituent selected from a halogen atom, such as chlorine, bromine or fluorine etc.; C1-6 alkyl group such as methyl, ethyl or n-propyl and the like; C6-10 aryl, such as phenyl or naphthyl and the like; C7-12 aracelio group, such as benzyl or phenylethyl etc.; and the nitro group and the like, (9) pyranyl or furanyl, which may have 1-4 substituent selected from a halogen atom, such as chlorine, bromine or fluorine etc.; C1-6 alkyl group, t is Kuyu as methyl, ethyl or n-propyl and the like; C6-10 aryl, such as phenyl or naphthyl and the like; C7-12 aracelio group, such as benzyl or phenylethyl etc.; and the nitro group and the like, or (10) tri-C1-4 alkylsilane, such as trimethylsilyl or triethylsilyl and the like.

"Substituents" in the "amino group which may have a Deputy (deputies)"represented by R2includes hydrocarbon group which may have a Deputy (deputies), -SO2R201, =NR202, -OR203(where R201-R203represents a hydrocarbon group which may have a Deputy (deputies)and the like. "Hydrocarbon group which may have a Deputy (deputies)" has the same meaning as the "hydrocarbon group which may have a Deputy (deputies)"defined in "protective group" "acidic group which may be protected"represented by R1. Preferred as the "substituents" in the "amino group which may have a Deputy (deputies)"represented by R2is the "hydrocarbon group which may have a Deputy (deputies)".

"3-15 membered heterocyclic group which may have a Deputy (deputies)"represented by R2has the same value as "3 to 15-membered heterocyclic group, which moretime Deputy (deputies)", represented by ring A or ring B. Preferred as a 3-15 membered heterocyclic group which may have a Deputy (deputies)"represented by R2is piperidine or piperazine, which may have a Deputy (deputies), and more preferred is

(where the arrow shows the position of bonding with the ring D, and R31, R32, R33and R34each, independently, have the same meanings as the "substituents" of the "3 to 15-membered heterocyclic group which may have a Deputy (deputies)"represented by ring A or ring B) and the like.

Preferred R2is, for example, hydrocarbon group which may have a Deputy (deputies) or amino group which may have a Deputy (deputies), and the like, and more preferred is

(where the arrow shows the position of bonding with the ring D, and R51, R52, R53and R54are each, independently, a hydrogen atom, a hydrocarbon group which may have a Deputy (deputies), 3-15 membered heterocyclic group which may have a Deputy (deputies), C1-4 alkoxygroup, which may have a Deputy (deputies), phenoxy, which may have to cover the spruce (deputies) or benzyloxy, which may have a Deputy (deputies)), etc. "Hydrocarbon group which has a Deputy (deputies)and 3-15 membered heterocyclic group which may have a Deputy (deputies)" have the same meanings as described above, respectively. C1-4 alkoxygroup includes, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy or tert-butoxy and the like. C1-4 alkoxygroup, fenoxaprop or benzyloxy may have optional substituents. The substituents C1-4 alkoxygroup, fenoxaprop or benzyloxy include, for example, the above-described "substituents" of "hydrocarbon group which has a Deputy (deputies)".

Preferably R51, R52, R53or R54represents a hydrogen atom, a hydrocarbon group which may have a Deputy (deputies), or 3-15 membered heterocyclic group which may have a Deputy (deputies), and the like. In addition, the connection, in which one of R52and R53represents a hydrogen atom, is preferred.

In the present invention, the compound represented by formula (I)containing a combination of the above-described preferred groups and rings, is preferred. For example, a compound in which the ring D is piperidine or piperazine, and Predstavljaet methylene group, that is, the compound represented by formula (Ia)

(where ring D1arepresents piperidine or piperazine, which may have a Deputy (deputies), and other symbols have the same meanings as described above); a compound in which the ring D is piperidine or piperazine, R2is

,

that is, the compound represented by formula (Ib)

(where all the symbols have the same meanings as described above); a compound where R1is-SO2NR102R103or-NR101SO2R104X represents a bond, -CR7R8-, -NR9-, -CO-, -O-, -S-, -SO-, -SO2-, -C(=N-OR10)- (where R7and R8are each, independently, a hydrogen atom, C1-4 alkyl, -OR11or phenyl, R9represents a hydrogen atom, C1-4 alkyl or phenyl, R10and R11are each, independently, a hydrogen atom or C1-4 alkyl), Y is methylene, ring A and ring B represent each independently a benzene which may have a Deputy (deputies), ring D is piperidine, and R2is

that is, the compound represented by formula (Ic)

(where R1-1ais-SO2NR102R103the Li-NR 101SO2R104X1arepresents a bond, -CR7R8-, -NR9-, -CO-, -O-, -S-, -SO-, -SO2-, -C(=N-OR10)- (where R7and R8are each, independently, a hydrogen atom, C1-4 alkyl, -OR11or phenyl, R9represents a hydrogen atom, C1-4 alkyl or phenyl, R10and R11are each, independently, a hydrogen atom or C1-4 alkyl), ring A1aand ring B1arepresent each independently a benzene which may have a Deputy (deputies), ring D1brepresents piperidine, which may have a Deputy (deputies), and other symbols have the same meanings as described above); or a compound, where R1is-SO2NR102R103or-NR101SO2R104X represents a bond, -CR7R8-, -NR9-, -CO-, -O-, -S-, -SO-, -SO2-, -C(=N-OR10)- (where R7and R8are each, independently, a hydrogen atom, C1-4 alkyl, -OR11or phenyl, R9represents a hydrogen atom, C1-4 alkyl or phenyl, R10and R11are each, independently, a hydrogen atom or C1-4 alkyl), Y is methylene, ring A and ring B represent each independently a benzene or unsaturated managerialism group which may have a Deputy (deputies), ring D is piperidine or piperazine, R2the submitted Jerusalem.

that is, the compound represented by formula (Id)

(where ring A1band ring B1brepresent each independently a benzene or 5 - or 6-membered aromatic ring which may have a Deputy (deputies), and other symbols have the same meanings as described above) and the like, is preferred.

Specifically, the compound of the present invention includes a compound described in the example, or

2-[3-methyl-4-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperazine-1-yl]-N-phenylhexanoic,

N-{4-[4-({4-[(anilinoacrolein)(butyl)amino]-4'-methyl-1,4'-bipiperidine-1'-yl}methyl)phenoxy]phenyl}methanesulfonamide,

N-[4-(4-{[3-[(anilinoacrolein)(butyl)amino]-4-(3-forfinal)pyrrolidin-1-yl]methyl}phenoxy)phenyl]methanesulfonamide,

N-[4-(4-{[3-(butylamino)-4-(3-forfinal)pyrrolidin-1-yl]methyl}phenoxy)phenyl]methanesulfonamide,

N-butyl-N-(1-{3-ethyl-1-[4-(methylsulphonyl)benzyl]-1H-pyrazole-4-yl}piperidine-4-yl)-N'-phenylacetone,

N-butyl-N-[1-({4-methyl-2-[4-(trifluoromethyl)phenyl]-1H-imidazol-5-yl}methyl)piperidine-4-yl]-N'-phenylacetone,

N-{4-[4-({3-[(anilinoacrolein)(butyl)amino]-8-azabicyclo[3.2.1]Oct-8-yl}methyl)phenoxy]phenyl}methanesulfonamide,

N-[4-(4-{[4-(3-isopropyl-5-methyl-4H-1,2,4-triazole-4-yl)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide,

N-[4-(4-{[4-(2-methyl-1H-benzoni the azole-1-yl)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide,

N-[4-(4-{[4-[(anilinoacrolein)(butyl)amino]-3,4-dihydroquinoline-1(2H)-yl]methyl}phenoxy)phenyl]methanesulfonamide,

N-[4-(4-{[4-(2-oxo-3-phenyl-6-propyltetrahydropyran-1(2H)-yl)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide,

N-(4-{4-[(3-butyl-2-oxo-1,2,3,3a,4,5-hexahydro-6H-pyrido[4,3,2-de]hinzelin-6-yl)methyl]phenoxy}-phenyl)methanesulfonamide,

N-(4-{4-[(1-butyl-2-oxo-4-fenilatsetamida[4,3-d]pyrimidine-6(2H)-yl)methyl]phenoxy}phenyl)methanesulfonamide,

N-{4-[4-({8-[(anilinoacrolein)(butyl)amino]-3-azabicyclo[3.2.1]Oct-3-yl}methyl)phenoxy]phenyl}methanesulfonamide,

N-[4-(4-{[(2Z)-1-butyl-2-(phenylimino)hexahydro-2H-pyrido[4,3-d][1,3]oxazin-6(4H)-yl]methyl}phenoxy)phenyl]-methanesulfonamide or

N-[7-({4-[(anilinoacrolein)(butyl)amino]piperidine-1-yl}methyl)-9H-xanthene-2-yl]methanesulfonamide and the like.

Especially preferred are the compounds described in the examples and their salts and solvate and prodrug.

More preferred are

N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide,

N-[4-(4-{[4-(butyl{[(6-methyl-3-pyridinyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide,

N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl} - for 3,5-dimethyl-1H-pyrazole-1-yl)phenyl]-methanesulfonamide,

N-[4-(4-{[4-(butyl{[(1-methyl-1H-pyrazole-4-yl)amino]-Carboni is}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide,

3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]benzamide,

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(phenyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide,

5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]-2-perbenzoic,

5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]-2,4-diflorasone,

N-[4-(4-{[4-(butyl{[(3-cyano-4-forfinal)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide,

N-[4-(4-{[4-(butyl{[(3-hydroxycyclohexyl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide or

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(1,3-thiazol-4-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide,

their salts and solvate and prodrug.

Unless specifically provided otherwise, all isomers are included in the present invention. For example, alkyl, alkenyl, quinil, alkoxy, alkylthio, alkylene, albaniles and akinyan includes molecules with straight chain and branched chain. In addition, all isomers associated with a double bond, ring and fused ring (E-, Z-, CIS - and TRANS-forms), isomers associated with the presence of asymmetric atom (atoms) of carbon, and the like, (R-, S-, α - and β-configuration, enantiomer and the diastereoisomer), optically active the e substances, having optical rotation (D-, L-, d - and l-forms), polar compound with respect to chromatographic separation (more polar compound and less polar compound), equilibrium compounds, rotary isomers, a mixture thereof in any proportion and a racemic mixture are included in the present invention.

In accordance with the present invention, unless otherwise indicated and as is clear to experts in this field, the symbolindicates that the link is directed in the opposite direction from the sheet (namely α-configuration), symbolindicates that the link is directed from the leaf to the observer (namely β-configuration), and the symbolindicates that it is a mixture of α-configuration and β-configuration.

The compound of the present invention can be converted to a salt by known methods. The salt is preferably a pharmacologically acceptable salt.

Salt includes a salt of an alkaline metal salt, alkaline earth metal, ammonium salt, amine salt or an acid additive salt and the like.

The salt is preferably water-soluble. Suitable is, for example, salt of an alkali metal (such as sodium and potassium), alkali earth metal salt (such as calcium and magnesium), salt ammo the Oia and salt with a pharmacologically acceptable organic amine (such as Tetramethylammonium, the triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, Tris(hydroxymethyl)methylaminomethyl, lysine, arginine and n-methyl-D-glucamine).

An acid additive salt is preferably water-soluble. Suitable for use acid additive salt is, for example, salt of an inorganic acid such as hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate and nitrate; or a salt of organic acid such as acetate, lactate, tartrate, benzoate, citrate, methanesulfonate, aconsultant, bansilalpet, toluensulfonate, isothionate, glucuronate and gluconate; and the like.

The compound represented by formula (I)and its salt can be converted to a solvate.

MES preferably is non-toxic and water soluble. Suitable for use MES is, for example, MES water or alcohol (e.g. ethanol).

All of the compounds represented by formula (I)or their pharmacologically acceptable salt is preferable; specifically, compounds described in the examples, or their pharmacologically acceptable salts are preferred.

In addition, the salt includes a salt of Quaternary ammonium. Salt of Quaternary ammonium, and compounds represented by formula (I)is a compound where nitrogen is unity, represented by formula (I)is quaternion by R0.

R0represents C1-8 alkyl or C1-8 alkyl substituted by phenyl.

The compound of the present invention can be converted to N-oxide by known methods. N-oxide is the compound where nitrogen compounds are represented by formula (I)is oxidized.

The prodrug compounds of the formula (I) means a compound which is converted to the compound of formula (I) by reaction with an enzyme, gastric acid or the like in a living organism. For example, prodrugs of the compounds of formula (I)where the compound of formula (I) has an amino group, compounds in which the amino group is, for example, acylated, alkilirovanny or phosphorylated (for example, compounds in which the amino group of compounds of formula (I) is eicosanoides, albilineans intramyocardially, (5-methyl-2-oxo-1,3-dioxolan-4-yl)methoxycarbonylamino, tetrahydrofurfurylamine, pyrrolidinylcarbonyl, pivaloyloxymethyl, acetoxystyrene, tert-butylated, etc.); when the compound of formula (I) has a hydroxyl group, compounds where the hydroxyl group is, for example, acylated, alkilirovanny, phosphorylated or Bororo is Anna (e.g., compounds in which the hydroxyl group of compounds of formula (I) is acetylated, palmitoylation, propanolamine, pualeilani, succinylamino, polarisierung, albilineans or dimethylaminomethylphenol); and that the carboxyl group of the compounds of formula (I) is, for example, esterified or amidinophenoxy (for example, compounds in which the carboxyl group of the compounds of formula (I) is transformed into a complex of ethyl ether complex phenyl ether complex phenethyl ester, complex carboxymethylate ether complex dimethylaminomethylene ether complex pivaloyloxymethyl ether complex ethoxycarbonylmethylene ether, an ester of phthalic acid, compound (5-methyl-2-oxo-1,3-dioxolan-4-yl)methyl ester, complex cyclohexyloxycarbonyloxy ether or methylamide). These compounds can be obtained in a known manner. The prodrug compounds of the formula (I) may be either a hydrate or non-hydrate. The prodrug compounds of the formula (I) may also be a compound which is converted to the compound of formula (I) under physiological conditions as described in "Iyakuhin no kaihatsu, Vol.7 (Bunshi-sekkei), pp.163-198 (Hirokawa-Shoten), 1990". And the compound of formula (I) can also be observed radioactive isotope (such as3H,14C,35S125I and Tom is one).

Methods for obtaining compounds of the present invention:

The compound of the present invention, represented by formula (I)can be obtained by using advanced methods such as the methods described below, the methods described in the examples or the methods described in Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition (Richard C. Larock, John Wiley & Sons Inc, 1999). Each method described below, the source material may be used in the form of its salt. An example of a salt is the salt of the compounds of formula (I)described above.

Among the compounds represented by formula (I), a compound in which a spacer, which is located near the ring, D represents-CH2-, -CO - or-SO2-can be obtained by alkylation, amidation or sulfonmethane compounds represented by formula (II)

(where Z represents a hydroxy-group or a leaving group (such as halogen atom, p-toluensulfonate, methysulfonylmethane, triftormetilfullerenov and the like),represents a bond or a spacer containing 1 or 2 atoms as a main chain,represents-CH2-, -CO - or-SO2- X', ring A' and ring B' have the same meanings as R1, X ring, and ring B, respectively. This should satisfy the condition that carboxypropyl, the hydroxy-group, amino group or Tolna groupX', ring A or ring B' can be protected, if necessary. Other symbols have the same meanings as described above), and the compound represented by formula (III)

(whereand ring D' have the same meanings as R2and D, respectively. This should satisfy the condition that carboxypropyl, the hydroxy-group, amino group or Tolna groupor ring D' can be protected, if necessary)if necessary, after removal of the protective group.

The alkylation is known. For example, it may be carried out in an organic solvent (such as dimethylsulfoxide)in the presence of alkali (e.g. potassium carbonate or sodium carbonate) and sodium iodide or potassium iodide, at 0-150°C.

The amidation is known. For example, it includes the way

(1) through allhelgona,

(2) by the mixed anhydride of the acid,

(3) using a condensing agent.

These methods are explained as follows.

(1) the Way through allalone may be, for example, by reaction of carboxylic acid with allelochemical (e.g. the R, oxalylamino or thionyl chloride) in an organic solvent (e.g. chloroform, dichloromethane, simple diethyl ether or tetrahydrofuran) or without a solvent, at a temperature from -20°C to the temperature of reflux distilled. And then the derived acylhomoserine subjected to interaction with the amine in an organic solvent (e.g. chloroform, dichloromethane, simple diethyl ether or tetrahydrofuran) in the presence of a base (e.g. pyridine, triethylamine, dimethylaniline, dimethylaminopyridine or diisopropylethylamine and the like), at 0-40°C. alternatively, the received derived acylhomoserine can interact with the amine in an organic solvent (e.g. dioxane, tetrahydrofuran) using an aqueous solution of alkali (such as sodium bicarbonate, sodium hydroxide)at 0-40°C.

(2) the Method via a mixed acid anhydride may be carried out, for example, by reacting carboxylic acid with allelochemical (for example, revalorisation, mozillateam or methylchloride) or acid derivative (for example, etelcharge.com or isobutylparaben) in an organic solvent (e.g. chloroform, dichloromethane, simple diethyl ether, tetrahydrofuran) or without a solvent, in the presence of a base (e.g. pyridine, triethylene is a, of dimethylaniline, dimethylaminopyridine or diisopropylethylamine) at 0-40°C. And then derived the mixed acid anhydride can interact with the amine in an organic solvent (e.g. chloroform, methylene chloride, simple diethyl ether or tetrahydrofuran), at 0-40°C.

(3) the Method using a condensing agent may be carried out, for example, by reaction of carboxylic acid with amine in an organic solvent (e.g. chloroform, dichloromethane, dimethylformamide, simple diethyl ether or tetrahydrofuran) or without a solvent, in the presence or in the absence of a base (e.g. pyridine, triethylamine, dimethylaniline or dimethylaminopyridine), using a condensing agent (for example, 1,3-DICYCLOHEXYL carbodiimide (DCC), 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide (EDC), 1,1'-carbodiimide (CDI), 2-chloro-1-methylpyridinium iodide, or a cyclic anhydride of 1-papapostolou acid (PPA)), in the presence or in the absence of 1-hydroxybenzotriazole (HOBt), at 0-40°C.

The reaction described in (1), (2) and (3)may be carried out in an inert gas (e.g. argon, nitrogen)to avoid the presence of water to obtain the preferred result.

Sulfenamidovy is a well-known manner. For example, it can be done by interaction is the major sulfonic acid with allelochemical (for example, oxalylamino or thionyl chloride, pentachloride phosphorus or trichloride phosphorus) in an organic solvent (e.g. chloroform, dichloromethane, dichloroethane, simple diethyl ether, tetrahydrofuran or simple methyl tert-butyl ether) or without solvent, at temperatures from -20°C to the temperature of reflux distilled. And then sulphonylchloride derived can interact with the amine in an organic solvent (e.g. chloroform, dichloromethane, simple diethyl ether or tetrahydrofuran) in the presence of a base (for example, diisopropylethylamine, pyridine, triethylamine, dimethylaniline or dimethylaminopyridine and the like), at 0-40°C.

The removal of the protective group is known and can be carried out using the following method.

Carboxylamide group includes, for example, methyl, ethyl, allyl, tert-butyl, trichloroethyl, benzyl (Bn) or pencil and the like.

Protective hydroxy-group includes, for example, methyl, trityl, methoxymethyl (MOM), 1-ethoxyethyl (EE), methoxyethoxymethyl (MEM), 2-tetrahydropyranyl (THP), trimethylsilyl (TMS), triethylsilyl (TES), tert-butyldimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS), acetyl (Ac), pivaloyl, benzoyl, benzyl (Bn), p-methoxybenzyl, allyloxycarbonyl (Alloc), and 2,2,2-trichlorocyanuric (Troc) and the like.

Protective amino group includes the hat group, as benzyloxycarbonyl, tert-butoxycarbonyl, allyloxycarbonyl (Alloc), 1-methyl-1-(4-biphenyl)etoxycarbonyl (Bpoc), TRIFLUOROACETYL, 9-fluorenylmethoxycarbonyl, benzyl (Bn), p-methoxybenzyl, benzoyloxymethyl (BOM) or 2-(trimethylsilyl)ethoxymethyl (SEM) and the like.

The protective group of the thiol includes, for example, benzyl, methoxybenzyl, methoxymethyl (MOM), 2-tetrahydropyranyl (THP), diphenylmethyl and acetyl (Ac), and the like.

Relative to the protective group for carboxyl, hydroxyl, amino and thiol, there are no restrictions on these groups because they represent a group which can easily and selectively be separated. For example, the reaction of removing the protection can be carried out using the method discussed in "T. W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons Inc, 1999".

The reaction for removing the protective group for carboxyl, hydroxyl, amino or thiol is known and its examples are as follows.

(1) hydrolysis with alkali;

(2) the reaction of removing the protection under acidic conditions;

(3) the reaction of removing the protection by hydrogenolysis;

(4) the reaction unprotect silila;

(5) the reaction remove protection using metal; and

(6) the reaction unprotect using complex metal.

These methods will be specifically illustrated as follows.

(1) the Reaction of removing the protection with the use of alkali is carried out, for example, when 0-40°C, using a hydroxide of alkaline metal (such as sodium hydroxide, potassium hydroxide and lithium hydroxide), a hydroxide of alkaline earth metal (such as barium hydroxide and calcium hydroxide), a carbonate (such as sodium carbonate and potassium carbonate), an aqueous solution or a mixture thereof in an organic solvent (such as methanol, tetrahydrofuran and dioxane, and the like).

(2) the Reaction of removing the protection under acidic conditions is carried out, for example, at 0-100°C, in an organic acid (e.g. acetic acid, triperoxonane acid, methanesulfonic acid or p-tosylate), inorganic acid (e.g. hydrochloric acid and sulfuric acid) or mixtures thereof (such as hydrogen bromide/acetic acid)in an organic solvent (such as dichloromethane, chloroform, dioxane, ethyl acetate and anisole and the like).

(3) the Reaction of removing the protection by hydrogenolysis is carried out, for example, at 0-200°C, in an atmosphere of hydrogen at normal pressure or at elevated pressure, or in the presence of ammonium formate, in the presence of a catalyst (such as palladium on charcoal, palladium black, palladium hydroxide, platinum oxide and Raney Nickel)in a solvent [for example, simple ether (such as tetrahydrofuran, dioxane, dimethoxyethane and simple diethyl ether), spirit is a solvent (such as methanol and ethanol), benzene (such as benzene and toluene), a ketone (such as acetone and methyl ethyl ketone), a nitrile (such as acetonitrile), amide (such as dimethylformamide), water, ethyl acetate, acetic acid or a mixed solvent containing two or more of them].

(4) the Reaction unprotect silila is carried out, for example, at 0-40°C, using tetrabutylammonium fluoride, in an organic solvent miscible with water (such as tetrahydrofuran and acetonitrile, and the like).

(5) the Reaction unprotect using the metal is, for example, at 0-40°C, with an ultrasonic wave or without it, in the presence of powdered zinc in an acid solvent such as acetic acid buffer with a pH of 4.2 to 7.2, and a mixed solution of a solution with an organic solvent, such as tetrahydrofuran).

(6) Reaction to unprotect the use of a complex of the metal is, for example, at 0-40°C, using a complex metal [such as tetranitroaniline palladium (0), bis(triphenylphosphine) palladium (II) dichloride, palladium (II) acetate and Tris(triphenylphosphine) rhodium (I) chloride] in the presence or in the absence of a phosphine agent (such as triphenylphosphine), in the presence of complexing reagent (such as anti-hydride, triethylsilane, dimedone, morpholine, diethylamine and pyrrolidine), organic key is lots (such as acetic acid, formic acid and 2-ethylhexanoate acid and/or salts of organic acids (such as 2-ethylhexanoate, sodium 2-ethylhexanoate and potassium) in an organic solvent (such as dichloromethane, dimethylformamide, tetrahydrofuran, ethyl acetate, acetonitrile, dioxane and ethanol), water or a mixed solvent.

In addition to the above removing protection can also be implemented in accordance with the methods described in T.W. Greene, Protective Groups in Organic Synthesis, Wiley, New York, 1999.

Specialists in this field will readily understand that the target compound of the present invention can easily be obtained through the use of appropriate reactions, these reactions remove the protection.

Among the compounds represented by formula (I), the compound in which R2represents an amino group which may have a Deputy (deputies), i.e. the compound represented by formula (I-a)

(where R2-1represents an amino group which may have a Deputy (deputies), and other symbols have the same meanings as described above), can be obtained by reductive amination of compounds represented by formula (IV)

(where all the symbols have the same meanings as described above) and the compound represented by formula (V)

(where R301and R302that are the same or different, represent a hydrogen atom or have the same meanings as the "substituents"described above "amino group which may have a Deputy (deputies), and other symbols have the same meanings as described above. This should satisfy the condition that carboxypropyl, the hydroxy-group, amino group or Tolna group in R301or R302may be protected, if necessary)if necessary, followed by removal of the protective group.

Reductive amination is well known. For example, it may be carried out in an organic solvent (e.g. dichloroethane, dichloromethane or dimethylformamide)in the presence of tertiary amine (e.g. triethylamine or diisopropylethylamine) and reducing agent (for example, triacetoxyborohydride sodium or cyanoborohydride sodium)at 0-40°C.

The removal of the protective group can be performed by the above described method.

Among the compounds represented by formula (I), the compound in which R2is

(where R304, R305and R306that are the same or different, have the same meanings as the "substituents" of the above "3-15 membered gamecycledelay group or heterocyclic the koi group, which may have a Deputy (deputies)"represented by ring a and ring B, and other symbols have the same meanings as described above), i.e. the compound represented by formula (I-b)

(where all the symbols have the same meanings as described above), can be obtained by cyclization of the compounds represented by formula (VI)

(where T represents C1-4 alkyl group, C5-6 monocarbonyl, or C1-4 alkyl, substituted C5-6 monocarbocyclic or 5 - or 6-membered monoheterocycles containing 1 or 2 nitrogen atom and/or one oxygen atom, R304', R305' and R306' have the same meanings as R304, R305and R306respectively, and other symbols have the same meanings as described above. This should satisfy the condition that carboxypropyl, the hydroxy-group, amino group or Tolna group in R304', R305' and R306' may be protected, if necessary)if necessary, followed by removal of the protective group.

Cyclization is well known. For example, it may be carried out in an organic solvent (e.g. dichloromethane or toluene), using a tertiary amine (e.g. triethylamine or diisopropylethylamine) or acid (e.g. acetic acid or triperoxonane acid), or without retinova amine or acid, at 60-120°C. the cyclization reaction is carried out with the removal of group T.

The removal of the protective group can be carried out using the above method.

Among the compounds represented by formula (I), the compound in which R2is

,

that is, the compound represented by formula (I-c)

(where all the symbols have the same meanings as described above), can be obtained by cyclization of the compounds represented by formula (VII)

(where all the symbols have the same meanings as described above), if necessary, followed by removal of the protective group.

Cyclization is well known. For example, it may be carried out in an organic solvent (e.g. dichloromethane or toluene), acid (e.g. hydrochloric acid, sulfuric acid or p-toluensulfonate acid)at 60-120°C.

The removal of the protective group can be carried out using the above method.

Among the compounds represented by formula (I), the compound in which R2is

,

that is, the compound represented by formula (I-d)

(where all the symbols have the same meanings as described above), can be obtained with p the power to the following reaction using compounds represented by formula (IX)

(wherehas the same meaning as R51and other symbols have the same meanings as described above. This should satisfy the condition that carboxypropyl, the hydroxy-group, amino group or Tolna groupcan be protected, if necessary), and compounds represented by (X)

(wherehas the same meaning as R52and other symbols have the same meanings as described above. This should satisfy the condition that carboxypropyl, the hydroxy-group, amino group or Tolna groupcan be protected, if necessary)if necessary, followed by removal of the protective group.

The reaction is well known. For example, it may be carried out in an organic solvent (such as N,N-dimethylformamide, toluene or tetrahydrofuran) with a base (e.g. pyridine, triethylamine, dimethylaniline, dimethylaminopyridine or diisopropylethylamine), at 20-120°C.

The removal of the protective group can be carried out using the above method.

In addition, the compound represented by formula (I-d)can be obtained using the following reaction, using EQ is whether the connection represented by formula (IX)and compounds represented by formula (XI)

(where the symbol has the same meaning as described above), if necessary, followed by removal of the protective group.

The reaction is well known. For example, it may be carried out in an organic solvent (such as tetrahydrofuran or N,N-dimethylformamidine) in the presence of triphosgene, with a base (e.g. triethylamine), at 0-40°C. in Addition, it can be carried out in an organic solvent (e.g. methylene chloride or N,N-dimethylformamidine), in the presence of 1,1'-carbonylbis-1H-imidazole (CDI), with base (e.g. triethylamine or N-methylmorpholine) or without reason, at 0-80°C.

The removal of the protective group can be carried out using the above method.

Among the compounds represented by formula (I), the compound in which Y is methylene, i.e., the compound represented by formula (I-e)

(where all the symbols have the same meanings as described above) can be obtained by reductive amination of compounds represented by formula (XII)

(where all the symbols have the same meanings as described above), and compounds represented by formula (III), if necessary, with the consequences which provide for the removal of the protective group.

Reductive amination is well known. For example, it may be carried out in an organic solvent (e.g. dichloroethane, dichloromethane, dimethylformamide, acetic acid or mixtures thereof)in the presence of a reducing agent (for example, triacetoxyborohydride sodium, cyanoborohydride sodium or sodium borohydride)at 0-40°C.

The removal of the protective group can be carried out using the above method.

Among the compounds represented by formula (I), a compound in which at least one nitrogen atom represents a salt of Quaternary ammonium compounds, i.e. the compounds of formula (I-2)

(where R1-2, R2-2X2, Y2ring A2ring B2and ring D2have the same meanings as R1, R2X, Y, ring A, ring B and ring D, respectively, and N2represents a nitrogen atom. This should satisfy the condition that at least one nitrogen atom represents a salt of Quaternary ammonium, and Q is halogen) can be obtained by reaction of compounds of formula (I) with compounds of the formula (VIII)

(where R0represents C1-4 alkyl or C1-4 alkyl substituted by phenyl, and Q is halogen).

The reaction is well known, and it can assests is sterile, for example, in an organic solvent (acetone, dimethylformamide or methyl ethyl ketone, and the like), at 0-40°C.

Among the compounds of formula (I), a compound in which at least one nitrogen is N-oxide, i.e., the compound of formula (I-3)

(where R1-3, R2-3X3, Y3ring A3ring B3and ring D3have the same meanings as R1, R2X, Y, ring A, ring B and ring D, respectively, and N3represents a nitrogen atom. This should satisfy the condition that at least one nitrogen atom is N-oxide), can be obtained by oxidation of compounds of formula (I).

Oxidation is well known, and it can be done, for example, in an appropriate organic solvent (e.g. dichloromethane, chloroform, benzene, hexane or tert-butyl alcohol)in the presence of an excess of oxidizing reagent (hydrogen peroxide, periodate sodium, acyl nitrite, sodium perborate, nagkalat (for example, 3-chloroperbenzoic acid or peracetic acid, and the like), OXONE (trade name, OXONE is reduced to peroxymonosulfate potassium), potassium permanganate or chromic acid, and the like), at 20-60°C.

The compound of the present invention can be obtained by using these re the capabilities of either of these reactions, which is partially modified.

Among the compounds represented by formula (I), compounds other than the above, can easily be obtained by combining known methods such as methods described in Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition (Richard C. Larock, John Willey & Sons Inc, 1999).

Other parent compound or compounds used as reagents, are known compounds and can be easily obtained by combining known methods such as methods described in Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition (Richard C. Larock, John Willey & Sons Inc, 1999) or Elmer J.Rauckman et al., J. Org. Chem., vol.41, No.3, 1976, p564-565 and the like.

In each reaction description of the reaction with heating, as will be clear to experts in the field, can be carried out using a water bath, oil bath, sand bath and microwaves.

In each reaction description can be used in solid-phase reagent, which can be applied to the polymer (for example, polystyrene, polyacrylamide, polypropylene or polyethylene glycol, and the like).

In each reaction, presented in the description, the products obtained can be purified using conventional techniques. For example, purification can be performed by distillation at atmospheric or reduced pressure, using a highly efficient liquids is Noah chromatography on silica gel or magnesium silicate, by thin-layer chromatography by ion-exchange resin through resin-absorber with column chromatography, by washing or by recrystallization. Cleaning may be performed after each reaction or after several reactions.

Toxicity:

The toxicity of the compounds of the present invention is very low, and for this reason, the connection can be considered safe for pharmaceutical use.

Application to pharmaceutical drugs:

Compounds of the present invention, represented by formula (I), regulate the action of the CCR5 receptor in animals, including humans, in particular humans, so they are used for prevention and/or treatment of various inflammatory diseases (asthma, nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, rhinitis, conjunctivitis, ulcerative colitis, etc.), immunological diseases (autoimmune diseases, rejection of organs in transplantation, immunosuppression, psoriasis, multiple sclerosis and the like), infection of human immunodeficiency virus (acquired immunodeficiency syndrome and the like), allergic diseases (atopic dermatitis, urticaria, allergic bronchopulmonary aspergillosis, al is ergicheskoe eosinophilic gastroenteritis, etc.), ischemic reperfusion injury, acute respiratory distress syndrome, shock accompanying bacterial infection, diabetes, cancer metastasis and so on.

For the purpose described above, the compounds of the present invention of formula (I), their salts or solvate salts or prodrugs can typically be entered systemic or local way, usually by oral or parenteral administration.

Dose that must be administered are determined depending on, for example, the age, body weight, symptom, the desired therapeutic effect, the route of administration and duration of treatment. Adult dose for one person are generally from 1 mg to 1000 mg, by oral administration, up to several times a day, and from 1 mg to 100 mg, by parenteral administration (preferably intravenous administration), up to several times per day, or continuous injection from 1 to 24 hours per day, through a vein.

As discussed above, the dose that should be used depend on various conditions. For this reason, can be used doses lower or greater than the ranges given above.

Compounds of the present invention can be administered, for example, in the form of a solid product for oral administration, liquid forms for oral administration, injections, liniments or is suppositories for parenteral administration.

Solid forms for oral administration include compressed tablets, pills, capsules, dispersible powders and granules. Capsules can be hard capsules and soft capsules.

In such solid forms one or more active compounds may be mixed with carriers such as lactose, mannitol, glucose, microcrystalline cellulose or starch), binders (such as hydroxypropylcellulose, polyvinylpyrrolidone or magnesium metasilicate aluminate), leavening agents (such as calcium picosatellite), lubricating agents (such as magnesium stearate), stabilizing agents and auxiliary substances in solution (such as glutamic acid or aspartic acid) and prepared in accordance with methods well known in normal pharmaceutical practice. Solid forms may, if desired, be covered by the agents for coatings (such as sugar, gelatin, hydroxypropylcellulose or phthalate of hydroxypropylmethylcellulose) or be covered by two or more films. And, in addition, the coating may include holding inside capsules of absorbing materials, such as gelatin.

Liquid forms for oral administration include pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs. In such forms one or more active is dinani can dissolve, to suspendibility or emulgirovanija in diluent (thinner), usually used in this field (such as purified water, ethanol or their mixture). In addition, such liquid formulations may also contain some additives, such as wetting agents, suspendresume agents, emulsifying agents, sweetening agents, flavouring agents, flavors, or preservatives and buffering agents.

Injections for parenteral administration include sterile aqueous solutions, suspensions, emulsions and solid forms that dissolve or suspendered in solvent (solvents) for injection immediately before use. When the injection of one or more active compounds can be dissolved, suspenderbelt or emulgirovanija in the solvent (the solvent). Solvents may include distilled water for injection, saline, vegetable oil, propylene glycol, polyethylene glycol, an alcohol, such as ethanol, or a mixture. Injections may contain some additives, such as stabilizing agents, excipients in solutions (such as glutamic acid, aspartic acid or POLYSORBATE80 (registered trade name)), suspendresume agents, emulsifying agents, analgesic agent, buffer agents, preservatives. They can sterilize is sterile at the final stage or can be prepared in accordance with the sterile methods. They can also be made in the form of sterile solid dosage forms, such as the products obtained freeze-drying, which can be dissolved in sterile water or some other sterile diluent (thinner) for injection immediately before use.

Other forms for parenteral administration include liquids for external use, liniments and undermydesk ointments, inhalations, sprays, suppositories and pessaries for vaginal administration, which contain one or more active compounds and can be obtained by methods known per se.

Sprays can contain additional substances other than the diluents, such as stabilizing agents, such as sodium sulfate, isotonic buffers, such as sodium chloride, sodium citrate or citric acid. To obtain such sprays can be used, for example, the method described in United States patents No. 2868691 or 3095355.

Compounds of the present invention, represented by formula (I), their salts or their solvate or prodrug can be used together with other drugs, such as agent (agents) for the prevention and/or treatment of HIV infection (in particular, agents for prevention and/or treatment of AIDS). In this case, the drug itself may) is about being with a pharmacologically acceptable excipient, binder, loosening agent, lubricating agent, stabilizer, solubilizer, solvent and the like, either separately or simultaneously with the receipt of a pharmaceutical preparation which can be administered either orally or parenterally, in the form of a pharmaceutical composition for prevention and/or treatment of HIV infection.

Compounds of the present invention, represented by formula (I), their salts or their solvate or prodrug have the activity of inhibiting infection by HIV-I, which acquires resistance to other agents for the prevention and/or treatment of HIV infection (in particular, agents for prevention and/or treatment of AIDS). Thus, they can also be used for HIV-infected patients for whom other agents for the prevention and/or treatment of HIV infection is no longer effective. In this case, although the connection of the present invention can be used by itself, it can also be used together with agents for the prevention and/or treatment of HIV infection, when the infecting strain of HIV-1 acquires resistance, or with other medicines.

The present invention covers the case where the compound represented by formula (I), their salts or their solvate or prodrug combined with medicines which mi, which does not inhibit HIV infection, with preventive and/or therapeutic effect on HIV infection is enhanced in comparison with the drug itself.

Examples of other agent for prevention and/or treatment of HIV infection, used in combination with the compounds of the present invention, represented by formula (I), their salts or their solvate or their prodrugs, are nucleoside reverse transcriptase inhibitor, protease inhibitor, antagonist of a chemokine (such as CCR2 antagonist, CCR3 antagonist, CCR4 antagonist, CCR5 antagonist and antagonist of CXCR4), fusion inhibitor, antibody to surface antigen of HIV-1 and vaccine of HIV-1.

Reverse transcriptase inhibitors specifically represent (1) a reverse transcriptase inhibitors nucleoside/nucleotide: zidovudine (trade name: Retrovir), didanosine (trade name: Videx), zalcitabine (trade name: HIVID), stavudine (trade name: Zerit), lamivudine (trade name: Epivir), abacavir (trade name: Ziagen), adefovir, adefovir dipivoxil, emtricitabine (trade name: Coviracil) or PMPA (trade name: Tenofovir), and the like, and (2) inhibitors non-nucleoside reverse transcriptase inhibitors: nevirapine (trade name: Viramune), delavirdine (trade name: Rescriptor), efavirenz (trade name: Sustiva, Stocklin) or to Proviron (AG1549) and the like.

Protease inhibitors are specifically indinavir (trade name: Crixivan), ritonavir (trade name: Norvir), nelfinavir (trade name: Viracept), shinaver (trade name: Invirase, Fortovase), APV (trade name: Agenerase), lopinavir (trade name: Kaletra), or tipranavir, and the like.

As antagonists of the chemokine, included internal ligand receptor of the chemokine, its derivatives, its ones low-molecular compound or antibody to the receptor of the chemokine.

Examples of internal ligand receptor of the chemokine which specifically represent the MIP-1α, MIP-1β, RANTES, SDF-1α, SDF-1β, MCP-1, MCP-2, MCP-4, Eotaxin and MDC and the like.

Derivatives of the internal ligand which specifically represent the AOP-RANTES, Met-SDF-1α, Met - SDF-1β, and the like.

Antibodies to the receptor of the chemokine which specifically represent the Pro-140, and the like.

Antagonists of CCR2 specifically recorded in the description of International patent applications WO99/07351, WO99/40913, WO00/46195, WO00/46196, WO00/46197, WO00/46198, WO00/46199, WO00/69432 or WO00/69815, or in Bioorg. Med. Chem. Lett.,10, 1803 (2000), and the like.

Antagonists of CCR3 specifically recorded in the description of the patent in Germany DE19837386, International patent applications WO99/55324, WO99/55330, WO00/04003, WO00/27800, WO00/27835, WO00/27843, WO00/29377, WO00/31032, WO00/31033, WO00/34278, WO00/35449, WO00/35451, WO00/35452, WO00/35453, WO00/35454, WO00/35876, WO00/35877, WO00/41685, WO00/51607, WO00/51608, WO00/51609, WO00/51610, WO00/53172, WO00/53600, WO00/58305, WO00/59497, WO00/59498,WO00/59502, WO00/59503, WO00/62814, WO00/73327 or WO01/09088, and the like.

The CCR5 antagonists specifically represent TAK-779, SCH-351125 (SCH-C), SCH-417690(SCH-D, UK-427857, GW873140A(ONO-4128), TAK-220, and the like. In addition, they include compounds that are recorded in the description of International patent applications WO99/17773, WO99/32100, WO00/06085, WO00/06146, WO00/10965, WO00/06153, WO00/21916, WO00/37455, European patent EP1013276, International patent applications WO00/38680, WO00/39125, WO00/40239, WO00/42045, WO00/53175, WO00/42852, WO00/66551, WO00/66558, WO00/66559, WO00/66141, WO00/68203, Japan patent JP2000309598, International patent applications WO00/51607, WO00/51608, WO00/51609, WO00/51610, WO00/56729, WO00/59497, WO00/59498, WO00/59502, WO00/59503, WO00/76933, WO98/25605 or WO99/04794, WO99/38514, or in Bioorg. Med. Chem. Lett.,10, 1803 (2000), and the like.

The CXCR4 antagonists specifically represent AMD-3100, AMD-070, T-22, KRH-1120, KRH-1636 or compounds that are recorded in the description of the application for international patent WO00/66112 and the like.

Fusion inhibitors, specifically, are T-20 (Pentafuside) and T-1249 and the like.

Examples of combinations of agents recorded above, are intended to illustrate the present invention but do not restrict it.

Typical examples of the normal level of dose in clinical trials of protease inhibitors or protease inhibitors, included below, are intended to illustrate the present invention but do not restrict it.

Zidovudine: 100 mg capsule, 200 mg per dose, 3 times a day; 300 mg, tablet, 300 mg per dose, twice in the Yan;

didanosine: 25-200 mg, tablet, 125-200 mg per dose, twice a day;

zalcitabine: the 0.375-0.75 mg tablet of 0.75 mg per dose, 3 times a day;

stavudine: 15-40 mg, capsule, 30-40 mg per dose, twice a day;

lamivudine 150 mg, tablet, 150 mg per dose, twice a day;

abacavir: 300 mg, tablet, 300 mg per dose, twice a day;

nevirapine: 200 mg tablet, 200 mg per dose, once daily, for 14 days and then twice a day.

delavirdine: 100 mg, tablet, 400 mg per dose, 3 times a day;

efavirenz: 50-200 mg, capsule, 600 mg per dose, once a day;

indinavir: 200-400 mg capsule, 800 mg per dose, 3 times a day;

ritonavir: 100 mg, capsule, 600 mg per dose, twice a day;

nelfinavir: 250 mg, tablet, 750 mg per dose, 3 times a day;

shinaver: 200 mg, capsule, 1200 mg per dose, 3 times a day;

APV: 50-150 mg tablet, 1200 mg per dose, twice a day.

Action inventions

Compounds of the present invention, represented by formula (I)have the effect of a CCR5 antagonist, so they are useful in the prevention and/or treatment of diseases involving the CCR5 receptor.

The best way to carry out the invention

The present invention is explained below in detail on the basis of the comparative examples, examples of biological samples or examples of cooking, but the present invention is not so is limited by them.

When the chromatographic separations and TLC solvents in parentheses show eluting and showing solvents and relations used solvents are given by volume.

If not indicated otherwise, the NMR data are data1H-NMR.

The solvents in parentheses in the NMR data show the solvents used for the measurement.

All compounds described in the present description, are named using ACD/Name (registered trademark, ver. 6.0, Advanced Chemistry Development Inc.) or ACD/Name Batch (registered trademark, ver. 4.5, Advanced Chemistry Development Inc.) or are named in accordance with IUPAC nomenclature. For example, the connection is represented as

referred to as N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)piperidine-4-yl]cyclohexanecarboxylic hydrochloride.

Example 1:

1-(4-(4-methylsulfonylmethane)benzyl)piperidine-4-ol

To a solution of 4-(4-methylsulfonylmethane)benzaldehyde (2.50 g) in dimethylformamide (25 ml) is added 4-hydroxypiperidine (1,74 g) and acetic acid (2.5 ml) and the solution stirred. To the reaction solution add triacetoxyborohydride sodium (2,18 g) and the solution stirred for 2 days. After completion of the reaction, the reaction solution is neutralized 2 N. aqueous sodium hydroxide solution and extracted with et is lacerata. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (methylene chloride:methanol=10:1) to obtain the specified title compound (1.90 g)having the following physical data.

TLC: Rf of 0.48 (chloroform:methanol=5:1);

NMR (DMSO-d6): δ 1,29-of 1.42 (m, 2H), 1,63-of 1.73 (m, 2H), 1,95-2,05 (m, 2H), 2,59 of 2.68 (m, 2H), 2.95 and (s, 3H), 3,38 (s, 2H), 3.43 points (m, 1H), 4,51 (d, J=4.5 Hz, 1H), 6,91 (d, J=8.5 Hz, 2H), 6,99 (d, J=9.0 Hz, 2H), 7,21 (d, J=9.0 Hz, 2H), 7,25 (d, J=8.5 Hz, 2H), 9,59 (user. s, 1H).

Example 2:

1-(4-(4-methylsulfonylmethane)benzyl)piperidine-4-one

To a solution of the compound obtained in example 1 (1,79 g)in dimethylsulfoxide (5 ml), add triethylamine (3 ml). To the reaction solution was added a complex of sulfur trioxide and pyridine (1.52 g) under cooling on ice and the solution is stirred for one hour. After completion of the reaction, water is added to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (methylene chloride:methanol=20:1) to obtain specified in the connection header (1,76 g)having the following physical data.

TLC: Rf of 0.51 (chloroform:IU is anal=10:1);

NMR (DMSO-d6): δ of 2.33 (t, J=6.0 Hz, 4H), to 2.66 (t, J=6.0 Hz, 4H), 2.95 and (s, 3H), of 3.57 (s, 2H), 6,94 (d, J=8.5 Hz, 2H), 7,00 (d, J=9.0 Hz, 2H), 7,22 (d, J=9.0 Hz, 2H), 7,33 (d, J=8.5 Hz, 2H), 9,59 (s, 1H).

Example 3:

N-[4-(4-{[4-(butylamino)piperidine-1-yl]methyl}phenoxy)-phenyl]methanesulfonamide the dihydrochloride

To a solution of the compound obtained in example 2 (400 mg)in dimethylformamide (5 ml) is added n-butylamine (0.2 ml) and triethylamine (0.2 ml) and the solution stirred. To the reaction solution was added sodium triacetoxyborohydride (440 mg) and the solution stirred for 20 hours. After completion of the reaction, water is added to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (methylene chloride:methanol=5:1). To the reaction mixture is added 4 n solution of hydrogen chloride/ethyl acetate, concentrated to obtain the compound of the present invention (267 mg)having the following physical data.

TLC: Rf is 0.22 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,99 (t, J=7.5 Hz, 3H), 1,38-is 1.51 (m, 2H), 1,63-of 1.74 (m, 2H), 1,97 is 2.10 (m, 2H), 2,31-to 2.41 (m, 2H), 2.95 and (s, 3H), 3,02-is 3.08 (m, 2H), 3,10-3,18 (m, 2H), 3.45 points (m, 1H), 3,55-the 3.65 (m, 2H), or 4.31 (s, 2H), 7,03 (d, J=9.0 Hz, 2H), 7,06 (d, J=9.0 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,53 (d, J=9.0 Hz, 2H).

Example 4:

<> N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]-2-(tetrahydro-2H-Piran-4-yl)ndimethylacetamide hydrochloride

To a solution of the compound obtained in example 3 (183 mg)in dimethylformamide (3 ml) is added 4-tetrahydropyranyloxy acid (70 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (105 mg) and dimethylaminopyridine (155 mg) and the solution stirred overnight. After completion of the reaction, water is added to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (methylene chloride:methanol=25:1). To the reaction mixture is added 4 n solution of hydrogen chloride/ethyl acetate, concentrated, to obtain the compounds of the present invention (79 mg)having the following physical data.

TLC: Rf is 0.49 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.0 Hz, 3H), 1,24 was 1.69 (m, 8H), 1,87-to 2.40 (m, 7H), 2.95 and (s, 3H), 3,02-of 3.48 (m, 6H), 3,49-3,61 (m, 2H), a 3.87-3,95 (m, 2H), 4,12 (m, 1H), 4,27-4,30 (m, 2H), 7,03 (d, J=9.0 Hz, 2H), 7,06 (d, J=8.5 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.5 Hz, 2H).

Example 4(1):

2-cyclohexyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]-N-propylacetamide hydrochloride

Using the same procedure as described in PR the least 3 → example 4, using n-Propylamine and the corresponding cyclohexyloxy acid instead of n-butylamine and 4-tetrahydropyranyloxy acid respectively receive the connection according to the present invention having the following physical data.

TLC: Rf of 0.40 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,86-of 1.39 (m, 9H), 1,48 with 2.14 (m, 9H), 2,22 (d, J=7,0 Hz, 2H), 2,27-2,39 (m, 2H), 2.95 and (s, 3H), 3,02-of 3.25 (m, 4H), 3,49-3,61 (m, 2H), 4,13 (m, 1H), 4,27-the 4.29 (m, 2H), 7,03 (d, J=9.0 Hz, 2H), 7,06 (d, J=8.5 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.5 Hz, 2H).

Comparative example 1:

1-tert-butoxycarbonyl-4-butylenediamine

To a solution of 1-tert-butoxycarbonylamino-4-she (10.0 g) in dimethylformamide (200 ml) is added n-butylamine (6,0 ml) and triethylamine (7.0 ml) and the solution stirred. To the reaction solution was added sodium triacetoxyborohydride (16.0 g) and the solution stirred for 1.5 hours. After completion of the reaction, water is added to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated to obtain specified in the title compound having the following physical data.

TLC: Rf 0.28 in (chloroform:methanol=10:1);

NMR (CDCl3): δ to 0.92 (t, J=7.0 Hz, 3H), 1,19-of 1.53 (m, 6H), 1,45 (s, 9H), 1,82-to 1.87 (m, 2H), 2,55-of 2.66 (m, 3H), 2,74-2,82 (m, 2H), 4,00-4,10 (m, 2H).

Comparative example 2:

1-tert-butoxycarbonyl-4-(N-cyclohexyl shall arbonyl-N-butylamino)piperidine

To a solution of the compound obtained in comparative example 1 in methylene chloride (100 ml) add cyclohexyloxy acid (7.5 g), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (14.5 g) and 4-N,N-dimethylaminopyridine (9.2 grams) and the solution stirred overnight. After completion of the reaction, water is added to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to obtain specified in the connection header (8,97 g)having the following physical data.

TLC: Rf of 0.50 (hexane:ethyl acetate=2:1);

NMR (CDCl3): δ 0.87 for-a 1.01 (m, 2H), of 0.95 (t, J=7.5 Hz, 3H), 1,05-of 1.81 (m, 16H), of 1.46 (s, 9H), 1,89 (m, 1H), 2,16 (d, J=7,0 Hz, 2H), 2,68-to 2.85 (m, 2H), is 3.08-3,18 (m, 2H), 4.09 to of 4.35 (m, 2H), to 4.52 (m, 1H).

Comparative example 3:

4-[(N-cyclohexylcarbonyl-N-butyl)amino]piperidine hydrochloride

To a solution of the compound obtained in comparative example 2 (of 8.92 g)in methylene chloride (20 ml) is added triperoxonane acid (20 ml) and the solution stirred for 30 minutes. After completion of the reaction, the reaction solution is alkalinized 1 N. aqueous sodium hydroxide solution and extracted with methylene chloride. The organic layer was washed with saturated salt solution, dried over Sul is an atom of magnesium and concentrate. To the obtained residue, add a 4 n solution of hydrogen chloride/ethyl acetate, concentrated, obtaining specified in the header of the compound (7.98 g)having the following physical data.

TLC: Rf of 0.35 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,92-1,08 (m, 2H), and 0.98 (t, J=7.5 Hz, 3H), 1,15-of 2.36 (m, 17H), of 2.23 (d, J=7,0 Hz, 2H), 3,01-3,30 (m, 4H), 3,41-of 3.53 (m, 2H), 4,15 (m, 1H).

Example 5 (1) - example 5 (54)

Using the same procedure as described in example 1, and converting into a cleaners containing hydrochloride salt using a conventional method using the compound obtained in comparative example 3, or the corresponding amine derivative instead of 4-hydroxypiperidine and using 4-(4-methylsulfonylmethane)benzaldehyde or the corresponding aldehyde derivative will receive the following compounds of the present invention.

Example 5 (1):

N-butyl-2-cyclohexyl-N-[1-(4-{2-methoxy-4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-yl]ndimethylacetamide hydrochloride

TLC: Rf is 0.49 (chloroform:methanol=10:1);

NMR (CDCl3): δ 0.87 for-a 1.01 (m, 2H), of 0.93 (t, J=7.0 Hz, 3H), 1,07 e 2.06 (m, 15H), 2,19 (d, J=7,0 Hz, 2H), 2,49-2,84 (m, 4H), to 3.02 (s, 3H), 3,17-of 3.27 (m, 2H), 3,49-3,59 (m, 2H), 3,81 (s, 3H), 4,10 (user s, 2H), 4.72 in (m, 1H), 6,88-6,93 (m, 3H), of 6.99 (d, J=8.5 Hz, 1H), 7,13 (d, J=2.5 Hz, 1H), 7,53 (d, J=8.5 Hz, 2H), 7,94 (user s, 1H), 12,14 (s, 1H).

Example 5 (2):

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-Ben who yl)piperidine-4-yl]cyclohexanecarboxylic hydrochloride

TLC: Rf 0,62 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,55-7,46 (m, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,10-7,00 (m, 4H), 4,33-of 4.25 (m, 2H), 4,19 (m, 1H), 3,62-of 3.48 (m, 2H), 3,30-to 3.02 (m, 4H), 2.95 and (s, 3H), 2,48 (m, 1H), 2,35-of 2.08 (m, 2H), 1,98-to 1.63 (m, 7H), 1,63-of 1.18 (m, 9H), 1,03-to 0.88 (m, 3H).

Example 5 (3):

N-butyl-2-cyclohexyl-N-[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)piperidine-4-yl]ndimethylacetamide hydrochloride

TLC: Rf 0,62 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,55-7,46 (m, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,10-7,00 (m, 4H), 4,32-4,24 (m, 2H), 4.16 the (m, 1H), 3,63-of 3.48 (m, 2H), 3,30-a 3.01 (m, 4H), 2.95 and (s, 3H), 2.40 a-2,08 (m, 4H), 2.00 in to 1.60 (m, 8H), 1.60-to 1,10 (m, 7H), 1,10-of 0.90 (m, 5H).

Example 5 (4):

N-butyl-3-cyclohexyl-N-[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)piperidine-4-yl]propanamide hydrochloride

TLC: Rf of 0.64 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,56-7,46 (m, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,10-7,00 (m, 4H), 4,32-to 4.23 (m, 2H), 4.16 the (m, 1H), 3,62-3,47 (m, 2H), 3,30-3,00 (m, 4H), 2.95 and (s, 3H), 2,50-2,03 (m, 4H), 2,02-of 1.84 (m, 2H), 1,82 is 1.60 (m, 5H), 1,60-1,10 (m, 10H), 1,05-0,83 (m, 5H).

Example 5 (5):

N-butyl-2-cyclohexyl-N-{1-[(3,5-dimethyl-1-{4-[(methylsulphonyl)amino]phenyl}-1H-pyrazole-4-yl)methyl]piperidine-4-yl}ndimethylacetamide hydrochloride

TLC: Rf of 0.41 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,91 was 1.06 (m, 2H), and 0.98 (t, J=7.5 Hz, 3H), 1,14-to 1.83 (m, 13H), 1,89-of 1.97 (m, 2H), 2,23 (d, J=6,5 Hz, 2H), 2,32-to 2.40 (m, 2H), a 2.36 (s, 3H), 2,39 (s, 3H), 3.04 from (s, 3H), 3,12-3,29 (m, 4H), 3,61-3,71 (m, 2H), 4,25 (s, 2H), 4,27 (m, 1H), 7,41 (d, J=9.0 Hz, 2H), 7,46 (d, J=9.0 Hz, 2H).

Example 5 (6):

N-(1-{4-[4-(aminosulfonyl)phenoxy]benzyl}piperidine--yl)-N-butyl-2-cyclohexylacetate hydrochloride

TLC: Rf of 0.37 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,91 of-1.04 (m, 2H), and 0.98 (t, J=7.0 Hz, 3H), 1,12-1,99 (m, 15H), 2,22 (d, J=6,5 Hz, 2H), 2,25-of 2.36 (m, 2H), 2,97-3,30 (m, 4H), 3.46 in-of 3.60 (m, 2H), 4,10 (m, 1H), 4,29 (s, 2H), 7,13 (d, J=9.0 Hz, 2H), 7,17 (d, J=8.5 Hz, 2H), 7,55 (d, J=8.5 Hz, 2H), of 7.90 (d, J=9.0 Hz, 2H).

Example 5 (7):

N-butyl-2-cyclohexyl-N-[1-({4'-[(methylsulphonyl)amino]-biphenyl-3-yl}methyl)piperidine-4-yl]ndimethylacetamide hydrochloride

TLC: Rf of 0.50 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,87-1,05 (m, 2H), of 0.96 (t, J=7.0 Hz, 3H), 1,13-2,14 (m, 15H), of 2.21 (d, J=7,0 Hz, 2H), 2,25-of 2.38 (m, 2H), 2,99 (s, 3H), is 3.08 of 3.28 (m, 4H), 3,54-the 3.65 (m, 2H), 4,15 (m, 1H), 4,37-4,39 (m, 2H), was 7.36 (d, J=9.0 Hz, 2H), 7,47 (d, J=7.5 Hz, 1H), EUR 7.57 (t, J=7.5 Hz, 1H), to 7.67 (d, J=9.0 Hz, 2H), 7,74-of 7.82 (m, 2H).

Example 5 (8):

N-{4-[4-({4-[butyl(2-cyclohexylethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide the dihydrochloride

TLC: Rf of 0.32 (chloroform:methanol=10:1);

NMR (CD3OD): δ were 0.94 (t, J=7.0 Hz, 3H), 0,98-1,08 (m, 2H), 1.18 to 1.41 for (m, 7H), 1,53 and 1.80 (m, 8H), 2,24-2,49 (m, 4H), 2,96 (s, 3H), 3,05-is 3.21 (m, 6H), 3,70-3,81 (m, 3H), 4,32 (d, J=13,0 Hz, 1H), 4,53 (d, J=13,0 Hz, 1H),? 7.04 baby mortality (d, J=9.0 Hz, 2H), was 7.08 (d, J=8.5 Hz, 2H), 7,30 (d, J=9.0 Hz, 2H), 7,56 (d, J=8.5 Hz, 2H).

Example 5 (9):

N-[(1S)-2-amino-1-(cyclohexylmethyl)-2-oxoethyl]-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-carboxamide hydrochloride

TLC: Rf of 0.34 (chloroform:methanol=4:1);

NMR (CD3OD): δ 0,84 was 1.06 (m, 2H), 1,13-of 1.41 (m, 4H), 1.55V with 2.14 (m, 11H), at 2.59 (m, 1H), 2.95 and (s, 3H), 2,97-to 3.09 (m, 2H), 3,50-3,59 (m, 2H), 4,29 (s, 2H), 4,39 (DD, J=a 9.5, 5.5 Hz, 1H), 7,03 (d, J=9.0 Hz, 2H), 7,06 (d, J=9.0 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H, 7,49 (d, J=9.0 Hz, 2H).

Example 5 (10):

N-{4-[4-({4-[(3S)-3-(cyclohexylmethyl)-2,5-dioxopiperidin-1-yl]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf to 0.73 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,49 (user. d, J=8.7 Hz, 2H), 7,29 (user. d, J=9.0 Hz, 2H), 7,07 (user. d, J=8.7 Hz, 2H), 7,03 (user. d, J=9.0 Hz, 2H), of 4.44 (m, 1H), 4,29 (s, 2H), Android 4.04 (d, J=16,8 Hz, 1H), 3.96 points (t, J=6,6 Hz, 1H), 3,83 (d, J=16,8 Hz, 1H), 3,64-to 3.52 (m, 2H), 3.15 in (m, 2H), 2.95 and (s, 3H), 2,20-to 1.60 (m, 10H), for 1.49 (m, 1H), 1,39-1,10 (m, 4H), 1,09 is 0.80 (m, 2H).

Example 5 (11):

N-{4-[4-({4-[4-(cyclohexylcarbonyl)-2-oxopiperidin-1-yl]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: to 0.45 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,50 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 4,50 (m, 1H), 4.26 deaths (m, 1H), 4,23 (s, 2H), 4,14 (m, 1H), 3,82 is 3.76 (m, 2H), 3,53-to 3.33 (m, 4H), 3,09-a 3.01 (m, 2H), 2.95 and (s, 3H), 2,65 (m, 1H), 2,19-of 1.88 (m, 4H), 1,79 is 1.70 (m, 5H), 1,49-to 1.21 (m, 5H).

Example 5 (12):

N-butyl-2-cyclohexyl-N-[1-(4-{2-methoxy-4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-3-yl]ndimethylacetamide hydrochloride

TLC: Rf is 0.49 (chloroform:methanol=10:1);

NMR (CDCl3): δ of 0.87 to 1.00 (m, 2H), were 0.94 (t, J=7.5 Hz, 3H), 1,08-of 1.93 (m, 16H), 2,11 (d, J=7,0 Hz, 2H, in), 2.25 (m, 1H), 2,45-of 2.64 (m, 2H), to 3.02 (s, 3H), 3,18-3,37 (m, 4H), of 3.80 (s, 3H), 3,86-4,00 (m, 2H), 4,20 (DD, J=13,0, 4.0 Hz, 1H), 6.87 in-6,92 (m, 3H), of 6.99 (d, J=8.5 Hz, 1H), 7,13 (d, J=2.5 Hz, 1H), 7,55 (d, J=8.5 Hz, 2H), 7,83 (user s, 1H), 11.87 per (s, 1H).

Example 5 (13):

N-butyl-2-cyclohexyl-N-[1-(4-{[(4-were)sulfonyl]-amino}benzyl)Pieper is DIN-4-yl]ndimethylacetamide hydrochloride

TLC: Rf of 0.45 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,89 was 1.06 (m, 2H), of 0.96 (t, J=7.0 Hz, 3H), 1,12-of 2.09 (m, 15H), of 2.21 (d, J=7,0 Hz, 2H), 2,22 of-2.32 (m, 2H), a 2.36 (s, 3H), 2,97-of 3.27 (m, 4H), 3,41-of 3.54 (m, 2H), 4,11 (m, 1H), 4,18-4,20 (m, 2H), 7,21 (d, J=8.5 Hz, 2H), 7,29 (d, J=8.5 Hz, 2H), was 7.36 (d, J=8.5 Hz, 2H), 7,69 (d, J=8.5 Hz, 2H).

Example 5 (14):

1-(4-(4-(N-cyclohexyloxycarbonyl-N-methylsulfonylamino)-phenoxy)benzyl)-4-(N-propyl-N-cyclohexylcarbodiimide)-piperidine hydrochloride

TLC: Rf 0,82 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0.77-a of 1.39 (m, 13H), 1,47 is 1.96 (m, 16H), was 2.05 (d, J=7,0 Hz, 2H), 2,22 (d, J=7,0 Hz, 2H), 2,24-to 2.41 (m, 2H), 3.04 from-3,26 (m, 4H), of 3.48 (s, 3H), 3,51-the 3.65 (m, 2H), 4,13 (m, 1H), or 4.31-to 4.33 (m, 2H), 7,13 (d, J=9.0 Hz, 2H), 7,18 (d, J=8.5 Hz, 2H), 7,38 (d, J=9.0 Hz, 2H), 7,56 (d, J=8.5 Hz, 2H).

Example 5 (15):

the hydrochloride of 4-(4-{[4-(4-bromobenzoyl)piperidine-1-yl]methyl}phenoxy)benzoic acid

TLC: Rf of 0.35 (chloroform:methanol=10:1);

NMR (DMSO-d6): δ 1,83-of 2.15 (m, 4H), 2,94-to 3.09 (m, 2H), 3,39-to 3.50 (m, 2H), 3,65 (s, 1H), or 4.31 (user s, 2H), to 7.09 (d, J=9.0 Hz, 2H), 7,19 (d, J=8.5 Hz, 2H), 7,65 (d, J=8.5 Hz, 2H), 7,76 (d, J=8.5 Hz, 2H), to 7.93 (d, J=8,5 Hz, 2H), of 7.97 (d, J=9.0 Hz, 2H), 10,52 (user s, 1H), 12,86 (user s, 1H).

Example 5 (16):

hydrochloride 4-[4-({4-[(3S)-3-(cyclohexylmethyl)-2,5-dioxopiperidin-1-yl]piperidine-1-yl}methyl)phenoxy]benzoic acid

TLC: Rf of 0.65 (chloroform:methanol=5:1);

NMR (CD3OD): δ 8,04 (user. d, J=8.7 Hz, 2H), to 7.59 (user. d, J=8.1 Hz, 2H), 7,17 (user. d, J=8.1 Hz, 2H), 7,07 (user. d, J=8.7 Hz, 2H), 4,46 (m, 1H), 4,34 (s, 2H), 4,05 (d, J=17,1 Hz, 1H), 3,97 (DD, J=6,6, a 5.4 Hz, 1H), 3,85 (d, J=17,1 Hz, 1H),3,68-of 3.53 (m, 2H), 3,17 (m, 2H), 2,24-2,04 (m, 2H), was 1.94 (m, 1H), 1,84-of 1.56 (m, 7H), to 1.48 (m, 1H), 1,38-1,08 (m, 4H), 1,08 is 0.80 (m, 2H).

Example 5 (17):

5-chloro-2-{4-[1-(3,4-dimethoxybenzyl)piperidine-4-yl]benzyl}-1H-isoindole-1,3(2H)-dione hydrochloride

TLC: Rf of 0.48 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,86-7,81 (m, 2H), 7,33(d, J=8.0 Hz, 2H), 7.23 percent(d, J=8.0 Hz, 2H), 7,14(s, 1H), 7,06-7,01 (m, 3H), 4,78(s, 2H), 4.26 deaths(s, 2H), 3,88(s, 3H), 3,85(s, 3H), to 3.58-of 3.54 (m, 2H), 3,10-3,00 (m, 2H), 2,90(m, 1H), 2,10-1,90 (m, 4H).

Example 5 (18):

N-butyl-2-cyclohexyl-N-[1-(4-phenoxybenzyl)piperidine-4-yl]ndimethylacetamide hydrochloride

TLC: Rf 0,82 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,50-7,37 (m, 4H), 7,18(t, J=7.2 Hz, 1H), 7,07-7,02(m, 4H), 4,27(s, 2H), 4,15(m, 1H), 3,60-to 3.50 (m, 2H), 3,30-3,00 (m, 4H), 2,20-2,00 (m, 4H), from 2.00 and 1.80 (m, 2H), 1,80-of 1.40 (m, 8H), 1,40-1,10 (m, 5H), 1,00-of 0.90 (m, 2H), 0,97(t, J=7.4 Hz, 3H).

Example 5 (19):

hydrochloride 4-[4-({4-[butyl(cyclopentylacetyl)amino]-piperidine-1-yl}methyl)phenoxy]benzoic acid

TLC: Rf of 0.43 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 8.04(d, J=8,3 Hz, 2H), 7,56(d, J=8,3 Hz, 2H), 7,17(d, J=8,3 Hz, 2H), 7,07(d, J=8,3 Hz, 2H), or 4.31(s, 2H), 4.16 the(m, 1H), 3,60-to 3.50 (m, 2H), 3,30-3,00 (m, 4H), 2,20-2,00 (m, 4H), from 2.00 and 1.80 (m, 2H,), 1,80-of 1.40 (m, 8H), 1,40-1,10 (m, 5H), 1,00-of 0.90 (m, 2H), 0,97(t, J=7.0 Hz, 3H).

Example 5 (20):

N-butyl-2-cyclohexyl-N-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]piperidine-4-yl}ndimethylacetamide the dihydrochloride

TLC: Rf of 0.47 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,58 was 7.45(m, 5H), 4,24(s, 2H), 4,15(m, 1H), 3,60-to 3.50 (m, 2H), 3,30-3,00 (m, 4H), is 2.37(s, 3H), of 2.36(s, 3H), 2.40 a is 2.10 (m, 4H), from 2.00 and 1.80 (who, 2H), 1,80-of 1.40 (m, 8H), 1,40-1,10 (m, 5H), 1,00-of 0.90 (m, 2H), and 0.98(t, J=7.4 Hz, 3H).

Example 5 (21):

N-butyl-2-cyclohexyl-N-(1-{[1-(4-hydroxyphenyl)for 3,5-dimethyl-1H-pyrazole-4-yl]methyl}piperidine-4-yl)ndimethylacetamide the dihydrochloride

TLC: Rf of 0.37 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,26(d, J=9.0 Hz, 2H), 6,92(d, J=9.0 Hz, 2H), 4,24(s, 2H), 4,15(m, 1H), 3,70-of 3.60 (m, 2H), 3,30-3,00 (m, 4H), is 2.37(s, 3H), 2,32(s, 3H), 2.40 a-2,20 (m, 4H), from 2.00 and 1.80 (m, 2H), 1,80-of 1.40 (m, 8H), 1,40-1,10 (m, 5H), 1,00-of 0.90 (m, 2H), and 0.98(t, J=7.4 Hz, 3H).

Example 5 (22):

N-{4-[4-({4-[4-(cyclohexylcarbonyl)piperazine-1-yl]-piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide the dihydrochloride

TLC: Rf 0,59 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 1,21-1,49 (m, 6H), 1.70 to to 1.98 (m, 10H), of 2.20 to 2.35 (m, 2H), 2,60-2,70 (m, 2H), 2.95 and (s, 3H), 2.95 and is 3.23 (m, 4H), 3,55-of 3.80 (m, 4H), 4,28 (s, 2H), 7,03 (d, J=8.5 Hz, 2H), 7,06 (d, J=8.5 Hz, 2H), 7,29 (d, J=8.5 Hz, 2H), 7,49 (d, J=8.5 Hz, 2H).

Example 5 (23):

N-{4-[4-({4-[5-(cyclohexylcarbonyl)-2,5-diazabicyclo[2,2,1]hept-2-yl]piperidine-1-yl}methyl)phenoxy]-phenyl}methanesulfonamide the dihydrochloride

TLC: Rf 0,46 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 1,15-1,49 (m, 6H), 1.60-to to 1.98 (m, 10H), 2,35-is 2.88 (m, 6H), 2.95 and (s, 3H), is 3.08-and 3.72 (m, 4H), to 3.89 (d, J=9.5 Hz, 1H), Android 4.04 (s, 2H), to 4.62 (d, J=22,5 Hz, 1H), 7,01 (d, J=8.7 Hz, 2H), 7,02 (d, J=8.7 Hz, 2H,), 7,28 (d, J=8.7 Hz, 2H), 7,42 (d, J=8.7 Hz, 2H).

Example 5 (24):

2-cyclohexyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]ndimethylacetamide hydrochloride

TLC: Rf 0,46 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0.89 as of 1.00 (m, 2), 1,21-of 1.29 (m, 3H), 1,68-1,71 (m, 8H), 2,03 (d, J=6,9 Hz, 2H), 2,11-of 2.16 (m, 2H), 2.95 and (s, 3H), 3,06-3,14 (m, 2H), 3,49-of 3.53 (m, 2H), 3,90 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H,), 7,29 (d, J=8.7 Hz, 2H), 7,47 (d, J=8.7 Hz, 2H).

Example 5 (25):

2-cyclohexyl-N-[1-(4-phenoxybenzyl)piperidine-4-yl]ndimethylacetamide hydrochloride

TLC: Rf 0,62 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,00 (m, 2H), 1,13-of 1.29 (m, 3H), 1,67-of 1.78 (m, 8H), 2,03 (d, J=6,9 Hz, 2H), 2,12-of 2.15 (m, 2H), 3,05-3,13 (m, 2H), 3,49-of 3.53 (m, 2H), 3,90 (m, 1H), 4,27 (s, 2H), 7,02-was 7.08 (m, 4H), 7,18 (m, 1H), 7,37-7,42 (m, 2H), 7,46 is 7.50 (m, 2H).

Example 5 (26):

2-cyclohexyl-N-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]piperidine-4-yl}ndimethylacetamide the dihydrochloride

TLC: Rf of 0.40 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,91-1,02 (m, 2H), 1,14-of 1.34 (m, 3H), 1,69-of 1.85 (m, 8H), was 2.05 (d, J=6,9 Hz, 2H), 2,13-2,19 (m, 2H), a 2.36 (s, 3H), of 2.38 (s, 3H), 3,14-3,24 (m, 2H), 3,61-3,66 (m, 2H), 3,93 (m, 1H), 4,25 (s, 2H), 7,45-of 7.60 (m, 5H).

Example 5 (27):

N-{4-[4-({4-[(5S)-5-(cyclohexylmethyl)-1-isopropyl-3,6-dioxopiperidin-2-yl]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,69 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-of 2.36 (m, 24H), 2,95 (s, 3H), 3.04 from (m, 1H), 3.46 in at 3.69 (m, 3H), 3,78-4,12 (m, 3H), 4.26 deaths (user. s, 2H), 7,00-to 7.18 (m, 4H), 7,26-7,34 (m, 2H), 7,40-of 7.48 (m, 2H).

Example 5 (28):

N-{4-[4-({4-[(5S)-5-(cyclohexylmethyl)-1-(2-methoxyethyl)-3,6-dioxopiperidin-2-yl]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.67 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80 of-2.32 (m, 21H), 2,95 (who, 3H), 2,84-to 3.02 (m, 3H), 3,40-of 3.60 (m, 4H), 3,80-to 4.14 (m, 3H), 4.26 deaths (user. s, 2H), 7,00-7,14 (m, 4H), 7,21-to 7.32 (m, 2H), 7,41-7,52 (m, 2H).

Example 5 (29):

N-{4-[4-({4-[(5S)-5-(cyclohexylmethyl)-1-methyl-3,6-dioxopiperidin-2-yl]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.64 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,96 (m, 1H), 1,12-of 1.36 (m, 3H), 1,44-of 2.38 (m, 14H), 2,95 (s, 3H), 2,98 (m, 2H), 3,36 (user. s, 3H), 3,42-of 3.60 (m, 2H), 3,86-4,34 (m, 2H), 4,25 (user. s, 2H), 6,98-was 7.08 (m, 4H), 7.24 to 7,30 (m, 2H), 7,40-7,52 (m, 2H).

Example 5 (30):

N-{4-[4-({4-[(5S)-1-benzyl-5-(cyclohexylmethyl)-3,6-dioxopiperidin-2-yl]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf to 0.78 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-to 2.40 (m, 18H), 2,95 (s, 3H), 3,44 of 3.56 (m, 3H), 3,79 (m, 1H), was 4.02-4,30 (m, 4H), 5,22 (m, 2H), 7,00-was 7.08 (m, 4H), 7.24 to 7,40 (m, 6H), 7,40-to 7.50 (m, 3H).

Example 5 (31):

(3S)-3-(cyclohexylmethyl)-1-isopropyl-6-[1-(4-phenoxybenzyl)piperidine-4-yl]piperazine-2,5-dione hydrochloride

TLC: Rf 0.84 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-of 2.38 (m, 24H), 3,03 (m, 2H), 3.46 in-3,70 (m, 3H), 3,76-4,10 (m, 2H), 4.26 deaths (user. s, 2H), 7,00-7,06 (m, 4H), 7,19 (m, 1H), was 7.36-7,58 (m, 4H).

Example 5 (32):

(3S)-3-(cyclohexylmethyl)-1-(2-methoxyethyl)-6-[1-(4-phenoxybenzyl)piperidine-4-yl]piperazine-2,5-dione hydrochloride

TLC: Rf 0,77 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-1,10 (m, 2H), 1,12-2,10 (m, 16H), 2,16-2,62 (m, 2H), 2,98-4,14 (m, 11H), 4.26 deaths (user. s, 2H), 7,00-7,10 (m, 4H), 7,18 (m, 1H), 7,30-rate of 7.54 (m, 4H).

Example 5 (33):

(3S)-1-be the ZIL-3-(cyclohexylmethyl)-6-[1-(4-phenoxybenzyl)-piperidine-4-yl]piperazine-2,5-dione hydrochloride

TLC: Rf 0,86 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,84-to 2.40 (m, 18H), was 2.76-3.04 from (m, 2H), 3,42-of 3.60 (m, 2H), 3,78 (m, 1H), 4,10 (m, 1H), 4,16-4,34 (m, 3H), 5,20 (m, 1H), 6,98-7,14 (m, 4H), 7,19 (m, 1H), 7,20-7,52 (m, 9H).

Example 5 (34):

(3S)-3-(cyclohexylmethyl)-6-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]piperidine-4-yl}-1-isopropylpiperazine-2,5-dione hydrochloride

TLC: Rf 0,74 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,84-of 2.36 (m, 24H), 2,36 (user. s, 3H), 2,38 (user. s, 3H), 3.04 from-3,24 (m, 2H), 3,60-4,10 (m, 5H), 4,25 (user. s, 2H), 7,40-of 7.60 (m, 5H).

Example 5 (35):

(3S)-3-(cyclohexylmethyl)-6-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]piperidine-4-yl}-1-methylpiperazine-2,5-dione hydrochloride

TLC: Rf 0,74 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,84-to 2.40 (m, 18H), to 2.35 (m, 6H), 3.00 and (OSiR. s, 3H), to 3.09 (m, 2H), 3,56-3,70 (m, 2H), 3,82-4,12 (m, 2H), 4,24 (user. s, 2H), 7,40-of 7.60 (m, 5H).

Example 5 (36):

(3S)-3-(cyclohexylmethyl)-6-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]piperidine-4-yl}-1-(2-methoxyethyl)piperazine-2,5-dione hydrochloride

TLC: Rf 0,74 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-to 2.40 (m, 18H), 2,35 (user. s, 3H), 2,38 (user. s, 3H), 3,00-3,20 (m, 3H), of 3.33 (s, 3H), 3,49-and 3.72 (m, 4H), 3,88-4,16 (m, 3H), 4,25 (user. s, 2H), 7,40 to 7.62 (m, 5H).

Example 5 (37):

N-butyl-1-(4-phenoxybenzyl)piperidine-4-carboxamide hydrochloride

TLC: Rf of 0.58 (chloroform:methanol=10:1);

NMR (CD3OD): δ to 0.92 (t, J=7.2 Hz, 3H), 1,28-of 1.52 (m, 4H), 1,82-2,05 (m, 4H), 2.49 USD (m, 1H), 2,98-of 3.07 (m, 2H), and 3.16 (t, J=7,0 Hz, 2H), 3,52 of 3.56 (m, 2H), 4,28 (s, 2H), 7,02-7,06 (m, 4H), 7,18 (t, J7,5 Hz, 1H), 7,37-7,42 (m, 2H), of 7.48 (d, J=8.7 Hz, 2H).

Example 5 (38):

N-(cyclohexylmethyl)-1-(4-phenoxybenzyl)piperidine-4-carboxamide hydrochloride

TLC: Rf of 0.64 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,86 to 0.97 (m, 2H), 1,15 of 1.28 (m, 4H), of 1.46 (m, 1H), 1.60-to of 1.78 (m, 4H), 1,89-2,05 (m, 4H), 2,52 (m, 1H), 3,00 (d, J=7.2 Hz, 2H), 3.00 and-of 3.07 (m, 2H), 3,51 of 3.56 (m, 2H), 4,29 (s, 2H), 7,01-7,06 (m, 4H), to 7.18 (m, 1H), 7,37-7,42 (m, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 5 (39):

N-butyl-N-(cyclohexylmethyl)-1-(4-phenoxybenzyl)piperidine-4-carboxamide hydrochloride

TLC: Rf 0,71 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0.89 as of 1.00 (m, 5H), 1.18 to 1,71 (m, 13H), 1,92 is 2.00 (m, 5H), 2,92-3,55 (m, 6H), 3,51-3,55 (m, 2H), 4,28 (s, 2H), 7,02-7,07 (m, 4H), 7,18 (t, J=7.2 Hz, 1H), 7,37-7,42 (m, 2H), 7,47 (d, J=8,4 Hz, 2H).

Example 5 (40):

1-benzyl-4-{[1-(4-phenoxybenzyl)piperidine-4-yl]carbonyl}-piperazine the dihydrochloride

TLC: Rf is 0.59 (chloroform:methanol=10:1);

NMR (CD3OD): δ 1,90-2,10 (m, 4H), 3.00 and-of 3.60 (m, 12H), 4,30 (s, 2H), 4,39 (s, 2H), 4,63 (m, 1H), 7,02-7,06 (m, 4H), 7,18 (t, J=7,0 Hz, 1H), 7,37-7,42 (m, 2H), of 7.48-7,58 (m, 7H).

Example 5 (41):

1-(cyclohexylmethyl)-4-{[1-(4-phenoxybenzyl)piperidine-4-yl]carbonyl}piperazine the dihydrochloride

TLC: Rf and 0.62 (chloroform:methanol=10:1);

NMR (CD3OD): δ 1,02 was 1.43 (m, 5H), 1.70 to a 2.01 (m, 10H), 3,03 (d, J=6.6 Hz, 2H), 3,03 at 3.69 (m, 12H), or 4.31 (s, 2H), 4,59 (m, 1H), 7,02-7,07 (m, 4H), 7,18 (t, J=7.5 Hz, 1H), 7,37-7,42 (m, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 5 (42):

N-butyl-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-piperidine-4-carboxamide hydrochloride

TLC: Rf 0.26 (chlorine the product:methanol=10:1);

NMR (CD3OD): δ to 0.92 (t, J=7.2 Hz, 3H), 1.30 and of 1.52 (m, 4H), 1,84-2,04 (m, 4H), 2,48 (m, 1H), 2.95 and (s, 3H), 2.95 and-of 3.07 (m, 2H), and 3.16 (t, J=7.2 Hz, 2H), 3,51 of 3.56 (m, 2H), 4,28 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,47 (d, J=8.7 Hz, 2H).

Example 5 (43):

N-(cyclohexylmethyl)-1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)piperidine-4-carboxamide hydrochloride

TLC: Rf 0.28 in (chloroform:methanol=10:1);

NMR (CD3OD): δ of 0.85 to 1.00 (m, 2H), 1,15-of 1.46 (m, 5H), 1,65 and 2.13 (m, 8H), 2.49 USD (m, 1H), 2.95 and (s, 3H), of 3.00 (d, J=7,0 Hz, 2H), 3.00 and-a 3.06 (m, 2H), 3,52 of 3.56 (m, 2H), 4,28 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8.7 Hz, 2H), 7,47 (d, J=8,4 Hz, 2H).

Example 5 (44):

N-butyl-N-(cyclohexylmethyl)-1-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)piperidine-4-carboxamide hydrochloride

TLC: Rf of 0.45 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0.89 as of 1.00 (m, 5H), 1,21-2,00 (m, 18H), 2,95 (s, 3H), 3.00 and-to 3.36 (m, 6H), 3,51-of 3.54 (m, 2H), 4,27 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,47 (d, J=8.1 Hz, 2H).

Example 5 (45):

N-{4-[4-({4-[(4-benzylpiperazine-1-yl)carbonyl]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide the dihydrochloride

TLC: Rf 0.28 in (chloroform:methanol=10:1);

NMR (CD3OD): δ 1,90-2,10 (m, 4H), 2.95 and (s, 3H), 3,05 of 3.56 (m, 12H), 4,30 (s, 2H), 4,39 (s, 2H), 4,63 (m, 1H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,47-of 7.55 (m, 7H).

Example 5 (46):

N-(4-{4-[(4-{[4-(cyclohexylmethyl)piperazine-1-yl]carbonyl}-piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.30 (chloroform:methanol=10:1);

NMR (CD3OD): δ 1,05 was 1.43 (m, 5H), 1.70 to a 2.01 (m, 10H), 2.95 and (s, 3H), 3,03 (d, J=6,9 is C, 2H), 3,03-3,63 (m, 12H), or 4.31 (s, 2H), 4,59 (m, 1H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 5 (47):

trihydrochloride 1-(cyclohexylmethyl)-4-[1-(4-phenoxybenzyl)piperidine-4-yl]piperazine-2-carboxylic acid

TLC: Rf 0,07 (chloroform:methanol:acetic acid=10:1:1);

NMR (CD3OD): δ 1,01-1,11 (m, 2H), 1,19-of 1.41 (m, 4H), 1,66-2,02 (m, 8H), 2,19-2,31 (m, 2H), 2,97-3,37 (m, 8H), 3.45 points-to 3.64 (m, 3H), 3,80 (m, 1H), 4,29 (s, 2H), 4,35 (s, 1H), 7,01-7,06 (m, 4H), 7,18 (t, J=8.0 Hz, 1H), 7,39 (t, J=8.0 Hz, 2H), 7,52 (d, J=9.0 Hz, 2H).

Example 5 (48):

trihydrochloride 1-benzyl-4-[1-(4-phenoxybenzyl)piperidine-4-yl]piperazine-2-carboxylic acid

TLC: Rf of 0.05 (chloroform:methanol:acetic acid=10:1:1);

NMR (CD3OD): δ 1,86-2,03 (m, 2H), 2,15-of 2.27 (m, 2H), 2,86-3,62 (m, 11H), 4,13 is 4.35 (m, 4H), of 4.57 (d, J=12,5 Hz, 1H), 7,01-7,06 (m, 4H), 7,18 (t, J=7.5 Hz, 1H), 7,39 (t, J=8.0 Hz, 2H), 7,45-7,56 (m, 7H).

Example 5 (49):

the dihydrochloride of 1-(cyclohexylcarbonyl)-4-[1-(4-phenoxybenzyl)piperidine-4-yl]piperazine-2-carboxylic acid

TLC: Rf 0.14 (chloroform:methanol:acetic acid=10:1:1);

NMR (CD3OD): δ 1,22-of 1.57 (m, 5H), 1,67-of 1.85 (m, 5H), 2.06 to 2,78 (m, 5H), 2,96 is 3.23 (m, 4H), 3.46 in-3,70 (m, 5H), 4,08 (m, 1H), or 4.31 (m, 1H), 4,33 (s, 2H), of 5.53 (s, 1H), 7,02-7,07 (m, 4H), 7,18 (t, J=7.5 Hz, 1H), was 7.36-7,42 (m, 2H), 7,54 (d, J=8.5 Hz, 2H).

Example 5 (50):

the dihydrochloride of 1-benzoyl-4-[1-(4-phenoxybenzyl)piperidine-4-yl]piperazine-2-carboxylic acid

TLC: Rf 0,09 (chloroform:methanol:acetic acid=10:1:1);

NMR (CD3OD): δ 1,92-to 2.41 (m, 4H), 2,87-3,95 (m, 11H), or 4.31 (s, 2H), of 5.53 (s, 1H), ,02-7,07 (m, 4H), 7,18 (t, J=7.5 Hz, 1H), was 7.36-7,42 (m, 2H), 7,45-rate of 7.54 (m, 7H).

Example 5 (51):

4-(cyclohexylmethyl)-2-methyl-1-[1-(4-phenoxybenzyl)-piperidine-4-yl]piperazine trihydrochloride

TLC: Rf of 0.18 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 is 1.13 (m, 2H), 1,20-of 1.44 (m, 3H), of 1.55 (d, J=6.5 Hz, 3H), 1,65-of 1.95 (m, 6H), 2,08-2,47 (m, 4H), 3,10-of 3.28 (m, 4H), 3,40-is 4.21 (m, 10H)to 4.33 (s, 2H), 7,02-7,07 (m, 4H), 7,18 (t, J=7.5 Hz, 1H), 7,37-7,42 (m, 2H), 7,53 (d, J=8.5 Hz, 2H).

Example 5 (52):

4-benzyl-2-methyl-1-[1-(4-phenoxybenzyl)piperidine-4-yl]piperazine trihydrochloride

TLC: Rf of 0.20 (chloroform:methanol=10:1);

NMR (CD3OD): δ 1,48 (d, J=6.5 Hz, 3H), 2,01-of 2.38 (m, 4H), 3,12-of 3.25 (m, 2H), 3,38-and 3.72 (m, 8H), 3,92 (user s, 2H), or 4.31 (s, 2H), to 4.41 (d, J=13,0 Hz, 1H), 4,47 (d, J=13,0 Hz, 1H), 7,01-7,06 (m, 4H), 7,18 (t, J=7.5 Hz, 1H), was 7.36-7,42 (m, 2H), 7,49-7,53 (m, 5H), 7,58 to 7.62 (m, 2H).

Example 5 (53):

4-(cyclohexylcarbonyl)-2-methyl-1-[1-(4-phenoxybenzyl)-piperidine-4-yl]the piperazine dihydrochloride

TLC: Rf of 0.38 (chloroform:methanol=10:1);

NMR (CD3OD): δ 1,16-of 1.57 (m, 8H), 1,66-of 1.84 (m, 5H), 2.05 is is 2.75 (m, 5H), 3.00 and-to 4.73 (m, 12H), to 4.33 (s, 2H), 7,01-7,07 (m, 4H), 7,18 (t, J=7.5 Hz, 1H), was 7.36-7,42 (m, 2H), 7,53 (d, J=8.5 Hz, 2H).

Example 5 (54):

4-benzoyl-2-methyl-1-[1-(4-phenoxybenzyl)piperidine-4-yl]-piperazine of the dihydrochloride

TLC: Rf of 0.40 (chloroform:methanol=10:1);

NMR (CD3OD): δ 1,29-1.55V (user, 3H, Me), 2,07-of 2.54 (m, 4H), 3,09-4,17 (m, 12H), to 4.33 (s, 2H), 7,01-7,07 (m, 4H), 7,18 (t, J=7.5 Hz, 1H), was 7.36-7,42 (m, 2H), 7,46-of 7.55 (m, 7H).

Comparative example 4:

N-(4-(4-bis(2-chloroethyl)aminomethylphenol)phenyl)-metasolv the amide

To a solution of 4-(4-methylsulfonylmethane)benzaldehyde (1.27 g) in dimethylformamide (5 ml)/acetic acid (0.5 ml) is added N,N-bis(2-chloroethyl)amine (856 mg) and the solution stirred at room temperature for 10 minutes. Add sodium triacetoxyborohydride (31,39 g) to the solution, which was stirred at room temperature overnight. Add water to the reaction mixture, which is extracted with ethyl acetate three times. The extract is washed with saturated salt solution (30 ml), dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (hexane:ethyl acetate=5:1) to obtain the specified title compound (790 mg)having the following physical data.

TLC: Rf of 0.60 (chloroform:methanol=9:1);

NMR (CDCl3): δ 7,32 (user. d, J=8,4 Hz, 2H), 7,22 (user. d, J=8.7 Hz, 2H), 7,01 (user. d, J=8.7 Hz, 2H), of 6.96 (user. d, J=8,4 Hz, 2H), and 3.72 (s, 2H), 3,51 (t, J=7.2 Hz, 4H), of 3.00 (s, 3H), of 2.93 (t, J=7.2 Hz, 4H).

Example 6:

1-(4-(4-methylsulfonylmethane)benzyl)-4-(1-methoxycarbonylethyl)piperazine

To a solution of the compound obtained in comparative example 2 (266 mg)in dimethylformamide (3 ml) is added hydrochloride complex DL-noracymethadol ester (117 mg). To the resulting solution was added triethylamine (0,267 ml) and a catalytic amount of sodium iodide and the solution stirred at 60°C for the night. Add water to the reaction mixture, which is extracted with ethyl acetate three times. The extract is washed with saturated salt solution (30 ml), dried over anhydrous sodium sulfate and concentrated to obtain the compound of the present invention (210 mg)having the following physical data.

TLC: Rf of 0.67 (chloroform:methanol=9:1);

NMR (CDCl3): δ 7,32-7,24 (m, 2H), 7,20 (user. d, J=9.0 Hz, 2H), 6,98 (user. d, J=9.0 Hz, 2H), 6,94 (user. d, J=9.0 Hz, 2H), and 3.72 (s, 2H), 3,69 (s, 3H), 3.15 in (DD, J=4,8, 3.6 Hz, 1H), 3.00 and (s, 3H), 2,70-of 2.36 (m, 8H), 1,80-of 1.18 (m, 6H), to 0.89 (t, J=5.4 Hz, 3H).

Example 7:

the dihydrochloride of 2-[4-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperazine-1-yl]hexanoic acid

To a solution of the compound obtained in example 6 (210 mg)in ethanol (5 ml) add 2 N. aqueous sodium hydroxide solution (0,215 ml) and the solution stirred at 40°C during the night. The reaction mixture was concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=8:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (141,6 mg)having the following physical data.

TLC: Rf of 0.55 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,53 (user. d, J=8.7 Hz, 2H), 7,29 (user. d, J=9.0 Hz, 2H), 7,06 (user. d, J=8.7 Hz, 2H), 7,03 (user. d, J=9.0 Hz, 2H), 4,37 (s, 2H), 3,75 (user. t, J=6.3 Hz, 1H), 3,56-to 3.34 (m, 8H), 2.95 and (s, 3H), 1,92 and 1.80 (m, 2H) 1,48-1,32 (m, 4H), 1.00 and is 0.86 (m, 3H).

Example 8:

N-cyclohexyl-2-[4-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperazine-1-yl]hexanamide the dihydrochloride

To a solution of the compound obtained in example 7 (46,7 mg)in dimethylformamide (2 ml) add cyclohexylamine (16,8 μl), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (28,2 mg) and 1-hydroxybenzotriazol (19,87 mg) and the solution stirred at room temperature overnight. The reaction mixture was concentrated. The resulting residue is purified by column chromatography on silica gel (chloroform:methanol=9:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (22.7 mg)having the following physical data.

TLC: Rf of 0.75 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,49 (user. d, J=8.7 Hz, 2H), 7,29 (user. d, J=9.0 Hz, 2H), 7,05 (user. d, J=9.0 Hz, 2H), 7,02 (user. d, J=8.7 Hz, 2H), 4,30 (s, 2H), 3,68 (m, 1H), 3,50 3.00 for (m, 8H), 2.95 and (s, 3H), 1,90 is 1.58 (m, 8H), 1,44 -1,12 (m, 9H), 0,92 (user. t, J=7.5 Hz, 3H).

Example 9 (1) example 9 (3)

Using the same procedure as described in comparative example 4→example 6 →example 7→example 8, using 4-(4-methylsulfonylmethane)benzamide, complex DL-noracymethadol ether and cyclohexylamine or using the corresponding aldehyde derivative, amino acid derivative and an amine derivative instead of what they respectively receive the following compounds of the present invention.

Example 9 (1):

N-(cyclohexylmethyl)-2-[4-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)piperazine-1-yl]hexanamide the dihydrochloride

TLC: Rf 0,82 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,53 (user. d, J=8.7 Hz, 2H), 7,29 (user. d, J=9.0 Hz, 2H), 7,06 (user. d, J=9.0 Hz, 2H), 7,03 (user. d, J=8.7 Hz, 2H), 4,37 (s, 2H), 3,61 (m, 1H), 3,60 of 3.28 (m, 8H), 3.15 in (DD, J=7,5, of 15.0 Hz, 1H), 2,99 (DD, J=7,5, of 15.0 Hz, 1H), 2.95 and (s, 3H), 1,90-of 1.62 (m, 6H), 1,58 is 1.16 (m, 9H), 1.04 million-to 0.88 (m, 2H), of 0.93 (t, J=7.2 Hz, 3H).

Example 9 (2):

N-cyclohexyl-2-[4-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperazine-1-yl]pentamid the dihydrochloride

TLC: Rf to 0.78 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,52 (user. d, J=6.6 Hz, 2H), 7,29 (user. d, J=8,4 Hz, 2H), 7,10-7,01 (m, 4H), 4,36 (user. s, J=2H), 3,69 (m, 1H), 3,60-3,20 (m, 9H), 2.95 and (s, 3H), 1,92 is 1.70 (m, 6H), of 1.65 (m, 1H), 1,46-1,14 (m, 7H), of 0.97 (t, J=7.5 Hz, 3H).

Example 9 (3):

2-(4-{4-[4-(aminosulfonyl)phenoxy]benzyl}piperazine-1-yl)-N-cyclohexylglycine the dihydrochloride

TLC: Rf 0.84 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 7.90 (user. d, J=9,3 Hz, 2H), 7,63 (user. d, J=11,4 Hz, 2H), 7,18 (user. d, J=11,4 Hz, 2H), 7,13 (user. d, J=9,3 Hz, 2H), of 4.45 (s, 2H), 3,80-of 3.42 (m, 9H), 1,96-of 1.56 (m, 7H), 1,46-of 1.18 (m, 10H), of 0.93 (t, J=7.2 Hz, 3H).

Comparative example 5:

tert-butyl 1-benzyloxycarbonyl-4-cyclohexylethylamine-carbonitriding-4-ylcarbamate

To a solution of 1-benzyloxycarbonyl-4-(tert-butoxycarbonylamino)piperidine-4-carboxylic acid (297 mg) in dimethylformamide (2.5 ml) was added 1-ethyl-3-[3(dimethylamino)propyl]carbodiimide hydrochloride (226 mg), 4-N,N-dimethylaminopyridine (144 mg) and cyclohexylethylamine (0.15 ml) and the solution stirred at room temperature overnight. Add water to the reaction mixture, which is extracted with ethyl acetate. The extract is washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=40:1-10:1) to obtain specified in the title compound having the following physical data.

TLC: Rf 0,18 (dichloromethane:methanol=5:1).

Comparative example 6:

tert-butyl 4-cyclohexylcarbodiimide-4-ylcarbamate

To a solution of the compound obtained in comparative example 5, in methanol (3 ml) is added 5% palladium on coal (15 mg). The reaction mixture was stirred at room temperature for 2 hours in hydrogen atmosphere. In argon atmosphere, the reaction mixture was filtered through CELITE (trade name). The filtrate is concentrated and the resulting residue used in the next reaction without purification.

Example 10:

1-(4-(4-methylsulfonylmethane)benzyl)-4-cyclohexyl-methylaminomethyl-4-(tert-butoxycarbonylamino)the piperidine dihydrochloride

To a solution of the compound obtained in comparative example 6, in dimethylformamide (5 ml) and acetic acid (0.2 ml) dobavlaut-(4-methylsulfonylmethane)benzaldehyde (274 mg) and sodium triacetoxyborohydride (249 mg) and the solution stirred at room temperature overnight. The reaction mixture is concentrated and purified by column chromatography on silica gel (ethyl acetate:methanol=50:1 to 40:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining specified in the title compound (190 mg)having the following physical data.

TLC: Rf 0,49 (dichloromethane:methanol=10:1);

NMR (CD3OD): δ to 7.35 (d, J=9.0 Hz, 2H), 7,25 (d, J=9.0 Hz, 2H), 6,98 (d, J=9.0 Hz, 2H), of 6.96 (d, J=9.0 Hz, 2H), 3,69 (s, 2H), 3,01-to 2.99 (m, 2H), 2,93 (s, 3H), 2,88-to 2.85 (m, 2H), 2,53 is 2.44 (m, 2H), 2,16-2,02 (m, 4H), a 1.75-of 1.64 (m, 6H), USD 1.43 (s, 9H), 1,28-of 1.18 (m, 3H), 0,96-0,89 (m, 2H).

Example 11:

1-(4-(4-methylsulfonylmethane)benzyl)-4-cyclohexanecarbonyl-4-aminopiperidin the dihydrochloride

To a solution of the compound obtained in example 10 (190 mg)in tetrahydrofuran (3 ml) and dioxane (3 ml)add a solution of 4 N. hydrogen chloride/ethyl acetate (9 ml) and the solution stirred at room temperature overnight. The reaction mixture was concentrated to obtain the compound of the present invention having the following physical data. The connection used in the next reaction without purification.

TLC: Rf 0.35 in (methylene chloride:methanol=10:1).

Example 12 (1) and example 12 (2)

To a solution of the compound obtained in example 11, in dimethylformamide (3 ml) and acetic acid (0.1 ml) add butanal (0,03 ml) and triacetoxyborohydride sodium (103 mg) and the solution was stirred at room t is mperature during the night. Add water to the reaction mixture, which is extracted with ethyl acetate. The extract is washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=50:1) and high-performance thin-layer chromatography (dichloromethane:methanol=10:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention having the following physical data.

Example 12 (1):

4-(butylamino)-N-(cyclohexylmethyl)-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-carboxamide the dihydrochloride

TLC: Rf of 0.48 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,52 (d, J=9.0 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,06 (d, J=9.0 Hz, 2H), 7,03 (d, J=9.0 Hz, 2H), 4,34 (s, 2H), 3,70 of 3.56 (m, 3H), 3,20-and 2.79 (m, 7H), 2.95 and (s, 3H), 2,46-of 2.30 (m, 2H), 1,73 is 1.58 (m, 8H), 1,46-to 1.38 (m, 2H), 1,28-of 1.15 (m, 3H), of 1.05 to 0.95 (m, 2H), 0,97 (t, J=7.2 Hz, 3H).

Example 12 (2):

N-(cyclohexylmethyl)-4-(dibutylamino)-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-carboxamide the dihydrochloride

TLC: Rf 0,46 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ rate of 7.54 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 4,33 (s, 2H), 3,67-3,63 (m, 2H), 3,37-3,00 (m, 8H), 2.95 and (s, 3H), 2,84 is 2.80 (m, 2H), 2,64 is 2.51 (m, 2H,), 1,84-of 1.57 (m, 10H), 1,46-1,17 (m, 7H), of 1.05 to 0.92 (m, 2H), and 0.98 (t, J=7.2 Hz, 6H).

Example 13:

<> methyl (2S)-2-{[4-[(butylamino)carbonyl]-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-yl]amino}-3-cyclohexylpropionate hydrochloride

To a solution of the compound obtained in example 2 (200 mg), in methanol (5,3 ml) is added L-cyclohexylamine (91,4 mg), n-utilizationin (50,8 mm) and triethylamine (74,5 μl) and the solution stirred at 65°C for 12 hours. After cooling at 0°C is added a solution of 4 N. hydrogen chloride/ethyl acetate (0.3 ml). The solution is stirred and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=8:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (102,2 mg)having the following physical data.

TLC: Rf of 0.55 (chloroform:methanol=9:1);

NMR (CD3OD): δ 7,60-7,44 (m, 2H), 7,29 (user. d, J=9.0 Hz, 2H), 7,09-of 6.96 (m, 4H), or 4.31 (user. s, 2H), 3,80-3,62 (m, 5H), 3,52-to 3.02 (m, 5H), 2.95 and (s, 3H), 2,30-to 1.82 (m, 2H), 1,80-of 1.40 (m, 11H), 1,40-of 1.10 (m, 6H), 1.04 million -0,80 (m, 5H).

Example 14:

1-(4-(4-methylsulfonylmethane)benzyl)piperidine-4-ylmethanol

To a solution of 4-piperidinemethanol (1.0 g) and 4-(4-methylsulfonylmethane)benzaldehyde (2,53 g) in dimethylformamide (10 ml) is added acetic acid (1.0 ml) and the solution stirred at room temperature for 5 minutes. Add sodium triacetoxyborohydride (,75 g) to the reaction solution, which is stirred for 12 hours. Water (20 ml) and ethyl acetate (30 ml) are added to the reaction mixture, which is stirred and extracted with ethyl acetate three times. The organic layer was washed with saturated salt solution (15 ml), dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give the compounds of the present invention (2,40 g)having the following physical data.

TLC: Rf of 0.16 (chloroform:methanol=5:1);

NMR (CDCl3): δ 7,31-7,26 (m, 2H), 7.23 percent-of 7.00 (m, 2H), 7,02-6,92 (m, 4H), 3,50 (d, J=6.3 Hz, 2H), 3,47 (s, 2H), 3.00 and (s, 3H), 2,98-of 2.86 (m, 2H), 1,97 (TD, J=11,7, 2.7 Hz, 2H), 1,79-of 1.64 (m, 2H), 1,50 (m, 1H), 1,36-1,20 (m, 2H).

Example 15:

1-(4-(4-methylsulfonylmethane)benzyl)-4-piperidinecarboxylic

To a solution of the compound obtained in example 14 (2,40 g)in methylene chloride (20 ml), add triethylamine (3,43 ml) and dimethylsulfoxide (1,99 ml). The complex of sulfur and trioxypurine (1,96 g) are added to the reaction mixture, which was stirred at room temperature for 5 hours. Add water to the reaction mixture, which is extracted with methylene chloride three times. The organic layer was washed with saturated salt solution (20 ml), dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (Gex is n:ethyl acetate=1:1) to give the compounds of the present invention (totaling 3.04 g), having the following physical data.

TLC: Rf of 0.32 (chloroform:methanol=5:1);

NMR (CDCl3): δ 9,65 (d, J=1.2 Hz, 1H), 7,32-7,24 (m, 2H), 7.24 to to 7.18 (m, 2H), 7,02-of 6.90 (m, 4H), 3,47 (s, 2H), 3.00 and (s, 3H), 2,82 (m, 2H), and 2.26 (m, 2H), 2,11 (m, 2H), 1,90 (m, 2H), 1,71 (m, 2H).

Example 16:

N-{4-[4-({4-[(5S)-1-butyl-5-(cyclohexylmethyl)-3,6-dioxopiperidin-2-yl]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

A solution of the compound obtained in example 15 (500 mg), N-(tert-butoxycarbonyl)-L-cyclohexylamine (396 mg), n-butylamine (0,140 ml) and 2-morpholinomethylnicotinic (0,179 ml) in methanol (13 ml) was stirred at 65°C for 12 hours. Add concentrated hydrochloric acid (0.5 ml) to the reaction solution, which is stirred for 2 hours, and concentrated. To it add methylene chloride (15 ml) and sodium bicarbonate solution (15 ml). The solution is stirred and extracted twice with methylene chloride. The organic layer was washed with saturated salt solution (15 ml), dried over anhydrous sodium sulfate and concentrated. To the obtained residue, add 1,25M solution of acetic acid/ethyl acetate (20 ml) and the solution stirred at 70°C for 12 hours. Add ethyl acetate to the reaction solution, which is washed with water. To it add sodium bicarbonate (15 ml) and the solution is stirred and extracted twice with ethyl acetate. Organizes the th layer is washed with saturated salt solution (15 ml), dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=8:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (470,4 mg)having the following physical data.

TLC: Rf of 0.58 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 7.48 (user. d, J=8.7 Hz, 2H), 7,29 (user. d, J=8.7 Hz, 2H), 7,08-7,00 (m, 4H), 4.26 deaths (s, 2H), 4,12 (m, 1:2H), 4.04 the-3,92 (m, 1H), 3,88 (d, J=5,2 Hz, 1:2H), 3,82 (d, J=6.0 Hz, 1:2Hz), 3,80 (m, 1:2H ), 3,60-of 3.48 (m, 2H), is 3.08-2,78 (m, 3H), 2.95 and (s, 3H), 2,34 is 2.10 (m, 1H), 2,10-of 1.44 (m, 13H), 1,40 by 1.12 (m, 6H), 1,10-0,84 (m, 2H), were 0.94 (t, J=7.2 Hz, 3:2H), of 0.93 (t, J=7.2 Hz, 3:2H).

Example 16 (1)-(3)

Using the same procedure as described in example 14→example 15→example 16, using the appropriate carboxylic acid and aldehyde instead of N-(tert-butoxycarbonyl)-L-cyclohexylamine and 4-(4-methylsulfonylmethane)benzaldehyde respectively receive the compounds of the present invention having the following physical data.

Example 16 (1):

N-(4-{4-[(4-{(5R)-1-butyl-5-[(R)-cyclohexyl(hydroxy)-methyl]-3,6-dioxopiperidin-2-yl}piperidine-1-yl)methyl]phenoxy}-phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.51 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,47 (user. d, J=9.0 Hz, 2H), 7,29 (user. d, J=9.0 Hz, 2H), 7,07-7,00 (m, 4H), 4,25 (s, 2H), 4,18(m, 1H), 3,98-and 3.72 (m, 2H), 3,57 is-3.45 (m, 2H), 3,26 (m, 1H), 3,06-2,78 (m, 3H), 2.95 and (3H), 2,46-to 2.18 (m, 1H), 2,14 is 1.86 (m, 4H), 1,86 is 1.48 (m, 7H), 1,44-of 0.82 (m, 8H), were 0.94 (t, J=7.2 Hz, 3H).

Example 16 (2):

hydrochloride 4-[4-({4-[(5S)-1-butyl-5-(cyclohexylmethyl)-3,6-dioxopiperidin-2-yl]piperidine-1-yl}methyl)phenoxy]benzoic acid

TLC: Rf of 0.53 (chloroform:methanol=5:1);

NMR (CD3OD): δ 8,04 (user. d, J=8.7 Hz, 2H), 7,54 (user. d, J=8.7 Hz, 2H), 7,16 (user. d, J=8.7 Hz, 2H), 7,06 (user. d, J=8.7 Hz, 2H), 4,30 (s, 2H), 4,12 (m, 1/2H), 4,05-to 3.92 (m, 1H), 3,92 is 3.76 (m, 3/2H), 3,61-of 3.46 (m, 2H), 3,10-2,78 (m, 3H), 2,36-of 1.92 (m, 5H), 1,90-of 1.44 (m, 10H), 1,40-to 1.14 (m, 5H), 1.04 million-of 0.82 (m, 5H).

Example 16 (3):

hydrochloride 4-{4-[(4-{(5R)-1-butyl-5-[(R)-cyclohexyl(hydroxy)methyl]-3,6-dioxopiperidin-2-yl}piperidine-1-yl)methyl]phenoxy}benzoic acid

TLC: Rf to 0.39 (chloroform:methanol=5:1);

NMR (CD3OD): δ 8.07-a of 8.00 (m, 2H), 7,60-7,46 (m, 2H), 7,17 (user. d, J=8.7 Hz, 2H), 7,10-7,00 (m, 2H), 4,30 (s, 2H), 4,21-to 4.14 (m, 1H), 4,00-3,74 (m, 2H), 3.72 points-of 3.46 (m, 2H), 3,26 (m, 1H), 3,09-2,84 (m, 3H), 2,50-of 2.20 (m, 2H), 2,16-of 1.88 (m, 5H), 1,88 is 1.48 (m, 6H), 1,44-0,84 (m, 10H).

Comparative example 7

1-benzyl-4-[N-(2-dimethoxymethyl)amino]piperidine

To a solution of 4-amino-1-benzylpiperidine (5 g) in dimethylformamide (100 ml) add dimethoxybenzaldehyde (5.5 ml), triacetoxyborohydride sodium (at 8.36 g) and acetic acid (1.5 ml) and the solution stirred overnight. Add water to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. the received residue purified by column chromatography on silica gel (ethyl acetate:methanol=40:1-1:1) to obtain specified in the connection header (2,74 g), having the following physical data.

TLC: Rf 0,27 (dichloromethane:methanol=5:1)

NMR (CDCl3): δ 7,31-7,20 (m, 5H), to 4.46 (t, J=5.5 Hz, 1H), 3,50 (s, 2H), 3,38 (s, 6H), 2,87-and 2.83 (m, 2H), 2,74 (d, J=5.5 Hz, 2H), 2,45 (m, 1H), 2,07-to 1.98 (m, 2H), 1,86-to 1.82 (m, 2H), 1,46 is 1.34 (m, 2H).

Comparative example 8

1-benzyl-4-(N-(2-dimethoxymethyl)-N-(2-cyclohexylcarbonyl-aminoacetyl)amino)piperidine

To a solution of the compound obtained in comparative example 7 (2,74 g)in dimethylformamide (30 ml) was added 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (2,82 g), 4-N,N-dimethylaminopyridine (2.4 g) and N-cyclohexylcarbonyl (2.0 g) and the solution stirred at room temperature overnight. Add water to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=10:1) to obtain the specified title compound (1.45 g)having the following physical data.

TLC: Rf of 0.36 (ethyl acetate:methanol=10:1).

Comparative example 9:

4-(N-(2-dimethoxymethyl)-N-(2-cyclohexylcarbodiimide)amino)piperidine

To a solution of the compound obtained in comparative example 7 (900 mg)in methanol (8 ml) is added palladium hydroxide on coal (200 mg) and the solution peremeci is up at 50°C for 3 hours in hydrogen atmosphere. After cooling, the reaction mixture was filtered through CELITE (trade name) and the filtrate concentrated to obtain specified in the connection header. The compound was used in the next reaction without purification.

Example 17:

1-(4-(4-methylsulfonylmethane)benzyl)-4-(N-(2-dimethoxymethyl)-N-(2-cyclohexylcarbodiimide)-amino)piperidine

To a solution of the compound obtained in comparative example 9 (300 ml)in dimethylformamide (5 ml)/acetic acid (0.2 ml) is added 4-(4-methylsulfonylmethane)benzaldehyde (270 mg) and triacetoxyborohydride sodium (268 mg) and the solution stirred at room temperature overnight. The reaction mixture was concentrated and purified by column chromatography on silica gel (ethyl acetate:methanol=30:1-10:1) to obtain the specified title compound (223 mg)having the following physical data.

TLC: Rf 0,41 (ethyl acetate:methanol=10:1);

NMR (CDCl3): δ 7.29 trend-7,21 (m, 4H), of 6.99 (d, J=9.0 Hz, 2H), 6,94 (d, J=9.0 Hz, 2H), 4,60 (t, J=5.5 Hz, 1H), 4,20 (m, 1H), 4,13 (DD, J=16.5, and 4.0 Hz, 2H), 3,56-to 3.33 (m, 6H), 3,40 (s, 6H), 3,05-2,96 (m, 2H), 2,19-1,22 (m, 15H).

Example 18:

N-{4-[4-({4-[4-(cyclohexylcarbonyl)-2-oxo-3,4-dihydropyridin-1(2H)-yl]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

To a suspension of the compound obtained in example 17 in toluene (9 ml) is added p-toluols honoluu acid (20 mg) and the suspension is stirred and heated at 100°C for 3 hours. After cooling, add saturated aqueous sodium bicarbonate solution to the reaction mixture, which is extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=30:1) and high-performance thin-layer chromatography (dichloromethane:methanol=15:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (20 mg)having the following physical data.

TLC: Rf 0,78 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,50 (d, J=9.0 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,06 (d, J=9.0 Hz, 2H), 7,03 (d, J=9.0 Hz, 2H), 6,60 (d, J=6.0 Hz, 1H), 5,86 (d, J=6.0 Hz, 1H), 4,58 (m, 1H), 4,30 (s, 2H), 4,27 (s, 2H), 3,61-3,57 (m, 2H), 3,20-of 3.12 (m, 2H), 2.95 and (s, 3H), 2.26 and-to 1.21 (m, 15H).

Example 18 (1):

1-(1-benzylpiperidine-4-yl)-4-(cyclohexylcarbonyl)-3,4-dihydropyrazine-2(1H)-he hydrochloride

Using the same procedure as described in example 18 using compound obtained in comparative example 8, instead of the compound obtained in comparative example 17, to obtain the compound of the present invention having the following physical data.

TLC: Rf of 0.53 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 7,52 (s, 5H), 6,60 (d, J=6.0 Hz, 1H), of 5.84 (d, J=6.0 Hz, 1H), 4,58 (m, 1H), 4,33 (s, 2H), 4,27 (s, 2H), 3,6-of 3.56 (m, H), 3,22-3,14 (m, 2H), 2,69 (m, 1H), 2,19-of 1.29 (m, 14H).

Example 19:

E-form: hydrochloride 4-[4-({4-[(E)-(4-bromophenyl)-(amoxiillin)methyl]piperidine-1-yl}methyl)phenoxy]benzoic acid

Z-form: hydrochloride 4-[4-({4-[(Z)-(4-bromophenyl)-(amoxiillin)methyl]piperidine-1-yl}methyl)phenoxy]benzoic acid

To a solution of the compound obtained in example 5 (15) (912 mg)in ethanol (10 ml) is added pyridine (5 ml) and O-ethylhydroxylamine hydrochloride (340 mg) and the solution heated under reflux for 3 hours. After completion of the reaction, the reaction solution is concentrated. Add water and 2 N. hydrochloric acid and the solution extracted with ethyl acetate. The organic layer was washed with saturated salt solution and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=25:1) and add a solution of 4 N. hydrogen chloride/ethyl acetate to the resulting residue, which was concentrated, to obtain the compounds of the present invention (E-form: 409 mg, Z-form: 500 mg)having the following physical data.

E-form:

TLC: Rf of 0.37 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 1.29 (t, J=7.0 Hz, 3H), 1,90-2,00 (m, 2H), 2,14-of 2.28 (m, 2H), 2,86-2,96 (m, 2H), 3,38-of 3.48 (m, 3H), of 4.16 (s, 2H), 4,18 (kV, J=7,0 Hz, 2H), 7,02 (d, J=9.0 Hz, 2H), 7,11 (d, J=9.0 Hz, 2H), was 7.36 (d, J=9,0 Hz, 2H), 7,50 (d, J=9.0 Hz, 2H), 7,52 (d, J=9.0 Hz, 2H), 8,00 (d, J=9.0 Hz, 2H).

Z-form:

TLC: Rf of 0.35 (chloroform:IU is anal=10:1);

NMR (CD3OD): δ of 1.16 (t, J=7.0 Hz, 3H), 1,76 is 1.91 (m, 2H), 2,03 with 2.14 (m, 2H), 2,89 (m, 1H), 3,02-3,11 (m, 2H), 3,50-to 3.58 (m, 2H), 4,03 (kV, J=7,0 Hz, 2H), or 4.31 (s, 2H), 7,06 (d, J=9.0 Hz, 2H), 7,16 (d, J=9.0 Hz, 2H), 7,25 (d, J=9.0 Hz, 2H), 7,55 (d, J=9.0 Hz, 2H), EUR 7.57 (d, J=9.0 Hz, 2H), 8,03 (d, J=9.0 Hz, 2H).

Example 20 (1) example 20 (79)

Using the same procedure as described in example 1, and converting into a cleaners containing hydrochloride salt using a conventional method, using the appropriate amine derivative instead of 4-hydroxypiperidine and using 4-(4-methylsulfonylmethane)benzaldehyde or the corresponding aldehyde derivative instead get the following compounds of the present invention.

Example 20 (1):

N-benzyl-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf of 0.67 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 1,92-2,03 (m, 4H), of 2.51 (m, 1H), 2,82 of 2.92 (m, 2H), 2.95 and (s, 3H), 3,40-3,44 (m, 2H), 4,15 (s, 2H), 4,35 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7.23 percent-7,33 (m, 7H), was 7.45 (d, J=8.7 Hz, 2H).

Example 20 (2):

hydrochloride 4-[4-({4-[(cyclopentylacetyl)amino]-1-piperidinyl}methyl)phenoxy]benzoic acid

TLC: Rf of 0.37 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 0,94-1,00 (m, 2H), 1,14-of 1.30 (m, 4H), 1,60-1,80 (m, 6H), 1,99-2,17 (m, 5H), is 3.08-and 3.16 (m, 2H), 3,52 of 3.56 (m, 2H), 3,92 (m, 1H), or 4.31 (s, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,18 (d, J=8.7 Hz, 2H), 7,56 (d, J=8.7 Hz, 2H), 8,04 (d, J=8.7 Hz, 2H).

Example 20 (3):

p> hydrochloride 4-[4-({4-[(benzylamino)carbonyl]-1-piperidinyl}methyl)phenoxy]benzoic acid

TLC: Rf 0.26 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 1,90-of 2.08 (m, 4H), of 2.56 (m, 1H), 2,99-of 3.07 (m, 2H), 3,48-of 3.53 (m, 2H), 4,28 (s, 2H), 4,36 (s, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,16 (d, J=8,4 Hz, 2H), 7,21-7,34 (m, 5H), 7,54 (d, J=8,4 Hz, 2H), 8,03 (d, J=8.7 Hz, 2H).

Example 20 (4):

hydrochloride 4-[4-({4-[(butylamino)carbonyl]-1-piperidinyl}methyl)phenoxy]benzoic acid

TLC: Rf 0,20 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ of 0.93 (t, J=7.2 Hz, 3H), 1,28-of 1.53 (m, 4H), 1,95-2,00 (m, 4H), of 2.51 (m, 1H), 3,06-3,20 (m, 4H), 3,51-of 3.53 (m, 2H), 4,32 (s, 2H), 7,07 (d, J=9.0 Hz, 2H), 7,17 (d, J=8.5 Hz, 2H), 7,55 (d, J=8.5 Hz, 2H,), of 8.04 (d, J=9.0 Hz, 2H).

Example 20 (5):

hydrochloride 4-{4-[(4-{[(cyclohexylmethyl)amino]carbonyl}-1-piperidinyl)methyl]phenoxy}benzoic acid

TLC: Rf 0.21 in (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 0.87 (m, 2H), 1,19 -1,31 (m, 3H), of 1.46 (m, 1H), 1,64-of 1.73 (m, 5H), 1,90 e 2.06 (m, 4H), 2,52 (m, 1H), 3.00 and-to 3.09 (m, 4H), 3,53-to 3.58 (m, 2H), 4,33 (s, 2H), 7,07 (d, J=9.0 Hz, 2H), 7,18 (d, J=8.7 Hz, 2H), 7,56 (d, J=8.7 Hz, 2H), 8,04 (d, J=9.0 Hz, 2H).

Example 20 (6):

N-(cyclohexylmethyl)-4-hydroxy-1-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf of 0.36 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,82-1,02 (m, 2H), 1,12-of 1.36 (m, 4H), for 1.49 (m, 1H), 1.60-to a 1.88 (m, 6H), 2,31 (m, 2H), 2.95 and (s, 3H), 3.04 from (user. t, J=6.6 Hz, 2H), 3,22 is-3.45 (m, 4H), 4,32 (s, 2H), 6,98-7,01 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), 7,50 (user. d, J=9.0 Hz, 2H), 8,09 (m, 1H).

Example 20 (7):

<> N-(cyclohexylmethyl)-4-methoxy-1-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf of 0.50 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80 was 1.04 (m, 2H), 1,18-of 1.40 (m, 4H), 1,50 (m, 1H), 1.60-to 1,90 (m, 6H), is 2.30 (m, 2H), 2.91 in (s, 3H), 3.04 from (m, 2H), 3,20-to 3.52 (m, 7H), to 4.33 (s, 2H), 7,02-to 7.18 (m, 4H), 7,45 (user. t, J=9.0 Hz, 2H), 7,53 (user. t, J=8.7 Hz, 2H), 8,08 (m, 1H).

Example 20 (8):

N-[4-(4-{[4-(cyclohexylcarbonyl)-1-piperazinil]methyl}-phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,89 (chloroform:methanol=5:1);

NMR (CD3OD): δ 1.18 to and 1.56 (m, 5H), 1,64-of 1.85 (m, 5H), to 2.65 (m, 1H), 2.95 and (m, 3H), 2,90-3,20 (m, 3H), 3,32-to 3.58 (m, 3H), 4,28 (m, 1H), 4,35 (s, 2H), 4,67 (m, 1H), 7,00 for 7.12 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), 7,52 (user. d, J=8.7 Hz, 2H).

Example 20 (9):

N-[4-(4-{[4-(cyclohexylethyl)-1-piperazinil]methyl}-phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,85 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0.90 or was 1.06 (m, 2H), 1,08-of 1.40 (m, 3H), 1,60-1,80 (m, 6H), 2,31 (user. d, J=6.0 Hz, 2H), 2.95 and (s, 3H), 2,86-3,18 (m, 3H), 3,36-of 3.60 (m, 3H), is 4.21 (m, 1H), 4,35 (s, 2H), 4,69 (m, 1H), 7,00 for 7.12 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), 7,51 (user. d, J=8.7 Hz, 2H).

Example 20 (10):

N-(cyclohexylmethyl)-4-methyl-1-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf of 0.67 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-1,00 (m, 2H), 1,12-of 1.32 (m, 4H), for 1.49 (m, 1H), 1,62 and 1.80 (m, 6H), 2,22-of 2.34 (m, 2H), 2.95 and (s, 6H), 2,96-is 3.08 (m, 2H), 3,24-to 3.38 (m, 4H), 4,22 (s, 2H), 6,98-7,10 (m, 4H), 7,29 (user. d, J=9,3 Hz, 2H), 7,46 (user. d, J=8.7 Hz, 2H), 7,81 (m, 1).

Example 20 (11):

4 butoxy-N-(cyclohexylmethyl)-1-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf 0,87 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 0,82 of-1.04 (m, 2H), 1,10-1,58 (m, 7H), 1,58-of 1.78 (m, 6H), 2.06 to 2,24 (m, 4H), 2.95 and (s, 3H), 3,05 (t, J=3.0 Hz, 2H), is 3.08-3,44 (m, 6H), 4,32 (s, 2H), 7,00 for 7.12 (m, 4H), 7,29 (user. d, J=8.7 Hz, 2H), 7,50(user. d, J=8.7 Hz, 2H), 8,00 (m, 1H).

Example 20 (12):

N-cyclohexyl-4-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)-1-piperazinecarboxamide hydrochloride

TLC: Rf 0,77 (chloroform:methanol=5:1);

NMR (CD3OD): δ 1,08-of 1.44 (m, 5H), 1,58-of 1.92 (m, 5H), 2.95 and (s, 3H), 2.95 and-of 3.60 (m, 9H), or 4.31 (s, 2H), 7,00 for 7.12 (m, 4H), 7,29 (user. d, J=9,3 Hz, 2H), 7,49 (user. d, J=8,4 Hz, 2H).

Example 20 (13):

N-benzyl-4-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-1-piperazinecarboxamide hydrochloride

TLC: Rf to 0.73 (chloroform:methanol=5:1);

NMR (CD3OD): δ 2.95 for (s, 3H), up 3.22 (m, 4H), 3,70 (m, 4H), 4,28 (s, 2H), 4,35 (s, 2H), 7,00-was 7.08 (m, 4H), 7,18 and 7.36 (m, 7H), 7,44-7,56 (m, 2H).

Example 20 (14):

4-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-N-phenyl-1-piperazinecarboxamide hydrochloride

TLC: Rf to 0.73 (chloroform:methanol=5:1);

NMR (CD3OD): δ 2.95 for (s, 3H), 3,10-of 3.42 (m, 8H), the 4.29 (s, 2H), 7,00-7,10 (m, 5H), 7,21-7,40 (m, 6H), 7,49 (user. d, J=8,4 Hz, 2H).

Example 20 (15):

N-[4-(4-{[4-(cyclohexylethyl)-1-piperidinyl]methyl}-phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf is 0.59 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0.8 to 1,02 (m, 2H), 1,08-of 1.40 (m, 3H), 1.60-to 1,90 (m, 8H), 2,04-of 2.20 (m, 2H), 2,41 (d, J=6,9 Hz, 2H), 2,72 (m, 1H), 2.95 and (s, 3H), 3,05 (m, 2H), 3,48 (m, 2H), 4,27 (s, 2H), 7,00-7,10 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), of 7.48 (user. d, J=9.0 Hz, 2H).

Example 20 (16):

N-(4-{4-[(4-hydroxy-1-piperidinyl)methyl]phenoxy}-phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.38 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 1,71-of 2.16 (m, 4H), 2.95 and (s, 3H), 3,06-of 3.53 (m, 4H), 4,08 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=9.0 Hz, 2H), 7,06 (d, J=9.0 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), of 7.48 (d, J=9.0 Hz, 2H).

Example 20 (17):

1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf 0.36 and (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 1,83-of 2.21 (m, 4H), of 2.54 (m, 1H), 2.95 and (s, 3H), 2,98-of 3.06 (m, 2H), 3,52 of 3.56 (m, 2H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H).

Example 20 (18):

benzyl 1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinecarboxylate hydrochloride

TLC: Rf 0.36 and (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1.85 to was 1.94 (m, 2H), 2.06 to a 2.12 (m, 2H), 2,60-2,78 (m, 3H), equal to 2.94 (s, 3H), 3,20-of 3.25 (m, 2H), 3,99 (s, 2H), 5,14 (s, 2H), 6,99-7,02 (m, 4H), 7,27 (d, J=8.7 Hz, 2H), to 7.32 and 7.36 (m, 5H), 7,40 (d, J=8.7 Hz, 2H).

Example 20 (19):

tert-butyl 1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinylcarbonyl

TLC: Rf 0.35 in (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 1.42 (s, 9H), 1,42-of 1.53 (m, 2H), 1,81-of 1.85 (m, 2H), 2,07 with 2.14 (m, 2H), 2,83-2,87 (m, 2H), 2,93 (s, 3H), 3,30-to 3.36 (m, 1H), 3,49 (s, 2H), 6,93 (d, J=8.7 Hz, 2H), 6,97 (d, J=8.7 Hz, 2H), 7,24 (d, J=to 8.7 Hz, 2H), 7,30 (d, J=8.7 G is, 2H).

Example 20 (20):

N-{4-[4-(1-piperidinylmethyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0.34 in (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1,48-of 1.97 (m, 6H), 2,90-to 2.99 (m, 2H), 2.95 and (s, 3H), 3,42-of 3.46 (m, 2H), 4,25 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,47 (d, J=8.7 Hz, 2H).

Example 20 (21):

N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]-2-tetrahydro-2H-Piran-4-ylacetamide hydrochloride

TLC: Rf to 0.17 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1,20-1,40 (m, 2H), 1,54-of 1.64 (m, 2H), 1,67-of 1.84 (m, 2H), 1,88-of 2.21 (m, 5H), 2.95 and (s, 3H), 3,06-3,18 (m, 2H), 3,30-of 3.46 (m, 2H), 3.46 in of 3.56 (m, 2H), 3,85-of 3.97 (m, 3H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H,), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 20 (22):

1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-N-(tetrahydro-2H-Piran-4-ylmethyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf of 0.18 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1.18 to 1.32 to (m, 2H), 1.56 to of 1.64 (m, 2H), 1,73 (m, 1H), of 1.84-2.10 (m, 4H), 2,53 (m, 1H), 2.95 and (s, 3H), 2,96-3,11 (m, 4H), 3,28-of 3.42 (m, 2H), 3,49-to 3.58 (m, 2H), a 3.87-of 3.96 (m, 2H), 4,29 (s, 2H), 7,03 (d, J=8,7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 20 (23):

4-methyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]benzosulfimide hydrochloride

TLC: Rf of 0.65 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 1.56 to 1.76 (m, 2H), 1,84-2,04 (m, 2H), 2,41 (s, 3H), 2.95 and (s, 3H), of 3.00 (m, 1H), 3,14 is-3.45 (m, 4H), 4,20 (s, 2H), 6,98-7,10 (m, 4H), 7,22-7,34 (m, 2H), 7,38-7,52 (m, 4H), 7,72-7,80 (m, 2H).

Example 20 (24):/p>

N-{[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]carbonyl}benzosulfimide hydrochloride

TLC: Rf of 0.44 (chloroform:methanol=5:1);

NMR (CD3OD): δ 1,68 is 1.86 (m, 2H), 1,92 is 2.10 (m, 2H), 2,53 (m, 1H), 2.95 and (s, 3H), 2,90 totaling 3.04 (m, 2H), 3,42-of 3.54 (m, 2H), 4.26 deaths (s, 2H), 6,98-7,06 (m, 4H), 7,22 and 7.36 (m, 2H), 7,40-to 7.50 (m, 2H), 7,52 to 7.62 (m, 2H), 7,68 (m, 1H), 8,00 (user. d, J=7.5 Hz, 2H).

Example 20 (25):

N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]methanesulfonamide hydrochloride

TLC: Rf to 0.78 (chloroform:methanol=5:1);

NMR (CD3OD): δ 1.70 to of 1.92 (m, 2H), 2,08-of 2.26 (m, 2H), 2.95 and (s, 3H), 2,98 (s, 3H), 3.00 and-3,18 (m, 2H), 3,28-of 3.46 (m, 2H), 3,54 (m, 1H), 4,22 (s, 2H), 6,98-7,10 (m, 4H), 7,26-7,34 (m, 2H), 7,42-7,56 (m, 2H).

Example 20 (26):

hydrochloride 4-[(cyclohexylcarbonyl)amino]-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinecarboxylic acid

TLC: Rf of 0.20 (chloroform:methanol:acetic acid=20:4:1);

NMR (CD3OD): δ of 1.18 to 1.48 (m, 6H), 1,63 is 1.86 (m, 4H), 2,16-to 2.42 (m, 5H), 2.95 and (s, 3H), 3.00 and-3,14 (m, 2H), 3,26-to 3.41 (m, 2H), 4,23 (s, 2H), 7,00-7,10 (m, 4H), 7,28 (user. d, J=9.0 Hz, 2H), 7,47 (user. d, J=8.7 Hz, 2H).

Example 20 (27):

4-cyclohexyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)-4-piperidinyl]butanamide hydrochloride

TLC: Rf 0,58 (methanol:methylene chloride=1:8);

NMR (CD3OD): δ 0,80-to 0.96 (m, 2H), 1,12-of 1.30 (m, 6H), 1,54-of 1.84 (m, 9H), 2.00 in to 2.18 (m, 4H), 2.95 and (s, 3H), 3,03-3,14 (m, 2H), 3.46 in of 3.56 (m, 2H), with 3.89 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 20 (28):

3-cyclohe the power-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)-4-piperidinyl]propanamide hydrochloride

TLC: Rf value of 0.52 (methanol:methylene chloride=1:8);

NMR (CD3OD): δ 0,83-0,98 (m, 2H), 1,12-of 1.53 (m, 4H), to 1.48 (DD, J=6,6, 15,0 Hz, 2H), 1.60-to of 1.78 (m, 7H), 2,04-of 2.24 (m, 4H), 2.95 and (s, 3H), 3,02-3,24 (m, 2H), 3,35-to 3.58 (m, 2H), 3,90 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8,7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H).

Example 20 (29):

N-[1-({1-[4-(aminosulfonyl)phenyl] - for 3,5-dimethyl-1H-pyrazole-4-yl}methyl)-4-piperidinyl]-2-cyclohexylacetate the dihydrochloride

TLC: Rf of 0.30 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1.60-to 1,90 (m, 8H), was 2.05 (d, J=6.6 Hz, 2H) 2,10-of 2.20 (m, 2H), 2,39 (s, 3H), of 2.44 (s, 3H), 3,10-3,30 (m, 2H), 3,60-3,70 (m, 2H), 3,90 (m, 1H), 4.26 deaths (s, 2H), 7,70 (d, J=7.7 Hz, 2H), 8,07 (d, J=7.7 Hz, 2H).

Example 20 (30):

2-cyclohexyl-N-{1-[(1-{4-[(cyclohexylamino)sulfonyl]-phenyl} - for 3,5-dimethyl-1H-pyrazole-4-yl)methyl]-4-piperidinyl}ndimethylacetamide the dihydrochloride

TLC: Rf 0,46 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 8H), 1.60-to 1,90 (m, 13H), was 2.05 (d, J=7.2 Hz, 2H) 2,10-of 2.30 (m, 2H), 2,39 (s, 3H), of 2.44 (s, 3H), 3,00-3,20 (m, 3H), 3,60-3,70 (m, 2H), 3,93 (m, 1H), 4.26 deaths (s, 2H), 7,71 (d, J=8.7 Hz, 2H), 8,03 (d, J=8.7 Hz, 2H).

Example 20 (31):

2-cyclohexyl-N-[1-({1-[4-({[2-(dimethylamino)ethyl]amino}-sulfonyl)phenyl] - for 3,5-dimethyl-1H-pyrazole-4-yl}methyl)-4-piperidinyl]ndimethylacetamide trihydrochloride

TLC: Rf 0,08 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1.60-to 1,90 (m, 8H), was 2.05 (d, J=6,9 Hz, 2H) 2,10-of 2.30 (m, 2H), 2,39 (s, 3H), 2,47 (s, 3H), 2.95 and (s, 6H), of 3.10-3.20 (m, 6H), 3,60-3,70 (m, 2H), 3,90 (m, 1H), 4.26 deaths (with, 2H), 7,78 (d, J=8,9 Hz, 2H), 8,07 (d, J=8,9 G is, 2H).

Example 20 (32):

2-cyclohexyl-N-[1-({3,5-dimethyl-1-[4-({[2-(4-morpholinyl)ethyl]amino}sulfonyl)phenyl]-1H-pyrazole-4-yl}methyl)-4-piperidinyl]ndimethylacetamide trihydrochloride

TLC: Rf 0.39 to (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1.60-to 1,90 (m, 8H), was 2.05 (d, J=7.2 Hz, 2H) 2,10-of 2.30 (m, 2H), 2,39 (s, 3H), of 2.46 (s, 3H), 3,10 is 3.40 (m, 8H), 3,50-3,70 (m, 4H), 3,80-3,90 (m, 3H), 4,10-4,20 (m, 2H), 4.26 deaths (s, 2H), to 7.77 (d, J=8.7 Hz, 2H), 8,07 (d, J=8.7 Hz, 2H).

Example 20 (33):

2-cyclohexyl-N-{1-[(1-{4-[(dimethylamino)sulfonyl]phenyl} - for 3,5-dimethyl-1H-pyrazole-4-yl)methyl]-4-piperidinyl}ndimethylacetamide the dihydrochloride

TLC: Rf of 0.53 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1.60-to 1,90 (m, 8H), was 2.05 (d, J=6,9 Hz, 2H) 2,10-of 2.30 (m, 2H), 2,39 (s, 3H), of 2.46 (s, 3H), 2,74 (s, 6H), of 3.10-3.20 (m, 2H), 3,60-3,70 (m, 2H), 3,90 (m, 1H), 4.26 deaths (with, 2H), 7,76-7,80 (m, 2H), 7,94-of 7.97 (m, 2H).

Example 20 (34):

2-cyclohexyl-N-(1-{[1-(4-{[(2-hydroxyethyl)(methyl)-amino]sulfonyl}phenyl) - for 3,5-dimethyl-1H-pyrazole-4-yl]methyl}-4-piperidinyl)ndimethylacetamide the dihydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1.60-to 1,90 (m, 8H), was 2.05 (d, J=6,9 Hz, 2H) 2,10-of 2.30 (m, 2H), 2,39 (s, 3H), of 2.45 (s, 3H), 2,87 (s, 3H), of 3.10-3.20 (m, 2H), 3,19 (t, J=5,9 Hz, 2H), 3,60-of 3.80 (m, 2H,), of 3.69 (t, J=5,9 Hz, 2H), 3,93 (m, 1H), 4.26 deaths (s, 2H), of 7.75 (d, J=8.7 Hz, 2H), to 7.99 (d, J=8.7 Hz, 2H).

Example 20 (35):

2-cyclohexyl-N-{1-[(1-{4-[(diethylamino)sulfonyl]phenyl} - for 3,5-dimethyl-1H-pyrazole-4-yl)methyl]-4-piperidinyl}ndimethylacetamide the dihydrochloride

TLC: Rf 0.53 per share (telengard:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H)and 1.15 (t, J=7,1 Hz, 6H), 1,10-1,40 (m, 3H), 1,60-1,75 m, 6H), 1,75-1,90 (m, 2H), 2,05 (d, J=7.2 Hz, 2H), 2,10-of 2.30 (m, 2H), 2.40 a (s, 3H), of 2.45 (s, 3H), of 3.10-3.20 (m, 2H), 3,20-3,40 (m, 4H), 3,60-of 3.80 (m, 2H), 3,94 (m, 1H), 4.26 deaths (s, 2H), 7,73 (d, J=8.6 Hz, 2H), to 7.99 (d, J=8.6 Hz, 2H).

Example 20 (36):

2-cyclohexyl-N-[1-({3,5-dimethyl-1-[4-(4-morpholinylcarbonyl)phenyl]-1H-pyrazole-4-yl}methyl)-4-piperidinyl]ndimethylacetamide the dihydrochloride

TLC: Rf of 0.50 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,75 m, 6H), 1,75-1,90 (m, 2H), 2.06 to (d, J=7.2 Hz, 2H), 2,10-of 2.30 (m, 2H), 2.40 a (s, 3H), 2,48 (s, 3H), to 3.02 (t, J=4,7 Hz, 4H), of 3.10-3.20 (m, 2H), 3,60-3,80 (m, 2H), 3,71 (t, J=4,7 Hz, 4H), of 3.94 (m, 1H), 4,27 (s, 2H), 7,80 (d, J=8.6 Hz, 2H), 7,95 (d, J=8.6 Hz, 2H).

Example 20 (37):

2-cyclohexyl-N-{1-[(3,5-dimethyl-1-{4-[(4-methyl-1-piperazinil)sulfonyl]phenyl}-1H-pyrazole-4-yl)methyl]-4-piperidinyl}ndimethylacetamide the dihydrochloride

TLC: Rf of 0.48 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,80 (m, 6H), 1,80-2,00 (m, 2H), 2.06 to (d, J=6,9 Hz, 2H), 2,10-of 2.30 (m, 2H), 2.40 a (s, 3H), 2,48 (s, 3H), 2,80-3,00 (m, 2H), 2,90 (s, 3H), 3,10 is 3.40 (m, 4H), 3,50-of 3.80 (m, 4H), 3,90-4,10 (m, 3H), 4,27 (s, 2H), to 7.84 (d, J=8.6 Hz, 2H), 8,01 (d, J=8.6 Hz, 2H).

Example 20 (38):

ethyl [4-({4-[4-({4-[(cyclopentylacetyl)amino]-1-piperidinyl}methyl) - for 3,5-dimethyl-1H-pyrazole-1-yl]phenyl}sulfonyl)-1-piperazinil]acetate trihydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), of 1.30 (t, J=7,1 Hz, 3H), 1.60-to 1,90 (m, 8H), was 2.05 (d, J=6,9 Hz, 2H), 2,10-of 2.30 (m, 2H), 2.40 a (s, 3H), 2.49 USD (s, 3H), 310-3,20 (m, 2H), 3,40-4,00 (m, 11H), 4,22 (s, 2H), 4,27 (s, 2H), 4,29 (kV, J=7.2 Hz, 2H), to 7.84 (d, J=8.6 Hz, 2H), 8,02 (d, J=8.6 Hz, 2H).

Example 20 (39):

2-cyclohexyl-N-{1-[(3,5-dimethyl-1-{4-[(methylsulphonyl)-amino]phenyl}-1H-pyrazole-4-yl)methyl]-4-piperidinyl}ndimethylacetamide the dihydrochloride

TLC: Rf of 0.45 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1.60-to 1,90 (m, 8H), was 2.05 (d, J=7.2 Hz, 2H), 2,10-of 2.30 (m, 2H), a 2.36 (s, 3H), is 2.37 (s, 3H), 3,03 (s, 3H), of 3.10-3.20 (m, 2H), 3,60-3,70 (m, 2H), 3,90 (m, 1H), 4,24 (s, 2H), 7,39-7,46 (m, 4H).

Example 20 (40):

2-cyclohexyl-N-[1-(4-{2,6-dimethyl-4-[(methylsulphonyl)-amino]phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf 0,46 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,80 (m, 8H), 2,03 (d, J=6,9 Hz, 2H), 2,07 (s, 6H), 2,10-of 2.20 (m, 2H), 2,97 (s, 3H), 3.00 and-3,10 (m, 2H), 3,40-of 3.60 (m, 2H), 3,90 (m, 1H), 4,24 (s, 2H), 6,84 (d, J=3,9 Hz, 2H),? 7.04 baby mortality (s, 2H), 7,45 (d, J=8.7 Hz, 2H).

Example 20 (41):

N-(1-{4-[4-(aminosulfonyl)phenoxy]benzyl}-4-piperidinyl)-2-cyclohexylacetate hydrochloride

TLC: Rf of 0.33 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,80 (m, 8H), 2,04 (d, J=7.2 Hz, 2H), 2,10-of 2.20 (m, 2H), 3.00 and-3,10 (m, 2H), 3,50-3,60 (m, 2H), 3,92 (m, 1H), 4,32 (s, 2H), 7,11-7,19 (m, 4H), 7,58 to 7.62 (m, 2H,), 7,88-to 7.93 (m, 2H).

Example 20 (42):

2-cyclohexyl-N-(1-{4-[4-(methylsulphonyl)phenoxy]benzyl}-4-piperidinyl)ndimethylacetamide hydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,80 (m, 8H), was 2.05 (d, J=6,9 Hz, 2H), 2,10-2.20 m, 2H), 3.00 and-3,10 (m, 2H), 3,12 (s, 3H), 3,50-3,60 (m, 2H), 3,91 (m, 1H), 4,33 (s, 2H), 7,19-of 7.23 (m, 4H), to 7.59 (d, J=8.6 Hz, 2H), 7,95 (d, J=8.6 Hz, 2H).

Example 20 (43):

2-cyclohexyl-N-[1-({4'-[(methylsulphonyl)amino]-1,1'-biphenyl-3-yl}methyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.38 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,80 (m, 8H), 2,02 (d, J=6,9 Hz, 2H), 2,10-of 2.20 (m, 2H), 2,99 (s, 3H), 3.00 and-3,10 (m, 2H), 3,50-3,60 (m, 2H), 3,90 (m, 1H), 4,37 (s, 2H), 7,35 (d, J=8.7 Hz, 2H), 7,45-of 7.60 (m, 2H), to 7.67 (d, J=8.7 Hz, 2H), 7,70-7,80 (m, 2H).

Example 20 (44):

2-cyclohexyl-N-(1-{4-[4-(methylsulfanyl)phenoxy]benzyl}-4-piperidinyl)ndimethylacetamide hydrochloride

TLC: Rf 0,60 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,80 (m, 8H), 2,03 (d, J=7.2 Hz, 2H), 2,10-of 2.20 (m, 2H), 2,47 (s, 3H), 3.00 and-3,10 (m, 2H), 3,50-3,60 (m, 2H), 3,90 (m, 1H), 4,27 (s, 2H), 6,99 (d, J=8.5 Hz, 2H),? 7.04 baby mortality (d, J=8.5 Hz, 2H) to 7.32 (d, J=8.5 Hz, 2H), of 7.48 (d, J=8.5 Hz, 2H).

Example 20 (45):

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]propanamide hydrochloride

TLC: Rf 0.34 in (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,10 (t, J=7.4 Hz, 3H), 1,20-1,70 (m, 4H), 1,80-2,10 (m, 2H), 2,20-of 2.50 (m, 2H), 2,35 (kV, J=7,6 Hz, 2H), 2.95 and (s, 3H), 3.00 and is 3.40 (m, 4H), 3,40-of 3.60 (m, 2H), 4,11 (m, 1H), 4.26 deaths (s, 2H), 7,03 (d, J=8,9 Hz, 2H), 7,06 (d, J=8,9 Hz, 2H) 7,29 (d, J=8,9 Hz, 2H), of 7.48 (d, J=8,9 Hz, 2H).

Example 20 (46):

N-benzyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]propanamide hydrochloride

TLC: Rf of 0.44 (methylene chloride:methanol=10:1);

p> NMR (CD3OD): δ 1,08 (t, J=7.5 Hz, 3H), 1,80-2,00 (m, 2H), 2.00 in of 2.20 (m, 2H), 2,37 (kV, J=7.5 Hz, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,40-of 3.60 (m, 2H), 4,22 (s, 2H), and 4.40 (m, 1H), br4.61 (s, 2H), 7,00-7,05 (m, 4H), 7,22-7,46 (m, 7H), was 7.45 (d, J=8,4 Hz, 2H).

Example 20 (47):

N-(2-methoxyethyl)-N-[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]propanamide hydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 1.07 (t, J=7.4 Hz, 3H), 1,90-2,00 (m, 2H), 2,42 (kV, J=7,4 Hz, 2H), 2,40-2,60 (m, 2H), 2,96 (s, 3H), 3,00-3,20 (m, 2H), 3,34 (s, 3H), 3,40-of 3.60 (m, 4H), of 4.05 (m, 1H), 4,28 (s, 2H), 7,01-7,06 (m, 4H), 7,28-7,31 (m, 2H), 7,51-7,56 (m, 2H).

Example 20 (48):

N-(3-hydroxybutyl)-N-[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]propanamide hydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1,10 (t, J=7.2 Hz, 3H), 1,19 (t, J=6.0 Hz, 2H), 1,60-1,80 (m, 2H), 1,80-to 2.40 (m, 6H), 2,41 (kV, J=7,4 Hz, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,40-of 3.60 (m, 4H), 3,80 (m, 1H), of 4.05 (m, 1H), 4,28 (, 2H), 7,03 (t, J=8.7 Hz, 2H), 7,05 (t, J=7.4 Hz, 2H), 7,29 (t, J=7.4 Hz, 2H), 7,50 (t, J=8.7 Hz, 2H).

Example 20 (49):

N-(cyclohexylmethyl)-N-[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]propanamide hydrochloride

TLC: Rf 0,54 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,87-of 0.91 (m, 2H), with 1.07 (t, J=7.2 Hz, 3H), 1,10-1,40 (m, 5H), 1,60-1,80 (m, 4H), 1,80-2,00 (m, 2H), 2,36 (kV, J=7.2 Hz, 2H), 2,40-2,60 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), and 3.16 (d, J=7.5 Hz, 2H), 3,40-of 3.60 (m, 2H), 3,80 (m, 1H), 4.26 deaths (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H).

Example 20 (50):

4-(acetylamino) - N-(cyclohexylmethyl)-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf to 0.39 (chloroform:methanol=9:1);

NMR (CD3OD): δ 0,80-1,00 (m, 2H), 1,08-of 1.32 (m, 4H), to 1.48 (m, 1H), 1.60-to of 1.78 (m, 4H), 2.05 is (user. s, 3H), 2,10-of 2.50 (m, 4H), 2.95 and (s, 3H), of 3.00 (t, J=6.3 Hz, 2H), 3.04 from-to 3.50 (m, 4H), 4,30 (s, 2H), 6,98-was 7.08 (m, 4H), 7,28 (user. d, J=9.0 Hz, 2H), 7,49 (user. d, J=8.7 Hz, 2H).

Example 20 (51):

4-[4-({4-[(cyclopentylacetyl)amino]-1-piperidinyl}methyl)-phenoxy]phenyl methanesulfonate hydrochloride

TLC: Rf of 0.50 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,20-1,40 (m, 3H), 1,60-1,80 (m, 8H), 2,04 (d, J=7.2 Hz, 2H), 2,10-of 2.20 (m, 2H), of 3.10-3.20 (m, 2H), 3,23 (s, 3H), 3,40-of 3.60 (m, 2H), 3,91 (m, 1H), 4,29 (s, 2H), 7,08-7,14 (m, 4H), 7,34 (d, J=8.6 Hz, 2H), 7,54 (d, J=8.6 Hz, 2H).

Example 20 (52):

N-(cyclopropylmethyl)-N-[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]propanamide hydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,30-0,40 (m, 2H), 0,60-0,70 (m, 2H), 0,95 (m, 1H), 1,10 (t, J=7.4 Hz, 3H), 1,90-2,10 (m, 2H), 2,40-2,60 (m, 2H), 2,43 (kV, J=7.2 Hz, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), up 3.22 (d, J=6.3 Hz, 2H), 3.45 points-of 3.60 (m, 2H), 4.00 points (m, 1H), 4,28 (s, 2H), 7,02-was 7.08 (m, 4H), 7,27-to 7.32 (m, 2H), 7,50 (t, J=8,1 Hz, 2H).

Example 20 (53):

N-(2-cyclohexylethyl)-1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf of 0.64 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 0.89 to 0.97 (m, 2H), 1.18 to 1.41 for (m, 7H), 1.60-to around 1.74 (m, 4H), 1,87-2,04 (m, 4H), 2,47 (m, 1H), 2.95 and (s, 3H), 2.95 and totaling 3.04 (m, 2H), 3,16-is 3.21 (m, 2H), 3,52 of 3.56 (m, 2H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,47 (d, J=8.7 Hz, 2H).

Example 20 (54):

2-the CEC is hexil-N-(1-{4-[4-(methylsulfinyl)phenoxy]benzyl}-4-piperidinyl)ndimethylacetamide hydrochloride

TLC: Rf 0.21 in (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,80 (m, 8H), 2,04 (d, J=6,9 Hz, 2H), 2,10-of 2.20 (m, 2H), 2,80 (s, 3H), of 3.10-3.20 (m, 2H), 3,50-3,60 (m, 2H), 3,90 (m, 1H), or 4.31 (s, 2H), 7,16 (d, J=8.7 Hz, 2H), 7,22 (d, J=9.0 Hz, 2H), 7,58 (d, J=9.0 Hz, 2H), 7,74 (d, J=8.7 Hz, 2H).

Example 20 (55):

N-[2-(ethylsulfanyl)ethyl]-1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf of 0.30 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 1.23 (t, J=7.5 Hz, 3H), 1,88-of 2.08 (m, 4H), 2,46-to 2.67 (m, 5H), 2,94-of 3.07 (m, 2H), 2.95 and (s, 3H), 3,37 (t, J=7,0 Hz, 2H), 3,52 of 3.56 (m, 2H), 4,28 (s, 2H), 7,03 (d, J=9.0 Hz, 2H), 7,06 (d, J=9.0 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), of 7.48 (d, J=9.0 Hz, 2H).

Example 20 (56):

2-cyclohexyl-N-[1-(4-{2-methoxy-4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.30 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,80 (m, 8H), 2,03 (d, J=6,9 Hz, 2H), 2,10-of 2.20 (m, 2H), 2,99 (s, 3H), 3,00-3,20 (m, 2H), 3,40-of 3.60 (m, 2H), and 3.72 (s, 3H), with 3.89 (m, 1H), or 4.31 (s, 2H), 6,83-6,94 (m, 3H), 6,99-7,05 (m, 2H), 7,39 was 7.45 (m, 2H).

Example 20 (57):

2-cyclohexyl-N-[1-(4-{3-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.30 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,90-1,10 (m, 2H), 1,10-1,40 (m, 3H), 1,60-1,80 (m, 8H), 2,04 (d, J=6,9 Hz, 2H), 2,10-of 2.20 (m, 2H), 2,96 (s, 3H), 3,00-3,20 (m, 2H), 3,40-of 3.60 (m, 2H), 3,90 (m, 1H), 4,29 (s, 2H), 6,79 (DD, J=7,5, 2,4 Hz, 1H), 6,95-7,01 (m, 2H), 7,08-7,11 (m, 2H), 7,31-7,34 (m, 1H), 7,51-rate of 7.54 (m, 2H).

Example 20 (58):

N-[4-(4-{[4-(cyclohexylethyl)-3-ethyl-1-piperazinil]-methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf to 0.72 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,82-of 1.44 (m, 8H), 1.60-to of 1.85 (m, 6H), 2,30-to 2.42 (m, 2H), 2.95 and (s, 3H), 2.95 and-the 3.65 (m, 5H), 4,10-of 5.15 (m, 4H), 7,00 for 7.12 (m, 4H), 7.24 to 7,38 (m, 2H), 7,52 (user. d, J=8.7 Hz, 2H).

Example 20 (59):

1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl cyclohexylcarbamate hydrochloride

TLC: Rf 0,69 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 1,06-of 1.42 (m, 6H), 1,54-of 1.92 (m, 6H), 1,95-2,17 (m, 2H), and 2.26 (m, 1H), 2.95 and (s, 3H), 3,05-to 3.58 (m, 5H), the 4.29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (DD, J=4.2, and to 8.7 Hz, 2H).

Example 20 (60):

hydrochloride (2R,3R)-3-cyclohexyl-3-hydroxy-2-({[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]carbonyl}-amino)propanoic acid

TLC: Rf of 0.23 (methylene chloride:methanol=8:2);

NMR (CD3OD): δ 1.00 and is 1.34 (m, 5H), to 1.48 (m, 1H), 1,58 and 1.80 (m, 4H), 1,83-2,11 (m, 5H), 2,58 (m, 1H), 2.95 and (s, 3H), 2,87-3,00 (m, 2H), 3,40-to 3.49 (m, 2H), 3,51 (t, J=6.0 Hz, 1H), 4,18 (s, 2H), 4,39 (d, J=6.0 Hz, 1H), 7,02 (d, J=8.7 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,28 (d, J=8.7 Hz, 2H), 7,46 (d, J=8.7 Hz, 2H).

Example 20 (61):

N-butyl-2-cyclohexyl-N-[1-(4-{3-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.32 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,80-1,10 (m, 2H), 0,97 (t, J=7.2 Hz, 3H), 1,20-1,40 (m, 5H), 1,40-1,60 (m, 2H), 1,60-2,00 (m, 8H), 2,30-to 2.40 (m, 2H), 2,32 (d, J=7.2 Hz, 2H), 2,96 (s, 3H), 3,10-3,30 (m, 4H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,30 (s, 2H), to 6.80 (m, 1H), 6,95 (m, 1H), 7,00 (m, 1H), was 7.08 (d, J=8.7 Hz, 2H), 7,33 (t, J=8,1 Hz, 1H), 7,55-to 7.61 (m, 2H).

Example 20 (62):

hydrochloride 4-[4-({4-[b is Teal(hexanoyl)amino]-1-piperidinyl}methyl)phenoxy]benzoic acid

TLC: Rf of 0.34 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,90-1,00 (m, 3H), of 0.97 (t, J=7.4 Hz, 3H), 1,20-1,40 (m, 6H), 1,50-1,70 (m, 4H), 1,80-2,00 (m, 2H), 2,20-2,40 (m, 4H), 3,00-3,20 (m, 4H), 3,50-3,70 (m, 2H), 4,10 (m, 1H), or 4.31 (s, 2H), 7,07 (d, J=9,0 Hz, 2H), 7,17 (d, J=9.0 Hz, 2H), 7,56 (d, J=9.0 Hz, 2H), 8,04 (d, J=9.0 Hz, 2H).

Example 20 (63):

hydrochloride 4-[4-({4-[benzyl(hexanoyl)amino]-1-piperidinyl}methyl)phenoxy]benzoic acid

TLC: Rf of 0.40 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,86 (t, J=7.2 Hz, 3H), 1,20-1,50 (m, 4H), 1,50-1,70 (m, 2H), 1,88-of 1.95 (m, 2H), 2.00 in of 2.20 (m, 2H), 2,30-to 2.40 (m, 2H), 3,00-3,20 (m, 2H), 3,50-3,60 (m, 2H), 4,27 (s, 2H), of 4.45 (m, 1H), to 4.62 (s, 2H), 7,03-7,07 (m, 2H), 7,13-7,37 (m, 7H), 7,52 (d, J=8,4 Hz, 2H), 8,01-of 8.04 (m, 2H).

Example 20 (64):

N-butyl-2-cyclohexyl-N-[1-(4-{2-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.50 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,90-1,00 (m, 2H), 0,97 (t, J=7.2 Hz, 3H), 1,20-1,40 (m, 5H), of 1.40 and 1.80 (m, 8H), 1,80-2,00 (m, 2H), 2,21 (d, J=6,9 Hz, 2H), 2,30-to 2.40 (m, 2H), 2,98 (s, 3H), 3.00 and-3,30 (m, 4H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,28 (s, 2H), 6,98 (m, 1H), 7,12 (d, J=8.7 Hz, 2H), 7.18 in-7,21 (m, 2H), 7,52-rate of 7.54 (m, 3H).

Example 20 (65):

benzyl butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]carbamate hydrochloride

TLC: Rf 0,77 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.90 (t, J=7.2 Hz, 3H), 1,21-of 1.36 (m, 2H), 1,42 is 1.58 (m, 2H), 1,88 is 2.00 (m, 2H), 2,09-of 2.34 (m, 2H), 2.95 and (s, 3H), 3.00 and-3,14 (m, 2H), 3,17 of 3.28 (m, 2H), 3.43 points-to 3.58 (m, 2H), 3,93 (m, 1H), 4,25 (s, 2H), 5,12 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7.24 to 7,38 (m, 7H), 7,47 (d, J=8.7 Hz, 2H).

Example 20 (66):

benzyl allyl [1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)-4-piperidinyl]carbamate hydrochloride

TLC: Rf of 0.75 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 1,90 for 2.01 (m, 2H), 2,09-2,19 (m, 2H), 2.95 and (s, 3H), 3,01-of 3.12 (m, 2H), 3,44-3,55 (m, 2H), 3,89 (d, J=5.5 Hz, 2H), a 4.03 (m, 1H), 4,25 (s, 2H), 5,09-to 5.21 (m, 2H), 5,13 (s, 2H), of 5.83 (DDD, J=22,5, 10,2, 5,4 Hz, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,25-7,38 (m, 7H), 7,47(d, J=8.7 Hz, 2H).

Example 20 (67):

benzyl 2-butenyl [1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)-4-piperidinyl]carbamate hydrochloride

TLC: Rf 0,76 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 1.75 (t, J=2.1 Hz, 3H), 1,95-of 2.08 (m, 2H), 2,18-of 2.36 (m, 2H), 2.95 and (s, 3H), 3,03-3,18 (m, 2H), 3,47 is 3.57 (m, 2H), a 4.03 (d, J=2.1 Hz, 2H), 4,07 (m, 1H), 4.26 deaths (s, 2H), 5,16 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,25-7,41 (m, 7H), 7,47 (d, J=8.7 Hz, 2H).

Example 20 (68):

N-butyl-2-cyclohexyl-N-(1-{3-[(methylsulphonyl)amino]-4-phenoxybenzyl}-4-piperidinyl)ndimethylacetamide hydrochloride

TLC: Rf of 0.48 (chloroform:methanol:acetic acid=20:2:1);

NMR (CD3OD): δ 0,90-1,00 (m, 2H), 0,97 (t, J=7.2 Hz, 3H), 1,10-1,40 (m, 5H), 1,50-1,80 (m, 8H), 1,80-2,00 (m, 2H), 2,21 (d, J=6,9 Hz, 2H), 2,30-to 2.40 (m, 2H), 3.04 from (s, 3H), 3,05-3,30 (m, 4H), 3,50-3,70 (m, 2H), 4,14 (m, 1H), 4,28 (s, 2H), 6.89 in (d, J=8,4 Hz, 1H), 7,10 (d, J=7.5 Hz, 2H), 7,20-7,29 (m, 2H), 7,40-7,46 (m, 2H), 7,68 (d, J=2.1 Hz, 1H).

Example 20 (69):

N-butyl-2-cyclohexyl-N-{1-[4-(4-nitrophenoxy)benzyl]-4-piperidinyl}ndimethylacetamide hydrochloride

TLC: Rf of 0.54 (chloroform:methanol:acetic acid=20:2:1);

NMR (CD3OD): δ 0,90-1,00 (m, 2H), and 0.98 (t, J=7.2 Hz, 3H), 1,10-1,0 (m, 5H), 1,50-1,80 (m, 8H), 1,80-2,00 (m, 2H), 2,22 (d, J=6.6 Hz, 2H), 2,30-to 2.40 (m, 2H), 3,10-3,30 (m, 4H), 3,50-3,60 (m, 2H), 4,19 (m, 1H), 4,34 (s, 2H), 7,16 (d, J=9.1 Hz, 2H), 7,24 (d, J=8,4 Hz, 2H), 7,63 (d, J=8,4 Hz, 2H), of 8.27 (d, J=9.1 Hz, 2H).

Example 20 (70):

4-[4-({4-[butyl(cyclopentylacetyl)amino]-1-piperidinyl}-methyl)phenoxy]phenyl methanesulfonate hydrochloride

TLC: Rf 0,79 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,90-1,00 (m, 2H), 0,97 (t, J=7.2 Hz, 3H), 1,10-1,40 (m, 5H), of 1.40 and 1.80 (m, 8H), 1,80-2,00 (m, 2H), 2,21 (d, J=6,9 Hz, 2H), 2,30-to 2.40 (m, 2H), 3,00-3,20 (m, 4H), 3,23 (s, 3H), 3,50-3,60 (m, 2H), 4,18 (m, 1H), 4,29 (s, 2H), 7,11 (d, J=9.0 Hz, 4H), 7,35 (d, J=9.0 Hz, 2H), 7,54 (d, J=9.0 Hz, 2H).

Example 20 (71):

N-butyl-2-cyclohexyl-N-[1-(4-{2-methyl-4-[(methylsulphonyl)-amino]phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.44 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,90-1,00 (m, 2H), 0,97 (t, J=7.2 Hz, 3H), 1,10-1,40 (m, 5H), of 1.40 and 1.80 (m, 8H), 1,80-2,00 (m, 2H), 2,16 (s, 3H), of 2.21 (d, J=6,9 Hz, 2H), 2,30-to 2.40 (m, 2H), 2,96 (s, 3H), 3,00-3,20 (m, 4H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,25 (s, 2H), 6,91-6,98 (m, 3H), 7,13 (DD, J=8,6, and 2.6 Hz, 1H), 7,20 (m, 1H), 7,44-7,49 (m, 2H).

Example 20 (72):

N-butyl-2-cyclohexyl-N-[1-(4-{2,6-dimethyl-4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.33 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,90-1,00 (m, 2H), 0,97 (t, J=7.2 Hz, 3H), 1,10-1,40 (m, 5H), of 1.40 and 1.80 (m, 8H), 1,80-2,00 (m, 2H), 2,07 (s, 6H), of 2.21 (d, J=6.6 Hz, 2H), 2,30-to 2.40 (m, 2H), 2,97 (s, 3H), 3,00-3,20 (m, 4H), 3,50-3,60 (m, 2H), 4,17 (m, 1H), 4,24 (s, 2H), 6,86 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (s, 2H), 7,45 (d, J=8.7 Hz, 2H).

Example 20 (73):

N-butyl-N-[1-(4-2-chloro-4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]-2-cyclohexylacetate hydrochloride

TLC: Rf of 0.60 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,90-1,00 (m, 2H), 0,97 (t, J=7.4 Hz, 3H), 1,20-1,40 (m, 5H), 1,40-1,60 (m, 2H), 1,60-2,00 (m, 8H), of 2.21 (d, J=6.6 Hz, 2H), 2,30-to 2.40 (m, 2H), 3,01 (s, 3H), 3,10-3,30 (m, 4H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,27 (s, 2H), 6,99 (d, J=8,4 Hz, 2H), 7,13 (d, J=9.0 Hz, 1H), 7,24 (DD, J=9,0, 2.6 Hz, 1H), 7,43 (d, J=2.6 Hz, 1H), of 7.48-7,52 (m, 2H).

Example 20 (74):

(2R)-2-cyclohexyl-2-hydroxy-N-[1-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.48 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 1.06 a-to 1.38 (m, 5H), 1,45-of 1.94 (m, 8H), 2.05 is-of 2.16 (m, 2H), 2.95 and (s, 3H), 3,03-3,17 (m, 2H), 3,48 is 3.57 (m, 2H), 3,79 (d, J=4.0 Hz, 1H), 3.96 points (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=to 8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H).

Example 20 (75):

(2S)-2-cyclohexyl-2-hydroxy-N-[1-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.48 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 1.06 a-to 1.38 (m, 5H), 1,45-of 1.94 (m, 8H), 2.05 is-of 2.16 (m, 2H), 2.95 and (s, 3H), 3,03-3,17 (m, 2H), 3,48 is 3.57 (m, 2H), 3,79 (d, J=4.0 Hz, 1H), 3.96 points (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=to 8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H).

Example 20 (76):

methyl 2-[4-({4-[butyl(cyclopentylacetyl)amino]-1-piperidinyl}methyl)phenoxy]-5-[(methylsulphonyl)amino]benzoate hydrochloride

TLC: Rf of 0.50 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,90-1,00 (m, 2H), 0,97 (t, J=7.2 Hz, 3H), 1,10-1,40 (m, 5H), 1,50-1,60 (m, 2H), of 1.65 and 1.80 (m, 6H), 1,80-2,00 (m, 2H), 2,21 (d, J=6,9 Hz, 2H), 2,30-to 2.40 (m, 2H), 3.00 and (s, 3H), 3,10-3,30 (m, 4H), 3,50-of 3.60 (m, 2H), 3,74 (s, 3H), 4,10 (m, H), 4.26 deaths (s, 2H), 6,98 (d, J=8.7 Hz, 2H), 7,10 (d, J=8.7 Hz, 1H), 7,45-7,52 (m, 3H), 7,79 (d, J=3.0 Hz, 1H).

Example 20 (77):

hydrochloride of 2-[4-({4-[butyl(cyclopentylacetyl)amino]-1-piperidinyl}methyl)phenoxy]-5-[(methylsulphonyl)amino]benzoic acid

TLC: Rf of 0.40 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,95-1,05 (m, 2H), 0,97 (t, J=7,3 Hz, 3H), 1,10-1,40 (m, 5H), 1,50-1,80 (m, 8H), 1,80-2,00 (m, 2H), 2,21 (d, J=6,9 Hz, 2H), 2,30-to 2.40 (m, 2H), 3,01 (s, 3H), 3,05-of 3.25 (m, 4H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4.26 deaths (s, 2H), 6,95 (d, J=8.7 Hz, 2H), to 7.09 (d, J=8.7 Hz, 1H), 7,46-7,51 (m, 3H), 7,83 (d, J=2.7 Hz, 1H).

Example 20 (78):

(2R)-N-butyl-2-cyclohexyl-2-hydroxy-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.55 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,90-of 2.58 (m, 22H), 2,95 (s, 3H), 3,02-to 3.35 (m, 4H), 3,50-3,60 (m, 2H), 3,94-4,17 (m, 2H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,45-rate of 7.54 (m, 2H).

Example 20 (79):

(2S)-N-butyl-2-cyclohexyl-2-hydroxy-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]ndimethylacetamide hydrochloride

TLC: Rf of 0.55 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,90-of 2.58 (m, 22H), 2,95 (s, 3H), 3,02-to 3.35 (m, 4H), 3,50-3,60 (m, 2H), 3,94-4,17 (m, 2H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,45-rate of 7.54 (m, 2H).

Example 20 (80):

(3,4-TRANS)-N-(cyclohexylmethyl)-3-methyl-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf of 0.40 (chloroform:methanol=9:1);

NMR (CD3OD): δ ,84-1,04 (m, 2H), with 0.93 (d, J=6.0 Hz, 3H), 1,14-of 1.34 (m, 4H), to 1.48 (m, 1H), 1,60-1,80 (m, 4H), 1,88-2,04 (m, 2H), 2.06 to to 2.18 (m, 2H), 2,72 (m, 1H), 2,88-of 3.12 (m, 3H), 2.95 and (s, 3H), 3,22-of 3.60 (m, 2H), 4,28 (user. s, 2H), 7,00-to 7.18 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), of 7.48 (user. d, J=8.7 Hz, 2H).

Example 20 (81):

(3,4-CIS)-N-(cyclohexylmethyl)-3-methyl-1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperazinecarboxamide hydrochloride

TLC: Rf of 0.25 (chloroform:methanol=9:1);

NMR (CD3OD): δ 0,82 was 1.06 (m, 2H), and 1.00 (d, J=6.9 Hz, 3H), of 1.13 to 1.34 (m, 4H), of 1.46 (m, 1H), 1,62 and 1.80 (m, 4H), 1,92-of 2.24 (m, 3H), by 2.55 (m, 1H), 2,90-of 3.12 (m, 2H), 2.95 and (s, 3H), 3,13-3,62 (m, 4H), 4,29 (user. s, 2H), 6,98-7,10 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), 7,51 (user. d, J=8.7 Hz, 2H).

Example 20 (82):

N-(cyclohexylmethyl)-1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-3-azetidinone hydrochloride

TLC: Rf to 0.73 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-1,02 (m, 2H), 1,19-of 1.35 (m, 4H), for 1.49 (m, 1H), 1,60-1,80 (m, 4H), 2.95 and (s, 3H), 3,06 (m, 2H), 3,61 (m, 1H), 4,12-4,32 (m, 4H), 4,39 (s, 2H), 6,98-7,06 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), 7,45 (user. d, J=8.7 Hz, 2H).

Example 20 (83):

(1R,3s,5S)-N-(cyclohexylmethyl)-8-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)-8-azabicyclo[3,2,1]Octan-3-carboxamide hydrochloride

TLC: Rf of 0.53 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,85 was 1.04 (m, 2H), 1,20-of 1.36 (m, 4H), of 1.46 (m, 1H), 1.60-to of 1.78 (m, 4H), 1,85-1,90 (m, 2H), 2,08-of 2.16 (m, 4H), 2,38-of 2.50 (m, 2H), 2,88 (m, 1H), 2.95 and (s, 3H), of 3.00 (d, J=6,9 Hz, 2H), 3.96 points (m, 2H), 4,16 (s, 2H), 7,00-7,10 (m, 4H), 7.24 to 7,32 (m, 2H), 7,53 (user. d, J=8.7 Hz, 2H).

Example 20 (84):

(3aR,5s,6aS)-N-(cyclo is exility)-2-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)octahydrocyclopenta[c]pyrrol-5-carboxamide hydrochloride

TLC: Rf of 0.55 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-1,02 (m, 2H), 1.04 million-of 1.36 (m, 3H), of 1.46 (m, 1H), 1.60-to to 2.18 (m, 9H), was 2.76-3.04 from (m, 7H), 2.95 and (s, 3H), 3,60-of 3.78 (m, 2H), 4,35 (s, 2H), 7,00-7,19 (m, 4H), 7.24 to 7,32 (m, 2H), 7,42-7,58 (m, 2H).

Example 20 (85):

(3aR,5r,6aS)-N-(cyclohexylmethyl)-2-(4-{4-[(methylsulphonyl)-amino]phenoxy}benzyl)octahydrocyclopenta[c]pyrrol-5-carboxamide hydrochloride

TLC: Rf to 0.39 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-1,00 (m, 2H), 1,10-of 1.36 (m, 3H), of 1.42 (m, 1H), 1.60-to is 1.82 (m, 6H), to 2.18 (m, 1H), 2,24-of 2.38 (m, 2H), 2,78 is 3.40 (m, 9H), 2.95 and (s, 3H), 4,30 (s, 2H), 7,00-7,10 (m, 4H), 7,22-7,38 (m, 2H), 7,42-7,58 (m, 2H).

Example 21 (1)-(11)

Using the same procedure as described in example 14→example 15→example 16, using N-(tert-butoxycarbonyl)-L-cyclohexylamine or the corresponding carboxylic acid derivative instead; the corresponding aldehyde derivative instead of 4-(4-methylsulfonylmethane)benzaldehyde and n-butylamine or a corresponding amine derivative instead get a connection according to the present invention having the following physical data.

Example 21 (1):

(3S)-1-benzyl-3-(cyclohexylmethyl)-6-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]-4-piperidinyl}-2,5-piperazinone hydrochloride

TLC: Rf to 0.73 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,82-to 2.42 (m, 24H), 2,80-312 (m, 2H), 3,56-3,70 (m, 2H), 3,79 (m, 1H), was 4.02-4,16 (m, 4H), 5,12 is 5.38 (m, 1H), 7,20 to 7.62 (m, 10H).

Example 21 (2):

(3S)-1-butyl-3-(cyclohexylmethyl)-6-[1-(4-phenoxybenzyl)-4-piperidinyl]-2,5-piperazinone hydrochloride

TLC: Rf to 0.73 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-1,08 (m, 5H), 1,10-of 1.42 (m, 6H), 1,42-of 2.38 (m, 14H), 2,78-is 3.08 (m, 3H), 3,44-of 3.60 (m, 2H), 3,62-to 4.14 (m, 3H), 4.26 deaths (user. s, 2H), 7,00-7,06 (m, 4H), 7,18 (m, 1H), 7,38-7,52 (m, 4H).

Example 21 (3):

(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-6-[1-(4-phenoxybenzyl)-4-piperidinyl]-2,5-piperazinone hydrochloride

TLC: Rf and 0.62 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,86-2,48 (m, 23H), 2,81-is 3.08 (m, 3H), of 3.27 (m, 1H), 3.45 points-to 3.58 (m, 2H), 3,64-4,00 (m, 2H), 4,18 (m, 1H), 4,25 (user. s, 2H), 7,00-7,07 (m, 4H), 7,18 (m, 1H), 7,28-7,52 (m, 4H).

Example 21 (4):

(3S)-3-benzyl-1-butyl-6-[1-(4-phenoxybenzyl)-4-piperidinyl]-2,5-piperazinone hydrochloride

TLC: Rf of 0.65 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,78-of 2.30 (m, 12H), 2,52-of 3.96 (m, 9H), 4,14-to 4.28 (m, 2H), to 4.38 (m, 1H), 6,98-7,52 (m, 14H).

Example 21 (5):

(3S)-1-butyl-3-cyclohexyl-6-[1-(4-phenoxybenzyl)-4-piperidinyl]-2,5-piperazinone hydrochloride

TLC: Rf of 0.65 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,78 of 1.00 (m, 3H), 1.00 and-of 2.38 (m, 20H), 2,78-is 3.08 (m, 3H), 3,48-Android 4.04 (m, 5H), 4.26 deaths (m, 2H), 6,98-7,10 (m, 4H), 7,18 (m, 1H), 7,39-rate of 7.54 (m, 4H).

Example 21 (6):

(3S)-1-butyl-3-(hydroxymethyl)-6-[1-(4-phenoxybenzyl)-4-piperidinyl]-2,5-piperazinone hydrochloride

TLC: Rf and 0.46 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0.76 to a 1.01 (m, 3H), 1,2-to 1.42 (m, 2H), 1,44-1,72 (m, 3H), 1,86-of 2.38 (m, 4H), 2,80-is 3.08 (m, 3H), 3,44-of 3.60 (m, 2H), 3,64-4,12 (m, 5H), 4.26 deaths (user. s, 2H), of 6.96-7,10 (m, 4H), 7,18 (m, 1H), was 7.36-7,52 (m, 4H).

Example 21 (7):

(3S)-1-butyl-3-(cyclohexylmethyl)-6-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]-4-piperidinyl}-2,5-piperazinone hydrochloride

TLC: Rf of 0.68 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,86-1,08 (m, 5H), 1,16-2,12 (m, 20H), 2,39 (m, 6H), 2,78-and 3.16 (m, 3H), 3,56-3,70 (m, 2H), 3,76-to 4.14 (m, 3H), 4,24 (user. s, 2H), 7,47-7,56 (m, 5H).

Example 21 (8):

(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-6-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]-4-piperidinyl}-2,5-piperazinone hydrochloride

TLC: Rf of 0.67 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0.90 or with 2.14 (m, 23H), 2,32-to 2.40 (m, 6H), 2,80-3,14 (m, 3H), of 3.28 (m, 1H), 3,56-3,68 (m, 2H), 3,68-4,00 (m, 2H), 4,19 (m, 1H), 4,24 (user. s, 2H), 7,42-of 7.60 (m, 5H).

Example 21 (9):

(3S)-3-benzyl-1-butyl-6-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]-4-piperidinyl}-2,5-piperazinone hydrochloride

TLC: Rf 0,74 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,78-to 2.40 (m, 12H), 2,32-to 2.40 (m, 6H), 2,32-3,95 (m, 8H), 4,12-of 4.44 (m, 4H), 7,10-7,28 (m, 5H), 7,40-to 7.61 (m, 5H).

Example 21 (10):

(3S)-1-butyl-3-cyclohexyl-6-{1-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-yl)methyl]-4-piperidinyl}-2,5-piperazinone hydrochloride

TLC: Rf 0,74 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-1,00 (m, 3H), 1,02-2,22 (m, 20H), 2,32-to 2.40 (m, 6H), 2,80-3,18 (m, 3H), to 3.58-4,08 (m, 5H), 4,24 (user. s, 2H), 7,40-of 7.60 (m, 5H).

Example 21 (11):

(3S)-1-butyl-3-(cyclohexylmethyl)-6-[1-(4-phenoxybenzyl is)-4-piperidinyl]-2-piperazinone the dihydrochloride

TLC: Rf 0,82 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.95 (t, J=7.5 Hz, 3H), 0,85-1,10 (m, 2H), 1,16-of 1.42 (m, 6H), 1,46 is 2.10 (m, 13H), of 2.21 (m, 1H), 2,81 (m, 1H), 3,00-3,20 (m, 2H), 3,34-and 3.72 (m, 5H), 3,92-4,08 (m, 2H), 4,30 (s, 2H), 7,00-7,10 (m, 4H), to 7.18 (m, 1H), was 7.36-7,44 (m, 2H), 7,54 (user. d, J=8,4 Hz, 2H).

Example 22:

A mixture of n-{4-[4-({4-[(1E)-2-cyclohexyl-N-amoxilcanineyl]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride and N-{4-[4-({4-[(1Z)-2-cyclohexyl-N-amoxilcanineyl]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

Using the same procedure as described in example 19, by using the compound obtained in example 20 (15)instead of the compound obtained in example 5 (15)are compounds according to the present invention having the following physical data.

TLC: Rf of 0.67, to 0.73 (chloroform:methanol=9:1);

NMR (CD3OD): δ 0,84 was 1.06 (m, 2H), 1,08-of 1.36 (m, 4H), of 1.18 (t, J=7.2 Hz, 3H), 1,58-to 2.18 (m, 9H), of 2.23 (d, J=7.2 Hz, 2H), 2,42 (m, 1H), 2.95 and (s, 3H), to 3.02 (m, 2H), 3,38 of 3.56 (m, 2H), 4.00 points (kV, J=7.2 Hz, 2H), 4.26 deaths (with, 2H), 7,00-7,10 (m, 4H), 7,22 and 7.36 (m, 2H), 7,47 (user. d, J=8,4 Hz, 2H).

Example 23:

N-[4-(4-{[4-(butyl{[(1-methylcyclohexyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

To a solution of the compound obtained in example 3 (117 mg)in N,N-dimethylformamide (3 ml) and triethylamine (0.1 ml) was added 1-methylcyclohexanecarboxylic acid (50 mg) defenestrated (0,077 ml) and the solution stirred at 80°C for 2 hours. After cooling, add saturated aqueous solution of sodium bicarbonate in the reaction mixture, which is extracted with ethyl acetate. The organic layer was washed with saturated salt solution and dried over anhydrous sodium sulfate. The resulting residue is purified by column chromatography on silica gel (ethyl acetate) and high-performance thin-layer chromatography and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (58 mg)having the following physical data.

TLC: Rf of 0.60 (ethyl acetate);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,30-1,60 (m, 12H), 1,32 (s, 3H), 1,87-2,07 (m, 6H), 2.95 and (s, 3H), 3,05 is 3.15 (m, 4H), 3,52 of 3.56 (m, 2H), 4,19 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=9.0 Hz, 2H), 7,06 (d, J=9,0 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,49 (d, J=9.0 Hz, 2H).

Example 23 (1) - (151)

Using the same procedure as described in example 23, using the compound obtained in example 3, or the corresponding amine derivative and using 1-methylcyclohexanecarboxylic acid or the corresponding carboxylic acid derivative will receive the following compounds of the present invention.

Example 23 (1):

hydrochloride 3-[({[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)-4-piperidinyl]amino}carbonyl)amino]benzoic acid

TLC: Rf of 0.75 (n-butanol:acetic acid:water=4:2:1);

NMR (CD3OD): δ 1.70 to a 1.96 (m, 2H), 2,10-2,30 (who, 2H), 2,96 (s, 3H), 3,07-3,20 (m, 2H), 3.46 in-of 3.60 (m, 2H), 3,84 (m, 1H), or 4.31 (s, 2H), 7,02-was 7.08 (m, 4H), 7,30 (d, J=8.7 Hz, 2H), 7,35 (t, J=7.8 Hz, 1H), 7,51 (d, J=8.7 Hz, 2H), to 7.59-7,66 (m, 2H), 8,04 (s, 1H).

Example 23 (2):

N-(4-{4-[(4-{butyl[(butylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.51 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ to 0.92 (t, J=6.9 Hz, 3H), were 0.94 (t, J=6.9 Hz, 3H), 1,40-of 1.26 (m, 4H), 1.56 to to 1.42 (m, 4H), 1,95 of-1.83 (m, 2H), 2,20-2,02(m, 2H), 2.95 and (s, 3H), 3,17-3,05 (m, 6H), 3,60-to 3.50(m, 2H), 4,13 (m, 1H), 4,27 (s, 2H), 7,03(d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (3):

N-(4-{4-[(4-{butyl[(tert-butylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.65 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), of 1.33 (s, 9H), 1,40-1,25 (m, 2H), 1,58-of 1.44 (m, 2H), 1,92 of-1.83 (m, 2H), 2,10-of 1.97 (m, 2H), 2.95 and (s, 3H), 3,15-to 3.02 (m, 4H), to 3.58-to 3.50 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,30 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (4):

N-(4-{4-[(4-{butyl[(cyclohexylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,62 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ were 0.94 (t, J=7.2 Hz, 3H), 1,95-of 1.10 (m, 18H), 2,20-2,02 (m, 2H), 2.95 and (s, 3H), 3,18-to 3.02 (m, 4H), 3,60-to 3.50 (m, 3H), 4,18 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (5):

N-(4-{4-[(4-{benzyl[(butylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenylmethanesulfonyl hydrochloride

TLC: Rf of 0.71 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 0,84-of 0.95 (m, 3H), 1,14-1,50 (m, 4H), 1,86-of 2.09 (m, 4H), 2.95 and (s, 3H), 3,01-of 3.12 (m, 2H), 3,13 (t, J=6.9 Hz, 2H), 3,44-to 3.52 (m, 2H), 4,24 (s, 2H), 4,35 (m, 1H), 4,46 (s, 2H), 7,02 (d, J=9.0 Hz, 2H),? 7.04 baby mortality (d, J=9.0 Hz, 2H), 7,20-7,35 (m, 7H), 7,46 (d, J=9.0 Hz, 2H).

Example 23 (6):

N-(4-{4-[(4-{benzyl[(cyclohexylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,70 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1,02-of 1.40 (m, 6H), 1,52-of 2.08 (m, 8H), 2.95 and (s, 3H), 3,02-3,13 (m, 2H), 3,44-of 3.60 (m, 3H), 4,22 (s, 2H), 4,39 (m, 1H), 4,43 (s, 2H), 7,02 (d, J=9.0 Hz, 2H),? 7.04 baby mortality (d, J=9.0 Hz, 2H), 7,20 was 7.36 (m, 7H), 7,46 (d, J=9.0 Hz, 2H).

Example 23 (7):

N-(4-{4-[(4-{benzyl[(ethylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf is 0.42 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1,02-of 1.13(m, 3H), 1,84-of 2.08 (m, 4H), 2.95 and (s, 3H), 3.00 and-of 3.12 (m, 2H), 3.15 and 3.21-in(m, 2H), 3,42-to 3.52 (m, 2H), 4,23 (s, 2H), 4,32 (m, 1H), 4,46 (s, 2H), 7,01 (d, J=9.0 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,20-7,34 (m, 7H), 7,46 (d, J=8.7 Hz, 2H).

Example 23 (8):

N-{4-[4-({4-[[(cyclohexylamino)carbonyl](2-methoxyethyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.55 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1,12-of 1.44 (m, 6H), 1,54 and 2.13 (m, 8H), 2.95 and (s, 3H), 3,02-3,14 (m, 2H), 3,28 is 3.40 (m, 2H), 3,37 (s, 3H), 3,42-to 3.58 (m, 5H), of 4.13 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (9):

hydrochloride 4-[({[1-(4-{4-[(methylsulphonyl)aminophenoxy}-benzyl)-4-piperidinyl]amino}carbonyl)amino]benzoic acid

TLC: Rf of 0.30 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 1,71-to 1.82 (m, 2H), 2.21 are of 2.26 (m, 2H), 2,96 (s, 3H), 2,99-3,17 (m, 2H), 3,52 is 3.57 (m, 2H), 3,84 (m, 1H), 4,30 (s, 2H), 7.03 is-was 7.08 (m, 4H), 7,30 (d, J=8.6 Hz, 2H), 7,47 (d, J=8.6 Hz, 2H), 7,51 (d, J=8.6 Hz, 2H), to $ 7.91 (d, J=8.6 Hz, 2H).

Example 23 (10):

N-[4-(4-{[4-(2,4-dioxo-1,4-dihydro-3(2H)-hintline)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,62 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1.93 and-of 1.97 (m, 2H), 2.95 and (s, 3H), 2,96-3,30 (m, 4H), 3,55-3,59 (m, 2H), or 4.31 (s, 2H), 5,19 (m, 1H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,13 (m, 1H), 7,22 (m, 1H), 7,29 (d, J=8.7 Hz, 2H,), to 7.50 (d, J=8.7 Hz, 2H), 7,63 (m, 1H), 8,02 (m, 1H).

Example 23 (11):

N-{4-[4-({4-[(anilinoacrolein)(butyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.71 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,30-1,45 (m, 2H), 1,54-of 1.66 (m, 2H), 1,94-2,04 (m, 2H), 2,14 of-2.32 (m, 2H), 2.95 and (s, 3H), 3,05-3,18 (m, 2H), 3,24-to 3.34 (m, 2H), 3,51-3,63 (m, 2H), 4,19 (m, 1H), 4,29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7.23 percent-7,34 (m, 7H), 7,51 (d, J=8.7 Hz, 2H).

Example 23 (12):

N-[4-(4-{[4-(butyl{[(2-phenylethyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.75 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ of 0.90 (t, J=7.2 Hz, 3H), 1,20-of 1.46 (m, 4H), 1,84-of 1.93 (m, 2H), 2.00 in to 2.18 (m, 2H), and 2.79 (t, J=7.2 Hz, 2H), 2.95 and (s, 3H), 2,99-of 3.12 (m, 4H), 3,39 (t, J=7.2 Hz, 2H), 3,48 is 3.57 (m, 2H), 4,06 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,13-7,27 (m, 5H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

P the emer 23 (13):

N-[4-(4-{[4-(butyl{[(4-forfinal)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,78 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,33-1,44 (m, 2H), 1,55-of 1.66 (m, 2H), 1,94-2,02 (m, 2H), 2,14-of 2.30 (m, 2H), 2.95 and (s, 3H), 3.04 from-3,14 (m, 2H), 3,22-of 3.32 (m, 2H), 3,52-3,62 (m, 2H), 4,17 (m, 1H), 4,29 (s, 2H), 6,97-was 7.08 (m, 6H), 7,27-7,33 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (14):

N-[4-(4-{[4-(butyl{[(2,5-dimetilfenil)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,79 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 0,99 (t, J=7.2 Hz, 3H), of 1.34 to 1.48 (m, 2H), 1.60-to 1,71 (m, 2H), 1,95-2,04 (m, 2H), 2,14-of 2.30 (m, 2H), 2,16 (s, 3H), and 2.27 (s, 3H), 2.95 and (s, 3H), 3.04 from-and 3.16 (m, 2H), 3,24-to 3.34 (m, 2H), 3,52-of 3.60 (m, 2H), to 4.15(m, 1H), 4,28 (s, 2H), 6,91-7,10 (m, 7H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (15):

N-[4-(4-{[4-(benzyl{[(4-forfinal)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,82 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1,94-of 2.20 (m, 4H), 2.95 and (s, 3H), 3,02-3,14 (m, 2H), 3,44-3,55 (m, 2H), 4,25 (s, 2H), 4,36 (m, 1H), with 4.64 (s, 2H), 6,97 (d, J=8.7 Hz, 2H), 7,02 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7.24 to 7,41 (m, 9H), 7,46 (d, J=8.7 Hz, 2H).

Example 23 (16):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2-methoxyethyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.50 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1,98-of 2.08 (m, 2H), 2,10-of 2.26 (m, 2H), 2.95 and (s, 3H), 3,02-3,18 (m, 2H), 3,47 (s, 3H), 3,44-3,4 (m, 6H), 4,14 (m, 1H), 4,29 (s, 2H), 6,98-7,06 (m, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,22-7,28 (m, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (17):

N-{4-[4-({4-[butyl({[3-(methylsulfanyl)phenyl]amino}-carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,73 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,33 of 1.46 (m, 2H), 1,54-of 1.66 (m, 2H), 1.93 and-2,04 (m, 2H), 2,14-of 2.24 (m, 2H), 2,46 (s, 3H), 2.95 and (s, 3H), 3.04 from-3,18 (m, 2H), 3,24-to 3.34 (m, 2H), 3,48-of 3.60 (m, 2H), 4.16 the (m, 1H), the 4.29 (s, 2H), 6,76 (m, 1H), 7,00-7,22 (m, 7H), 7,30 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (18):

N-{4-[4-({4-[benzyl({[3-(methylsulfanyl)phenyl]amino}-carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,76 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1,90-2,02 (m, 2H), 2,04-of 2.20 (m, 2H), 2,43 (s, 3H), 2.95 and (s, 3H), 3.00 and is 3.15 (m, 2H), 3,42-of 3.54 (m, 2H), 4,23(s, 2H), 4,36 (m, 1H), of 4.66 (s, 2H), 6,92 (m, 1H), 7,03 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=to 8.7 Hz, 2H), 7,15 (d, J=7.8 Hz, 2H), 7,25-7,39 (m, 9H), was 7.45 (d, J=8.7 Hz, 2H).

Example 23 (19):

N-[4-(4-{[4-(butyl{[(2-chloro-6-were)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,77 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), of 1.34 to 1.48 (m, 2H), 1,65 is 1.75 (m, 2H), 1,96-to 2.06 (m, 2H), 2,16 of-2.32 (m, 2H), and 2.26 (s, 3H), 2.95 and (s, 3H), 3.04 from-and 3.16 (m, 2H), 3,26-to 3.34 (m, 2H), 3,51-of 3.60 (m, 2H), 4.16 the (m, 1H), to 4.28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,14-7,21 (m, 2H), 7,28-7,31 (m, 3H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (20):

N-(4-{4-[(4-{butyl[(mesiti is amino)carbonyl]amino}piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,77 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,34 of 1.46 (m, 2H), 1,61-of 1.73 (m, 2H), 1,94-2,04 (m, 2H), 2,13-of 2.30 (m, 2H), 2,15 (s, 6H), of 2.23 (s, 3H), 2.95 and (s, 3H), 3.04 from-and 3.16 (m, 2H), 3,24-of 3.32 (m, 2H), 3,52-of 3.60 (m, 2H), to 4.15 (m, 1H), 4,28 (s, 2H), 6.87 in (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (21):

N-{4-[4-({4-[{[(3-acetylphenyl)amino]carbonyl}(butyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,79 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,33-of 1.45 (m, 2H), 1,55 by 1.68 (m, 2H), 1,96-to 2.06 (m, 2H), 2,15 of-2.32 (m, 2H), 2,58 (s, 3H), 2.95 and (s, 3H), 3,06-3,19 (m, 2H), of 3.25 to 3.35 (m, 2H), 3,53-3,62 (m, 2H), 4,19 (m, 1H), 4,30 (s, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,41 (t, J=8.0 Hz, 1H), 7,50 (d, J=8.7 Hz, 2H), 7.62mm (DDD, J=8,0, 2,1, 1.2 Hz, 1H), 7,68 (DDD, J=8.0 a, 1,5, 1.2 Hz, 1H), 8,00 (m, 1H).

Example 23 (22):

N-{4-[4-({4-[[(benzylamino)carbonyl](butyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,73 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ were 0.94 (t, J=7.2 Hz, 3H), 1,26-of 1.40 (m, 2H), 1,47 is 1.60 (m, 2H), 1,87-to 1.98 (m, 2H), 2.06 to of 2.21 (m, 2H), 2.95 and (s, 3H), 3,02-3,18 (m, 4H), 3,49-3,59 (m, 2H), 4,15 (m, 1H),4,27 (s, 2H) 4,36 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (J=8.7 Hz, 2H), 7.23 percent-7,31 (m, 7H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (23):

N-{4-[4-({4-[[(1-adamantylamine)carbonyl](3-hydroxybutyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,66 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ of 1.18 (d, J=6.3 Hz, 3H), 1,38 of 1.50 (m, 2H) 1,64 and 1.80 (m, 7H), 1,80-of 1.94 (m, 2H), 1,95-2,12 (m, 10H), 2.95 and (s, 3H), 3.00 and-of 3.54 (m, 4H), 3,48 is 3.57 (m, 2H), 3,74 (m, 1H), 4,12 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (24):

N-[4-(4-{[4-(butyl{[(2-cyclohexylethyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf value of 0.52 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 0,85-1,02 (m, 2H), 1,13-1,58 (m, 10H), 1.61 of and 1.80 (m, 5H), 1,83-of 1.95 (m, 2H), 2,03-2,19 (m, 2H), 2.95 and (s, 3H), 3,02-3,13 (m, 6H), 3,48-to 3.58 (m, 2H), 4,14 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (25):

N-[4-(4-{[4-({[(2-cyclohexylethyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf is 0.24 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.85 to 1.00 (m, 2H), 1,10-1,40 (m, 7H), 1.60-to of 1.78 (m, 6H), 2,08-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,02-3,18 (m, 4H), 3,45-3,55 (m, 2H), and 3.72 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (26):

N-{4-[4-({4-[{[(2-cyclohexylethyl)amino]carbonyl}-(methyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.29 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ from 0.84 to 1.00 (m, 2H), 1,15-of 1.44 (m, 7H), 1.60-to of 1.78 (m, 6H), 1,97 and 2.13 (m, 2H), 2,74 (s, 3H), 2.95 and (s, 3H), 3,03-3,20 (m, 4H), 3,51-of 3.60 (m, 2H), 4,28 (s, 2H),4,30(m, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (27):

N-{4-[4-({4-[{[(2-cyclohexylethyl)amino]carbonyl}-ethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.57 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,84-a 1.01 (m, 2H), 1,12 (t, J=6.9 Hz, 3H), 1,08-of 1.45 (m, 6H), 1,58 and 1.80 (m, 5H), 1.85 to was 1.94 (m, 2H), 1,97-to 2.18 (m, 2H), 2.95 and (s, 3H), 3,02-3,14 (m, 6H), 3,48-3,59 (m, 2H), 4,20 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (28):

N-{4-[4-({4-[{[(2-cyclohexylethyl)amino]carbonyl}-(propyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,69 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.5 Hz, 3H), of 0.82 to 1.00 (m, 2H), 1,15-of 1.40 (m, 6H), 1,42 and 1.80 (m, 6H), 1,80-2,20 (m, 5H), 2.95 and (s, 3H), 2,98-up 3.22 (m, 6H), 3,42-to 3.58 (m, 2H), 4,12 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,30 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (29):

N-{4-[4-({4-[{[(2-cyclohexylethyl)amino]carbonyl}(2-methoxyethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.64 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.85 to 1.00 (m, 2H), 1,08-of 1.40 (m, 6H), 1,60-1,80 (m, 5H), 1,87-to 2.18 (m, 4H), 2.95 and (s, 3H), 3,02-3,18 (m, 2H), 3.15 in (t, J=6.2 Hz, 2H), 3,29-to 3.38 (m, 2H),on 3.36 (s, 3H), 3.45 points is 3.57 (m, 4H), 4,08 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H).

Example 23 (30):

N-[4-(4-{[4-(benzyl{[(2-cyclohexylethyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,73 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,78 with 0.93 (m, 2H), 1,02-of 1.33 (m, 6H), 1.56 to to 1.70 (m, 5H), 1.85 to 2,03 (m, 4H), 2.95 and (s, 3H), 2,98-3,20 (m, 4H), 3,42-of 3.53 (m, 2H), 4,23 (s, 2H), 4,36 (m, 1H), 4,4 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,15-7,38 (m, 7H), was 7.45 (d, J=8.7 Hz, 2H).

Example 23 (31):

N-{4-[4-({4-[{[(2-cyclohexylethyl)amino]carbonyl}-(cyclohexylmethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.71 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,83 by 1.12 (m, 4H), 1,15-of 1.41 (m, 10H), of 1.52 and 1.80 (m, 10H), 1,87-of 1.95 (m, 2H), 2,18-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,02-3,14 (m, 4H), 3,17 (t, J=6.2 Hz, 2H), 3,48 is 3.57 (m, 2H), 3,91 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (32):

N-[4-(4-{[4-(butyl{[(cyclohexylmethyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,69 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 0,82-of 1.05 (m, 2H), 1,14-of 1.42 (m, 5H), 1,43 is 1.58 (m, 3H), 1,62-of 1.81 (m, 5H), 1.85 to to 1.98 (m, 2H), 1,99-2,22 (m, 2H), 2.95 and (s, 3H), 2,99 (d, J=6,9 Hz, 2H), 3,02-3,17 (m, 4H), 3,48-of 3.60 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (33):

N-[4-(4-{[4-({[(cyclohexylmethyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.48 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,83-1,02 (m, 2H), 1,12-of 1.33 (m, 4H), 1,58 and 1.80 (m, 6H), 2,03 (m, 1H), 2,09-2,11 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 4H), 3,50-to 3.58 (m, 2H), and 3.72 (m, 1H), 4,27 (s, 2H), 7,03 (d, J =8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (34):

N-{4-[4-({4-[{[(cyclohexylmethyl)amino]carbonyl}-(methyl)amino]-1-p is pyridinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf value of 0.52 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,81 of 1.00 (m, 2H), 1,13-of 1.32 (m, 4H), to 1.48 (m, 1H), 1.60-to 1,90 (m, 6H), 1.93 and-a 2.12 (m, 2H), 2,75 (s, 3H), 2.95 and (s, 3H), 2,98 (d, J=6,9 Hz, 2H), 3.04 from-3,19 (m, 2H), 3,49-of 3.60 (m, 2H), 4,28 (s, 2H), 4,33 (m, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (35):

N-{4-[4-({4-[{[(cyclohexylmethyl)amino]carbonyl} (ethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.55 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,83 is 0.99 (m, 2H), 1.14 in (t, J=6.9 Hz, 3H), 1,08-of 1.32 (m, 2H), 1,47 (m, 1H), 1.60-to to 1.79 (m, 6H), 1,86-of 1.95 (m, 2H), 2.00 in 2,17 (m, 2H), 2.95 and (s, 3H), 2,98 (DD, J=7,2, 2.0 Hz, 2H), 3,02-of 3.25 (m, 4H), 3,49-to 3.58 (m, 2H), 4,22 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (36):

N-{4-[4-({4-[{[(cyclohexylmethyl)amino]carbonyl}-(propyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,59 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.2 Hz, 3H), 0,83 is 0.99 (m, 2H), 1,10-of 1.33 (m, 4H), of 1.40 and 1.80 (m, 7H), 1,85 is 1.96 (m, 2H), 2,02-of 2.20 (m, 2H), 2.95 and (s, 3H), 2,98 (d, J=7.2 Hz, 2H), 3.00 and-3,17 (m, 4H), 3,50-to 3.58 (m, 2H), 4,14 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (37):

N-{4-[4-({4-[{[(cyclohexylmethyl)amino]carbonyl}(2-methoxyethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.57 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.85 to 1.00 (m, 2H), 1,15-1,35 (m, 3H), USD 1.43 (m, 1H), 1,63 and 1.80 (m, 5H), 1,8-to 2.18 (m, 4H), 2.95 and (s, 3H), 2.95 points (d, J=6.6 Hz, 2H), 3,02 is 3.15 (m, 2H), 3.25 to to 3.38 (m, 2H), on 3.36 (s, 3H), 3.46 in-to 3.58 (m, 4H), 4,10 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=to 8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (38):

N-[4-(4-{[4-(benzyl{[(cyclohexylmethyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 070 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,72-of 0.85 (m, 2H), 1,08-of 1.40 (m, 4H), 1,50-1,79 (m, 5H), 1,90-of 2.08 (m, 4H), 2.95 and (s, 3H), 2,96 (d, J=6,9 Hz, 2H), 3,02-3,17 (m, 2H), 3,44 of 3.56 (m, 2H), 4,24 (s, 2H), to 4.38 (m, 1H), 4,46 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,20-7,38 (m, 7H), 7,46 (d, J=8.7 Hz, 2H).

Example 23 (39):

N-[4-(4-{[4-((cyclohexylmethyl){[(cyclohexylmethyl)amino]-carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf 0,72 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,82-of 1.05 (m, 4H), 1,13-of 1.35 (m, 6H), of 1.46 (m, 1H), 1.60-to of 1.85 (m, 11H), 1,87-to 1.98 (m, 2H), 2,15-2,31 (m, 2H), 2.95 and (s, 3H), 2,98 (d, J=6.6 Hz, 2H), 2,94-3,13 (m, 4H), 3,50-3,59 (m, 2H), with 3.89 (m, 1H), 4.26 deaths (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,30 (d, J=8.7 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H).

Example 23 (40):

N-{4-[4-({4-[[(cyclohexylamino)carbonyl](ethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.44 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 1.12 (t, J=7.0 Hz, 3H), 1,07 was 1.43 (m, 5H), 1,59 is 1.96 (m, 7H), 1,97-to 2.18 (m, 2H), 2.95 and (s, 3H), 3,03-3,26 (m, 4H), 3,48-3,61 (m, 3H), is 4.21 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=to 8.7 Hz, 2H), 7,30 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (41):

N-{4-[-({4-[(anilinoacrolein)(ethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.56 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 1.23 (t, J=7.0 Hz, 3H), 1,94-2,04 (m, 2H), 2,10-to 2.29 (m, 2H), 2.95 and (s, 3H), 3,05-3,19 (m, 2H), 3,38 (kV, J=7,0 Hz, 2H), 3,52-3,61 (m, 2H), 4,25 (m, 1H), 4,30 (s, 2H),? 7.04 baby mortality (d, J =8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7.24 to 7,38 (m, 7H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (42):

N-{4-[4-({4-[[(benzylamino)carbonyl](ethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf value of 0.52 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 1.16 (t, J=7.0 Hz, 3H), 1,89-of 1.97 (m, 2H), 2,02-to 2.18 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 2H), 3,25 (kV, J=7,0 Hz, 2H), 3,50-to 3.58 (m, 2H), 4,21 (m, 1H), 4,28 (s, 2H), 4,36 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7.18 in-7,30 (m, 7H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (43):

N-[4-(4-{[4-(ethyl{[(2-phenylethyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.67 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 1.06 a (t, J=7.0 Hz, 3H), 1,84-of 1.93 (m, 2H), 1,98-of 2.15 (m, 2H), and 2.79 (t, J=7.5 Hz, 2H), 2.95 and (s, 3H), 3,01-3,20 (m, 4H), to 3.38 (t, J=7.5 Hz, 2H), 3,50-3,59 (m, 2H), 4,19 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,12-7,33 (m, 7H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (44):

N-(4-{4-[(4-{ethyl[(ethylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.20 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 1.09 (t, J=7.2 Hz, 3H), of 1.13 (t, J=7.2 Hz, 3H), 1.85 to 1,95 (m, 2H), 1,98-to 2.18 (m, 2H), 2.95 and (s, 3H), 3,03-3,24 (m, 6H), 3,50-3,59 (m, 2H), 4,21 (m, 1H), 4,29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,30 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (45):/p>

N-{4-[4-({4-[[(tert-butylamino)carbonyl](ethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,41 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 1.13 (t, J=7.2 Hz, 3H), of 1.33 (s, 9H), 1,82-of 1.93 (m, 2H), 1,95-2,11 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 2H), 3,18 (t, J=7.2 Hz, 2H), 3,49-3,59 (m, 2H), 4,22 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (46):

N-{4-[4-({4-[[(butylamino)carbonyl](ethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.37 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.93 (t, J=7.2 Hz, 3H), of 1.13 (t, J=7.0 Hz, 3H), 1,26-of 1.40 (m, 2H), 1,42-and 1.54 (m, 2H), 1.85 to a 1.96 (m, 2H), 1,98-of 2.15 (m, 2H), 2.95 and (s, 3H), 3,02-3,24 (m, 6H), 3,49-to 3.58 (m, 2H), 4,21 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (47):

N-{4-[4-({4-[[(cyclohexylamino)carbonyl](propyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.67 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.93 (t, J=7.2 Hz, 3H), 1,13-of 1.41 (m, 5H), 1,48-to 1.67 (m, 3H), 1,71-of 1.92 (m, 6H), 2,03-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,03-3,14 (m, 4H), 3,50-3,59 (m, 3H), 4,10 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (48):

N-{4-[4-({4-[(anilinoacrolein)(propyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,73 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,59-1,72 (m, 2H), 1,95-to 2.06 (m, 2H) 2,15-2,31 (m, 2H), 2.95 and (s, 3H), 3,05-3,18 (m, 2H), 3,22-of 3.32 (m, 2H), 3,52-3,61 (m, 2H), 4,18 (m, 1H), 4,29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7.23 percent-7,37 (m, 7H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (49):

N-{4-[4-({4-[[(benzylamino)carbonyl](propyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,74 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.0 Hz, 3H), 1,50-of 1.66 (m, 2H), 1,87-to 1.98 (m, 2H), 2,04-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 4H), 3,49-to 3.58 (m, 2H), 4,14 (m, 1H), 4,27 (s, 2H), 4,36 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,15-to 7.32 (m, 7H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (50):

N-{4-[4-({4-[{[(2-phenylethyl)amino]carbonyl}(propyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,72 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.85 (t, J=7.2 Hz, 3H), 1,38-is 1.51 (m, 2H), 1,84-of 1.93 (m, 2H), 2.00 in 2,19 (m, 2H), 2,75-2,82 (m, 2H), 2.95 and (s, 3H), 2,94 is 3.15 (m, 4H), 3.33 and-to 3.41 (m, 2H), 3,48-to 3.58 (m, 2H), 4,11 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,13-7,31 (m, 7H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (51):

N-{4-[4-({4-[[(ethylamino)carbonyl](propyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.56 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.0 Hz, 3H), of 1.09 (t, J=7.2 Hz, 3H), 1,46 is 1.60 (m, 2H), 1,86-of 1.95 (m, 2H), 2,03-2,19 (m, 2H), 2.95 and (s, 3H), 3.00 and-up 3.22 (m, 6H), 3,50-3,59 (m, 2H), 4,13 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=to 8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (52):

N-{4-[4-({4-[[(tert-butylamino)carbonyl](propyl)amino]-1-piperidinyl}methyl)fenoc and]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,68 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.2 Hz, 3H), of 1.32 (s, 9H), 1,47-to 1.61 (m, 2H), 1,84-of 1.94 (m, 2H), 1,95-2,11 (m, 2H), 2.95 and (s, 3H), 3,01 is 3.15 (m, 4H), 3,50 is 3.57 (m, 2H), 4.16 the (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (53):

N-{4-[4-({4-[[(butylamino)carbonyl](propyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,74 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.5 Hz, 3H), of 0.92 (t, J=7.5 Hz, 3H), 1,27-of 1.39 (m, 2H), 1.41 to to 1.59 (m, 4H), 1.85 to a 1.96 (m, 2H), 2,03-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,02-up 3.22 (m, 6H), 3,50-to 3.58 (m, 2H), 4,13 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (54):

N-(4-{4-[(4-{butyl[(pentylamine)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,69 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.2 Hz, 3H), of 0.95 (t, J=7.2 Hz, 3H), 1,23-of 1.41 (m, 6H), 1,44 is 1.58 (m, 4H), 1,86-of 1.95 (m, 2H), 2,03-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,02-3,17 (m, 6H), 3,48-to 3.58 (m, 2H), 4,14 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (55):

N-(4-{4-[(4-{benzyl[(pentylamine)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.71 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,86 (t, J=7.2 Hz, 3H), 1,10-1,50 (m, 6H), 1,88-of 2.09 (m, 4H), 2.95 and (s, 3H), 3,01-3,17 (m, 2H), 3,13 (t, J=7,0 Hz, 2H), 3,44-to 3.52 (m, 2H), 4,24 (s, 2H), 4,35 (m, 1H), 4,46 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,20 was 7.36 (m, 7H), was 7.45 (d, J=8.7 Hz, 2H).

Example 23 (56):

N-(4-{4-[(4-{(2-methoxyethyl)[(pentylamine)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.29 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.0 Hz, 3H), 1,22-to 1.38 (m, 4H), 1.41 to and 1.54 (m, 2H), 1,87-2,19 (m, 4H), 2.95 and (s, 3H), 3,02-and 3.16 (m, 2H), 3,11 (t, J=7,0 Hz, 2H), 3,28-to 3.38 (m, 2H), on 3.36 (s, 3H), 3.45 points-to 3.58 (m, 4H), 4,10 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (57):

N-(4-{4-[(4-{butyl[(isopropylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.65 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.2 Hz, 3H), of 1.13 (d, J=6.6 Hz, 6H), 1,28-of 1.40 (m, 2H), 1,43-of 1.57 (m, 2H), 1.85 to a 1.96 (m, 2H), 2,02-2,19 (m, 2H), 2.95 and (s, 3H), 3,03 is 3.15 (m, 4H), 3,48-to 3.58 (m, 2H), 3,91 (m, 1H), 4,13 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (58):

N-(4-{4-[(4-{benzyl[(isopropylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,70 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 1.05 (d, J=6.6 Hz, 6H), 1,86 is 2.10 (m, 4H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 2H), 3,44-of 3.53 (m, 2H), 3,91 (m, 1H), 4,24 (s, 2H), 4,35 (m, 1H), 4,47 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H,), 7,21-7,39 (m, 7H), 7,46 (d, J=8.7 Hz, 2H).

Example 23 (59):

N-{4-[4-({4-[[(butylamino)carbonyl](2-methoxyethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.33 (ethyl acetate:meta is ol=10:1);

NMR (CD3OD): δ of 0.93 (t, J=7.2 Hz, 3H), 1,26-is 1.51 (m, 4H), 1,87-to 1.98 (m, 2H), 2.00 in to 2.18 (m, 2H), 2.95 and (s, 3H), 3,01-and 3.16 (m, 2H), 3,12 (t, J=7,0 Hz, 2H), 3,28-3,37 (m, 2H), on 3.36 (s, 3H), 3.45 points - to 3.58 (m, 4H), 4,10 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (60):

N-[4-(4-{[4-({[(2-methoxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0.39 to (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1,66-of 1.73 (m, 2H), 2,22-of 2.26 (m, 2H), 2.95 and (s, 3H), is 3.08-3,17 (m, 2H), 3,51-3,55 (m, 2H), 3,80 (m, 1H), 3,86 (s, 3H), 4,29 (s, 2H), 6,86 (m, 1H), 6,94 (m, 2H),? 7.04 baby mortality (d, J=9.0 Hz, 2H), 7,07 (d, J=9.0 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,49 (d, J=9.0 Hz, 2H), of 7.96 (m, 1H).

Example 23 (61):

N-[4-(4-{[4-({[(3-methoxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.30 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1,67-to 1.79 (m, 2H), 2,20-of 2.24 (m, 2H), 2,96 (s, 3H), is 3.08-and 3.16 (m, 2H), 3,51-3,55 (m, 2H, in), 3.75 (s, 3H), 3,81 (m, 1H), 4,29 (s, 2H), 6,56 (m, 1H), PC 6.82 (m, 1H), 7,02-7,16 (m, 6H), 7,30 (d, J=9.0 Hz, 2H), 7,50 (d, J=9.0 Hz, 2H).

Example 23 (62):

N-[4-(4-{[4-({[(4-methoxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0.25 in (methylene chloride:methanol=10:1);

NMR (d6-DMSO): δ of 1.66 and 1.75 (m, 2H), 1,99-of 2.23 (m, 2H), 2,97 (s, 3H), 2,97 was 3.05 (m, 2H), 3,31-to 3.35 (m, 2H), to 3.64 (m, 1H), to 3.67 (s, 3H), 4,22 (d, J=4,8 Hz, 2H), 6,38 (user d, J=7.2 Hz, 1H), 6,79 (d, J=9.0 Hz, 2H), 7,03 (d, J=9.0 Hz, 2H), 7,06 (d, J=9.0 Hz, 2H), 7,25 (d, J=9.0 Hz, 2H), 7,26 (d, J=9.0 Hz, 2H), 7,55 (d, J=9.0 Hz, 2H), 8,24 (s, H), to 9.70 (s, 1H).

Example 23 (63):

N-(4-{4-[(4-{[(cyclohexylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.25 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 1,06-of 1.41 (m, 5H), 1,53-of 1.88 (m, 6H), for 2.01 (m, 1H), 2,09-to 2.18 (m, 2H), 2.95 and (s, 3H), 3,02-of 3.12 (m, 2H), 3,40-3,55 (m, 3H), and 3.72 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (64):

N-{4-[4-({4-[(anilinoacrolein)amino]-1-piperidinyl}-methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0.26 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 1,64-1,89 (m, 2H), 2,10-of 2.25 (m, 2H), 2.95 and (s, 3H), 3,03-of 3.25 (m, 2H), 3,36 is 3.57 (m, 2H), 3,85 (m, 1H), 4,29 (s, 2H), 6,97 (t, J=7.5 Hz, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,20-7,38 (m, 6H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (65):

N-(4-{4-[(4-{butyl[(cyclopropylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf and 0.46 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,42-0,50 (m, 2H), 0,62 is 0.71 (m, 2H), of 0.93 (t, J=7.2 Hz, 3H), of 1.23 to 1.37 (m, 2H), 1.41 to 1,53 (m, 2H), 1,84 is 1.96 (m, 2H), 2,04-of 2.23 (m, 2H), of 2.51 (m, 1H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 4H), 3,49-3,59 (m, 2H,), 4.09 to (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (66):

N-(4-{4-[(4-{butyl[(cyclobutylamine)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.58 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,26-of 1.41 (m, 2H), 1,44-of 1.56 (m, 2H), 1,60-1,3 (m, 2H), 1,84-of 2.30 (m, 8H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 4H), 3,48-3,59 (m, 2H), 4,10 (m, 1H), 4,20 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=to 8.7 Hz, 2H).

Example 23 (67):

N-(4-{4-[(4-{butyl[(cyclopentylamine)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.60 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ were 0.94 (t, J=7.2 Hz, 3H), of 1.25 to 1.76 (m, 10H), 1.85 to to 1.98 (m, 4H), 2,02-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,02-and 3.16 (m, 4H), 3,48-3,59 (m, 2H), a 4.03 (m, 1H), 4,14 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (68):

N-(4-{4-[(4-{butyl[(tetrahydro-2H-Piran-4-ylamino)-carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)-methanesulfonamide hydrochloride

TLC: Rf 0.31 in (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,26-of 1.64 (m, 6H), 1,72-of 1.95 (m, 4H), 2,03-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,02-3,17 (m, 4H), 3,38-3,59 (m, 4H), of 3.78 (m, 1H), 3,86-of 3.96 (m, 2H), 4,13 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (69):

N-(4-{4-[(4-{butyl[(cyclohexylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.67 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ were 0.94 (t, J=7.2 Hz, 3H),1.26 in-1,72 (m, 14H), 1,78-of 1.94 (m, 4H), 2,03-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,02-and 3.16 (m, 4H), 3,49-3,59 (m, 2H), 3,74 (m, 1H), 4,14 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (70):

N-{4-[4-({4-[(anilinoacrolein)(pentyl)amino]-1-Pipa is idini}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,76 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ to 0.92 (t, J=7.2 Hz, 3H), 1,28-of 1.44 (m, 4H), 1,55 was 1.69 (m, 2H), 1.93 and-2,04 (m, 2H), 2,12-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,03-3,18 (m, 2H), 3,23-of 3.32 (m, 2H), 3,51-of 3.60 (m, 2H), 4,19 (m, 1H), 4,29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,22-to 7.35 (m, 5H), 7,41 (d, J=7.5 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (71):

N-{4-[4-({4-[[(cyclohexylamino)carbonyl](pentyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,78 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (t, J=7.2 Hz, 3H), 1,12-of 1.41 (m, 9H), 1,46-of 1.93 (m, 9H), 2,02-2,19 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 4H), 3,48-of 3.60 (m, 3H), of 4.13 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=to 8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (72):

N-(4-{4-[(4-{allyl[(cyclohexylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,74 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 1,08-of 1.42 (m, 6H), 1,55-2,12 (m, 8H), 2.95 and (s, 3H), 3,03-and 3.16 (m, 2H), 3,47-3,59 (m, 3H), 3,81 (d, J=5.0 Hz, 2H), 4,27 (s, 2H), 4,32 (m, 1H), 5,18 (DD, J=a 10.5, 1.5 Hz, 1H), 5,20 (DD, J=20,2, 1.5 Hz, 1H), of 5.83 (DDD, J=20,2, to 10.5, 5.0 Hz, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (73):

N-(4-{4-[(4-{2-butenyl[(cyclohexylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.75 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 1,15 was 1.43 (m, 5H), 1.77 in (t, J=2,4 Hz, 3H), 1,58 is 2.00 (m, 7H), 2.05 is-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,03-3,18 (m, 2H), 3,50-3,62 (m, 3H), 3,92 (d, J=2.4 Hz, 2H), 4,23 (m, 1H) 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (74):

N-(4-{4-[(4-{butyl[(propylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.71 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.89 (t, J=7.2 Hz, 3H), were 0.94 (t, J=7.2 Hz, 3H), 1,26-of 1.41 (m, 2H), 1,45 is 1.58 (m, 4H), 1.85 to 1,95 (m, 2H), 2,04-2,22 (m, 2H), 2.95 and (s, 3H), 3,03-and 3.16 (m, 6H), 3,48-3,59 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (75):

N-(4-{4-[(4-{pentyl[(propylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,73 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.89 (t, J=7.2 Hz, 3H), of 0.92 (t, J=7.0 Hz, 3H), 1,23-of 1.40 (m, 4H), 1,44-to 1.59 (m, 4H), 1.85 to 1,95 (m, 2H), 2,03-of 2.21 (m, 2H), 2.95 and (s, 3H), 3.04 from is 3.15 (m, 6H), 3,49-to 3.58 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (76):

N-{4-[4-({4-[[(butylamino)carbonyl](pentyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.75 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.91 (d, J=7.2 Hz, 3H), of 0.92 (t, J=7.2 Hz, 3H), 1,24-of 1.41 (m, 6H), 1,43-to 1.59 (m, 4H), 1.85 to a 1.96 (m, 2H), 2,03-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,03-3,20 (m, 6H), 3,49-to 3.58 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (77):

N-{4-[4-({4-[[(butylamino)carbonyl](cyclohexylmethyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}means ltname hydrochloride

TLC: Rf 0,74 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ to 0.92 (t, J=7.2 Hz, 3H), or 0.83 to 1.00 (m, 2H), 1,15-of 1.80 (m, 13H), 1,87-to 1.98 (m, 2H), 2.13 and of-2.32 (m, 2H), 2.95 and (s, 3H), 3.00 and-3,17 (m, 6H), 3,48 is 3.57 (m, 2H), with 3.89 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (78):

N-(4-{4-[(4-{butyl[(hexylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,72 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.89 (t, J=7.2 Hz, 3H), were 0.94 (t, J=7.2 Hz, 3H), 1,22-of 1.39 (m, 8H), 1.41 to and 1.56 (m, 4H), 1.85 to was 1.94 (m, 2H), 2,03-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,02-3,19 (m, 6H), 3,49-to 3.58 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (79):

N-(4-{4-[(4-{pentyl[(pentylamine)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.71 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.90 (t, J=7.2 Hz, 3H), of 0.92 (t, J=7.2 Hz, 3H), 1,23-of 1.40 (m, 8H), 1,44 is 1.60 (m, 4H), 1,86-of 1.95 (m, 2H), 2,03-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,02-3,20 (m, 6H), 3,49-to 3.58 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (80):

N-(4-{4-[(4-{benzyl[(tert-butylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,69 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 1.18 (s, 9H), 1,90-of 2.09 (m, 4H), 2.95 and (s, 3H), 3,05-3,17 (m, 2H), 3,47 of 3.56 (m, 2H), 4.26 deaths (s, 2H), 4,42 (s, 2H), of 4.45 (m, 1H), 7,02 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7.23 percent-7,39 (m, 7H), 7,49 (d, J=8.7 Hz, 2H).

the example 23 (81):

N-[4-(4-{[4-({[(2-hydroxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.53 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 1.65-1.77 in (m, 2H), 2,20-of 2.25 (m, 2H), 2.95 and (s, 3H), of 3.07-3.15 in (m, 2H), 3,50-3,55 (m, 2H), 3,81 (m, 1H), 4,29 (s, 2H), 6,72-6,85 (m, 3H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=to 8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H), 7,69 (m, 1H).

Example 23 (82):

N-[4-(4-{[(3aR,6aS)-5-{butyl[(cyclohexylamino)carbonyl]-amino}of hexahydrotriazine[c]pyrrol-2(1H)-yl]methyl}-phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.50 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0.88 to 1.00 and (m, 3H), 1,14-of 1.84 (m, 16H), 2,00-2,22 (m, 2H), 2,70-with 3.79 (m, 9H), 2.95 and (s, 3H), 4,08 (m, 1H), 4,35 (m, 2H), 7,00-7,10 (m, 4H), 7,22-7,34 (m, 2H), 7,45-7,58 (m, 2H).

Example 23 (83):

N-[4-(4-{[4-(butyl{[(2-methoxyethyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.27 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,27-of 1.41 (m, 2H), 1,45-to 1.59 (m, 2H), 1,87-of 1.97 (m, 2H), 2,03-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 4H), to 3.33 (s, 3H), 3,32-to 3.36 (m, 2H), 3,40-3,47 (m, 2H), 3,51-to 3.58 (m, 2H,), 4,14 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (84):

N-[4-(4-{[4-(butyl{[(4-hydroxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.64 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H)and 1.3 (m, 2H), 1,62 (m, 2H), 1,92 (m, 2H), 2,22 (m, 2H), 2.95 and (s, 3H), 3,18 (m, 2H), 3,25 (m, 2H), 3,52 (m, 2H), 4,14 (m, 1H), 4,27 (s, 2H), 6,68-of 6.78 (m, 2H), 7,00-7,10 (m, 6H), 7.24 to 7,34 (m, 2H), 7,49 (user. d, J=8,4 Hz, 2H).

Example 23 (85):

N-[4-(4-{[4-(butyl{[(3-hydroxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.64 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.96 (t, J=7.5 Hz, 3H), of 1.39 (m, 2H), 1,60 (m, 2H), up to 1.98 (m, 2H), of 2.21 (m, 2H), 2.95 and (s, 3H), 3,11 (m, 2H), or 3.28 (m, 2H), to 3.58 (m, 2H), 4,18 (m, 1H), 4,28 (s, 2H), 6.48 in (m, 1H), 6,78 (m, 1H), at 6.84 (m, 1H), 7,0 0-7,12 (m, 5H), 7,22-7,40 (m, 2H), 7,50 (user. d, J=8.7 Hz, 2H).

Example 23 (86):

N-[4-(4-{[4-({[(4-hydroxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.44 (chloroform:methanol=5:1);

NMR (CD3OD): δ to 1.70 (m, 2H), 2,19 (m, 2H), 2.95 and (s, 3H), is 3.08 (m, 2H), 3,48 (m, 2H), 3,78 (m, 1H), 4,25 (s, 2H), 6,62-of 6.78 (m, 2H), 7,00 was 7.36 (m, 8H), 7,47 (user. d, J=8,4 Hz, 2H).

Example 23 (87):

N-[4-(4-{[4-({[(3-hydroxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.51 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 1.52 (m, 2H), 1,95 (m, 2H), 2,24 (m, 2H), 2,89 (m, 2H), 2,93 (s, 3H), of 3.56 (s, 2H), 3,60 (m, 1H), 6,39 (m, 1H), of 6.71 (m, 1H), 6.90 to-was 7.08 (m, 5H), 7.18 in-7,38 (m, 5H).

Example 23 (88):

N-[4-(4-{[4-(butyl{[(4-methoxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,71 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,26-,44 (m, 2H), 1,52 and 1.80 (m, 6H), 2,28 (m, 2H), 2,93 (s, 3H), to 3.02 (m, 2H), up 3.22 (m, 2H), 3,54 (s, 2H, in), 3.75 (s, 3H), Android 4.04 (m, 1H), 6,80-to 6.88 (m, 2H), 6.90 to-7,02 (m, 4H), 7.18 in-7,38 (m, 6H).

Example 23 (89):

N-{4-[4-({4-[butyl({[4-(trifluoromethyl)phenyl]amino}carbonyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf to 0.78 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1.32 to 1,50 (m, 2H), 1,53 by 1.68 (m, 2H), 1,94-to 2.06 (m, 2H), 2,08-of 2.34 (m, 2H), 2.95 and (s, 3H), of 3.12 (m, 2H), 3,32 (m, 2H), to 3.58 (m, 2H), 4,18 (m, 1H), 4,30 (s, 2H), 7,00 for 7.12 (m, 4H), 7,22-7,38 (m, 2H), 7,42-of 7.60 (m, 6H).

Example 23 (90):

N-{4-[4-({4-[(aminocarbonyl)(butyl)amino]-1-piperidinyl}-methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.15 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,27-of 1.42 (m, 2H), 1,50-to 1.63 (m, 2H), 1,81-2,02 (m, 2H), 2,11-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,05-is 3.21 (m, 4H), 3,51-of 3.60 (m, 2H), 4,13 (m, 1H), 4,29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,52 (d, J=8.7 Hz, 2H).

Example 23 (91):

N-[4-(4-{[4-(butyl{[(4-hydroxycyclohexyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf to 0.19 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,27-of 1.41 (m, 2H), 1,45-to 1.79 (m, 10H), 1,86-of 1.95 (m, 2H), 2,03-2,22 (m, 2H), 2.95 and (s, 3H), 3,02-3,17 (m, 4H), 3,48-the 3.65 (m, 3H), a 3.87 (m, 1H), 4,15 (m, 1H), 4,29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (92):

N-[4-(4-{[4-(butyl{[(2-forfinal)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]means honami hydrochloride

TLC: Rf 0,73 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,32 is 1.48 (m, 2H), 1,58-1,72 (m, 2H), 1,95-to 2.06 (m, 2H), 2,14 is 2.33 (m, 2H), 2.95 and (s, 3H), 3,03-3,18 (m, 2H), of 3.25 to 3.35 (m, 2H), 3,52-3,61 (m, 2H), 4,17 (m, 1H), 4,29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,10-to 7.18 (m, 3H), 7,29 (d, J=8.7 Hz, 2H), 7,45 (dt, J=2,4, 7.2 Hz, 1H), 7,51 (d, J=8.7 Hz, 2H).

Example 23 (93):

N-[4-(4-{[4-(butyl{[(3-forfinal)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,73 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,33 of 1.46 (m, 2H), 1,54-to 1.67 (m, 2H), 1.93 and e 2.06 (m, 2H), 2,15 of-2.32 (m, 2H), 2.95 and (s, 3H), 3,05-3,18 (m, 2H), 3,26-to 3.35 (m, 2H), 3,52-3,62 (m, 2H), 4,18 (m, 1H), 4,29 (s, 2H), 6,74 (dt, J=2,4, 8,1 Hz, 1H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,12 (d, J=4.0 Hz, 1H), 7,20-7,31 (m, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H).

Example 23 (94):

N-(4-{4-[(4-{butyl[(4-pyridinylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.53 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 2,00-2,10 (m, 2H), 2,30-to 2.40 (m, 2H), 2.95 and (s, 3H), 3,10-3,30 (m, 2H), 3,40-to 3.50 (m, 2H), 3,50-3,60 (m, 2H), 4,30 (m, 1H), or 4.31 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8.6 Hz, 2H), 7,54 (d, J=8.6 Hz, 2H), of 8.09 (d, J=7.5 Hz, 2H), of 8.47 (d, J=7.5 Hz, 2H).

Example 23 (95):

N-(4-{4-[(4-{butyl[(3-pyridinylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.50 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 2,0 is 2.10 (m, 2H), 2,30-to 2.40 (m, 2H), 2.95 and (s, 3H), 3,10-3,30 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,70 (m, 2H), 4,30 (m, 1H), or 4.31 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,53 (d, J=9.0 Hz, 2H), 7,95 (DD, J=8,5 that 2.4 Hz, 1H), 8,43 (d, J=8.5 Hz, 1H), 8,61 (d, J=8.5 Hz, 1H), 9,20 (d, J=2.4 Hz, 1H).

Example 23 (96):

hydrochloride of 2-[({butyl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]amino}carbonyl)amino]benzoic acid

TLC: Rf 0.36 and (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,35-is 1.51 (m, 2H), 1.60-to 1,72 (m, 2H), 1,92-2,04 (m, 2H), 2,16 to 2.35 (m, 2H), 2.95 and (s, 3H), is 3.08-3,11 (m, 2H), 3,23-to 3.35 (m, 2H), 3,52-3,63 (m, 2H), 4,22 is 4.36 (m, 3H), 7,02 (t, J=7.8 Hz, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (dt, J=1,8, and 7.8 Hz, 1H), 7,54 (d, J=8.7 Hz, 2H), with 8.05 (DD, J=7,8, 1.8 Hz, 1H), 8,42 (d, J=7.8 Hz, 1H).

Example 23 (97):

hydrochloride 3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]amino}carbonyl)amino]benzoic acid

TLC: Rf of 0.30 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 0.95 (t, J=7.5 Hz, 3H), 1.30 and the 1.44 (m, 2H), 1,53-of 1.64 (m, 2H), 1,90-2,03 (m, 2H), 2,20-of 2.38 (m, 2H), 2.95 and (s, 3H), 3,05-3,19 (m, 2H), 3.25 to to 3.36 (m, 2H), 3,49-3,59 (m, 2H), 4,23 (m, 1H), 4,29 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), was 7.36 (t, J=7.8 Hz, 1H), 7,53 (d, J=8.7 Hz, 2H), 7,60 (DDD, J=7,8, 2,4, 1.8 Hz, 1H), 7,69 (dt, J=7,8, and 2.4 Hz, 1H), 8,04 (t, J=1.8 Hz, 1H).

Example 23 (98):

hydrochloride 4-[({butyl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]amino}carbonyl)amino]benzoic acid

TLC: Rf 0.34 in (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,33 of 1.46 (m, H), 1,54-of 1.66 (m, 2H), 1,94-2,05 (m, 2H), 2,20-of 2.38 (m, 2H), 2.95 and (s, 3H), 3,06-3,20 (m, 2H), 3.25 to 3,37 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7.29 trend (d, J=8.7 Hz, 2H), 7,49 (d, J=8.5 Hz, 2H), 7,52 (d, J=8.7 Hz, 2H), 7,92 (d, J=8.5 Hz, 2H).

Example 23 (99):

hydrochloride [({butyl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]amino}carbonyl)amino]acetic acid

TLC: Rf 0,41 (methylene chloride:methanol=4:1);

NMR (CD3OD): δ were 0.94 (t, J=7.2 Hz, 3H), 1,27-of 1.41 (m, 2H), 1,48-of 1.62 (m, 2H), 1,84-of 1.95 (m, 2H), 2,08-of 2.26 (m, 2H), 2.95 and (s, 3H), 2,98-3,18 (m, 4H), 3,44-of 3.53 (m, 2H), 3,80 (s, 2H), 4,15 (m, 1H), 4,25 (s, 2H), 7,02 (d, J=8.7 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,53 (d, J=8.7 Hz, 2H).

Example 23 (100):

N-{4-[4-({4-[[(cyclohexylamino)carbonyl](3-hydroxypropyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1,10-1,50 (m, 6H), 1,60-1,80 (m, 4H), 1,80-2,00 (m, 4H), 2.00 in of 2.20 (m, 2H), 2.95 and (s, 3H), 3.00 and is 3.15 (m, 2H), 3,20-3,30 (m, 2H), 3,40-3,70 (m, 5H), 4,10 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), of 7.48 (d, J=9.0 Hz, 2H).

Example 23 (101):

N-{4-[4-({4-[[(cyclohexylamino)carbonyl](4-hydroxybutyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,42 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1,10-1,40 (m, 6H), 1,40-1,70 (m, 5H), 1.70 to 2,00 (m, 6H), 2.00 in of 2.20 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 4H), 3,50-3,60 (m, 2H)and 3.59 (t, J=6.0 Hz, 2H), 4,10 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8,8 Hz, 2H), 7,07 (d, J=8,8 Hz, 2H), 7,29 (d, J=8,8 Hz, 2H), of 7.48 (d, J=8,8gts, 2H).

Example 23 (102):

N-{4-[4-({4-[[(cyclohexylamino)carbonyl](3-hydroxybutyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1,10-1,50 (m, 6H), of 1.17 (d, J=6.3 Hz, 3H), 1.70 to 2,00 (m, 9H), 2.00 in of 2.20 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 4H), 3,50-3,60 (m, 2H), 3,70 (m, 1H), 4,10 (m, 1H), 4,27 (s, 2H), 7,02-7,07 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,50 (d, J=8,9 Hz, 2H).

Example 23 (103):

N-{4-[4-({4-[[(cyclohexylamino)carbonyl](2-hydroxybutyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.44 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,10-2,20 (m, 16H), to 2.99 (s, 3H), of 3.10-3.20 (m, 4H), 3,40-of 3.60 (m, 4H), 4,10 (m, 1H), 4,27 (s, 2H), 7,01-was 7.08 (m, 4H), 7,28-7,31 (m, 2H), of 7.48 (d, J=8.7 Hz, 2H).

Example 23 (104):

hydrochloride 4-[({butyl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]amino}carbonyl)amino]butane acid

TLC: Rf 0,73 (methylene chloride:methanol=4:1);

NMR (CD3OD): δ of 0.95 (t, J=7.5 Hz, 3H), 1,28-of 1.41 (m, 2H), 1,44-to 1.59 (m, 2H), 1,74-of 1.85 (m, 2H), 1,87-of 1.97 (m, 2H), 2,03-of 2.20 (m, 2H), 2,31 (t, J=6.9 Hz, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 4H), 3,20 (t, J=6.9 Hz, 2H), 3,50-to 3.58 (m, 2H), 4,13 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (105):

N-[4-(4-{[4-(butyl{[(4-chlorophenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.53 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,96 (t, J7,2 Hz, 3H), 1,30-1,40 (m, 2H), 1,55-1,60 (m, 2H), 1,95-2,00 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 7,01-was 7.08 (m, 4H), 7.23 percent-7,40 (m, 6H), 7,51 (d, J=8,4 Hz, 2H).

Example 23 (106):

N-[4-(4-{[4-(butyl{[(3-chlorophenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.53 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,40 (m, 2H), 1,55-1,65 (m, 2H), 1,95-2,05 (m, 2H), 2,20-of 2.30 (m, 2H), 2,96 (s, 3H), of 3.10-3.20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,29 (s, 2H), 7,00-to 7.09 (m, 5H), 7.23 percent-7,31 (m, 4H), of 7.48-7,51 (m, 3H).

Example 23 (107):

N-[4-(4-{[4-(butyl{[(2-chlorophenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.53 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,99 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 2,00-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 7,02-7,10 (m, 4H), 7,14 (DD, J=7,5, 1.5 Hz, 1H), 7,27-7,31 (m, 3H), 7,42 (DD, J=7,5, 1.5 Hz, 1H), 7,50 (d, J=8,4 Hz, 2H), 7,63 (DD, J=7,5, 1.5 Hz, 1H).

Example 23 (108):

N-[4-(4-{[4-(butyl{[(4-were)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.53 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,40 (m, 2H), 1,55-1,65 (m, 2H), 1,95-2,05 (m, 2H), 2,20-of 2.30 (m, 2H), 2,28 (s, 3H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,20-3,30 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), the 4.29 (s, 2H), 7,02-7,10 (m, 6H), 7,19 (d, J=8,4 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,50 (d, J=9.0 Hz, 2H).

Example 23 (109):

N-[4(4-{[4-(butyl{[(3-were)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf is 0.59 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2,30 (s, 3H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), the 4.29 (s, 2H), 6.87 in (d, J=6,6 Hz, 1H), 7,01-to 7.15 (m, 7H), 7,29 (d, J=8,9 Hz, 2H), 7,50 (d, J=8,9 Hz, 2H).

Example 23 (110):

N-[4-(4-{[4-(butyl{[(2-were)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.50 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2,22 (s, 3H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,14 (m, 1H), to 4.28 (s, 2H), 7,02-to 7.15 (m, 7H), 7,19 (m, 1H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (111):

N-[4-(4-{[4-(butyl{[(3-methoxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.53 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,30-1,40 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 3,76 (s, 3H), 4,15 (m, 1H), the 4.29 (s, 2H), 6,63 (m, 1H), 6,91 (m, 1H), 7,01-was 7.08 (m, 5H), 7,16 (m, 1H), 7,29 (d, J=8,9 Hz, 2H), 7,50 (d, J=8,9 Hz, 2H).

Example 23 (112):

N-[4-(4-{[4-(butyl{[(2-methoxyphenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.55 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 1.02 (t, J=7.4 Hz, 3H), of 1.40-1.50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), and 3.8 (s, 3H), 4.26 deaths (m, 1H), 4,29 (s, 2H), 6.89 in (m, 1H), 6,99-was 7.08 (m, 6H), 7,29 (d, J=8.7 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H), 7,76 (DD, J=7,8, 1.5 Hz, 1H).

Example 23 (113):

N-{4-[4-({4-[butyl({[3-(trifluoromethyl)phenyl]amino}-carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.55 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 7,02-was 7.08 (m, 4H), 7,27-7,31 (m, 3H), 7,45 (m, 1H), 7,51 (d, J=8.7 Hz, 2H), 7,60 (d, J=8,4 Hz, 1H), 7,78 (s, 1H).

Example 23 (114):

N-[4-(4-{[4-({[(4-hydroxycyclohexyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf to 0.19 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1,52-1,72 (m, 9H), for 2.01 (m, 1H), 2,10-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,02-3,14 (m, 2H), 3,47-3,62 (m, 3H), and 3.72 (m, 1H), 3,78 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7.29 trend (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (115):

hydrochloride of 2-[({butyl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)-4-piperidinyl]amino}carbonyl)amino]-4-methylpentanoic acid

TLC: Rf 0.39 to (methylene chloride:methanol=4:1);

NMR (CD3OD): δ 0,93 (d, J=6.0 Hz, 6H), of 0.95 (t, J=7.5 Hz, 3H), 1,28-of 1.42 (m, 2H), 1,48-to 1.79 (m, 5H), 1,82-of 1.95 (m, 2H), 1,97-2,19 (m, 2H), 2.95 and (s, 3H), 2,90 was 3.05 (m, 2H), is 3.08-of 3.25 (m, 2H), 3,42-to 3.52 (m, 2H), 4,13 (m, 1H), 4,19 (s, 2H), 4,32 (DD, J=9,0, 6.0 Hz, 1H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,28 (d, J=8.7 Hz, 2H), 7,47 (d, J=8.7 Hz, 2H).

Example 23 (116):

N-{3-[({butyl[1-(4-{4-[(metals Lionel)amino]phenoxy}-benzyl)-4-piperidinyl]amino}carbonyl)amino]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.32 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 2,96 (s, 3H), 3,05-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,23 (m, 1H), the 4.29 (s, 2H), 6.90 to (m, 1H), 6,99-was 7.08 (m, 4H), 7,11 (m, 1H), 7,22 (t, J=8,1 Hz, 1H), 7,29 (d, J=9.0 Hz, 2H), 7,38 (t, J=2.1 Hz, 1H), 7,53 (d, J=9.0 Hz, 2H).

Example 23 (117):

N-{4-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)-4-piperidinyl]amino}carbonyl)amino]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.50 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2,90 (s, 3H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), the 4.29 (s, 2H), 7,02-was 7.08 (m, 4H), 7,18 (t, J=9.0 Hz, 2H), 7,28-7,33 (m, 4H), 7,55 (d, J=9.0 Hz, 2H).

Example 23 (118):

N-[4-(4-{[4-(butyl{[(3-hydroxypropyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,70 (methylene chloride:methanol=4:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,26-of 1.41 (m, 2H), 1,45 is 1.58 (m, 2H), 1,65-to 1.77 (m, 2H), 1,86-of 1.97 (m, 2H), 2,03-2,22 (m, 2H), 2.95 and (s, 3H), 3,03 is 3.15 (m, 4H), of 3.27 (t, J=6.3 Hz, 2H)and 3.59 (t, J=6.3 Hz, 2H), 3,50-the 3.65 (m, 2H), 4,14 (m, 1H), 4,25 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (119):

N-[4-(4-{[4-({[(3-hydroxypropyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.32 (methylene chloride:methanol=4:1);

NMR (CD3OD): δ 1.60-to of 1.84 (m, 3H), 2,02 (m, 1H), 2,09-of 2.20 (m, 2), 2,95 (s, 3H), 3,02 is 3.15 (m, 2H), 3,20 (t, J=6.5 Hz, 2H), 3,45-3,61 (m, 2H), only 3.57 (t, J=6.5 Hz, 2H), and 3.72 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (120):

N-(4-{4-[(4-{butyl[(3-thienylene)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0.31 in (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,05-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 7,02-7,11 (m, 5H), 7,18 (t, J=3.3V, 1.5 Hz, 1H), 7,25-7,31 (m, 3H), 7,51 (d, J=8.7 Hz, 2H).

Example 23 (121):

N-(4-{4-[(4-{butyl[(2-thienylene)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide

TLC: Rf 0.31 in (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.4 Hz, 3H), 1,30-1,40 (m, 2H), 1,50-1,60 (m, 2H), 1,60-1,80 (m, 2H), 1,80-1,90 (m, 2H), 2,10-of 2.20 (m, 2H), 2.91 in (s, 3H), 2.95 and was 3.05 (m, 2H), 3,20-3,30 (m, 2H), 3,51 (s, 2H), 4.00 points (m, 1H), of 6.65 (m, 1H), 6,77-6,79 (m, 2H), 6,92-of 6.96 (m, 4H), 7,21-7,24 (m, 2H), 7,31 (d, J=8.7 Hz, 2H).

Example 23 (122):

N-(4-{4-[(4-{butyl[(2,3-dihydro-1,4-benzodioxin-6-ylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)-methanesulfonamide hydrochloride

TLC: Rf of 0.40 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.4 Hz, 3H), 1,30-1,40 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,20 (s, 4H), to 4.28 (s, 2H), 6,72 (s, 2H), 6,85 (t, J=1.4 Hz, 1H), 7,02-7,11 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), of 7.48 (d, J=8,9 Hz, 2H).

Example 23 (123):

N-[4-(4-{[4(butyl{[(3,5-differenl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.40 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,30-1,40 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,30 (s, 2H), 6,55 (m, 1H), 7,02-7,11 (m, 6H), 7,29 (d, J=8,4 Hz, 2H), 7,51 (d, J=8,4 Hz, 2H).

Example 23 (124):

N-[4-(4-{[4-(butyl{[(3,4-differenl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.44 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,30-1,40 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,29 (s, 2H), 7,02-7,16 (m, 6H), 7,29 (d, J=8.6 Hz, 2H), 7,40 (m, 1H), 7,55 (d, J=8.6 Hz, 2H).

Example 23 (125):

N-[4-(4-{[4-(butyl{[(1-oxido-3-pyridinyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,69 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ of 0.96 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,30-to 2.40 (m, 2H), 2.95 and (s, 3H), 3,10-3,30 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), or 4.31 (s, 2H), 4,35 (m, 1H), 7,02-7,07 (m, 4H), 7,29 (d, J=8.6 Hz, 2H), 7,55 (d, J=8.6 Hz, 2H) 7,88 (DD, J=8,9, 3.5 Hz, 1H), 8,39 (d, J=2.7 Hz, 1H), and 8.50 (d, J=2.7 Hz, 1H), 9,39 (s, 1H).

Example 23 (126):

N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.58 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-340 (m, 2H), 3,50-3,60 (m, 2H), 4,17 (m, 1H), 4,29 (s, 2H), 6,92-7,00 (m, 2H), 7,02-was 7.08 (m, 4H), 7,26-7,41 (m, 3H), 7,49-7,52 (m, 2H);

amorphous;

softening temperature: about 196-198°C.

Example 23 (127):

N-{4-[4-({4-[{[(4-bromophenyl)amino]carbonyl}(butyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.57 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.4 Hz, 3H), 1,30-1,40 (m, 2H), 1,50-1,60 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,05-3,20 (m, 2H), 3,20-3,30 (m, 2H), 3,50-3,60 (m, 2H), 4,19 (m, 1H), 4,29 (s, 2H), 7,02-was 7.08 (m, 4H), 7,27-7,31 (m, 4H), 7,39 (d, J=8.7 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H).

Example 23 (128):

N-(4-{4-[(4-{butyl[(isobutylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.51 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 0.87 (d, J=6.6 Hz, 6H), of 0.95 (t, J=7.4 Hz, 3H), 1,30-1,40 (m, 2H), 1,50-1,60 (m, 2H), 1,76 (m, 1H), 1,80-2,00 (m, 2H), 2.00 in of 2.20 (m, 2H), 2,96 (s, 3H), 2,96 (d, J=7.5 Hz, 2H), 3.00 and is 3.40 (m, 4H), 3,50-of 3.60 (m, 2H), 4.16 the (m, 1H), 4,28 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,50 (d, J=8,9 Hz, 2H).

Example 23 (129):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(3-methyl-2-butenyl)amino]-1-piperidinyl}methyl)phenoxy]-phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,62 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 1.75 (s, 6H), 1,92-2,03 (m, 2H), 2,07-of 2.23 (m, 2H), 2.95 and (s, 3H), 3,05-3,19 (m, 2H), 3,50-3,60 (m, 2H), 3,94-was 4.02 (m, 2H), 4,20 is 4.35 (m, 3H), by 5.18 (m, 1H), 6,98-7,10 (m, 6H), 7,26 -7,34 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (130):

N-[4-(4-{[4-(3-butenyl{[(4-forfinal)amino]carbonyl}amino)-1-PI is original]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,61 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,97 is 2.10 (m, 2H), 2,19-of 2.20 (m, 2H), 2,43 (m, 1H), 2,49-of 2.58 (m, 2H), 2.95 and (s, 3H), 3,02-3,19 (m, 2H), 3.46 in-3,61 (m, 4H), 4,08 (m, 1H), 4,29 (s, 2H), 6,98-7,10 (m, 6H), 7,26-7,34 (m, 4H), 7,50 (d, J=8,7 Hz, 2H).

Example 23 (131):

N-[4-(4-{[4-(3-butenyl{[(4-forfinal)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,61 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,95-to 2.06 (m, 2H), 2,15 is 2.44 (m, 4H), 2.95 and (s, 3H), 3,03-3,18 (m, 2H), 3,28-to 3.41 (m, 2H), 3,50-3,61 (m, 2H), 4,13 (m, 1H), 4,29 (s, 2H), 5,08 (d, J=10,2 Hz, 1H), 5,14 (d, J=17,1 Hz, 1H), 5,86 (m, 1H), 6,98-7,10 (m, 6H), 7,26-7,35 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (132):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2-hydroxybutyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,59 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 1.02 (t, J=7.5 Hz, 3H), 1,44 is 1.60 (m, 2H), 1,95-of 2.28 (m, 4H), 2.95 and (s, 3H), 3,01-to 3.36 (m, 4H), 3,47-of 3.60 (m, 2H), 3,66 (m, 1H), 4,10 (m, 1H), 4,28 (s, 2H), 6,98-7,10 (m, 6H), 7,22-7,34 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (133):

N-{4-[4-({4-[[(1,3-benzodioxol-5-ylamino)carbonyl](butyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.29 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,40 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,00 (m, 2H), 2,10-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,05-3,20 (m, 2H), 3,20-3,30 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,29 (s, 2H), 5,90 (s, 2H), 6,70-of 6.71 (m, 2H), 6.89 in (d, J=1.8 Hz, 1H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (134)

N-[4-(4-{[4-((4-terbisil){[(4-forfinal)amino]-carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf is 0.59 (chloroform:methanol=9:1);

NMR (CD3OD): δ 7,46 (user. d, J=8,4 Hz, 2H), 7,40-7,24 (m, 6H), 7,14-to 6.80 (m, 8H), to 4.62 (s, 2H), 4,32 (m, 1H), 4,24 (s, 2H), 3,48 (m, 2H), 3,06 (m, 2H), 2.95 and (s, 3H), 2,20-of 1.88 (m, 4H).

Example 23 (135):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2-methoxybenzyl)amino]-1-piperidinyl}methyl)phenoxy]-phenyl}methanesulfonamide hydrochloride

TLC: Rf and 0.62 (chloroform:methanol=9:1);

NMR (CD3OD): δ 7,45 (user. d, J=8.7 Hz, 2H), 7,30-7,19 (m, 6H), 7,16-of 6.90 (m, 8H), 4,59 (s, 2H), 4,32 (m, 1H), 4,23 (s, 2H), 3,88 (s, 3H), 3,47 (m, 2H), is 3.08 (m, 2H), 2.95 and (s, 3H), 2,18-of 1.88 (m, 4H).

Example 23 (136):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2-methylbenzyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.68 (chloroform:methanol=9:1);

NMR (CD3OD): δ 7,45 (user. d, J=8.7 Hz, 2H), 7,30-7,10 (m, 8H), 7,08-of 6.90 (m, 6H), 4,56 (s, 2H), 4,43 (m, 1H), 4,24 (s, 2H), 3,49 (m, 2H), of 3.07 (m, 2H), 2.95 and (s, 3H), of 2.35 (s, 3H), 2,16 is 1.86 (m, 4H).

Example 23 (137):

N-[4-(4-{[4-(butyl{[(3-hydroxy-4-were)amino]-carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf is 0.42 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,20-1,40 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,00 (m, 2H), 2,10-of 2.30 (m, 2H), 2,12 (s, 3H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4.16 the (m, 1H), to 4.28 (s, 2H), only 6.64 (DD, J=8,0, 2.0 Hz, 1H), 6,83 (d, J=2.0 Hz, 1H), 6,94 (d, J=8, Hz, 1H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,4 Hz, 2H), 7,49 (d, J=8,4 Hz, 2H).

Example 23 (138):

N-[4-(4-{[4-(butyl{[(3,5-dihydroxyphenyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.75 (methylene chloride:methanol=5:1);

NMR (d6-DMSO): δ to 0.88 (t, J=7.2 Hz, 3H), 1,20-1,40 (m, 2H), of 1.40-1.50 (m, 2H), 1,70-1,80 (m, 2H), 2,10-of 2.30 (m, 2H), and 3.16 (s, 3H), 3,30 is 3.40 (m, 2H), 3,60-3,90 (m, 4H), 4,14 (m, 1H), 4,22 (d, J=4,8 Hz, 2H), of 5.83 (t, J=2.1 Hz, 1H), 6,37 (d, J=2.1 Hz, 2H), 7,02-was 7.08 (m, 4H), 7,25 (d, J=8.6 Hz, 2H), EUR 7.57 (d, J=8.6 Hz, 2H), 7,88 (s, 1H), 9,71 (s, 1H), 10,51 (s, 1H).

Example 23 (139):

N-[4-(4-{[4-(butyl{[(2-hydroxy-2-methylpropyl)amino]-carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.50 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H)and 1.15 (s, 6H), 1,28-of 1.44 (m, 2H), 1,50-of 1.62 (m, 2H), 1,88-to 1.98 (m, 2H), 2,08 was 2.25 (m, 2H), 2.95 and (s, 3H), 3,02-up 3.22 (m, 6H), 3,50-3,60 (m, 2H), 4.16 the (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (140):

N-[4-(4-{[4-({[(2-hydroxy-2-methylpropyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.15 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 1.15 (s, 6H), 1.60-to of 1.78 (m, 2H), 2.00 in of 2.21 (m, 2H), 2.95 and (s, 3H), 3,01 is 3.15 (m, 4H), 3,44-3,55 (m, 2H), to 3.73 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H ), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (141):

N-[4-(4-{[4-((cyclopropylmethyl){[(4-forfinal)amino]-carbonyl}amino)-1-piperidinyl]IU the Il}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,32 is 0.37 (m, 2H), or 0.57 to 0.63 (m, 2H), 1.06 a (m, 1H), 1,97 is 2.10 (m, 2H), 2,25-to 2.42 (m, 2H), 2.95 and (s, 3H), 3,05-3,18 (m, 2H), 3,25 (d, J=6.6 Hz, 2H), 3,51-3,62 (m, 2H), 4,06 (m, 1H), 4,29 (s, 2H), 6,98-7,10 (m, 6H), 7,27-7,35 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (142):

N-[4-(4-{[4-((cyclobutylmethyl){[(4-forfinal)amino]-carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,75 with 2.14 (m, 8H), 2,23-to 2.40 (m, 2H), 2,62 (m, 1H), 2.95 and (s, 3H), 3,03 is 3.15 (m, 2H), 3,36 (d, J=6,9 Hz, 2H), 3,50-3,60 (m, 2H), 3,95 (m, 1H), 4,28 (s, 2H), 6,98-was 7.08 (m, 6H), 7,27-to 7.32 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (143):

N-(4-{4-[(4-{{[(4-forfinal)amino]carbonyl}[(1-oxido-3-pyridinyl)methyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)-methanesulfonamide hydrochloride

TLC: Rf 0.14 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,98 of-2.32 (m, 4H), 2.95 and (s, 3H), 3,09-is 3.21 (m, 2H), 3,50-3,60 (m, 2H), 4,30 (s, 2H), and 4.40 (m, 1H), 4.72 in (s, 2H), 6,97-7,10 (m, 6H), 7,29 (d, J=8.7 Hz, 2H), 7,37 (DD, J=9,0, 5,1 Hz, 2H), 7,53 (d, J=to 8.7 Hz, 2H), to 7.84 (t, J=7,0 Hz, 1H), 8,08 (d, J=7,0 Hz, 1H), to 8.62 (d, J=7,0 Hz, 1H), 8,69 (s, 1H).

Example 23 (144):

N-[4-(4-{[4-((3-terbisil){[(4-forfinal)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.65 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,47 (m, 2H), 7,40-7,22 (m, 5H), 7,16 (m, 1H), 7,10-of 6.96 (m, 8H)and 4.65 (s, 2H), 4,37 (m, 1H), 4,24 (s, 2H), 3,50 (m, 2H), to 3.09 (m, 2H), 2.95 and (s, 3H), 2,20-1,90 (m, 4H).

Example 23 (145):

N-[4-(4-{[4-((2-forb nil){[(4-forfinal)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.65 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,46 (user. d, J=8.7 Hz, 2H), 7,40-7,22 (m, 6H), 7,20-6,92 (m, 8H), 4,69 (s, 2H), 4,39 (m, 1H), 4,25 (s, 2H), 3,51 (m, 2H), 3,10 (m, 2H), 2.95 and (s, 3H), 2,20-1,89 (m, 4H).

Example 23 (146):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(4-methoxybenzyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,69 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,45 (user. d, J=8.7 Hz, 2H), 7,40-7,20 (m, 6H), 7,10-to 6.88 (m, 8H), of 4.57 (s, 2H), 4,29 (m, 1H), 4,23 (s, 2H), 3,76 (s, 3H), 3,49 (m, 2H), is 3.08 (m, 2H), 2.95 and (s, 3H), 2,22 is 1.86 (m, 4H).

Example 23 (147):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(3-methoxybenzyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,81 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,46 (user. d, J=9.0 Hz, 2H), 7,30-7,20 (m, 5H), 7,08-6,94 (m, 6H), 6,92-6,76 (m, 3H), to 4.62 (s, 2H), 4,35 (m, 1H), 4,24 (s, 2H), of 3.77 (s, 3H), 3,49 (m, 2H), is 3.08 (m, 2H), 2.95 and (s, 3H), 2,20-1,90 (m, 4H).

Example 23 (148):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(3-methylbenzyl)-amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,85 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,47 (user. d, J=9.0 Hz, 2H), 7,34-to 7.18 (m, 6H), 7,16-6,92 (m, 8H), br4.61 (s, 2H), 4,36 (m, 1H), 4,25 (s, 2H), 3,49 (m, 2H), is 3.08 (m, 2H), 2.95 and (s, 3H) 2,32 (s, 3H), 2,22-1,90 (m, 4H).

Example 23 (149):

hydrochloride 4-{{[(4-forfinal)amino]carbonyl}[1-(4-

{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]amino}-butane acid

TLC: Rf0,18 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,82-2,02 (m, 4H), 2,10-of 2.30 (m, 2H), 2,43 (t, J=6.3 Hz, 2H), 2.95 and (s, 3H), 3.04 from-3,18 (m, 2H), of 3.25 to 3.35 (m, 2H), 3,50-3,60 (m, 2H), 4,22 is 4.35 (m, 3H), 7,00 (DD, J=17,1, 9,0 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,42-of 7.55 (m, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 23 (150):

N-[4-(4-{[4-(butyl{[(3,5-dimethyl-4-isoxazolyl)amino]-carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.53 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1.32 to about 1.47 (m, 2H), 1,58 is 1.70 (m, 2H), 1,95-2,03 (m, 2H), 2,12 (s, 3H), and 2.26 (s, 3H), 2,15 was 2.25 (m, 2H), 2.95 and (s, 3H), 3,03-3,17 (m, 2H), 3,21-of 3.32 (m, 2H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,29 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 23 (151):

N-[4-(4-{[4-(butyl{[(6-methyl-3-pyridinyl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide the dihydrochloride

TLC: Rf 0,51 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,31-of 1.45 (m, 2H), 1,57-to 1.67 (m, 2H), 1,97-of 2.08 (m, 2H), 2,22-of 2.38 (m, 2H), 2,70 (s, 3H), 2.95 and (s, 3H), 3,10-of 3.25 (m, 2H), 3,28-to 3.36 (m, 2H), 3,52-3,62 (m, 2H), 4,30 (m, 1H), or 4.31 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,53 (d, J=8.7 Hz, 2H), 7,79 (d, J=8.7 Hz, 1H), 8,49 (DD, J=8,7, 2.7 Hz, 1H), of 9.02 (s, 1H).

Example 24:

N-[4-(4-{[4-(butyl{[(cyclohexylmethyl)amino]-carbonothioyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

To a solution of the compound obtained in example 3 (70 mg)in dimethylformamide (1 ml) is added triethylamine (38 μl). The solution is added dropwise to a solution of cyclohexylmethyl isothiocyanate (43 mg) in dimethylformamide (0.5 ml) and the mixture is stirred for 1 hour. Add water to the reaction mixture, which is extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=10:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (81,9 mg)having the following physical data.

TLC: Rf 0,69 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ from 0.88 to 1.03 (m, 2H), of 0.96 (t, J=7.2 Hz, 3H), 1,14-of 1.44 (m, 5H), 1,47 is 1.60 (m, 2H), 1,62-to 1.82 (m, 6H), 1.93 and-of 2.08 (m, 4H), 2.95 and (s, 3H), 3,05-3,20 (m, 2H), 3,24-to 3.36 (m, 2H), 3,47 (d, J=6.6 Hz, 2H), 3,50-of 3.60 (m, 2H), 4,29 (s, 2H), to 5.66 (m, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H).

Example 24 (1) and example 24 (2)

Using the same procedure as described in example 24, using the appropriate amine derivative instead of the compound obtained in example 3, to obtain compounds of the present invention having the following physical data.

Example 24 (1):

N-[4-(4-{[4-({[(cyclohexylmethyl)amino]carbonothioyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,62 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ from 0.88 to 1.05 (m, 2H), 1,13-of 1.34 (m, 3H), 1,50 of-1.83 (m, 8H), 2,22 to 2.35 (m, 2H), 2.95 and (s, 3H), 3,05-3,18 (m, 2H), 3,21-of 3.42 (m, 2H), 3,47-to 3.58 (m, 2H), 4,28 (s, 2H), 4,42 (m, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H,), to 7.50 (d, J=8.7 Hz, 2H).

Example 24 (2):

N-[4-(4-{[4-(benzyl{[(cyclohexylmethyl)amino]-carbonothioyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.67 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,62-0,78 (m, 2H), and 1.00-1.14 in (m, 3H), 1.30 and of 1.62 (m, 6H), 1,89 and 2.13 (m, 4H), 2.95 and (s, 3H), 3,09-is 3.21 (m, 2H), 3,36 (d, J=6.6 Hz, 2H), 3.45 points of 3.56 (m, 2H), 4,27 (s, 2H), 4,71 (s, 2H), by 5.87 (m, 1H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,17-7,38 (m, 7H), of 7.48 (d, J=8.7 Hz, 2H).

Example 25:

N-[4-(4-{[4-(butyl{[(3-hydroxybutyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

To a solution of (3-{[tert-butyl(dimethyl)silyl]oxy}butyl)amine (72,3 mg) in tetrahydrofuran (1 ml), add triethylamine (97 μl) and triphosgene (to 44.1 mg) under cooling on ice and stirred, and then the solution was stirred at room temperature for 1 hour. A solution of the compound obtained in example 3 (100 mg), and triethylamine (55 μl) in N,N-dimethylformamide (1 ml) is added dropwise to the reaction mixture, which is stirred for 15 minutes. Add saturated aqueous sodium bicarbonate solution to the reaction mixture, which is extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate and concentrate the Ute. Add a solution of 4 N. hydrochloric acid in ethyl acetate to the resulting residue. The reaction mixture is stirred for 15 minutes and concentrated. The organic layer is dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=10:1), and is converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (a 99.6 mg)having the following physical data.

TLC: Rf 0,46 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), 1,26-of 1.41 (m, 2H), 1,44 is 1.70 (m, 4H), 1.85 to of 1.97 (m, 2H), 2.05 is-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,03-3,13 (m, 4H), 3,17-to 3.38 (m, 2H), 3,50-to 3.58 (m, 2H), 3,78 (m, 1H), 4,13 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 25 (1) - example 25 (10)

Using the same procedure as described in example 25, using (3-{[tert-butyl(dimethyl)silyl]oxy}butyl)amine or the corresponding amine derivative and using the compound obtained in example 3, or the corresponding amine derivative gain compounds of the present invention having the following physical data.

Example 25 (1):

N-{4-[4-({4-[butyl({[(1R,2R)-2-hydroxycyclohexyl]amino}-carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.29 (those who acetate:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,23-of 1.42 (m, 6H), 1,47-to 1.61 (m, 2H), 1,65-to 1.77 (m, 2H), 1,88-2,05 (m, 4H), 2.05 is-2,22 (m, 2H), 2.95 and (s, 3H), 3,02-3,20 (m, 4H), 3,34-of 3.48 (m, 2H), 3,50-3,59 (m, 2H), 4,14 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 25 (2):

N-{4-[4-({4-[butyl({[(1S,2S)-2-hydroxycyclohexyl]amino}-carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.29 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,23-of 1.42 (m, 6H), 1,47-to 1.61 (m, 2H), 1,65-to 1.77 (m, 2H), 1,88-2,05 (m, 4H), 2.05 is-2,22 (m, 2H), 2.95 and (s, 3H), 3,02-3,20 (m, 4H), 3,34-of 3.48 (m, 2H), 3,50-3,59 (m, 2H), 4,14 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 25 (3):

N-{4-[4-({4-[({[(1-hydroxycyclohexyl)methyl]amino}-carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.23 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1.26 in is 1.75 (m, 11H), 2,02(m, 1H), 2,10-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,03-and 3.16 (m, 4H), 3,45-3,55 (m, 2H), and 3.72 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 25 (4):

N-{4-[4-({4-[({[(1R,2R)-2-hydroxycyclohexyl]amino}-carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.64 (methylene chloride:methanol=4:1);

NMR (CD3OD): δ 1,12-of 1.40 (m, 4H), 1,59 to 1.76 (m, 3H), 1,88-to 2.06 (m, 3H), 2,11-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,02-3,14 (m, 2H), 3,18-to 3.38 (m, 2H), 3.46 in-3,55 (m, 2H), to 3.73 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (q, j =8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 25 (5):

N-{4-[4-({4-[({[(1S,2S)-2-hydroxycyclohexyl]amino}-carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.64 (methylene chloride:methanol=4:1);

NMR (CD3OD): δ 1,12-of 1.40 (m, 4H), 1,59 to 1.76 (m, 3H), 1,88-to 2.06 (m, 3H), 2,11-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,02-3,14 (m, 2H), 3,18-to 3.38 (m, 2H), 3.46 in-3,55 (m, 2H), to 3.73 (m, 1H), 4,27 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 25 (6):

N-(4-{4-[(4-{butyl[(4-piperidylamine)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf 0.24 to (n-butanol:acetic acid:water=4:2:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,30-1,40 (m, 2H), of 1.40-1.50 (m, 2H), 1,70-1,80 (m, 2H), 1,80-2,00 (m, 2H), 2.00 in of 2.20 (m, 4H), 2.95 and (s, 3H), 3,00-3,20 (m, 6H), 3,30-to 3.50 (m, 2H), 3,50-3,60 (m, 2H), 3,80 (m, 1H), 4,10 (m, 1H), 4,28 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 25 (7):

N-[4-(4-{[4-({[(2-hydroxybutyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.48 (methylene chloride:methanol=4:1);

NMR (CD3OD): δ were 0.94 (t, J=7.2 Hz, 3H), 1.32 to of 1.52 (m, 2H), 1,58 is 1.75 (m, 1,6H), 1,98-of 2.08 (m, 0,4H), 2,10-of 2.20 (m, 2H), 2.95 and (s, 3H), 3.00 and-3,14 (m, 2H), 3,16 is 3.40 (m, 2,6H), 3.45 points-of 3.54 (m, 2,4H), 3,68-of 3.78 (m, 0,8H), 3,90-3,95 (m, 0,2H), 4,27 (s, 1,6H), 4,33 (s, 0,4H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 25 (8):

N-[4-(4-{[4-({[(3-hydroxybutyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanol UNAMID hydrochloride

TLC: Rf of 0.33 (methylene chloride:methanol=4:1);

NMR (CD3OD): δ of 1.16 (d, J=6.3 Hz, 2,4H), of 1.17 (d, J=6.3 Hz, 0,6H), 1,48 is 1.75 (m, 3,6H), 1,98-2,05 (m, 0,4H), 2,10-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,02-3,30 (m, 4H), 3,48-3,55 (m, 2H), 3,65-a 3.83 (m, 2H), 4,27 (, 1,6H), 4,32 (s, 0,4H), 7,03 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 25 (9):

N-[4-(4-{[4-(butyl{[(2-hydroxybutyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.48 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 6H), 1,28-to 1.61 (m, 6H), 1,88-of 1.97 (m, 2H), 2,04-2,22 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 4H), 3,22-of 3.32 (m, 2H), 3,48-3,59 (m, 3H), 4,14 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 25 (10):

N-{4-[4-({4-[butyl({[(1-hydroxycyclohexyl)methyl]-amino}carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.56 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.5 Hz, 3H), 1,27 is 1.70 (m, 14H), 1,88-of 1.97 (m, 2H), 2,04-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,02-3,18 (m, 4H), 3,20 (s, 2H), 3,48-of 3.60 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 26:

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]-1-piperazinecarboxamide hydrochloride

In an argon atmosphere to a solution of the compound obtained in example 3 (50.0 mg)in N,N-dimethylformamide (1 ml) add ritilin (30,0 ml) and piperidine-1-carbonylchloride (13,4 μl) and the solution stirred at 40°C for 12 hours. The reaction mixture was diluted with ethyl acetate. Add water to the reaction mixture, which is extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (chloroform:methanol=7:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (14,9 mg)having the following physical data.

TLC: Rf and 0.61 (chloroform:methanol=5:1);

NMR (CD3OD): δ to 0.92 (t, J=7.5 Hz, 3H), 1,20-1,70 (m, 10H), 1,90-2,05 (m, 2H), 2.06 to 2,24 (m, 2H), 2.95 and (s, 3H), 3,02-3,18 (m, 4H), 3,18-to 3.38 (m, 4H), 3,45-3,62 (m, 3H), 4,27 (s, 2H), 7,00 for 7.12 (m, 4H), 7.24 to 7,34 (m, 2H,), 7,44-7,58 (m, 2H).

Example 26(1)- example 26(4)

Using the same procedure as described in example 26, using the appropriate chloranhydride derived instead piperidine-1-carbonylchloride get compounds of the present invention having the following physical data.

Example 26 (1):

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]-4-morpholinylcarbonyl hydrochloride

TLC: Rf of 0.64 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.93 (t, J=7.2 Hz, 3H), 1,20-1,40 (m, 2H), 1,42-of 1.56 (m, 2H), 1,88-2,02 (m, 2H), 2.06 to 2,30 (m, 2H), 2.95 and (s, 3H), 3,02-and 3.16 (m, 4H), 3,21-to 3.34 (m, 3H), 3,44-3,70 (m, 8H), to 4.23 (s, 2H), 7,00-7,10 (m, 4H), 7,12-7,38 (m, 2H), 7,49 (user. d, J=8.7 Hz, 2H).

Example 26 (2):/p>

N-(4-{4-[(4-{[(dibutylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.55 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.93 (t, J=7.5 Hz, 6H), to 1.31 (m, 4H), for 1.49 (m, 4H), 1.70 to a 1.88 (m, 2H), 2,04 with 2.14 (m, 2H), 2.95 and (s, 3H), is 3.08 (m, 2H), 3,14-to 3.35 (m, 4H), 3,50 (m, 2H), 3,79 (m, 1H), 4,27 (s, 2H), 7,00-7,10 (m, 4H), 7,22-7,34 (m, 2H), 7,49 (user. d, J=8.7 Hz, 2H).

Example 26 (3):

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-4-piperidinyl]-1-pyrrolidinecarboxylic hydrochloride

TLC: Rf to 0.63 (chloroform:methanol=5:1);

NMR (CD3OD): δ to 0.92 (t, J=7.5 Hz, 3H), 1,22-of 1.36 (m, 2H), 1,38-of 1.52 (m, 2H), 1,80-2,02 (m, 6H), 2,04-of 2.24 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 4H), 3,26-to 3.38 (m, 4H), 3,52 (m, 2H), and 3.72 (m, 1H), 4.26 deaths (s, 2H), 7,00-7,10 (m, 4H), 7,22 and 7.36 (m, 2H), 7,42-7,56 (m, 2H).

Example 26 (4):

N-(4-{4-[(4-{butyl[(dibutylamino)carbonyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf is 0.59 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,80-of 1.02 (m, 9H), 1,20-1,60 (m, 12H), 1,92-of 2.20 (m, 4H), 2.95 and (s, 3H), 3.00 and is 3.40 (m, 7H), 3,44-3,68 (m, 4H), 4.26 deaths (2H), 7,00 for 7.12 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), of 7.48 (user. d, J=8,4 Hz, 2H).

Example 27:

N-[4-(4-{[4-({[(benzyloxy)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

While cooling on ice and stirring is added dropwise 1,1'-carbonylbis-1H-imidazole (CDI) (129 mg) in tetrahydrofuran (6.5 ml) to a solution of O-benzylhydroxylamine (100 mg) in tetrahedr is the furan (2.5 ml). After stirring for 30 minutes added N-(4-{4-[(4-aminopiperidin-1-yl)methyl]phenoxy}phenyl)methanesulfonamide (200 mg)obtained by using a method based on example 1, and the solution stirred at 55°C for 24 hours. Add distilled water to the reaction mixture, which is extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:methanol=10:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (144,3 mg)having the following physical data.

TLC: Rf is 0.42 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 1,63-to 1.79 (m, 2H), 1,96-2,07 (m, 2H), 2,96 (s, 3H), 3.00 and-of 3.12 (m, 2H), 3,44-of 3.54 (m, 2H), 3,74 (m, 1H), 4.26 deaths (s, 2H), amounts to 4.76 (s, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,33-the 7.43 (m, 5H), of 7.48 (d, J=8.7 Hz, 2H).

Example 28:

the hydrochloride of 4-(4-{[4-(butyl{[(2,4-differenl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)benzoic acid

N-tert-butoxycarbonylamino-4-one and n-butylamine is subjected to reductive alkylation in acetic acid and dimethylformamide at room temperature using triacetoxyborohydride sodium. The obtained 1-tert-butoxycarbonyl-4-aminopiperidin interacts with ,4-diftorbenzofenonom in dimethylformamide in the presence of triethylamine. With the reaction mixture remove protection using the processing hydrochloric acid to obtain hydrochloride of N-butyl-N'-(2,4-differenl)-N-piperidine-4-rocephine. Using the same procedure as described in example 1, and converting into a cleaners containing hydrochloride salt using a conventional method using N-butyl-N'-(2,4-differenl)-N-piperidine-4-rocephine and 4-(4-formylphenoxy)benzoic acid, receive a connection according to the present invention (48 mg)having the following physical data.

TLC: Rf 0,78 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,36 was 1.43 (m, 2H), 1,60-1,70 (m, 2H), 1,99-2,04 (m, 2H), 2,16-of 2.28 (m, 2H), is 3.08-3,17 (m, 2H), 3,24-3,30 (m, 2H), 3,56-3,61 (m, 2H), 4,15 (m, 1H), 4,32 (s, 2H), 6.90 to-7,05 (m, 2H,), 7,07 (d, J=8.7 Hz, 2H), 7,18 (d, J=8.7 Hz, 2H), 7,37 (m, 1H), 7,56 (d, J=8.7 Hz, 2H), 8,04 (d, J=8.7 Hz, 2H).

Example 28 (1) - example 28 (18)

Using the same procedure as described in example 28, using N-butyl-N'-(2,4-differenl)-N-piperidine-4-rocephine or appropriate piperidinol derivative and using the corresponding aldehyde derivative instead of 4-(4-formylphenoxy)benzoic acid will receive the following data of the compounds of the present invention.

Example 28 (1):

4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl}phenoxy)benzosulfimide hydrochloride

TLC: Rf 0,89 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,36-of 1.45 (m, 2H), 1,59 is 1.70 (m, 2H), 1,99-2,03 (m, 2H), 2,17-of 2.30 (m, 2H), is 3.08-3,17 (m, 2H), 3,23-3,30 (m, 2H), 3,56-of 3.60 (m, 2H), 4,15 (m, 1H), 4,32 (s, 2H), 6.90 to-7,03 (m, 2H), 7,14 (d, J=8.7 Hz, 2H), to 7.18 (d, J=8.7 Hz, 2H), 7,37 (m, 1H), EUR 7.57 (d, J=8.7 Hz, 2H), to $ 7.91 (d, J=8.7 Hz, 2H).

Example 28 (2):

the dihydrochloride of N-butyl-N'-(2,4-differenl)-N-[1-({3,5-dimethyl-1-[1-(methylsulphonyl)piperidine-4-yl]-1H-pyrazole-4-yl}methyl)piperidine-4-yl]urea

TLC: Rf 0,12 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.5 Hz, 3H), 1,33-of 1.45 (m, 2H), 1,59 is 1.70 (m, 2H), 1,98 is 2.01 (m, 4H), 2,12-of 2.30 (m, 4H), of 2.33 (s, 3H), 2,43 (s, 3H), 2,89 (s, 3H), 2,93-a 3.01 (m, 2H), 3,09-3,17 (m, 2H), 3.25 to 3.30 is (m, 2H), to 3.58-3,63 (m, 2H), 3,86-3,90 (m, 2H), 4,19 (s, 2H), 4,19 (m, 1H), 4,39 (m, 1H), 6.89 in-7,03 (m, 2H), 7,37 (m, 1H).

Example 28 (3):

N-(3'-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl}-1,1'-biphenyl-4-yl)methanesulfonamide hydrochloride

TLC: Rf 0,78 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,34-of 1.44 (m, 2H), 1,58 by 1.68 (m, 2H), 1,98 is 2.01 (m, 2H), 2,19 of-2.32 (m, 2H), 2,99 (s, 3H), 3,12-3,30 (m, 4H), to 3.58-3,63 (m, 2H), 4,19 (m, 1H), 4,39 (s, 2H), 6.89 in-7,02 (m, 2H), of 7.36 (d, J=8,4 Hz, 2H), 7,37 (m, 1H), 7,49 (d, J=7.5 Hz, 1H), EUR 7.57 (t, J=7.5 Hz, 1H), 7,68 (d, J=8,4 Hz, 2H), 7,76 (d, J=7.5 Hz, 1H), 7,82 (s, 1H).

Example 28 (4):

N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl} - for 3,5-dimethyl-1H-pyrazole-1-yl)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf of 0.29 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.5 Hz, 3H), 1,36-of 1.44 (m, 2H), 1,60-1,70 (m, 2H), 1,98 is 2.00 (m, 2H), measuring 2.20 to 2.35 (m, 2H), 2,35 (s, 3H), of 2.35 (s, 3H), 3,03 (s, 3H), 3,03-3,13 (m, 2H), 3.27 to 3.30 is (m,2H), to 3.58-3,62 (m, 2H), 4,17 (m, 1H), 4,17 (s, 2H), 6.90 to-7,03 (m, 2H), 7,35-7,45 (m, 5H).

Example 28 (5):

4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl}-N-{4-[(methylsulphonyl)amino]benzyl}-benzamide hydrochloride

TLC: Rf 0.36 and (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.5 Hz, 3H), 1,28-of 1.40 (m, 2H), 1,69-1,89 (m, 4H), 2,11-to 2.18 (m, 2H), 2,92 (s, 3H), 2,96-3,00 (m, 2H), 3,22-3,37 (m, 4H)and 3.59 (s, 2H), was 4.02 (m, 1H), 4.53-in (s, 2H), 6.87 in-7,01 (m, 2H), 7,21 (d, J=8.7 Hz, 2H), 7,33 (d, J=8.7 Hz, 2H), 7,38 (m, 1H), 7,44 (d, J=8,4 Hz, 2H), 7,82 (d, J=8,4 Hz, 2H).

Example 28 (6):

N-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl}phenyl)-2-{4-[(methylsulphonyl)amino]-phenyl}ndimethylacetamide hydrochloride

TLC: Rf 0.26 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,28-of 1.41 (m, 2H), 1,58 was 1.69 (m, 2H), 1,96 is 2.01 (m, 2H), 2,11-of 2.26 (m, 2H), 2,93 (s, 3H), 3,05-3,26 (m, 2H), 3,23-3,26 (m, 2H), 3,53 of 3.56 (m, 2H), to 3.67 (s, 2H), 4,13 (m, 1H), 4.26 deaths (s, 2H), 6.89 in-7,02 (m, 2H), 7,21 (d, J=8.7 Hz, 2H), 7,32 (d, J=8.7 Hz, 2H), 7,38 (m, 1H), 7,46 (d, J=8,4 Hz, 2H), of 7.70(d, J=8,4 Hz, 2H).

Example 28 (7):

N-{4-[(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)piperidine-1-yl]methyl}benzyl)oxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.40 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,34-of 1.42 (m, 2H), 1,55-1,60 (m, 2H), 1,94 is 2.00 (m, 2H), 2,12-of 2.20 (m, 2H), 2,99 (s, 3H), 3,03-of 3.12 (m, 2H), 3,23-of 3.25 (m, 2H), 3,47-3,51 (m, 2H), 4,13 (m, 1H), 4,25 (s, 2H), is 4.85 (s, 2H), of 6.68 (d, J=8.7 Hz, 2H), 6.89 in-7,03 (m, 2H), 7,13 (d, J=8.7 Hz, 2H), was 7.36 (m, 1H), 7,42 (s, 4H).

Example 28 (8):

4-(4-{[4-(butyl{[(2,4-debtor enyl)amino]carbonyl}amino)-piperidine-1-yl]methyl} - for 3,5-dimethyl-1H-pyrazole-1-yl)-N-methylbenzenesulfonamide the dihydrochloride

TLC: Rf of 0.38 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.5 Hz, 3H), 1,36-of 1.44 (m, 2H), 1,63 by 1.68 (m, 2H), 1,97-2,04 (m, 2H), 2,29-of 2.34 (m, 2H), 2,39 (s, 3H), of 2.46 (s, 3H), 2,58 (s, 3H), 3,16-to 3.36 (m, 4H), 3,66-3,70 (m, 2H), 4,23 (m, 1H), 4,27 (s, 2H), 6.89 in-7,03 (m, 2H), 7,38 (m, 1H), 7,73 (d, J=8.7 Hz, 2H), 8,00 (d, J=8.7 Hz, 2H).

Example 28 (9):

N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl}phenoxy)benzyl]methanesulfonamide hydrochloride

TLC: Rf of 0.30 (ethyl acetate);

NMR (CD3OD): δ 0,98 (t, J=7.5 Hz, 3H), 1,33-of 1.45 (m, 2H), 1,59 was 1.69 (m, 2H), 1,98-2,02 (m, 2H), 2,15-of 2.28 (m, 2H), 2,88 (s, 3H), 3,06 is 3.15 (m, 2H), 3,24-3,30 (m, 2H), 3,54-3,59 (m, 2H), 4,14 (m, 1H), 4,24 (s, 2H), to 4.28 (s, 2H), 6.89 in-7,03 (m, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,37 (m, 1H), 7,41 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 28 (10):

N-{4-[(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)methyl]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.27 (ethyl acetate);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,34-of 1.42 (m, 2H), 1.60-to of 1.66 (m, 2H), 1,96 is 2.01 (m, 2H), 2,12-of 2.20 (m, 2H), 2.95 and (s, 3H), 3.04 from-3,11 (m, 2H), 3,23-3,30 (m, 2H), 3,52 of 3.56 (m, 2H), 4,12 (m, 1H), 4,24 (s, 2H), at 5.10 (s, 2H), 6,86-7,03 (m, 2H), 7,10 (d, J=8.7 Hz, 2H), 7,25 (d, J=8.7 Hz, 2H), was 7.36 (m, 1H), 7,41 (d, J=8.7 Hz, 2H), 7,42 (d, J=8.7 Hz, 2H).

Example 28 (11):

N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl}phenoxy)phenyl]ndimethylacetamide hydrochloride

TLC: Rf 0.28 in (ethyl acetate);

NMR (CD3OD): δ 0,98 (t, J=7.5 Hz, 3H), 1,35-1,45 (m, 2H), 1,58 was 1.69 (m, 2H), 1,98-2,02 (m, 2H), 2,12 (s, 3H), 2,15-of 2.27 (m, 2H), 3,06-3,14 (m, 2H), 3,24-3,30 (m, 2H), 3,54 to 3.5 (m, 2H), 4,14 (m, 1H), 4,28 (s, 2H), 6.89 in-7,03 (m, 2H), 7,00 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), was 7.36 (m, 1H), 7,47 (d, J=8.7 Hz, 2H), EUR 7.57 (d, J=8.7 Hz, 2H).

Example 28 (12):

N-[4-(4-{[4-({butyl[(cyclohexylamino)carbonyl]amino}-methyl)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.47 (chloroform:methanol=5:1);

NMR (CD3OD): δ were 0.94 (t, J=7.5 Hz, 3H), 2.00 in the 1.06 (m, 19H), 2,95 (s, 3H), 3,02-is 2.88 (m, 2H), 3,30-and 3.16 (m, 4H), 3,56-3,44 (m, 3H), 4,25 (s, 2H), 7,10-7,00 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), of 7.48 (user. d, J=8,4 Hz, 2H).

Example 28 (13):

hydrochloride 4-[4-({4-[(N-acetylated)(butyl)amino] piperidine-1-yl}methyl)phenoxy]benzoic acid

TLC: Rf is 0.24 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 8.04 (d, J=9.0 Hz, 2H), 7,58 (d, J=9.0 Hz, 2H), 7,17 (d, J=9.0 Hz, 2H), 7,07 (d, J=9.0 Hz, 2H), and 4.75 (m, 1H), 4,40-4,10 (m, 3H), 3,70 was 3.05 (m, 6H), 2,40-of 1.30 (m, 14H), 1,01 with 0.93 (m, 9H).

Example 28 (14):

hydrochloride 4-[4-({4-[(N-acetyl-3-cyclohexylethyl)(butyl)amino]piperidine-1-yl}methyl)phenoxy]benzoic acid

TLC: Rf of 0.27 (ethyl acetate:methanol=10:1);

NMR (CD3OD): δ of 8.04 (d, J=9.0 Hz, 2H), 7,58 (d, J=8.7 Hz, 2H), 7,17 (d, J=8.7 Hz, 2H), 7,07 (d, J=9.0 Hz, 2H), and 4.75 (m, 1H), 4,40-4,10 (m, 3H), 3,70-3,00 (m, 6H), 2.40 a-0,80 (m, 27H).

Example 28 (15):

N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl}benzyl)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,68 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,34-of 1.41 (m, 2H), 1,58 was 1.69 (m, 2H), 1,96 is 2.00 (m, 2H), 2,12-of 2.23 (m, 2H), 2.91 in (s, 3H), 3,05-3,13 (m, 2H), 3,23-3,0 (m, 2H), 3,53 of 3.56 (m, 2H), 3,99 (s, 2H), 4,10 (m, 1H), 4,27 (s, 2H), 6.89 in-7,03 (m, 2H), 7,16 (d, J=8.7 Hz, 2H), 7,20 (d, J=8.7 Hz, 2H), 7,35 (m, 1H), 7,35 (d, J=8.0 Hz, 2H), 7,42 (d, J=8.0 Hz, 2H).

Example 28 (16):

N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl}phenoxy)-3-chlorophenyl]methanesulfonamide hydrochloride

TLC: Rf 0,63 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1.32 to the 1.45 (m, 2H), 1,59 was 1.69 (m, 2H), 1,98 is 2.01 (m, 2H), 2,13-of 2.26 (m, 2H), 3,01 (s, 3H), 3,06-3,14 (m, 2H), 3,24-3,30 (m, 2H), 3,54-to 3.58 (m, 2H), 4,13 (m, 1H), 4,28 (s, 2H), 6,90-7,05 (m, 2H), 7,00 (d, J=8.7 Hz, 2H), 7,13 (d, J=8.7 Hz, 1H), 7,24 (DD, J=8,7, 2.7 Hz, 1H), was 7.36 (dt, J=8,7, 6.0 Hz, 1H), 7,43 (d, J=2.7 Hz, 1H), of 7.48 (d, J=8.7 Hz, 2H).

Example 28 (17):

the dihydrochloride of N-butyl-N'-(2,4-differenl)-N-[1-({3,5-dimethyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-yl}methyl)-piperidine-4-yl]urea

TLC: Rf 0,74 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,99 (t, J=7.5 Hz, 3H), 1,36-of 1.44 (m, 2H), 1,61-1,71 (m, 2H), 2.00 in was 2.05 (m, 2H), 2,23-is 2.37 (m, 2H), 2,39 (s, 3H), of 2.44 (s, 3H), 3,16-3,24 (m, 2H), 3.27 to of 3.32 (m, 2H), 3,66-3,70 (m, 2H), 4,20 (m, 1H), 4,27 (s, 2H), 6.89 in-7,03 (m, 2H), 7,38 (dt, J=9,0, 6.0 Hz, 1H), 7,72 (d, J=8,4 Hz, 2H), 7,87 (d, J=8,4 Hz, 2H).

Example 28 (18):

N-{4-[(5-{[4-(butyl{[(2,4-differenl)amino]carbonyl}amino)piperidine-1-yl]methyl}pyridine-2-yl)oxy]phenyl}methanesulfonamide the dihydrochloride

TLC: Rf 0.31 in (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2,98 (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,35 (s, 2H), 6,86-7,05 (m, 2H), 7,10-7,17 (m, 3H), 7,32-7,38 (m,3H), of 8.09 (DD, J=8,7, 2.2 Hz, 1H), 8,32 (d, J=2.2 Hz, 1H).

Example 29 (1) - example 29 (131)

Using the same procedure as described in example 23, and, if necessary, hydrolysis, unprotect or oxidation using a conventional method using the compound obtained in example 3, or the corresponding amine derivative and using the appropriate carboxylic acid derivative instead of 1-methylcyclohexanecarboxylic acid will receive the following compounds of the present invention.

Example 29 (1):

N-(4-{4-[(4-{butyl[(pyrimidine-5-ylamino)carbonyl]amino}-piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.44 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,32 is 1.48 (m, 2H), 1,55-1,70 (m, 2H), 1,97-of 2.08 (m, 2H), 2,23-to 2.40 (m, 2H), 2.95 and (s, 3H), 3,10-of 3.23 (m, 2H), 3,29-to 3.38 (m, 2H), 3,50-3,62 (m, 2H), 4,25 (m, 1H), or 4.31 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,53 (d, J=8.7 Hz, 2H), 9,03 (s, 1H), 9,27 (s, 2H).

Example 29 (2):

N-(4-{4-[(4-{butyl[(pyridazin-4-ylamino)carbonyl]amino}-piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.45 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1.32 to about 1.47 (m, 2H), 1,55 was 1.69 (m, 2H), 2,00-2,10 (m, 2H), 2,27 at 2.45 (m, 2H), 2.95 and (s, 3H), 3,12-of 3.27 (m, 2H), 3.33 and is-3.45 (m, 2H), 3,50-3,62 (m, 2H), 4,24 is 4.35 (m, 3H), 7,03 (d, J=8,7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,53 (d, J=8.7 Hz, 2H), 8,49 (DD, J=7,2, 2.7 G is, 1H), 9,13 (d, J=7.2 Hz, 1H), 9,49 (d, J=2.7 Hz, 1H).

Example 29 (3):

N-{4-[4-({4-[{[(6-azidopyridine-3-yl)amino]carbonyl}(butyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.47 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,30-1,45 (m, 2H), 1,55-1,70 (m, 2H), 1,97-of 2.08(m, 2H), 2,24-to 2.41 (m, 2H), 2.95 and (s, 3H), 3,05-3,20 (m, 2H), 3.25 to to 3.38 (m, 2H), 3,55-the 3.65 (m, 2H), 4,19 (m, 1H), or 4.31 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H), 7,88 (DD, J=9,6, 1.5 Hz, 1H), to 7.99 (DD, J=9,6, 1.5 Hz, 1H), 9,42 (d, J=1.5 Hz, 1H).

Example 29 (4):

N-{4-[4-({4-[butyl({[3-(triptoreline)phenyl]amino}-carbonyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf is 0.49 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 2,00-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,17 (m, 1H), 4,29 (s, 2H), 6,93 (m, 1H), 7,02-was 7.08 (m, 4H), 7,27-7,34 (m, 4H), 7,45 (m, 1H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (5):

N-{4-[4-({4-[{[(4-acetylphenyl)amino]carbonyl}(butyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf is 0.42 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 2,00-2,10 (m, 2H), 2,20-2,40 (m, 2H), by 2.55 (s, 3H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,30 (s, 2H), 7,03 (d, J=8,9 Hz, 2H), 7,07 (d, J=8,9 Hz, 2H), 7,29 (d, J=8,9 Hz, 2H), 7,50 (d, J=8.1 Hz, 2H), 7,53 (d, J=8.1 Hz, 2H), 7,92 (d, J=8,9 Hz, 2H).

Example 29 (6):

N-{4-[4-({4-[butyl({[2(triptoreline)phenyl]amino}-carbonyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.51 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,35 of 1.50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,40-of 3.60 (m, 2H), 4.16 the (m, 1H), 4,29 (s, 2H), 7,02-was 7.08 (m, 4H), 7,19-7,34 (m, 5H), of 7.48-7,51 (m, 2H), 7,60 (m, 1H).

Example 29 (7):

N-{4-[4-({4-[[(benzoylamine)carbonyl](butyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.60 (chloroform:methanol=10:1);

NMR (CD3OD): δ to 0.92 (t, J=7.4 Hz, 3H), 1,30-1,40 (m, 2H), 1,60-1,70 (m, 2H), 2,00-2,10 (m, 2H), 2,30-to 2.40 (m, 2H), 2.95 and (s, 3H), 3,05-3,20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,27 (s, 2H), 7,02-7,06 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), of 7.48-7,53 (m, 4H), to 7.61 (m, 1H), 7,87 (d, J=7.2 Hz, 2H).

Example 29 (8):

N-[4-(4-{[4-(butyl{[(2,6-differenl)amino]carbonyl}amino)-piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.56 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,30 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 6,97-was 7.08 (m, 6H), 7,28-7,31 (m, 3H), 7,49-7,52 (m, 2H).

Example 29 (9):

N-{4-[4-({4-[butyl({[4-(triptoreline)phenyl]amino}-carbonyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.47 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,05-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 7,01-was 7.08 (m, 4H), 7,18 (d, J=9.0 Hz, 2H), 7,29 (d, J=9,3 Hz, 2H), 7,43(d, J=9,3 Hz, 2H), 7,51 (d, J=9.0 Hz, 2H).

Example 29 (10):

N-(4-{4-[(4-{butyl[(quinoline-3-ylamino)carbonyl]amino}-piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.40 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,99 (t, J=7.4 Hz, 3H), of 1.40-1.50 (m, 2H), 1,60-1,70 (m, 2H), 2,00-2,10 (m, 2H), 2,30-to 2.40 (m, 2H), 2.95 and (s, 3H), 3,20-3,30 (m, 2H), 3,20-3,40 (m, 2H), 3,55-the 3.65 (m, 2H), 4,30 (m, 1H), 4,32 (s, 2H), 7,02-to 7.09 (m, 4H), 7,30 (d, J=8,9 Hz, 2H), 7,54 (d, J=8,9 Hz, 2H), to $ 7.91 (td, J=7,2, 1.2 Hz, 1H), 8,02 (td, J=7,2, 1.2 Hz, 1H), 8,14 (d, J=8,4 Hz, 1H), to 8.20 (d, J=8,4 Hz, 1H), 9,05 (d, J=2.4 Hz, 1H), at 9.53 (d, J=2.4 Hz, 1H).

Example 29 (11):

N-(4-{4-[(4-{butyl[(cyclopent-3-EN-1-ylamino)carbonyl]-amino}piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf to 0.72 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.93 (t, J=7.2 Hz, 3H), 1,20-1,40 (m, 2H), 1,40-1,60 (m, 2H), 1,80-2,00 (m, 2H), 2.00 in of 2.20 (m, 2H), 2,24 (DD, J=14,6, and 5.6 Hz, 2H) 2,69 (DD, J=14,6, 8.0 Hz, 2H) 2,95 (s, 3H), 3,00-3,20 (m, 4H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 4,39 (m, 1H), 5,69 (s, 2H), 7,02-7,07 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,51 (d, J=8,9 Hz, 2H).

Example 29 (12):

N-[4-(4-{[4-(butyl{[(4-chloro-3-hydroxyphenyl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.41 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,00 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,29 (s, 2H), 6,77 (DD, J=8,9, and 2.4 Hz, 1H), 7,02-was 7.08 (m, 5H), to 7.15 (d, J=9.0 Hz, 1H), 7,29-7,31 (m, 2H), 7,47-7,51 (m, 2H).

Example 29 (13):

N-[4-(4-{[4-(b is Teal{[(4-fluoro-3-hydroxyphenyl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.40 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,29 (s, 2H), 6,70 (m, 1H), 6.90 to-7,00 (m, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,49 (d, J=8,9 Hz, 2H).

Example 29 (14):

N-(4-{4-[(4-{butyl[(quinoline-6-ylamino)carbonyl]amino}-piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.44 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 2,00-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,10-3,30 (m, 2H), 3,30-to 3.50 (m, 2H), 3,50-3,70 (m, 2H), 4,30 (m, 1H), 4,32 (s, 2H), 7,02-to 7.09 (m, 4H), 7,30 (d, J=8,9 Hz, 2H), 7,53 (d, J=8,9 Hz, 2H), 8,01 (DD, J=8,6, and 5.6 Hz, 1H), 8,15 (d, J=9,3 Hz, 1H), 8,31 (DD, J=9,3, 2.4 Hz, 1H), 8,42 (m, 1H), 9,01-9,05 (m, 2H).

Example 29 (15):

N-{4-[4-({4-[butyl({[2-(trifluoromethyl)phenyl]amino}carbonyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide

TLC: Rf 0,69 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1.60-to 1,90 (m, 4H), 2.00 in of 2.20 (m, 2H), 2,93 (s, 3H), 2.95 and was 3.05 (m, 2H), 3,20-3,40 (m, 4H), 3,51 (s, 2H), of 4.05 (m, 1H), 6,93-6,98 (m, 4H), from 7.24 (d, J=9.0 Hz, 2H), 7,32 (d, J=9.0 Hz, 2H), 7,34 (m, 1H), 7,58-of 7.60 (m, 2H), 7,66 (d, J=7.8 Hz, 1H).

Example 29 (16):

N-[4-(4-{[4-(butyl{[(6-oxo-1,6-dihydropyridines-3-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.45 (methylene chloride:methanol=4:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,30-1,45 (m, 2H), 1,50-of 1.65 (m, 2H), 1,92-2,05 (m, 2H), 2,18 to 2.35 (m, 2H), 295 (, 3H), is 3.08-to 3.35 (m, 4H), 3,50-3,60 (m, 2H), 4,21 (m, 1H), 4,30 (s, 2H), of 6.68 (d, J=9.6 Hz, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,53 (d, J=8.7 Hz, 2H), 7,72 (d, J=3.0 Hz, 1H), 7,79 (DD, J=9,6, 3.0 Hz, 1H).

Example 29 (17):

N-[4-(4-{[4-(butyl{[(4-oxocyclohexyl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.47 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ were 0.94 (t, J=7.2 Hz, 3H), 1,26 is 1.58 (m, 7H), 1,70-1,80 (m, 2H), 1.85 to of 2.20 (m, 7H), 2.95 and (s, 3H), 3,02-3,17 (m, 4H), 3,48-the 3.65 (m, 3H), of 4.13 (m, 1H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=to 8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (18):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(3-hydroxybenzyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf to 0.80 (chloroform:methanol=5:1);

NMR (CD3OD): δ 1,88-of 2.24 (m, 4H), 2.95 and (s, 3H), is 3.08 (m, 2H), 3,48 (m, 2H), 4,24 (s, 2H), 4,34 (m, 1H), 4,58 (s, 2H), 6,60-6,84 (m, 3H), 6.90 to-7,10 (m, 6H), 7,16 (m, 1H), 7,22-7,38 (m, 4H), 7,38-7,52 (m, 2H).

Example 29 (19):

N-[4-(4-{[4-(butyl{[(2,6-dimetilfenil)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf is 0.59 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), measuring 2.20 (s, 6H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), to 4.28 (s, 2H), 7,02-7,07 (m, 7H), 7,29 (d, J=8,9 Hz, 2H), 7,52 (d, J=8,9 Hz, 2H).

Example 29 (20):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2-methoxybutyl)amino]piperidine-1-yl}methylphenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0.34 in (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1.00 each (t, J=7.5 Hz, 3H), 1,57 is 1.70 (m, 2H), 1.93 and-of 2.30 (m, 4H), 2.95 and (s, 3H), 3,02-3,20 (m, 3H), 3,35 is-3.45 (m, 2H), 3,50 (s, 3H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,28 (s, 2H), 6,97-7,10 (m, 6H), 7,21-7,33 (m, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (21):

N-{4-[4-({4-[4-ethyl-3-(4-forfinal)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.33 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 1.02 (t, J=7.5 Hz, 3H), 2,15 was 2.25 (m, 4H), 2,28 (kV, J=7.5 Hz, 2H), 2,96 (s, 3H), 3,13-3,29 (m, 2H), to 3.58-3,70 (m, 2H), 4.26 deaths (m, 1H), 4,33 (s, 2H), to 6.39 (s, 1H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), to 7.09 (d, J=8,7 Hz, 2H), 7,20-7,35 (m, 6H), 7,52 (d, J=8.7 Hz, 2H).

Example 29 (22):

N-[4-(4-{[4-({[(4-forfinal)amino]carbonyl}{2-[(methylsulphonyl)amino]butyl}amino)piperidine-1-yl]methyl}-phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0.31 in (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1.06 a (t, J=7.5 Hz, 3H), of 1.48 (m, 1H), 1.69 in (m, 1H), 2.05 is-to 2.18 (m, 2H), 2.21 are 2,43 (m, 2H), 2.95 and (s, 3H), of 2.97 (s, 3H), 3,03-3,14 (m, 2H), 3,34 (d, J=7.5 Hz, 2H), 3,42-3,61 (m, 3H), 3,95 (m, 1H), 4,28 (s, 2H), of 6.96-7,10 (m, 6H), 7,26-7,40 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (23):

N-(4-{4-[(4-{{[(4-forfinal)amino]carbonyl}[(2S)-2-methylbutyl]amino}piperidine-1-yl)methyl]phenoxy}phenyl)-methanesulfonamide hydrochloride

TLC: Rf 0.39 to (methylene chloride:methanol=9:1);

NMR (CD3OD): δ were 0.94 (d, J=7.5 Hz, 3H), of 0.95 (t, J=7.5 Hz, 3H), of 1.16 (m, 1H), 1,50 (m, 1H), 1,74 (m, 1H), 1,95-2,07 (m, 2H), 2,28-2,47 (m, 2H), 2.95 and (s, 3H), 3,02-3,24 (m, 4H), 3,50-3,60 (m, 2H), 3,90 (m, 1H), 4,28 (s, 2H), 6,9-7,10 (m, 6H), 7,25-to 7.32 (m, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (24):

N-[4-(4-{[4-((2-ethylbutyl){[(4-forfinal)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0.39 to (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 0.93 (t, J=7.5 Hz, 6H), 1,27 of 1.50 (m, 4H), to 1.60 (m, 1H), 1,97-of 2.08 (m, 2H), 2,30-of 2.50 (m, 2H), 2.95 and (s, 3H), 3,03-3,18 (m, 2H), 3,26 (d, J=7.5 Hz, 2H), 3,50-3,60 (m, 2H), a 3.87 (m, 1H), 4,28 (s, 2H), of 6.96-7,10 (m, 6H), 7.24 to 7,33 (m, 4H), 7,49 (d, J=8.7 Hz, 2H).

Example 29 (25):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(Tien-2-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0.34 in (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,94-2,05 (m, 2H), 2,12-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,02-3,17 (m, 2H), 3,50-to 3.58 (m, 2H), 4.26 deaths (s, 2H), 4,27 (m, 1H), 4,79 (s, 2H), 6,94-was 7.08 (m, 8H), 7,26-7,34 (m, 5H), of 7.48 (d, J=8.7 Hz, 2H).

Example 29 (26):

N-{3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]phenyl}ndimethylacetamide hydrochloride

TLC: Rf 0,73 (ethyl acetate:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,28-of 1.45 (m, 2H), 1.56 to to 1.67 (m, 2H), 1,98-2,02 (m, 2H), 2,11 (s, 3H), 2,16-of 2.28 (m, 2H), 2,96 (s, 3H), of 3.07-3.15 in (m, 2H), 3,26-3,30 (m, 2H), 3,55-3,59 (m, 2H), 4.16 the (m, 1H), the 4.29 (s, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,10-of 7.23 (m, 3H), 7,30 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H), 7,69 (m, 1H).

Example 29 (27):

N-{4-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]phenyl}ndimethylacetamide hydrochloride

TLC: Rf 0,70 (atilas the tat:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,29-of 1.42 (m, 2H), 1,55-to 1.67 (m, 2H), 1,98-2,02 (m, 2H), 2,10 (s, 3H), 2,13-of 2.28 (m, 2H), 2,96 (s, 3H), 3,03 is 3.15 (m, 2H), 3.25 to 3.30 is (m, 2H), 3,55-3,59 (m, 2H), 4.16 the (m, 1H), the 4.29 (s, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,27 (d, J=8.7 Hz, 2H), 7,30 (d, J=8.7 Hz, 2H) 7,46 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (28):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2,2,3,3,4,4,4-heptafluorobutyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.57 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 2,08-of 2.38 (m, 4H), 2.95 and (s, 3H), is 3.08-3,11 (m, 2H), 3,52-the 3.65 (m, 2H), Android 4.04 (m, 1H), 4,18 is 4.35 (m, 4H), 6,99-was 7.08 (m, 6H), 7,26-7,37 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (29):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(isopentyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf value of 0.52 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 0.96 (d, J=6.6 Hz, 6H), 1,45-1,55 (m, 2H), 1,65 (m, 1H), 1,95-2,05 (m, 2H), 2,12-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,05-3,10 (m, 2H), 3,22-to 3.33 (m, 2H), 3,51-3,61 (m, 2H), 4,19 (m, 1H), 4,29 (s, 2H), 6,97-7,10 (m, 6H), 7,26-7,33 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (30):

N-[4-(4-{[4-((2,6-diferensial){[(4-forfinal)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf 0,54 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,88 of 1.99 (m, 2H), 2,19-of 2.34 (m, 2H), 2.95 and (s, 3H), 2,99-of 3.12 (m, 2H), 3,44-to 3.52 (m, 2H), 3,98 (m, 1H), 4,24 (s, 2H), and 4.75 (s, 2H), 6,95-was 7.08 (m, 8H), 7,25-7,40 (m, 5H), was 7.45 (d, J=8.7 Hz, 2H).

Example 29 (31):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(the feast of the DIN-2-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf 0.56 to (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 2,03-of 2.36 (m, 4H), 2.95 and (s, 3H), 3,13-3,26 (m, 2H), 3,54-to 3.64 (m, 2H), 4,32 (s, 2H), of 4.45 (m, 1H), to 4.87 (s, 2H), 7,00 (d, J=9.0 Hz, 2H), 7,02 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8,7 Hz, 2H), 7,39 (DD, J=9,0, 5.0 Hz, 2H), 7,56 (d, J=8.7 Hz, 2H), 7,94 (t, J=6.0 Hz, 1H), 8,03 (d, J=8.0 Hz, 1H), 8,54 (dt, J=1,8, 8.0 Hz, 1H), up 8.75 (DD, J=6,0, 1.8 Hz, 1H).

Example 29 (32):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(pyridin-3-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf of 0.47 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,98 is 2.10 (m, 2H), 2,18 to 2.35 (m, 2H), 2.95 and (s, 3H), 3,10-of 3.23 (m, 2H), 3,50-3,60 (m, 2H), 4,30 (s, 2H), 4,43 (m, 1H), 4,80 (s, 2H), 7,00 (d, J=9.0 Hz, 2H), 7,02 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,38 (DD, J=9,0, 5.0 Hz, 2H), 7,55 (d, J=8.7 Hz, 2H), with 8.05 (DD, J=8,4, 5.7 Hz, 1H), 8,59 (d, J=8,4 Hz, 1H), up 8.75 (d, J= 5.7 Hz, 1H), 8,84 (s, 1H).

Example 29 (33):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(pyridin-4-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf of 0.47 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 2,02-of 2.30 (m, 4H), 2.95 and (s, 3H), 3,10-of 3.23 (m, 2H), 3,50-3,60 (m, 2H), 4,30 (s, 2H), 4,48 (m, 1H), 4,88 (s, 2H), 6,99 (d, J=9.0 Hz, 2H), 7,02 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8,7 Hz, 2H), was 7.36 (DD, J=9,0, 5.0 Hz, 2H), 7,54 (d, J=8.7 Hz, 2H), 8,02 (d, J=6.6 Hz, 2H), 8,77 (d, J=6.6 Hz, 2H).

Example 29 (34):

N-(4-{4-[(4-{butyl[(methylamino)carbonyl]amino}piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.50 (chloroform:methanol=10:1);

NMR (CD3OD): δ were 0.94 (t, J=7.5 Hz, 3H), 1,30-1,40 (m, 2H), 1,40-1,60 (m, 2H), 1,80-2,00 (m, 2H), 2,10-of 2.20 (m, 2H), 2,72 (s, 3H), 2.95 and (s, 3H), 3.00 and is 3.15 (m, 4H), 3,50-3,60 (m, 2H), 4,12 (m, 1H), 4,27 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,49 (d, J=8,9 Hz, 2H).

Example 29 (35):

N-[4-(4-{[4-(butyl{[(5-hydroxypyridine-3-yl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide the dihydrochloride

TLC: Rf of 0.50 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,10-3,30 (m, 4H), 3,50-3,60 (m, 2H), 4,30 (m, 1H), or 4.31 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,54 (d, J=8,9 Hz, 2H), to 7.93 (d, J=2.1 Hz, 1H) to 8.12 (d, J=2.1 Hz, 1H), 8,68 (d, J=1.5 Hz, 1H).

Example 29 (36):

N-[4-(4-{[4-(butyl{[(1-isopropyl-1H-1,2,3-benzotriazol-5-yl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf of 0.65 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 1,74 (d, J=6.6 Hz, 6H), 2.00 in of 2.10 (m, 2H), 2,20-2,40 (m, 2H), 2,96 (s, 3H), 3,10-3,30 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,30 (m, 1H), 4,32 (s, 2H), of 5.34 (m, 1H), 7,02-was 7.08 (m, 4H), 7,30 (d, J=8,9 Hz, 2H), 7,54 (d, J=8,9 Hz, 2H), to 7.77 (DD, J=9,0, 1.5 Hz, 1H) to 7.95 (d, J=9.0 Hz, 1H), 8,17 (d, J=1.5 Hz, 1H).

Example 29 (37):

N-(4-{4-[(4-{{[(4-forfinal)amino]carbonyl}[(6-methylpyridin-2-yl)methyl]amino}piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.50 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 2,08-to 2.18 (m, 2H), 2,20-of 2.38 (m, 2H), 2,80 (s, 3H), 2.95 and (s, 3H), 3,14-3,26 (m, 2H), 3,52-3,62 (m, 2), 4,32 (s, 2H), 4,47 (m, 1H), a 4.83 (s, 2H), 7,00 (d, J=9.0 Hz, 2H), 7,02 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,37 (DD, J=9,0, 5.0 Hz, 2H), EUR 7.57 (d, J=8.7 Hz, 2H), 7,76 (d, J=8.0 Hz, 1H), 7,78 (d, J=8.0 Hz, 1H), 8,40 (t, J=8.0 Hz, 1H).

Example 29 (38):

N-[4-(4-{[4-(butyl{[(3-cyanophenyl)amino]carbonyl}amino)-piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf value of 0.52 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,28-of 1.44 (m, 2H), 1,55-of 1.66 (m, 2H), 1,98-2,03 (m, 2H), 2,20-of 2.33 (m, 2H), 2.95 and (s, 3H), 3,09-3,17 (m, 2H), 3,30 is 3.40 (m, 2H), 3,55-3,59 (m, 2H), 4,17 (m, 1H), 4,30 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), was 7.36 (m, 1H), 7,44 (t, J=8.0 Hz, 1H), 7,51 (d, J=8.7 Hz, 2H), to 7.64 (m, 1H), 7,82 (m, 1H).

Example 29 (39):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(tetrahydro-2H-Piran-4-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.57 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,27-of 1.42 (m, 2H), 1,60-1,70 (m, 2H), 1,87-of 2.08 (m, 3H), 2,25-to 2.42 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 2H), 3,19 of 3.28 (m, 2H), 3,31-of 3.42 (m, 2H), 3,48-of 3.60 (m, 2H), 3,88-4,00 (m, 3H), 4,28 (s, 2H), 6,97-7,10 (m, 6H), 7,25-7,33 (m, 4H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (40):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2-phenylethyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,68 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,82 of 2.92 (m, 2H), 2,10-of 2.28 (m, 2H), 2,93 (t, J=7.5 Hz, 2H), 2.95 and (s, 3H), 3.00 and-of 3.12 (m, 2H), 3,49-3,59 (m, 4H), 4,10 (m, 1H), 4,27 (s, 2H), 6,97-7,10 (m, 6H), 7.18 in-7,37 (m, 9H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (41):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2-pyridin-2-retil)amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide the dihydrochloride

TLC: Rf 0,59 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,98 is 2.10 (m, 2H), 2,28 is 2.44 (m, 2H), 2.95 and (s, 3H), 3,09-up 3.22 (m, 2H), 3,34 (t, J=7.2 Hz, 2H), 3,55-3,63 (m, 2H, in), 3.75 (t, J=7.2 Hz, 2H), 4,25 (m, 1H), 4,33 (s, 2H), 6,97-7,10 (m, 6H), 7,26-7,33 (m, 4H), EUR 7.57 (d, J=8.7 Hz, 2H), 7,92 (DDD, J=8,1, 5,7, 1.8 Hz, 1H), of 8.06 (d, J=8,1 Hz, 1H), 8,53 (dt, J=1,8, 8,1 Hz, 1H), total of 8.74 (d, J=5.7 Hz, 1H).

Example 29 (42):

N-[4-(4-{[4-(butyl{[(4-methyl-1,2,3-thiadiazole-5-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf to 0.78 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,99 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,30-to 2.40 (m, 2H), 2,68 (s, 3H), 2,96 (s, 3H), of 3.10-3.20 (m, 2H), 3,40-to 3.50 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), or 4.31 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,53 (d, J=8,9 Hz, 2H).

Example 29 (43):

N-[4-(4-{[4-(butyl{[(2-chloro-4-forfinal)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf to 0.72 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 2,00-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 7,02-was 7.08 (m, 5H), 7,27 (m, 1H), 7,29 (d, J=9.0 Hz, 2H), 7,50 (d, J=9.0 Hz, 2H), 7,51 (m, 1H).

Example 29 (44):

N-[4-(4-{[4-(butyl{[(4-cyanophenyl)amino]carbonyl}amino)-piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,71 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,34-of 1.41 (m, 2H), 1,57-of 1.62 (m, 2H), 1,98 is 2.01 (m, 2H), 2,20-of 2.33 (m, 2H), 2.95 and (s, 3H), is 3.08-and 3.16 (m, 2H), 3,30 is 3.40 (m, 2H), 3,55-3,59 (m, 2H), 4,17 (m, 1H), 4,29 (s, 2H), ? 7.04 baby mortality (d, J=8,9 Hz, 2H), 7,07 (d, J=8,9 Hz, 2H), 7,29 (d, J=8,9 Hz, 2H), 7,50 (d, J=8,9 Hz, 2H), 7,58 (d, J=9.0 Hz, 2H), to 7.61 (d, J=9.0 Hz, 2H).

Example 29 (45):

N-[4-(4-{[4-(butyl{[(2,2-debtor-1,3-benzodioxol-5-yl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.64 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,34-of 1.42 (m, 2H), 1,55-1,65 (m, 2H), 1,98-2,03 (m, 2H), 2,15 was 2.25 (m, 2H), 2.95 and (s, 3H), of 3.07-3.15 in (m, 2H), 3.25 to 3.30 is (m, 2H), 3,55-3,59 (m, 2H), 4,14 (m, 1H), 4,29 (s, 2H), 7,02-7,11 (m, 6H), 7,29 (d, J=8.7 Hz, 2H), 7,33 (m, 1H), 7,49 (d, J=8.7 Hz, 2H).

Example 29 (46):

N-[4-(4-{[4-(butyl{[(4-chloro-2-forfinal)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf and 0.46 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,29 (s, 2H), 7,02-was 7.08 (m, 4H), to 7.15 (m, 1H), 7,22 (DD, J=6.3, in the 2.1 Hz, 1H), 7,29 (d, J=8,9 Hz, 2H), 7,43 (m, 1H), 7,43 (d, J=8,9 Hz, 2H).

Example 29 (47):

N-[4-(4-{[4-(butyl{[(1-methyl-1H-1,2,3-benzotriazol-5-yl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)-phenyl]methanesulfonamide the dihydrochloride

TLC: Rf of 0.40 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 2,00-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), ,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,30 (m, 1H), or 4.31 (s, 2H), 4,39 (s, 3H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,53 (d, J=9.0 Hz, 2H), 7,69 (DD, J=9,0, 1.8 Hz, 1H), 7,80 (d, J=9.0 Hz, 1H), of 8.09 (d, J=1,8 Hz, 1H).

Example 29 (48):

2-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]benzamide

TLC: Rf 0,60 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,37-of 1.44 (m, 2H), 1,59 is 1.91 (m, 6H), 2,15-2,22 (m, 2H), 2,93 (s, 3H), 3.00 and totaling 3.04 (m, 2H), 3,22-of 3.27 (m, 2H), 3,54 (s, 2H), of 4.05 (m, 1H), 6,93-7,02 (m, 5H), 7,25 (d, J=8.7 Hz, 2H), 7,32 (d, J=8.7 Hz, 2H), 7,42 (t, J=8,3 Hz, 1H), 7,69 (d, J=8,3 Hz, 1H), 8,27 (d, J=8,3 Hz, 1H).

Example 29 (49):

N-[4-(4-{[4-(butyl{[(2,4-dimethylpyridin-3-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf of 0.45 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1.00 each (t, J=7.5 Hz, 3H), 1,39 of 1.46 (m, 2H), 1,63 is 1.70 (m, 2H), 2,01-to 2.06 (m, 2H), 2,22 to 2.35 (m, 2H), 2,52 (s, 3H), of 2.64 (s, 3H), 2.95 and (s, 3H), 3,12-3,20 (m, 2H), 3,30-3,37 (m, 2H), 3,56-of 3.60(m, 2H), 4,24 (m, 1H), 4,30 (s, 2H), 7,03 (d, J=8,9 Hz, 2H), 7,06 (d, J=8,9 Hz, 2H), 7,29 (d, J=8,9 Hz, 2H), 7,52 (d, J=8,9 Hz, 2H), 7,83 (d, J=6.3 Hz, 1H), 8,48 (d, J=6.3 Hz, 1H).

Example 29 (50):

N-[4-(4-{[4-(butyl{[(4-fluoro-2-hydroxyphenyl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.50 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,99 (t, J=7.5 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 6,53-6,60 (m, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8.7 Hz, 2H), 7,46 (m, 1H), 7,49 (d, J8,7 Hz, 2H).

Example 29 (51):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2-hydroxy-3-methylbutyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.45 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0,99 (d, J=6.9 Hz, 3H), and 1.00 (d, J=6.9 Hz, 3H), of 1.74 (m, 1H), 1,95 was 2.25 (m, 4H), 2.95 and (s, 3H), 3,07-3,20 (m, 2H), 3.25 to of 3.42 (m, 2H), 3,47-3,62 (m, 3H), of 4.16 (m, 1H), 4,29 (s, 2H), 6,99 (d, J=9,0 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,24 (DD, J=9,0, 5.0 Hz, 2H), 7,29 (d, J=8.7 MHz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (52):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(3-hydroxy-3-methylbutyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.44 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,25 (s, 6H), to 1.79 (t, J=7.5 Hz, 2H), 1,92-2,02 (m, 2H), 2,08-of 2.23 (m, 2H), 2.95 and (s, 3H), is 3.08-3,18 (m, 2H), 3,40 (t, J=7.5 Hz, 2H), 3,52-3,62 (m, 2H), 4.26 deaths is 4.36 (m, 3H), 6,98 (d, J=9.0 Hz, 2H), 7.03 is (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), was 7.36 (DD, J=9,0, 5.0 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (53):

N-[4-(4-{[4-(butyl{[(2,4-dimethyl-1-oxidability-3-yl)-amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.43 (methylene chloride:methanol=5:1);

NMR (CD3OD): δ 1.00 each (t, J=7.2 Hz, 3H), 1,39 of 1.46 (m, 2H), 1,63 is 1.75 (m, 2H), 1,97-2,05 (m, 2H), 2,23 to 2.35 (m, 2H), 2,43 (s, 3H), at 2.59 (s, 3H), 2,96 (s, 3H), of 3.10-3.20 (m, 2H), 3,30-to 3.38 (m, 2H), 3,53-3,59 (m, 2H), is 4.21 (m, 1H), 4,30 (s, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,30 (d, J=8.7 Hz, 2H), 7,52 (d, J=8.7 Hz, 2H), 7,66 (d, J=6,9 Hz, 1H), 8,59 (d, J=6,9 Hz, 1H).

Example 29 (54):

<> N-[4-(4-{[4-(butyl{[(1-oxidability-4-yl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0.35 in (methylene chloride:methanol=5:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,34-of 1.44 (m, 2H), 1,55-1,65 (m, 2H), 1,98-2,05 (m, 2H), 2.26 and-of 2.38 (m, 2H), 2.95 and (s, 3H), 3,13-is 3.21 (m, 2H), 3.33 and-to 3.38 (m, 2H), 3,56-of 3.60 (m, 2H), 4,24 (m, 1H), or 4.31 (s, 2H), ? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,07 (d, J=8,4 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,52 (d, J=8,4 Hz, 2H), of 8.06 (d, J=7,0 Hz, 2H), 8,59 (d, J=7,0 Hz, 2H).

Example 29 (55):

N-[4-(4-{[4-(butyl{[(1-methyl-1H-pyrazole-4-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf of 0.40 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,10-3,30 (m, 4H), 3,50-3,60 (m, 2H), of 3.97 (s, 3H), 4,20 (m, 1H), 4,30 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,52 (d, J=8,9 Hz, 2H), 7,88 (s, 1H), to 7.99 (s, 1H);

amorphous;

softening temperature: about 156-159°C.

Example 29 (56):

N-{4-[4-({4-[{[(2,4-differenl)amino]carbonyl}(2-hydroxybutyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,51 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1.00 each (t, J=7.5 Hz, 3H), 1,40-1,60 (m, 2H), 1,97-2,31 (m, 4H), 2.95 and (s, 3H), 3,02-to 3.41 (m, 4H), 3,50-3,71 (m, 3H), of 4.12 (m, 1H), 4,28 (s, 2H), 6,83-7,02 (m, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=to 8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H), 7,63 (dt, J=5,7, and 9.0 Hz, 1H).

Example 29 (57):

N-(4-{4-[(4-{{[(4-forfinal)amino]carbonyl}[(3-methylpyridin-2-yl)METI is]amino}piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf 0.56 to (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 2,01-of 2.30 (m, 4H), 2,62 (s, 3H), 2.95 and (s, 3H), 3,16-3,30 (m, 2H), 3,50-3,61 (m, 2H), or 4.31 (s, 2H), 4,51 (m, 1H), 4,88 (s, 2H), 6,98-was 7.08 (m, 6H), 7,28 (d, J=8.7 Hz, 2H), 7,42-to 7.50 (m, 2H), 7,56 (d, J=8.7 Hz, 2H), 7,86 (t, J=6,5 Hz, 1H), 8,39 (d, J=6,5 Hz, 1H), 8,54 (d, J=6,5 Hz, 1H).

Example 29 (58):

N-[4-(4-{[4-((cyclopentylmethyl){[(4-forfinal)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.57 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 1.20 and 1.35 (m, 2H), 1,52-to 1.87 (m, 6H), 1,98-2,07 (m, 2H), 2,22 (m, 1H), 2,30-2,48 (m, 2H), 2.95 and (s, 3H), 3,03-3,18 (m, 2H), 3,28-to 3.33 (m, 2H), 3,50-3,60 (m, 2H), 3,88 (m, 1H), 4,28 (s, 2H), 6,98-7,08 (m, 6H), 7.24 to 7,32 (m, 4H), 7,49 (d, J=8.7 Hz, 2H).

Example 29 (59):

N-[4-(4-{[4-(butyl{[(2-fluoro-5-methoxyphenyl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf value of 0.52 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H, in), 3.75 (s, 3H), 4,20 (m, 1H), the 4.29 (s, 2H), 6,67 (m, 1H), 7,02 for 7.12 (m, 6H), 7,29 (d, J=8,9 Hz, 2H), 7,52 (d, J=8,9 Hz, 2H).

Example 29 (60):

N-[4-(4-{[4-(butyl{[(2-fluoro-3-methoxyphenyl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf value of 0.52 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 3,85 (s, 3H), 4,20 (m, 1H), the 4.29 (s, 2), 6,89 (m, 1H), 7,02-was 7.08 (m, 6H), 7,29 (d, J=9.0 Hz, 2H), 7,50 (d, J=9.0 Hz, 2H).

Example 29 (61):

N-[4-(4-{[4-(butyl{[(2-fluoro-4-were)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.56 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,40 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2,31 (s, 3H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), to 4.28 (s, 2H), 6.90 to-7,00 (m, 2H), 7,02-was 7.08 (m, 4H), 7,26-7,31 (m, 3H), 7,50 (d, J=9.0 Hz, 2H).

Example 29 (62):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(1,3-thiazol-2-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf to 0.63 (chloroform:methanol=5:1);

NMR (CD3OD): δ 2.00 in to 2.13 (m, 2H), 2,13-2,31 (m, 2H), 2.95 and (s, 3H), and 3.16 (m, 2H), to 3.58 (m, 2H), or 4.31 (s, 2H), to 4.38 (m, 1H), is 4.93 (s, 2H), 6,98-to 7.18 (m, 6H), 7.24 to 7,42 (m, 4H), 7,52 (user. d, J=8.7 Hz, 2H), of 7.75 (d, J=3.6 Hz, 1H), to 7.93 (d, J=3.6 Hz, 1H).

Example 29 (63):

3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-piperidine-4-yl]amino}carbonyl)amino]-N-methylbenzamide hydrochloride

TLC: Rf of 0.34 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2,90 (s, 3H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), the 4.29 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8.7 Hz, 2H), 7,30-to 7.50 (m, 3H), 7,50 (d, J=8.7 Hz, 2H), 7,79 (s, 1H).

Example 29 (64):

N-{4-[4-({4-[butyl({[3-(dimethylamino)phenyl]amino}carbonyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.50 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,10 is 3.40 (m, 4H), of 3.28 (s, 6H), 3,50-3,60 (m, 2H), 4,30 (m, 1H), or 4.31 (s, 2H), 7,02-was 7.08 (m, 4H), 7,28-7,31 (m, 3H), of 7.48-rate of 7.54 (m, 4H), of 7.90 (m, 1H).

Example 29 (65):

N-[4-(4-{[4-(butyl{[(4-fluoro-2-were)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.47 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), of 2.21 (s, 3H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), to 4.28 (s, 2H), to 6.88 (m, 1H), 6,94-7,14 (m, 6H), 7,29 (d, J=8.7 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H).

Example 29 (66):

N-[4-(4-{[4-(butyl{[(2-fluoro-4-methoxyphenyl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf to 0.63 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), of 3.77 (s, 3H), 4,15 (m, 1H), to 4.28 (s, 2H), 6,70 to 6.75 (m, 2H), 7,02-was 7.08 (m, 4H), 7,22 (m, 1H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 29 (67):

N-[4-(4-{[4-(butyl{[(3-ethylphenyl)amino]carbonyl}amino)-piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.58 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,22 (t, J=7.5 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2,60 (kV, J=7,1 Hz, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,19 m, 1H), the 4.29 (s, 2H), 6.89 in (m, 1H), 7,01-was 7.08 (m, 4H), 7,12-7,20 (m, 3H), 7,29-to 7.32 (m, 2H), 7,49-7,52 (m, 2H).

Example 29 (68):

N-(4-{4-[(4-{{[(4-forfinal)amino]carbonyl}[(1-oxidability-2-yl)methyl]amino}piperidine-1-yl)methyl]-phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0.14 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 2,02-of 2.30 (m, 4H), 2.95 and (s, 3H), 3,12-of 3.25 (m, 2H), 3,50-3,60 (m, 2H), 4,30 (s, 2H), 4,43 (m, 1H), 6,95-was 7.08 (m, 6H), 7,29 (d, J=8.7 Hz, 2H), 7,35 (DD, J=9,0, 5.0 Hz, 2H), 7,52 (d, J=8.7 Hz, 2H), 7,73 (t, J=7.5 Hz, 1H), a 7.85 (d, J=7.5 Hz, 1H), 8,01 (t, J=7.5 Hz, 1H), 8,68 (d, J=7.5 Hz, 1H).

Example 29 (69):

N-[4-(4-{[4-(butyl{[(2-fluoro-4-hydroxyphenyl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.44 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,29 (s, 2H), 6,52-6,56 (m, 2H), 7,02-to 7.09 (m, 6H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 29 (70):

N-[4-(4-{[4-(butyl{[(1-methyl-1H-indol-3-yl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide the dihydrochloride

TLC: Rf is 0.42 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,99 (t, J=7.4 Hz, 3H), of 1.40-1.50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), 2,10-to 2.40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 3,76 (s, 3H), 4,25 (m, 1H), 4.26 deaths (s, 2H), 7,02-7,07 (m, 5H), 7,10-7,20 (m, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,30 (m, 1H), 7,45 (m, 1H), 7,49 (d, J=9.0 Hz, 2H).

Example 29 (71):

N-{4-[4-({4-[butyl({[3-(methylsulphonyl)phenyl]but the Ino}-carbonyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0.26 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,10 (s, 3H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,30 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,3 Hz, 2H), 7,51 (d, J=8,3 Hz, 2H) 7,54-to 7.59 (m, 2H), 7,69 (m, 1H), 8,07 (m, 1H).

Example 29 (72):

N-[4-(4-{[4-(butyl{[(3-chloro-1-methyl-1H-pyrazole-4-yl)-amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf is 0.42 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 3,81 (s, 3H), 4,10 (m, 1H), to 4.28 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8.7 Hz, 2H), 7,45 (s, 1H), 7,49 (d, J=8.7 Hz, 2H).

Example 29 (73):

N-[4-(4-{[4-((2,6-dimethylbenzyl){[(4-forfinal)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide

TLC: Rf of 0.50 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,40-1,49 (m, 2H), 1,79-1,90 (m, 2H), 2,15 of-2.32 (m, 2H), 2,39 (s, 6H), 2,80-2,90 (m, 2H), 2,92 (s, 3H), 3,14 (m, 1H), 3,40 (s, 2H), and 4.68 (s, 2H), 6.87 in-to 7.15 (m, 10H), 7,20-to 7.32 (m, 5H).

Example 29 (74):

N-[4-(4-{[4-((2-cyclopropylethyl){[(4-forfinal)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf 0.56 to (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 0.10 to 0.16 (m, 2H), 0,44-of 0.53 (m, 2H), 0.74 and (m, 1H), 1,48 is 1.60 (m, 2H), 1,95-2,07 (m, 2H), 2,12-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,07-3,19 (m, 2H), 3,35-of 3.43 (m, 2H), 3,51-3,62 (m, 2H), 4,17 (m, 1H), 4,29 (, 2H), 6,97-7,10 (m, 6H), 7,26-7,37 (m, H), to 7.50 (d, J=8.7 Hz, 2H).

Example 29 (75):

N-{4-[4-({4-[{[(2,4-differenl)amino]carbonyl}(pyridin-2-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf 0,71 (chloroform:methanol=5:1);

NMR (CD3OD): δ 2.06 to of 2.38 (m, 4H), 2.95 and (s, 3H), 3,18 (m, 2H)and 3.59 (m, 2H), 4,32 (s, 2H), and 4.40 (m, 1H), 4,88 (s, 2H), 6,88-was 7.08 (m, 6H), 7,21-7,34 (m, 2H), 7,41 (m, 1H), 7,56 (user. d, J=8,4 Hz, 2H), to $ 7.91 (m, 1H), 8,00 (m, 1H), charged 8.52 (m, 1H), 8,76 (user. d, J=5.4 Hz, 1H).

Example 29 (76):

N-[4-(4-{[4-(but-3-enyl{[(2,4-differenl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,82 (chloroform:methanol=5:1);

NMR (CD3OD): δ a 2.01 (m, 2H, in), 2.25 (m, 2H), 2,42 (m, 2H), 2.95 and (s, 3H), 3,10 (m, 2H), 3,37 (m, 2H), of 3.56 (m, 2H), 4,12 (m, 1H), 4,28 (m, 2H), 5,09 (user. d, J=9.9 Hz, 1H), 5,16 (user. d, J=17,1 Hz, 1H), 5,88 (m, 1H), 6,88 for 7.12 (m, 6H), 7,22-7,42 (m, 3H), 7,42-7,52 (m, 2H).

Example 29 (77):

3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]benzamide hydrochloride

TLC: Rf of 0.45 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,30 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,38 (m, 1H), 7,49-7,52 (m, 4H), to 7.84 (m, 1H).

Example 29 (78):

N-(4-{4-[(4-{butyl[(1H-pyrazole-4-ylamino)carbonyl]amino}-piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.47 (chloroform:methanol=5:1);

NMR (CD 3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,30 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,52 (d, J=9.0 Hz, 2H), 8,10 (s, 2H).

Example 29 (79):

N-{4-[4-({4-[butyl({[1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-yl]amino}carbonyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf 0,88 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,30 (m, 2H), 3,50-3,60 (m, 2H), 3,90 (s, 3H), 4,10 (m, 1H), to 4.28 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,49 (d, J=9.0 Hz, 2H), 7,71 (s, 1H).

Example 29 (80):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(1H-tetrazol-5-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.29 (n-butanol:acetic acid:water=20:4:1);

NMR (CD3OD): δ 1,98 was 2.25 (m, 4H), 2.95 and (s, 3H), 3.15 in (m, 2H), to 3.58 (m, 2H), 4,30 (s, 2H), 4,34 (m, 1H), 4,84 (s, 2H), 6,98-was 7.08 (m, 6H), 7.24 to 7,41 (m, 4H), 7,51 (user. d, J=8.7 Hz, 2H).

Example 29 (81):

N-[4-(4-{[4-(but-3-enyl{[(1-methyl-1H-pyrazole-4-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf of 0.75 (chloroform:methanol=5:1);

NMR (CD3OD): δ to 1.98 (m, 2H), of 2.21 (m, 2H), 2,35 (m, 2H), 2.95 and (s, 3H), of 3.12 (m, 2H), 3,24-to 3.38 (m, 2H), only 3.57 (m, 2H), a 3.87 (s, 3H), of 4.12 (m, 1H), 4,29 (s, 2H), 5,00-5,20 (m, 2H), 5,76-5,94 (m, 1H), 7,00-7,10 (m, 4H), 7,22-7,34 (m, 2H), 7,42-of 7.60 (m, 3H), 7,73 (m, 1H).

Example 29 (82):

N-{4-[4-({4-[{[(6-IU is espiridion-3-yl)amino]carbonyl}(pyridin-2-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide trihydrochloride

TLC: Rf of 0.68 (chloroform:methanol=5:1);

NMR (CD3OD): δ 2,00 (m, 2H), 2,22 (m, 2H), 2,70 (s, 3H), 2.95 and (s, 3H), 3,17 (m, 2H), 3,55 (m, 2H), 4,30 (s, 2H), 4,48 (m, 1H), and 4.75 (s, 2H), 6,98-7,10 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), of 7.48-7,56 (m, 3H), 7.62mm (m, 1H), 7,80 (d, J=8.7 Hz, 1H), 8,02 (m, 1H), 8,42 (m, 1H), 8,63 (m, 1H), 9,02 (d, J=1.8 Hz, 1H).

Example 29 (83):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(phenyl)amino]-piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,49 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,60-1,80 (m, 2H), 2,12-of 2.21 (m, 2H), 2.95 and (s, 3H), 3,10-is 3.21 (m, 2H), 3,42-to 3.52 (m, 2H), 4,22 (s, 2H), of 4.66 (m, 1H), 6,95 (t, J=9.0 Hz, 2H), 7,01 (d, J=8.7 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,19-7,35 (m, 6H), 7,42 (d, J=8.7 Hz, 2H), 7,46-EUR 7.57 (m, 3H).

Example 29 (84):

N-(4-{4-[(4-{butyl[(1H-indol-5-ylamino)carbonyl]amino}-piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf of 0.65 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,00 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,25 (s, 2H), 7,02-7,07 (m, 6H), 7,21 (s, 1H), 7,28-to 7.32 (m, 3H), 7,44 (m, 1H), 7,50 (d, J=9.0 Hz, 2H).

Example 29 (85):

N-{4-[4-({4-[butyl({[1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl]amino}carbonyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf 0.84 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,30-1,40 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,00 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 3,90 (s, 3H), 4,15 (m, 1H), to 4.28 (s, 2H), ,02-7,07 (m, 4H), 7,29 (d, J=9.0 Hz, 2H) 7,51 (d, J=9.0 Hz, 2H), 7,71 (s, 1H).

Example 29 (86):

N-[4-(4-{[4-(butyl{[(2-fluoro-5-hydroxyphenyl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,82 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,00 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), of 6.52 (m, 1H), to 6.88 (m, 1H), 6,95 (m, 1H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,51 (d, J=8,9 Hz, 2H).

Example 29 (87):

N-{4-[4-({4-[[(cyclobutylamine)carbonyl](1,3-thiazol-2-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.68 (chloroform:methanol=5:1);

NMR (CD3OD): δ 1.60-to of 1.78 (m, 2H), 1,84-of 2.36 (m, 8H), 2.95 and (s, 3H), of 3.12 (m, 2H), of 3.56 (m, 2H), 4,16-4,30 (m, 2H), 4,29 (s, 2H), 4,81 (m, 2H), 7,00 for 7.12 (m, 4H), 7,29 (user. d, J=8.7 Hz, 2H), 7,52 (user. d, J=8.7 Hz, 2H), to 7.77 (user. d, J=3.6 Hz, 1H), 7,92 (user. d, J=3.6 Hz, 1H).

Example 29 (88):

N-{4-[4-({4-[{[(6-methylpyridin-3-yl)amino]carbonyl}(1,3-thiazol-2-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf and 0.61 (chloroform:methanol=5:1);

NMR (CD3OD): δ 2.00 in to 2.18 (m, 2H), 2,18-to 2.40 (m, 2H), 2,71 (s, 3H), 2.95 and (s, 3H), 3,29 (m, 2H), only 3.57 (m, 2H), 4,32 (s, 2H), 4,59 (m, 1H), 5,00 (s, 2H), 7,00 for 7.12 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), 7,55 (user. d, J=8,4 Hz, 2H), to 7.77 (m, 1H), 7,82 (d, J=9.0 Hz, 1H), 7,94 (user. d, J=2.1 Hz, 1H), 8,58 (m, 1H), remaining 9.08 (user. d, J=2.1 Hz, 1H).

Example 29 (89):

N-{4-[4-({4-[{[(2,4-differenl)amino]carbonyl}(1,3-thiazol-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf to 0.73 (chloroform:methanol=5:1);

NMR (CD3OD): δ 2,00 of-2.32 (m, 4H), 2.95 and (s, 3H), of 3.12 (m, 2H), only 3.57 (m, 2H), 4,29 (s, 2H), 4,32 (m, 1H), 4,91 (s, 2H), 6.90 to for 7.12 (m, 6H), 7,29 (user. d, J=9.0 Hz, 2H), 7,39-of 7.60 (m, 3H), 7,70 (user. d, J=3.3 Hz, 1H), 7,88 (user. d, J=3.3 Hz, 1H).

Example 29 (90):

N-(4-{4-[(4-{{[(4-forfinal)amino]carbonyl}[(2-methylpyridin-3-yl)methyl]amino}piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.67 (chloroform:methanol=5:1);

NMR (CD3OD): δ 2,00-2,11 (m, 2H), 2,12-of 2.38 (m, 2H), 2,82 (s, 3H), 2.95 and (s, 3H), of 3.13 (m, 2H), 3,54 (m, 2H), 4,29 (s, 2H), 4,49 (m, 1H), 4,69 (s, 2H), of 6.96-7,10 (m, 6H), 7,14-7,38 (m, 4H), 7,54 (user. d, J=8,4 Hz, 2H), 7,82 (m, 1H), 8,32 (m, 1H), 8,56 (d, J=5.4 Hz, 1H).

Example 29 (91):

N-(4-{4-[(4-{{[(2,4-differenl)amino]carbonyl}[(3-methylpyridin-2-yl)methyl]amino}piperidine-1-yl)methyl]phenoxy}-phenyl)methanesulfonamide the dihydrochloride

TLC: Rf of 0.55 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 2.08 to 2.35 (m, 4H), 2,62 (s, 3H), 2.95 and (s, 3H), 3,12-of 3.25 (m, 2H), 3,52-3,61 (m, 2H), or 4.31 (s, 2H), 4,47 (m, 1H), 4.92 in (s, 2H), 6.90 to-7,00 (m, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,28 (d, J=8.7 Hz, 2H), 7,47 (dt, J=6,0, 9.0 Hz, 1H), 7,56 (d, J=8.7 Hz, 2H), 7,89 (DD, J=7,5, 5.7 Hz, 1H), 8,44 (d, J=7.5 Hz, 1H), to 8.57 (d, J=5.7 Hz, 1H).

Example 29 (92):

N-(4-{4-[(4-{[(cyclobutylamine)carbonyl][(3-methylpyridin-2-yl)methyl]amino}piperidine-1-yl)methyl]phenoxy}phenyl)-methanesulfonamide the dihydrochloride

TLC: Rf of 0.50 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,63 is 1.75 (m, 2H), 1,95-of 2.30 (m, 8H), at 2.59 (s, 3H), 2.95 and (s, 3H), 3,10-up 3.22 (m, 2H), 3,49-to 3.58 (m, 2H), 4,20-4,37 (m, 4), 4,74 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,28 (d, J=8.7 Hz, 2H), 7,54 (d, J=8.7 Hz, 2H), 7,86 (DD, J=7,5, 6.0 Hz, 1H), 8,40 (d, J=7.5 Hz, 1H), 8,51 (d, J=6.0 Hz, 1H).

Example 29 (93):

N-(4-{4-[(4-{{[(6-methylpyridin-3-yl)amino]carbonyl}[(3-methylpyridin-2-yl)methyl]amino}piperidine-1-yl)methyl]phenoxy}-phenyl)methanesulfonamide trihydrochloride

TLC: Rf of 0.47 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 2,10-2,39 (m, 4H), of 2.64 (s, 3H), 2,71 (s, 3H), 2.95 and (s, 3H), 3,22-to 3.35 (m, 2H), 3,50-3,60 (m, 2H), 4,32 (s, 2H), and 4.75 (m, 1H), 4,96 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,28 (d, J=8.7 Hz, 2H), EUR 7.57 (d, J=8.7 Hz, 2H), 7,83 (d, J=8.7 Hz, 1H), 7,89 (DD, J=7,5, 5,1 Hz, 1H), 8,44 (d, J=7.5 Hz, 1H), to 8.57 (d, J=5,1 Hz, 1H), 8,68 (DD, J=8,7, 2.4 Hz, 1H), 9,12 (d, J=2.4 Hz, 1H).

Example 29 (94):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(pyrimidine-2-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf of 0.40 (methylene chloride:methanol=9:1);

NMR (DMSO-d6): δ 1,80-1,89 (m, 2H), 2,10-of 2.30 (m, 2H), 2,96 (s, 3H), 2,97-3,10 (m, 2H), is 4.21 (s, 2H), 4,36 (m, 1H), 4,70 (s, 2H), 6,98-7,07 (m, 6H), 7,28 (d, J=8.7 Hz, 2H), 7,35-the 7.43 (m, 3H), 7,55 (d, J=8.7 Hz, 2H), at 8.60 (m, 1H), 8,78 (d, J=5,1 Hz, 2H), 9,35 (m, 1H).

Example 29 (95):

N-[4-(4-{[4-(butyl{[(2,4,6-tryptophanyl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,71 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 6,88-6,94 (m, 2H), 7,02-7,07 (m, 4H), 7,29 (d, J=2 Hz, 2H), 7,51 (d, J=9,2 Hz, 2H).

Example 29 (96):

N-(4-{4-[(4-{{[(2-hydroxybutyl)amino]carbonyl}[(3-methylpyridin-2-yl)methyl]amino}piperidine-1-yl)methyl]-phenoxy}phenyl)methanesulfonamide the dihydrochloride

TLC: Rf 0.39 to (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 0.96 (t, J=7.2 Hz, 3H), 1,37 is 1.58 (m, 2H), 1,97 was 2.25 (m, 4H), 2,60 (s, 3H), 2.95 and (s, 3H), 3,10-of 3.23 (m, 4H), 3,50-to 3.67 (m, 3H), 4,27-to 4.38 (m, 3H), 4,80 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=to 8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,55 (d, J=8.7 Hz, 2H), 7,88 (DD, J=7,8, 6.0 Hz, 1H), 8,42 (d, J=7.8 Hz, 1H), 8,54 (d, J=6.0 Hz, 1H).

Example 29 (97):

N-{4-[4-({4-[[(cyclobutylamine)carbonyl](pyridin-2-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf of 0.54 (chloroform:methanol=5:1);

NMR (CD3OD): δ 1.60-to around 1.74 (m, 2H), 1,90-of 2.30 (m, 8H), 2.95 and (s, 3H), 3,11 (m, 2H), of 3.56 (m, 2H), 4,18-4,32 (m, 2H), 4,30 (s, 2H), 4.72 in (s, 2H), 7,00-7,10 (m, 4H), 7,29 (user. d, J=9.0 Hz, 2H), 7,53 (user. d, J=8.7 Hz, 2H), 7,80-a 7.92 (m, 2H), 8,44 (m, 1H), 8,71 (user. d, J=5.4 Hz, 1H).

Example 29 (98):

N-{4-[4-({4-[{[(2-hydroxybutyl)amino]carbonyl}(2-methylbenzyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf and 0.61 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.90 (t, J=7.5 Hz, 3H), 1,20-1,50 (m, 2H), 1,90-2,02 (m, 4H), 2,32 (s, 3H), 2.95 and (s, 3H), 3.00 and-to 3.34 (m, 4H), 3,42-3,51 (m, 3H), 4,24 (s, 2H), 4,39 (s, 2H), to 4.41 (m, 1H), 6,98? 7.04 baby mortality (m, 4H), 7,08-7,20 (m, 4H), 7,28 (user. d, 9.0 Hz, 2H), 7,45 (user. d, J=8,4 Hz, 2H).

Example 29 (99):

5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}Carboni is)amino]-2-perbenzoic hydrochloride

TLC: Rf of 0.67 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,29 (s, 2H), 7,02-7,07 (m, 4H), 7,13 (m, 1H), 7,29 (d, J=9.0 Hz, 2H), 7,50 (d, J=9.0 Hz, 2H), 7,52 (m, 1H), 7,78 (m, 1H).

Example 29 (100):

3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-piperidine-4-yl]amino}carbonyl)amino]-2,6-diflorasone hydrochloride

TLC: Rf of 0.64 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,02-7,07 (m, 5H), 7,29 (d, J=8.7 Hz, 2H), 7,44 (m, 1H), 7,49 (d, J=8.7 Hz, 2H).

Example 29 (101):

5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-piperidine-4-yl]amino}carbonyl)amino]-2,4-diflorasone hydrochloride

TLC: Rf of 0.65 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,28 (s, 2H), 7,02-7,07 (m, 4H), 7,17 (t, J=10.5 Hz, 1H), 7,29 (d, J=9.0 Hz, 2H), 7,49 (d, J=9.0 Hz, 2H), a 7.85 (m, 1H).

Example 29 (102):

N-[4-(4-{[4-(butyl{[(3-cyano-4-forfinal)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf to 0.66 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1), the 4.29 (s, 2H), 7,02-7,07 (m, 4H), 7.23 percent-7,31 (m, 3H), 7,50 (d, J=8.7 Hz, 2H), 7,66 (m, 1H), to $ 7.91 (m, 1H).

Example 29 (103):

N-[4-(4-{[4-(butyl{[(5-cyano-2,4-differenl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf of 0.64 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,29 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,35 (m, 1H) 7,49 (d, J=8,9 Hz, 2H), 7,87 (m, 1H).

Example 29 (104):

N-[4-(4-{[4-((2-forfinal){[(4-forfinal)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,51 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1.55V and 1.80 (m, 2H), 2,16-of 2.23 (m, 2H), 2.95 and (s, 3H), 3,10-up 3.22 (m, 2H), 3,47 of 3.56 (m, 2H), 4,23 (s, 2H), with 4.64 (m, 1H), 6,93-7,06 (m, 6H), 7,20 was 7.45 (m, 9H), 7,51 (m, 1H).

Example 29 (105):

N-[4-(4-{[4-((3-forfinal){[(4-forfinal)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf value of 0.52 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,63-to 1.82 (m, 2H), 2,12-of 2.23 (m, 2H), 2.95 and (s, 3H), 3,10-is 3.21 (m, 2H), 3,44-3,55 (m, 2H), 4,23 (s, 2H), with 4.64 (m, 1H), 6,93-7,07 (m, 6H), to 7.15 (d, J=6,9 Hz, 2H), 7,20-to 7.32 (m, 5H), 7,42 (d, J=8.7 Hz, 2H), 7,54 (kV, J=6,9 Hz, 1H).

Example 29 (106):

N-[4-(4-{[4-((4-forfinal){[(4-forfinal)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,54 (methylene chloride:methanol=9:1);

NMR (CD3O): δ 1,59-to 1.79 (m, 2H), 2,10-of 2.20 (m, 2H), 2.95 and (s, 3H), 3,09-is 3.21 (m, 2H), 3.45 points-of 3.54 (m, 2H), 4,22 (s, 2H), with 4.64 (m, 1H), 6,91-7,05 (m, 6H), 7,20-7,38 (m, 8H), the 7.43 (d, J=8.7 Hz, 2H).

Example 29 (107):

N-[4-(4-{[4-(butyl{[(4-cyano-2-forfinal)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,81 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 7,02-7,07 (m, 4H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (m, 1H), 7,50 (d, J=8.7 Hz, 2H), 7,56 (DD, J=10,5, 1.8 Hz, 1H), 7,83 (m, 1H).

Example 29 (108):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(pyridin-3-yl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide the dihydrochloride

TLC: Rf 0,46 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,95 is 2.10 (m, 2H), 2,18-of 2.24 (m, 2H), 2.95 and (s, 3H), 3,11-of 3.23 (m, 2H), 3,49-to 3.58 (m, 2H), 4.26 deaths (s, 2H), with 4.64 (m, 1H), 6,97-7,07 (m, 6H), 7,26-7,35 (m, 4H), 7,50 (d, J=8.7 Hz, 2H), 8,15 (DD, J=8,7, 5,7 Hz, 1H), 8,58 (l kV, J=8,7, 2.4 Hz, 1H), 8,89 (d, J=5.7 Hz, 1H), 9,04 (d, J=2.4 Hz, 1H).

Example 29 (109):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(2-were)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.57 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 1.62 (m, 1H), 1,97 is 2.10 (m, 2H), 2,28-to 2.40 (m, 4H), 2.95 and (s, 3H), 3,07-3,20 (m, 2H), 3,40 is 3.57 (m, 2H), 4,22 (s, 2H), 4,55 (m, 1H), 6,95 (t, J=9.0 Hz, 2H), 7,01 (d, J=8.7 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,08-7,47 (m, 10H).

Example 29 (110):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(3-were)-amine is]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.57 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,62 and 1.80 (m, 2H), 2,11-of 2.20 (m, 2H), 2.40 a (s, 3H), 2.95 and (s, 3H), 3,09-is 3.21 (m, 2H), 3.45 points-of 3.54 (m, 2H), 4,23(s, 2H), 4,63 (m, 1H), 6,95 (t, J=9.0 Hz, 2H), 7,01 (d, J=8.7 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,12 (d, J=7.5 Hz, 1H), 7,15 (s, 1H), 7,21 (DD, J=9,0, 5.0 Hz, 2H), 7,25-7,35 (m, 3H), 7,40 (d, J=7.5 Hz, 1H), 7,42 (d, J=8.7 Hz, 2H).

Example 29 (111):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(4-were)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,58 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,59-of 1.78 (m, 2H), 2,10-of 2.20 (m, 2H), 2.40 a (s, 3H), 2.95 and (s, 3H), is 3.08-3,20 (m, 2H), 3,44-to 3.50 (m, 2H), is 4.21 (s, 2H), 4,67 (m, 1H), 6,95 (t, J=9.0 Hz, 2H), 6,98-was 7.08 (m, 4H), 7.18 in-of 7.23 (m, 4H), 7,29 (d, J=8.7 Hz, 2H), was 7.36 (d, J=7.8 Hz, 2H), 7,42 (d, J=8.7 Hz, 2H).

Example 29 (112):

N-[4-(4-{[4-(butyl{[(2-hydroxyphenyl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf to 0.63 (ethyl acetate);

NMR (CD3OD): δ 1.00 each (t, J=7.2 Hz, 3H), 1,37-1,49 (m, 2H), 1,63-1,71 (m, 2H), 1,98-2,03 (m, 2H), 2,14-of 2.27 (m, 2H), 2,96 (s, 3H), 3,09-3,17 (m, 2H), 3.25 to 3.30 is (m, 2H), 3,55-3,59 (m, 2H), 4,24 (m, 1H), 4,30 (s, 2H), 6,76-6,94 (m, 3H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,30 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H), to 7.59 (DD, J=7,8, 1.5 Hz, 1H).

Example 29 (113):

N-{2-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.50 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 2,00-2,10 (m, 2H), 2,10-of 2.20 (m, 2H), 2.95 and(C, 3H), of 2.97 (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,60-of 3.80 (m, 2H), 4,20 (m, 1H), 4,29 (s, 2H), 7,02-was 7.08 (m, 4H), to 7.15 (m, 1H), 7,26-7,31 (m, 4H), 7,50 (d, J=9.0 Hz, 2H), of 7.75 (d, J=8,1 Hz, 1H).

Example 29 (114):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(4-methylbenzyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,71 (chloroform:methanol=5:1);

NMR (CD3OD): δ 7,47 (user. d, J=8.7 Hz, 2H), was 7.36-7,14 (m, 8H), 7,10-6,92 (m, 6H), 4,60 (user. s, 2H), 4,37 (m, 1H), 4,25 (s, 2H), 3,50 (m, 2H), to 3.09 (m, 2H), 2.95 and (s, 3H), of 2.30 (s, 3H), 2.26 and-of 1.84 (m, 4H).

Example 29 (115):

N-[4-(4-{[4-(butyl{[(3,4-dihydroxyphenyl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.40 (chloroform:methanol=10:1);

NMR (CD3OD): δ of 0.96 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), to 6.58 (DD, J=8,4, 2.4 Hz, 1H), of 6.68 (d, J=8,4 Hz, 1H), 6,79 (d, J=2.4 Hz, 1H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,50 (d, J=8,9 Hz, 2H).

Example 29 (116):

N-[4-(4-{[4-((cyanomethyl){[(4-forfinal)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.55 (chloroform:methanol=5:1);

NMR (CD3OD): δ 2.00 in 2,28 (m, 4H), 2.95 and (s, 3H), 3.00 and-3,10 (m, 2H), 3,50-the 3.65 (m, 2H), 4.04 the-4,30 (m, 5H), 7,00-7,20 (m, 4H), 7,25-7,52 (m, 8H).

Example 29 (117):

N-{4-[4-({4-[butyl({[3-(2H-tetrazol-5-yl)phenyl]amino}-carbonyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,09 (PI is reform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), of 1.40 (m, 3H), of 1.62 (m, 3H), of 1.88 (m, 2H), 2,60 (m, 4H), to 2.94 (s, 3H), 3,24 (m, 2H), 3,92 (s, 2H), 4,18 (m, 1H), 7,00 (m, 4H), 7,20 is 7.50 (m, 5H), 7,71 (user. d, J=7.8 Hz, 1H), 7,86 (m, H).

Example 29 (118):

N-[4-(4-{[4-(but-3-EN-1-yl{[(6-methylpyridin-3-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf 0,51 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,98-of 2.09 (m, 2H), 2,22 at 2.45 (m, 4H), 2,70 (s, 3H), 2.95 and (s, 3H), 3,12-of 3.25 (m, 2H), 3,42 (t, J=7.8 Hz, 2H), 3,54-3,66 (m, 2H), 4.26 deaths (m, 1H), or 4.31 (s, 2H), 5,08 (d, J=10,2 Hz, 1H), 5,15 (d, J=17.1 to Hz, 1H), to 5.85 (m, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,07 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,52 (d, J=8.7 Hz, 2H), 7,80 (d, J=9.0 Hz, 1H), of 8.47 (DD, J=9,0, 2.4 Hz, 1H), 9,02 (d, J=2.4 Hz, 1H).

Example 29 (119):

N-(4-{4-[(4-{but-3-EN-1-yl[(cyclobutylamine)carbonyl]amino}piperidine-1-yl)methyl]phenoxy}phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,61 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,62-of 1.74 (m, 2H), 1,88 to 2.35 (m, 10H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 2H), 3,20 (t, J=7.8 Hz, 2H), 3,50-3,59 (m, 2H), 4,06 (m, 1H), 4,20 (m, 1H), 4,28 (s, 2H), of 5.05 (d, J=10,2 Hz, 1H), 5,11 (DD, J=17,1, and 2.1 Hz, 1H), of 5.81 (m, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 29 (120):

N-{4-[4-({4-[[(cyclobutylamine)carbonyl](3-methylbut-2-EN-1-yl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf 0,60 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1.60-to to 2.18 (m, 14H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,02 is 3.15 (m, 2H), 3,49-3,59 (m, 2H), of 3.77-3,82 (m, 2H), 4,15-of 4.25 (m, 2H), 4,27 (s, 2H), 5,0 (m, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H).

Example 29 (121):

N-{4-[4-({4-[{[(CIS-4-hydroxycyclohexyl)amino]carbonyl}(3-methylbut-2-EN-1-yl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.45 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,54 is 1.70 (m, 8H), of 1.74 (s, 6H), 1,80-2,10 (m, 4H), 2.95 and (s, 3H), 3,05 is 3.15 (m, 2H), 3,49-3,66 (m, 3H), 3,74-a-3.84 (m, 3H), 4,27 (s, 2H), or 4.31 (m, 1H), 5,08 (m, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 29 (122):

N-{4-[4-({4-[{[(CIS-4-hydroxycyclohexyl)amino]carbonyl}(2-methylbenzyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf 0,51 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,50-1,60 (m, 8H), 1,90-2,03 (m, 4H), of 2.33 (s, 3H), 2.95 and (s, 3H), 3,02-3,14 (m, 2H), 3.45 points-of 3.53 (m, 2H), 3,63 (m, 1H), 3,79 (m, 1H), 4,24 (s, 2H), and 4.40 (s, 2H), of 4.45 (m, 1H), 7,01 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,07-7,21 (m, 4H), 7,28 (d, J=8.7 Hz, 2H), 7,46 (d, J=8.7 Hz, 2H).

Example 29 (123):

N-[4-(4-{[4-((2-methylbenzyl){[(1-methyl-1H-pyrazole-4-yl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf of 0.53 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1.91 a-2,19 (m, 4H), to 2.35 (s, 3H), 2.95 and (s, 3H), 3,06-3,17 (m, 2H), 3,44-to 3.52 (m, 2H), of 3.94 (s, 3H), 4,29 (s, 2H), 4,49 (m, 1H), to 4.52 (s, 2H), 7,02 (d, J=8.7 Hz, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06-7,20 (m, 4H), 7,28 (d, J=8.7 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H), to 7.77 (s, 1H), 7,94 (s, 1H).

Example 29 (124):

N-(4-{4-[(4-{{[(1-methyl-1H-pyrazole-4-yl)amino]carb the Nile}[(3-methylpyridin-2-yl)methyl]amino}piperidine-1-yl)methyl]phenoxy}-phenyl)methanesulfonamide trihydrochloride

TLC: Rf 0,49 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 2,00 is 2.10 (m, 2H), 2,18 to 2.35 (m, 2H), 2.63 in (s, 3H), 2.95 and (s, 3H), 3,18-to 3.34 (m, 2H), 3,50-3,60 (m, 2H), 3.96 points (s, 3H), 4,32 (s, 2H), 4,54 (m, 1H), 4,91 (s, 2H), 7,02 (d, J=8.7 Hz, 2H),? 7.04 baby mortality (d, J=to 8.7 Hz, 2H), 7,28 (d, J=8.7 Hz, 2H), EUR 7.57 (d, J=8.7 Hz, 2H), 7,89 (DD, J=7,8, 6.0 Hz, 1H), 7,94 (s, 1H), of 8.06 (s, 1H), 8,45 (d, J=7.8 Hz, 1H), 8,54 (d, J=6.0 Hz, 1H).

Example 29 (125):

N-[4-(4-{[4-((3-methylbut-2-EN-1-yl){[(1-methyl-1H-pyrazole-4-yl)amino]carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf value of 0.52 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,72 (s, 3H), at 1.73 (s, 3H), 1,90-2,22 (m, 4H), 2.95 and (s, 3H), is 3.08-3,20 (m, 2H), 3,50-3,60 (m, 2H), 3,90-of 3.97 (m, 2H), of 3.97 (s, 3H), 4,23-4,32 (m, 3H), 5,12 (m, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H), a 7.85 (s, 1H), 7,98 (s, 1H).

Example 29 (126):

N-{3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]-2,4-differenl}ndimethylacetamide hydrochloride

TLC: Rf of 0.44 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), and 2.14 (s, 3H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), to 4.28 (s, 2H), 6,97-was 7.08 (m, 5H), 7,29 (d, J=9.0 Hz, 2H), 7,49 (d, J=9.0 Hz, 2H), 7,65 (m, 1H).

Example 29 (127):

N-{5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]-2,4-differenl}-ndimethylacetamide hydrochloride

TLC: Rf of 0.56 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1.60-to 170 (m, 2H), 1,90-2,10 (m, 2H), and 2.14 (s, 3H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), 4,28 (s, 2H), 7,02-7,10 (m, 5H), 7,29 (d, J=8,9 Hz, 2H), 7,49 (d, J=8,9 Hz, 2H), 7,95 (t, J=7.5 Hz, 1H).

Example 29 (128):

N-{3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]-4-forfinal}ndimethylacetamide hydrochloride

TLC: Rf of 0.48 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.5 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,10 (s, 3H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,15 (m, 1H), the 4.29 (s, 2H), 7,02-to 7.09 (m, 5H), 7,25 (m, 1H), 7,29 (d, J=8.7 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H), to 7.77 (DD, J=6,9, and 2.4 Hz, 1H).

Example 29 (129):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(tetrahydro-2H-Piran-4-yl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf of 0.50 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,65-of 1.78 (m, 2H), 1,80-1,90 (m, 2H), 1,95-of 2.08 (m, 2H), 2,78 of 2.92 (m, 2H), 2.95 and (s, 3H), 3,03-3,18 (m, 2H), 3,47-of 3.60 (m, 5H), 3,88-of 4.05 (m, 3H), 4,27 (s, 2H), 6,97-to 7.09 (m, 6H), 7.23 percent-7,31 (m, 4H), of 7.48 (d, J=8.7 Hz, 2H).

Example 29 (130):

N-[4-(4-{[4-(butyl{[(1,3-dimethyl-1H-pyrazole-4-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf to 0.66 (chloroform:methanol=4:1);

NMR (CD3OD): δ 0,97 (t, J=7.5 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2,28 (s, 3H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 3,99 (s, 3H), 4,20 (m, 1H), 4,29 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=9.0 Hz, 2H), 7,52 (d, J=9.0 Hz, 2H), 7,95 (m, 1H).

Primer (131):

N-[4-(4-{[4-({[(4-forfinal)amino]carbonyl}{[3-(trifluoromethyl)pyridin-2-yl]methyl}amino)piperidine-1-yl]methyl}-phenoxy)phenyl]methanesulfonamide the dihydrochloride

TLC: Rf 0.56 to (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,95-2,12 (m, 4H), 2.95 and (s, 3H), is 3.08 3.21-in (m, 2H), 3,47-to 3.58 (m, 2H), 4,27 (s, 2H), to 4.38 (m, 1H), 4,90 (s, 2H), 6,95-7,06 (m, 6H), 7,25-7,35 (m, 4H), of 7.48 (d, J=8.7 Hz, 2H), 7.62mm (DD, J=8,0, 5.0 Hz, 1H), 8,28 (d, J=8.0 Hz, 1H), 8,81 (d, J=5.0 Hz, 1H).

Example 30 (1) 30 (12)

Using the same procedure as described in example 25, using the appropriate amine derivative instead of (3-{[tert-butyl(dimethyl)silyloxy}butyl)amine get the following compounds of the present invention.

Example 30 (1):

N-[4-(4-{[4-(butyl{[(3S)-piperidine-3-ylamino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide the dihydrochloride

TLC: Rf of 0.15 (n-butanol:acetic acid:water=4:2:1);

NMR (DMSO-d6): δ of 0.91 (t, J=7,1 Hz, 3H), 1,20-1,40 (m, 2H), 1,40-1,60 (m, 2H), 1,60-2,00 (m, 6H), 2,20-2,40 (m, 2H), 2,80-of 3.60 (m, 10H), 2,96 (s, 3H), 3,99 (m, 1H), 4,15 (m, 1H), 4,18 (s, 2H), 6,23 (m, 1H), 7,03 (d, J=7.2 Hz, 4H), 7,28 (d, J=8.7 Hz, 2H), to 7.61 (d, J=8.7 Hz, 2H), 8,83 (m, 1H), 9,35 (m, 1H), for 9.47 (m, 1H).

Example 30 (2):

N-[4-(4-{[4-(butyl{[(3R)-piperidine-3-ylamino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide the dihydrochloride

TLC: Rf of 0.15 (n-butanol:acetic acid:water=4:2:1);

NMR (DMSO-d6): δ of 0.91 (t, J=7.4 Hz, 3H), 1,20-1,40 (m, 2H, 1,40-1,60 (m, 2H), 1,60-2,00 (m, 6H), 2,20-2,40 (m, 2H), 2,80-of 3.60 (m, 10H), 2,96 (s, 3H), 3,98 (m, 1H), 4,15 (m, 1H), 4,20 (s, 2H), from 6.22 (m, 1H), 7,03 (d, J=8.7 Hz, 4H), 7,28 (d, J=7.7 Hz, 2H), to 7.61 (d, J=7.7 Hz, 2H), 8,83 (m, 1H), 9,36 (m, 1H), for 9.47 (m, 1H).

Example 30 (3):

N-[4-(4-{[4-(butyl{[(3-metalization-5-yl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf of 0.35 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 2,00-2,10 (m, 2H), 2,30-to 2.40 (m, 2H), has 2.56 (s, 3H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), or 4.31 (s, 2H), 7,02-was 7.08 (m, 5H), 7,29 (d, J=8,9 Hz, 2H), 7,53 (d, J=8,9 Hz, 2H).

Example 30 (4):

N-[4-(4-{[4-(butyl{[(3-methyl-1,2-benzisothiazol-5-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide hydrochloride

TLC: Rf and 0.46 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,80 (m, 2H), 2,00-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2,70 (s, 3H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,30 (s, 2H), 7,02-was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,52 (d, J=8,9 Hz, 2H), 7,60 (DD, J=9,0, 1.7 Hz, 1H), of 7.90 (d, J=9.0 Hz, 1H), 8,08 (d, J=1.7 Hz, 1H).

Example 30 (5):

N-[4-(4-{[4-(butyl{[(1-methyl-1H-pyrazole-5-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf of 0.30 (chloroform:methanol=10:1);

NMR (CD3OD): δ 0,98 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 2,00-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), of 3.78 (s, 3H), 4,20 (m, 1H), the 4.29 (s, 2H), 6,34 (d, J=2.4 Hz, 1H), 7.0 and was 7.08 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,51 (d, J=8,9 Hz, 2H), 7,79 (d, J=2.4 Hz, 1H).

Example 30 (6):

N-[4-(4-{[4-(butyl{[(3-hydroxycyclohexyl)amino]carbonyl}-amino)piperidine-1-yl]methyl}phenoxy)phenyl]methanesulfonamide hydrochloride

TLC: Rf 0,24 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 0.95 (t, J=7.2 Hz, 3H), 1,23-of 2.20 (m, 16H), 2,95 (s, 3H), 3,02-and 3.16 (m, 4H), 3,50-3,59 (m, 2H), 3,66 (m, 1H), 3.95 to 4,22 (m, 2H), 4,28 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H).

Example 30 (7):

N-[4-(4-{[4-(butyl{[(1,3,5-trimethyl-1H-pyrazole-4-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf of 0.60 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), and 2.27 (s, 6H), 2.95 and (s, 3H), of 3.10-3.20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 3,93 (s, 3H), 4,24 (m, 1H), 4,30 (s, 2H), 7,02-7,07 (m, 4H), 7,29 (d, J=8.7 Hz, 2H), 7,54 (d, J=8.7 Hz, 2H).

Example 30 (8):

hydrochloride 5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)piperidine-4-yl]amino}carbonyl)amino]-2,4-diferential acid

TLC: Rf to 0.17 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-of 2.30 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,25 (s, 2H), 7,01-7,06 (m, 5H), 7,29 (d, J=8.7 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H), 7,89 (m, 1H).

Example 30 (9):

hydrochloride 5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)piperidine-4-yl]amino}carbonyl)amino]-2-Torben oinoi acid

TLC: Rf 0.21 in (ethyl acetate:methanol=7:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,30 (s, 2H), 7,02-was 7.08 (m, 4H), 7,12 (d, J=9.0 Hz, 1H), 7,29 (d, J=8.7 Hz, 2H), 7,53 (d, J=8.7 Hz, 2H), 7,58 (m, 1H), 7,92 (m, 1H).

Example 30 (10):

hydrochloride 3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)piperidine-4-yl]amino}carbonyl)amino]-2,6-diferential acid

TLC: Rf 0.21 in (ethyl acetate:methanol=7:1);

NMR (CD3OD): δ 0,97 (t, J=7.4 Hz, 3H), 1,30-1,50 (m, 2H), 1,60-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,20-3,40 (m, 2H), 3,50-3,60 (m, 2H), 4,20 (m, 1H), 4,28 (s, 2H), make 6.90 (m, 1H), 7,02-7,07 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,40 (m, 1H), 7,50 (d, J=8,9 Hz, 2H).

Example 30 (11):

2,4-debtor-5-[({[(3-methylpyridin-2-yl)methyl][1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-yl]amino}-carbonyl)amino]benzamide the dihydrochloride

TLC: Rf 0,70 (chloroform:methanol=4:1);

NMR (CD3OD): δ 2,10-of 2.20 (m, 2H), 2,20-2,40 (m, 2H), 2,62 (s, 3H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,50-3,60 (m, 2H), or 4.31 (s, 2H), 4,50 (m, 1H), 7,00-7,06 (m, 4H), 7,17 (t, J=10,2 Hz, 1H), 7,28 (d, J=9.0 Hz, 2H), 7,56 (d, J=9.0 Hz, 2H), of 7.90-7,98 (m, 2H), 8,44 (d, J=7.2 Hz, 1H), to 8.57 (d, J=8.7 Hz, 1H).

Example 30 (12):

5-[({but-3-EN-1-yl[1-(4-{4-[(methylsulphonyl)amino]-phenoxy}benzyl)piperidine-4-yl]amino}carbonyl)amino]-2,4-diflorasone hydrochloride

TLC: Rf to 0.63 (chloroform:methanol=4:1);

NMR (CD3OD): δ 2,10-of 2.20 (m, 2H), 2,20-of 2.30 (m, 2H), 2.40 a-2,50 (m, 2H), 2.95 and (s, 3H), 3,00-3,20 (m, 2H), 3,30 is 3.40 (m, 2H) 3,50-3,60 (m, 2H), 4,10 (m, 1H), 4,29 (s, 2H), 5.08 to 5,19 (m, 2H), to 5.85 (m, 1H), 7,02-was 7.08 (m, 4H), 7,14 (t, J=10.4 Hz, 1H), 7,29 (d, J=8,9 Hz, 2H), 7,49 (d, J=8,9 Hz, 2H), 7,86 (m, 1H).

Example 31 (1) and example 31 (2)

Using the same procedure as described in example 27, using O-benzylhydroxylamine or the corresponding amine derivative and using the compound obtained in example 3 instead of N-(4-{4-[(4-aminopiperidin-1-yl)methyl]phenoxy}phenyl)methanesulfonamide get the following compounds of the present invention.

Example 31 (1):

N-{4-[4-({4-[{[(benzyloxy)amino]carbonyl}(butyl)amino]-piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide hydrochloride

TLC: Rf of 0.53 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ of 0.90 (t, J=7.2 Hz, 3H), 1,21-of 1.32 (m, 2H), 1,40-of 1.52 (m, 2H), 1,87-of 1.97 (m, 2H), 2,11-of 2.30 (m, 2H), 2.95 and (s, 3H), 2,98-3,13 (m, 4H), 3,47-to 3.58 (m, 2H), 3,97 (m, 1H), 4,27 (s, 2H), 4,79 (s, 2H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,27-7,44 (m, 7H), 7,49 (d, J=8.7 Hz, 2H).

Example 31 (2):

N-[4-(4-{[4-(butyl{[(2-methyl-1,3-benzothiazol-6-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide the dihydrochloride

TLC: Rf 0,74 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 0.96 (t, J=7,1 Hz, 3H), 1,30-1,50 (m, 2H), 1,50-1,70 (m, 2H), 1,90-2,10 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), 2,99 (s, 3H), 3,10-3,30 (m, 2H), 3,30 is 3.40 (m, 2H), 3,50-3,60 (m, 2H), 4,30 (m, 1H), or 4.31 (s, 2H), 7,01-7,05 (m, 4H), 7,29 (d, J=8,9 Hz, 2H), 7,56 (d, J=8,9 Hz, 2H), to 7.67 (d, J=8,3 Hz, 1H), of 7.97 (d, J=8,3 Hz, 1H), 8,23 (s, 1H).

Example 32:

p> N-[4-(4-{[4-([(3,5-dimethylisoxazol-4-yl)methyl]{[(4-forfinal)amino]carbonyl}amino)piperidine-1-yl]methyl}-phenoxy)phenyl]methanesulfonamide hydrochloride

Using the same procedure as described in example 1, using N-(4-{4-[(4-aminopiperidin-1-yl)methyl]phenoxy}phenyl)methanesulfonamide used in example 27, and 3.5-dimethylisoxazol-4-carboxylic aldehyde instead of 4-hydroxypiperidine and 4-(4-methylsulfonylmethane)-benzaldehyde respectively receive the connection. Using the same procedure as described in example 23, using the compounds and 4-fermenting acid instead of the compound obtained in example 3 and 1-methylcyclohexane respectively, receive specified in the header connection (100,2 mg)having the following physical data.

TLC: Rf 0.56 to (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1.91 a is 2.00 (m, 2H), 2,12 of-2.32 (m, 2H, in), 2.25 (s, 3H), 2,39 (s, 3H), 2.95 and (s, 3H), 3,02-and 3.16 (m, 2H), 3,48 is 3.57 (m, 2H), of 4.05 (m, 1H), 4.26 deaths (s, 2H), 4,42 (s, 2H), 6,97-was 7.08 (m, 6H), 7,25-7,37 (m, 4H), 7,49 (d, J=8.7 Hz, 2H).

Example 32 (1) example 32 (4)

Using the same procedure as described in example 32, using the appropriate aldehyde derivative instead of 3,5-dimethylisoxazol-4-carboxylic aldehyde get the following compounds of the present invention.

Example 32 (1):

N-[4-(4-{[4-([(5-chloro-1,3-dimethyl-1H-pyrazole-4-the l)methyl]-{[(4-forfinal)amino]carbonyl}amino)piperidine-1-yl]methyl}-phenoxy)phenyl]methanesulfonamide the dihydrochloride

TLC: Rf of 0.55 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,92 is 2.01 (m, 2H), 2,15-2,31 (m, 2H), of 2.23 (s, 3H), 2.95 and (s, 3H), 3.00 and is 3.15 (m, 2H), 3,43-3,55 (m, 2H), 3,76 (s, 3H), 4,01 (m, 1H), 4,25 (s, 2H), 4,48 (s, 2H), 6,97-was 7.08 (m, 6H), 7,25-7,37 (m, 4H), 7,49 (d, J=8.7 Hz, 2H).

Example 32 (2):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(1,3-thiazol-4-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide hydrochloride

TLC: Rf is 0.42 (chloroform:methanol=5:1);

NMR (CD3OD): δ 1,92-2,04 (m, 2H), 2,16 is 2.33 (m, 2H), 2.95 and (s, 3H), 3,11 (m, 2H), 3,54 (m, 2H), 4,29 (s, 2H), or 4.31 (m, 1H), 4,69 (s, 2H), 6,98-was 7.08 (m, 6H), 7,22-7,40 (m, 4H), 7,44-7,58 (m, 2H), to 7.64 (m, 1H), which 9.22 (m, 1H).

Example 32 (3):

N-(4-{4-[(4-{{[(4-forfinal)amino]carbonyl}[(6-oxo-1,6-dihydropyridines-2-yl)methyl]amino}piperidine-1-yl)methyl]phenoxy}-phenyl)methanesulfonamide hydrochloride

TLC: Rf 0,17 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 2,00-2,30 (m, 4H), 2.95 and (s, 3H), 3,10-up 3.22 (m, 2H), 3,50-3,62 (m, 2H), 4,30 (s, 2H), to 4.38 (m, 1H), 4,57 (s, 2H), 6,78 (d, J=9.0 Hz, 1H), PC 6.82 (d, J=7.5 Hz, 1H), 7,01 (t, J=9.0 Hz, 2H), 7,02 (d, J=8,7 Hz, 2H), 7,05 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,37 (DD, J=9,0, 5.0 Hz, 2H), 7,53 (d, J=8.7 Hz, 2H), of 7.90 (DD, J=9,0, 7.5 Hz, 1H).

Example 32 (4):

N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(1H-imidazol-4-ylmethyl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}-methanesulfonamide the dihydrochloride

TLC: Rf 0,13 (methylene chloride:methanol=9:1);

NMR (CD3OD): δ 1,97-of 2.08 (m, 2H), 2,20-2,40 (m, 2H), 2.95 and (s, 3H), is 3.08 3.21-in (m, 2H), 3,52-2,60 (m, 2H), 4,25-and 4.40 (m, 3H), to 4.62 (s, 2H), 6,98-was 7.08 (m, 6H), 7,29 (d, J=8.7 Hz, 2H), 7,40 (DD, J=9,0, 5.0 Hz, 2H), 7,51 (s, 1H), 756 (d, J=8.7 Hz, 2H), 8,80 (s, 1H).

Example 33:

4-[4-({4-[(allyloxy)imino]piperidine-1-yl}methyl)phenoxy]-N-methylbenzamide hydrochloride

Using the same procedure as described in example 16, using N-methyl-4-{4-[(4-oxopiperidin-1-yl)methyl]phenoxy}benzamide and O-arylhydroxylamine instead of the compound obtained in example 15, and n-butylamine respectively receive the connection according to the present invention having the following physical data.

TLC: Rf of 0.60 (chloroform:methanol=10:1);

NMR (CD3OD): δ to 7.84 (d, J=9.0 Hz, 2H), EUR 7.57 (d, J=8,4 Hz, 2H), 7,15 (d, J=8,4 Hz, 2H), was 7.08 (d, J=9.0 Hz, 2H), 5,97 (m, 1H), 5,30-of 5.15 (m, 2H), 4,54 (dt, J=5,7, 1.5 Hz, 2H), to 4.38 (s, 2H), 3,68-3,59 (m, 2H), 3,44 (m, 1H), 3,23-of 3.07 (m, 2H), 2.91 in (s, 3H), of 2.68 2.63 in (m, 2H), 2.40 a (m, 1H).

Comparative example 11:

2-[4-(4-nitrophenoxy)phenyl]ethanol

To a solution of 4-(2-hydroxyethyl)phenol (2,94 g) and 1-fluoro-4-nitrobenzene (3.0 g) in dimethylformamide (21 ml) is added potassium carbonate (to 4.41 g) and the solution stirred at 120°C for 4 hours. After cooling to room temperature, water is added to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to obtain specified in the header with the unity, having the following physical data.

TLC: Rf to 0.80 (chloroform:methanol=5:1).

Comparative example 12:

2-[4-(4-aminophenoxy)phenyl]ethanol

In hydrogen atmosphere to a solution of the compound obtained in comparative example 11 (803 mg)in ethanol (15 ml) is added palladium on coal (wet, 10%, 100 mg) at room temperature for 1.5 hours. The reaction solution is filtered through CELITE (trade name) and concentrate. The obtained residue was washed with tert-butoxymethyl obtaining specified in the connection header (to 641.5 mg)having the following physical data.

TLC: Rf of 0.55 (chloroform:methanol=5:1);

NMR (CDCl3): δ of 1.37 (t, J=6,6 Hz, 1H), and 2.83 (t, J=6.6 Hz, 2H), only 3.57 (m, 2H), 3,84 (kV, J=6,6 Hz, 2H), 6,62-6,70 (m, 2H), 6,80-6,92 (m, 4H), 7,12-7,20 (m, 2H).

Comparative example 13:

2-(4-{4-[bis(methylsulphonyl)amino]phenoxy}phenyl)ethyl methanesulfonate

To a solution of the compound obtained in comparative example 12 (196,5 mg)in methylene chloride (8.6 ml) is added triethylamine (0,239 ml) and methylchloride (of 0.133 ml) at 0°C for 30 minutes. The reaction solution was stirred at room temperature for 12 hours. Add aqueous sodium bicarbonate solution to the reaction solution, extracted with methylene chloride. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated to obtain is shown in the connection header (292,4 mg), having the following physical data.

TLC: Rf 0,89 (chloroform:methanol=5:1);

NMR (CD3OD): δ of 2.97 (s, 3H), 3,05 (t, J=6.6 Hz, 2H), 3,41 (s, 6H), 4,43 (t, J=6.6 Hz, 2H), 6,98-was 7.08 (m, 4H), 7,30-7,42 (m, 4H).

Example 34:

N-(4-{4-[2-(4-{butyl[(cyclohexylamino)carbonyl]amino}-piperidine-1-yl)ethyl]phenoxy}phenyl)-N-(methylsulphonyl)-methanesulfonamide

To a solution of the compound obtained in comparative example 13 (68.6 mg), and N-butyl-N'-cyclohexyl-N-piperidine-4-rocephine (100 mg) in dimethylformamide (2 ml), add triethylamine (60,2 μl) and sodium iodide (64,6 mg) at room temperature for 12 hours. Add water to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (hexane:ethyl acetate=2:1) to give the compounds of the present invention (to 32.2 mg)having the following physical data.

TLC: Rf 0,74 (chloroform:methanol=5:1).

Example 35:

N-(4-{4-[2-(4-{butyl[(cyclohexylamino)carbonyl]amino}-piperidine-1-yl)ethyl]phenoxy}phenyl)methanesulfonamide hydrochloride

To a solution of the compound obtained in example 34 (32,2 mg)in ethanol (5 ml) and water (1 ml) is added potassium carbonate (13,7 mg) and the solution stirred at 60°C for 3 h for the owls. The reaction solution concentrate. The resulting residue is purified by column chromatography on silica gel (ethyl acetate) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (30,3 mg)having the following physical data.

TLC: Rf 0,69 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,97 (t, J=7.2 Hz, 3H), 2.00 in of 1.10 (m, 16H), 2,25-of 2.08 (m, 2H), 2,93 (s, 3H), 3,16-3,00 (m, 6H), 3,38-3,24 (m, 2H), 3,38-3,24 (m, 2H), 3,55 (m, 1H), 3,71 (m, 2H), 4,13 (m, 1H), 7,00-of 6.90 (m, 4H), 7,32-7,20 (m, 4H).

Comparative example 14:

tert-butyl[1-(4-hydroxyphenyl)ethyl]carbamate

To a solution of 4-(1-amino-ethyl)phenol (1.0 g) in ethanol (24 ml) is added di-tert-butyl dicarbonate (4.77 g) and sodium hydroxide (146 mg)at 0°C and the solution was stirred at room temperature for 4.5 hours. The reaction solution concentrate and add water to it. The solution is extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (hexane:ethyl acetate=7:1) to obtain specified in the connection header (2,18 g)having the following physical data.

TLC: Rf 0,88 (chloroform:methanol=5:1);

NMR (CDCl3): δ 1,36 of 1.50 (m, 13H), 4,79 (m, 1H), 7,10-to 7.18 (m, 2H), 7,26-to 7.32 (m, 2H).

Comparative example 15:

{1-[4-(4-nitrophenoxy)FeNi is]ethyl}amine hydrochloride

To a solution of the compound obtained in comparative example 14 (2,18 g)and 1-fluoro-4-nitrobenzene (1,028 g) in dimethylformamide (30 ml) is added potassium carbonate (1,21 g) and the solution stirred at 150°C for 3 hours. After cooling to room temperature, water is added to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (hexane:ethyl acetate=6:1). To a solution of compound (2,05 g) in ethyl acetate (30 ml) add a solution of 4 N. hydrochloric acid/ethyl acetate (7,15 ml). The solution was stirred at 40°C for 4 hours and additionally at room temperature for 3 days. The precipitate is collected to obtain specified in the connection header (1,37 g)having the following physical data.

NMR (DMSO-d6): δ of 1.52 (d, J=6.6 Hz, 3H), of 4.45 (m, 1H), 7,12 (user. d, J=9,3 Hz, 2H), 7,26 (user. d, J=8.7 Hz, 2H), 7.62mm (user. d, J=8.7 Hz, 2H), 8,28 (user. d, J=9,3 Hz, 2H), 8,44 (m, 2H).

Example 36:

1-{1-[4-(4-nitrophenoxy)phenyl]ethyl}piperidine-4-one hydrochloride

To a solution of the compound obtained in comparative example 15 (550 mg)in ethanol (was 9.33 ml) and water (4,67 ml) is added N-benzyl-N-methyl-4-piperidone iodide (927 mg) and potassium carbonate (670 mg) and the solution heated under reflux in those who tell 5 hours. After cooling to room temperature, water is added to the reaction solution, extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (hexane:ethyl acetate=3:1) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (515 mg)having the following physical data.

TLC: Rf 0,79 (chloroform:methanol=9:1);

NMR (DMSO-d6): δ of 1.75 (d, J=6.9 Hz, 3H), 2,38-3,20 (m, 6H), 3,52 (m, 1H), 3,82 (m, 1H), 4,78 (m, 1H), 7,19 (d, J=9.0 Hz, 2H), 7,29 (d, J=9.0 Hz, 2H), 7,73 (d, J=9.0 Hz, 2H), of 8.27 (d, J=9.0 Hz, 2H).

Example 37:

N-(4-{4-[1-(4-{butyl[(cyclohexylamino)carbonyl]amino}-piperidine-1-yl)ethyl]phenoxy}phenyl)methanesulfonamide hydrochloride

Using the same procedure as described in example 3 using the compound obtained in example 36, instead of the compound obtained in example 2, get a connection. Using the same procedure as described in example 23→comparative example 12→comparative example 13, using the compounds and cyclohexylcarbamate acid get a connection according to the present invention (107 mg)having the following physical data.

TLC: Rf to 0.39 (chloroform:methane is l=9:1);

NMR (CD3OD): δ were 0.94 (t, J=7.2 Hz, 3H), 1,14-of 2.28 (m, 18H), to 1.76 (d, J=6.9 Hz, 3H), 2,80 was 3.05 (m, 2H), 2.95 and (s, 3H), of 3.12 (m, 2H), 3,41 (m, 1H), 3,52 (m, 1H), 3,74 (m, 1H), was 4.02 (m, 1H), 4,46 (m, 1H), 7,00-7,19 (m, 4H), 7,29 (user. d, J=9,3 Hz, 2H), 7,50 (user. d, J=8.7 Hz, 2H).

Example 38:

ethyl N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-piperidine-4-yl]glycinate hydrochloride

To a solution of the compound obtained in example 2 (510 mg), and ethylglycine (190 mg) in dimethylformamide (10 ml) and acetic acid (1 ml) add triacetoxyborohydride sodium (345 mg) and stirred at room temperature for 12 hours. The reaction solution concentrate. The resulting residue is purified by column chromatography on silica gel (ethyl acetate) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (583 mg)having the following physical data.

TLC: Rf of 0.53 (chloroform:methanol=5:1).

Example 39:

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)-piperidine-4-yl]glycine

To a solution of cleaners containing hydrochloride salt of the compound obtained in example 38 (303 mg)in dimethylformamide (6 ml) and acetic acid (0.6 ml) successively add butanal (56,2 μl) and triacetoxyborohydride sodium (144 mg). The solution was stirred at room temperature for 12 hours. The reaction solution concentrate. Add water and a solution extragear the Ute with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate). To a solution of the obtained compound (179,2 mg) in ethanol (15 ml) add 2 N. aqueous sodium hydroxide solution (of 0.91 ml) and the solution stirred at 40°C for 12 hours. The reaction solution is concentrated and purified by column chromatography on silica gel (ethyl acetate:methanol=2:1) to give the compounds of the present invention having the following physical data.

TLC: Rf to 0.19 (chloroform:methanol=5:1).

Example 40:

N2-butyl-N1-cyclohexyl-N2-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-yl]glycinamide the dihydrochloride

To a solution of the compound obtained in example 39, in dimethylformamide (5 ml) add cyclohexylamin and 41.7 μl), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (87,2 mg) and 1-hydroxy-7-asobancaria (61,9 mg) and the solution stirred at room temperature for 12 hours. The reaction solution is concentrated and purified by column chromatography on silica gel (ethyl acetate) and converted into cleaners containing hydrochloride salt using a conventional method of obtaining the compounds of the present invention (41,4 mg)having the following physical the data.

TLC: Rf 0,71 (chloroform:methanol=5:1);

NMR (CD3OD): δ 0,98 (t, J=7.2 Hz, 3H), of 1.16 to 1.48 (m, 7H), 1,58-of 1.94 (m, 7H), 2,08-of 2.38 (m, 4H), 2.95 and (s, 3H), is 3.08-to 3.35 (m, 4H), 3,56-to 4.15 (m, 6H), or 4.31 (s, 2H), 7,00-was 7.08 (m, 4H), 7.24 to 7,34 (m, 2H), 7,55 (user. d, J=8.7 Hz, 2H).

Comparative example 16:

1-(2-chloropyrimidine-4-yl)ASEAN

To a solution of 2,4-dichloropyrimidine (25 g) in triethylamine (47 ml) and tetrahydrofuran (300 ml) is added ASEAN (17 g) at 0°C. After returning to room temperature the solution is stirred for 1 hour. To him, water is added and the solution extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (ethyl acetate:hexane=1:5→1:2) to obtain specified in the connection header (7,25 g)having the following physical data.

TLC: Rf of 0.43 (hexane:ethyl acetate=3:1);

NMR (CDCl3): δ 1.57 in (m, 4H), to 1.79 (m, 4H), of 3.45 (m, 2H), 3,79 (m, 2H), 6,29 (d, J=6.3 Hz, 1H), 7,98 (d, J=6.3 Hz, 1H).

Comparative example 17:

4-azepin-1-yl-N-piperidine-4-Yeremey-2-Amin trihydrochloride

The mixture of compounds obtained in comparative example 16 (500 mg)and 1-tert-butoxycarbonyl-4-aminopiperidine stirred at 125°C for 6 hours. After cooling, add saturated aqueous sodium bicarbonate solution to the reaction mixture, which is extracted with ethyl is the Etat. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate and concentrated. The resulting residue is purified by column chromatography on silica gel (hexane:ethyl acetate=3:1→0:1). To a solution of the obtained residue in ethyl acetate (1 ml) add a solution of 4 N. hydrochloric acid/ethyl acetate (4 ml) and the solution stirred for 1.5 hours at room temperature. The reaction solution is concentrated to obtain specified in the title compound (290 mg)having the following physical data.

TLC: Rf of 0.23 (dichloromethane:methanol:acetic acid=5:1:0,1);

NMR (CD3OD): δ 1,59-to 1.61 (m, 4H), 1,83-of 1.92 (m, 6H), 2,22-of 2.27 (m, 2H), 3,14-up 3.22 (m, 2H), 3,44-to 3.49 (m, 2H), 3,69 (t, J=6,1 Hz, 2H), 3,91 (t, J=6,1 Hz, 2H), 4,17 (m, 1H), 6,41 (d, J=7.5 Hz, 1H), 7,68 (d, J=7.5 Hz,, 1H).

Example 41:

N-{4-[4-({4-[(4-azepin-1-Yeremey-2-yl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide trihydrochloride

Using the same procedure as described in example 1 using the compound obtained in comparative example 17, instead of 4-hydroxypiperidine get a connection according to the present invention (159 mg)having the following physical data.

TLC: Rf of 0.38 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1.61 of the tariff-1.62 (m, 4H), 1,83-to 1.98 (m, 6H), 2,20-of 2.33 (m, 2H), 2.95 and (s, 3H), 3,16-3,24 (m, 2H), 3,55-3,61 (m, 2H), 3,69 (t, J=6.0 Hz, 2H), 3,91 (t, J=6.0 Hz, 2H), 4,15 (m, 1H), 4,3 (s, 2H), 6,40 (d, J=7.5 Hz, 1H), 7,03 (d, J=8.7 Hz, 2H), 7,06 (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,54 (d, J=8.7 Hz, 2H), 7,66 (d, J=7.5 Hz, 1H).

Example 41 (1):

N-{4-[4-({3-[(4-azepin-1-Yeremey-2-yl)amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide trihydrochloride

Using the same procedure as described in comparative example 17→ example 37, using 1-tert-butoxycarbonyl-3-aminopiperidine instead of 1-tert-butoxycarbonyl-4-aminopiperidine get a connection according to the present invention (51 mg)having the following physical data.

TLC: Rf of 0.53 (methylene chloride:methanol=10:1);

NMR (CD3OD): δ 1.55V and 1.80 (m, 9H), 2.00 in 2,17 (m, 3H), and 2.79 (m, 1H), 2.95 and (s, 3H), 3.04 from (m, 1H), 3,53-3,86 (m, 7H), 4,25 (d, J=13.5 Hz, 1H), 4,33 (m, 1H), of 4.44 (d, J=13.5 Hz, 1H), 6,40 (d, J=7.5 Hz, 1H), 7,02 (d, J=8,7 Hz, 2H),? 7.04 baby mortality (d, J=8.7 Hz, 2H), 7,29 (d, J=8.7 Hz, 2H), 7,55 (d, J=8.7 Hz, 2H), 7,66 (d, J=7.5 Hz, 1H).

Biological example

The fact that the compound of the present invention has the CCR5 antagonism to demonstrate, for example, using the following experiment. The total work is based on basic genetic engineering to obtain cells, intensely expressing genes, and used conventional methods. Also in the method of analysis according to the present invention for evaluating the compounds of the present invention the accuracy of the analyses and/or sensitivity analyses improve, as described below. Detailed experimental methods shown below

Biological example 1

The study of inhibition of binding of RANTES to CCR5:

(1) Isolation of the gene CCR5 man

Placental cDNA person obtained using amplication set Marathon cDNA (Clontech). PCR primers hCCR5Xbal-F1:

5'-AGCTAGTCTAGATCCGTTCCCCTACAAGAAACTCTCC-3' (SEQ ID NO:1)

and hCCR5Xbal-R1:

5'-AGCTAGTCTAGAGTGCACAACTCTGACTGGGTCACCA-3' (SEQ ID NO:2)

designed based on the sequence of GenBank U54994.

Using placental cDNA as template and using Ex Taq (Takara), carry out reaction PCR (2 min at 95°C → (30 seconds at 95°C, 45 seconds at 60°C, 1 minute at 72°C) × 35 times). Amplificatory thus the PCR product is subjected to electrophoresis on 1% agarose gel, purified using QIAquick Gel Extraction Kit (QUIAGEN), and then Carteret using the restriction enzyme XbaI. The mapped fragments with the subsequent ligation with the expression vector pEF-BOS-bsr, using DNA Ligation Kit Ver. 2 (Takara)and transformed into Escherichia coli DH5a. Through preparation obtained plasmid pEF-BOS-bsr/hCCR5 check its DNA sequence.

(2) Culturing the CHO cells

CHO-dhfr(-) culturious by using ham's F-12 (containing fetal calf serum (10%), penicillin (50 units/ml) and streptomycin (50 mg/ml)). Also transduced cells culturious by adding blasticidin (5 mg/ml) to the above environment.

(3) Transdu the tion in CHO cells

Plasmid pEF-BOS-bsr/hCCR5 transducer cells CHO-dhfr(-) using reagent DMRIE-C (Gibco BRL). After 48 hours the medium is replaced by a medium containing 5 mg/ml blasticidin, to implement the selection, thereby adapting stable sverkhekspressiya cells.

(4) a Study of the inhibition of binding of RANTES and CCR5 (RANTES activity while inducing a temporary increase in the level of ions Ca)

Thus adapted CHO cells, stably sverkhekspressiya human CCR5 (CCR5 cells/CHO), suspended in medium ham's F-12 containing FBS (10%), and seeded at a density of 3.0×106cells/well in 96-well plate. After one day of kulturarbeit at 37°C the culture supernatant is drained and the environment ham F-12 (containing Fura-2AM (5 μm), Probenecid (2.5 mm) and HEPES (20 mm; pH 7,4)) allocate portions 80 ál/well for the implementation of the 1 hour incubation at 37°C under conditions of shading. After twice washing with a solution of 1× Hanks/HEPES (20 mm; pH 7,4) the same solution distribute portions of 100 μl/well. Each of the investigated compounds are added to cells CCR5/CHO, incorporeality thus Fura-2AM, and after 3 minutes after that recombinant human RANTES (PeproTach), diluted 1× Hanks/HEPES (20 mm; pH 7,4), add up to a final concentration of 10 nm. A temporary increase in the intracellular concentration of Ca2+induced RANTES human measure is, using the detector Ca2+for use on 96 wells (Hamamatsu Photonics), and the ratio of inhibition (%) of the investigated compounds is calculated through the following formula for calculations.

The ratio of inhibition = (Ec - Ea)/Ec × 100

Ec: measured value, a temporary increase of Ca2+under the action of RANTES

Ea: the measured value of the temporary increase of Ca2+under the action of RANTES, when added investigated the connection.

In the compounds of the present invention demonstrate the attitude of the inhibition of 50% or more at 10 μm. For example, the compound of example 5 (2) shows the value of the IC500,077 microns.

Biological example 2

Study of the migration of cells expressing CCR5 on human cells hCCR5-Ba/F3):

(1) Adaptation of cells expressing CCR5 man

(1-A) Isolation of the gene CCR5 person

The selection is carried out in accordance with the method of selection of the gene CCR5 person, as described above in example 1.

(1-B) Culturing cells Ba/F3

Cells Ba/F3 culturious statically, using a medium RMMI-1640 (Gibco BRL)containing antibiotics (Antibiotic-Antimycotic) (final concentration: sodium penicillin G (100 units/ml), streptomycin sulfate (100 μg/ml), amphotericin B (0.25 microgram/ml) (Gibco BRL), fetal calf serum (FBS) (10%), 2-mercaptoethanol (55 μm) and interleukin-3 mouse (IL-3) (5 ng/ml) (Pepro Tech, Inc in the incubator with carbon dioxide (temperature: 37°C, CO2concentration: 5%, moisture: 95%). Cells with stable overexpression of exogenous gene culturious in the above environment in which add blasticidin (Kaken Pharmaceutical), obtaining a final concentration of 10 μg/ml.

(1-C) Transformation of Ba/F3 cells

A plasmid for expression of human CCR5 (pEF-BOS-bsr/hCCR5) directorout using AatII for linearization. The linearized plasmid purified using a Purification Kit QIA (QIAGEN) for fast PCR and introduced into cells Ba/F3 through electroporation (Gene Pulser (BIO RAD), 960 µf/250V). Cells were seeded in 96-well plate for kulturarbeit with a density of 1000, 100, 10 cells/100 μl/well and culturious within 48 hours. Then they added blasticidin obtaining a final concentration of 10 μg/ml with subsequent cloning of cell lines resistant to blasticidin in order to adapt the clone with stable overexpression of expressing the introduced exogenous gene (cell hCCR5-Ba/F3).

(1-D) Analysis of the expression of CCR5

The level of expression of CCR5 human clone, obtained by the method described above in (1-C), determined using FACS Sort (a trademark of Becton, Dickinson) by detection of cells labeled with fluorescent isothiocyanates (FITC) antibody anti-human CCR5 (BD Pharmingen) and analyzed. In this regard, labeled with FITC IgG2aκ mice (BD Pharmingen) is used as the DL antibody is the isotype control.

(2) the Study of cell migration

Examine the impact of the compounds on the ability to migrate cells Ba/F3 expressing CCR5 person, depending on RANTES, MIP-1α or MIP-1β. First, 0.3 ml of medium containing 0 or 3 nm of chemokine (RANTES, MIP-1α or MIP-1β), respectively, added to the lower compartment of the tablet Chemo T × 96 wells (Neuro Probe). Then set the filter (pore size: 5 μm) and the solution mixture (1×105cells/well) of the investigated compounds and cells CCR5-Ba/F3, prepared in advance, add in the amount of 65 ál. Analyzed the connection that should be added, is prepared by diluting it with medium containing 0.1% DMSO, final concentration in the filter 0, the 0.01 to 0.03, 0.1 or 0.3 μm. These cells culturious in the incubator with CO2(37°C, 5% CO2relative humidity: 95%) for 3 hours, and then the environment and non-migrating cells on the filter are removed. After that, the filter is removed, the microplate centrifuged (1500 rpm, 10 min, RT) and the supernatant removed by desantirovaniya. Cells in the microplate suspended in 100 μl of phosphate buffer (PBS), and 1/10 part of his further diluted with 90 µl PBS, placed on a white plate for fluorescence analysis and used as sample for the analysis of quantities of migrating cells (in the end: 100 µl/well).

Then the Cell Titer-Glo Reagent (trade is imenovanje Promega), prepared in advance, at room temperature, add to the above sample quantities of migrating cells (100 µl/well), followed by gentle stirring (300 rpm, 2 minutes, using KA-SCHUTTLER MTS4), for lizirovania cell mixture is incubated at room temperature for 10 minutes and measure the fluorescence using a Wallac ARVO SX 1420 MULTILABEL COUNTER (trade name Perkin Elmer) (detection in samples/second).

The number of migrating cells (the number of naturally falling cells) at a concentration of chemokine 0 nmol/l is used as background and calculate the ratio of inhibition of the compounds in comparison with the control group, with 0.1% DMSO.

The ratio of inhibition of migration (%) of the investigated compounds is calculated using the following equation:

Ec: (measured value of fluorescence upon addition of 0.1% DMSO) - (measured value of fluorescence naturally falling cells)

Ea: (measured value of fluorescence when adding the compounds) - (measured value of fluorescence naturally falling cells)

The results:

The compound obtained in example 23 (126), shows the relationship of inhibition of cell migration 42% and 77% at concentrations of 10 and 30 μm matched with the public depending on RANTES.

Sample preparation 1:

The following components are mixed in the usual way, press to obtain 100 tablets each containing 50 mg of active ingredient.

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-yl]cyclohexanecarboxylic hydrochloride5.0 g
calcium carboxymethylcellulose (baking powder)0.2 g
magnesium stearate (lubricating agent)0.1 g
microcrystalline cellulose4.7 grams

Example of preparation 2:

The following components are mixed according to a conventional technology. The solution is sterilized by the conventional methods, is filled in ampoules of 5 ml each, and dried by freezing in a conventional technology to obtain 100 ampoules containing 20 mg of each active ingredient.

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-yl]cyclohexanecarboxylic hydrochloride2.0 g
mannitol20 g
distilled water 500 ml

Example preparation of 3:

The following components are mixed in the usual manner, is pressed to obtain 10,000 tablets containing, each, 10 mg of the active ingredient.

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-yl]cyclohexanecarboxylic hydrochloride100 g
calcium carboxymethylcellulose (baking powder)20,0 g
magnesium stearate (lubricating agent)10.0 g
microcrystalline cellulose870 g

Example preparation of 4:

Each of the following components are mixed using a standard method and filtered through a filter for dust particles, and then an aliquot (5 ml) is loaded into the ampoule, which is subjected to the autoclave, thereby obtaining 10,000 ampoules containing, each, 20 mg of the active ingredient.

N-butyl-N-[1-(4-{4-[(methylsulphonyl)amino]phenoxy}benzyl)piperidine-4-yl]cyclohexanecarboxylic hydrochloride200 g
mannitol 2 kg
distilled water50 l

Industrial application

Compounds of the present invention, represented by formula (I), regulate the action of the CCR5 receptor, so they are useful in the prevention and/or treatment of various inflammatory diseases (asthma, nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, rhinitis, conjunctivitis, ulcerative colitis, etc.), immunological diseases (autoimmune diseases, rejection of organs in transplantation, immunosuppression, psoriasis, multiple sclerosis and the like), infection of human immunodeficiency virus (acquired immunodeficiency syndrome and the like), allergic diseases (atopic dermatitis, urticaria, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis, etc.), ischemic reperfusion injury, acute respiratory distress syndrome, shock accompanying bacterial infection, diabetes, cancer metastasis, and so on. For this reason, the CCR5 antagonist is suitable for use as a medicine.

1. The compound represented by formula (I):

where R1represents-SO2NR102R103, -NR101SO2R104or-COOR105where R101represents a hydrogen atom, R102and R103each independently represents a hydrogen atom or With 1-4 alkyl, R104represents a C1-alkyl, and R105represents a hydrogen atom or C1-alkyl;
X represents a bond, -CH2- or-O-;
Y represents-CH2-;
ring a and ring B, which are the same or different, each independently represents a benzene, pyridine, pyrazole or piperidine, which may have as a substituent With 1 to 4 alkyl or halogen;
ring D is piperidine;
R2represents a

where the arrow shows the position of connection with the ring D;
R51represents (1) hydrogen atom, (2) C1-alkyl, which may have as a substituent (a) hydroxy, (b) methoxy, (C) cyano, (d) carboxy, (e) halogen, (f) methylsulfonylamino, (g) C3-cycloalkyl or phenyl, which may have as a substituent methyl, halogen, hydroxy or methoxy, (h) thienyl, pyrazolyl, tetrahydropyranyl, thiazolyl, isoxazolyl, imidazolyl, tetrazolyl, pyridyl, pyrimidinyl, which may have as Deputy methyl, trifluoromethyl or hydroxy, (3) C2-alkenyl, (4) C2-alkynyl, (5) phenyl which may have as a substituent C1-alkyl or halogen, or (6) pyridine or tetrahydropyran;
R52represents (1) hydrogen atom, (2) C1-alkyl, which may have as a substituent (a) hydroxy, (b) methoxy, (C) carboxy, (d) C3-cycloalkyl, (e) phenyl or (f) oxo, (3) C3-cycloalkyl or phenyl, which may have as a substituent C1-alkyl, hydroxy, cyano, oxo, carbarnoyl, N-methylaminomethyl, carboxy, halogen, methoxy, triptoreline, methylthio, methylsulphonyl, acetylamino, dimethylamino, acetyl, tetrazolyl, trifluoromethyl or methylsulfonylamino (4) C3-tikiouine, (5) substituted, (6) thienyl, pyrazolyl, tetrahydropyranyl, isoxazolyl, isothiazolin, thiadiazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, hinely, indolyl, benzothiazolyl, benzothiazolyl, benzotriazolyl, dioxindole, benzodioxane, which may have as a substituent C1-alkyl, hydroxy, oxo, halogen, azido or trifluoromethyl, or (7) benzyloxy; and R53represents a hydrogen atom or C1-alkyl, its salt or its MES.

2. The compound according to claim 1, which represents the formula (Id)

where R1-1ais-SO2NR102R103or-NR101SO2R104;
X1arepresents a bond, -CH2or-O-;
ring And1band ring In1beach independently represents a benzene, pyridine or the feast of the ol, each of which may have as a substituent C1-alkyl or halogen;
ring D1arepresents piperidine; and
other symbols have the same meanings as described in claim 1.

3. The compound according to claim 2, where a1brepresents benzene which may have a substituent methyl or chlorine.

4. The compound according to claim 2, where In1brepresents a benzene, pyridine or pyrazole, each of which may have as a substituent methyl or chlorine.

5. The compound according to claim 2, where R51represents (1) C1-alkyl, which may have as a substituent (a) hydroxy, (b) methoxy, (C) cyano, (d) carboxy, (e) C3-cycloalkyl or phenyl, which may have as a substituent methyl, fluorine, hydroxy or methoxy, (f) thienyl, tetrahydropyranyl, imidazolyl, pyridyl, which may have as a substituent methyl, trifluoromethyl or hydroxy, (2) C2-alkenyl, (3) C2-alkynyl or (4) phenyl, which may have as a substituent methyl or fluorine.

6. The compound according to claim 2, where R52represents (1) C1-alkyl, which may have as a substituent (a) hydroxy, (b) methoxy, (C) carboxy, (d) cyclohexyl, (e) phenyl or (f) oxo, (2) C3-cycloalkyl or phenyl, which may have as a substituent C1-alkyl, hydroxy, cyano, oxo, carbarnoyl, N-methylaminomethyl, carboxy, halogen, methoxy, triptoreline, IU is ylthio, methylsulphonyl, acetylamino, acetyl, trifluoromethyl or methylsulfonylamino, (3) cyclopentenyl, (4) thienyl, pyrazolyl, tetrahydropyranyl, piperidinyl, pyridyl, hinely, indolyl, which may have as a substituent C1-alkyl, hydroxy, oxo, halogen or trifluoromethyl, or (5) benzyloxy.

7. The compound according to claim 5, where R51represents C1-alkyl.

8. The connection according to claim 6, where R52represents phenyl which may have as a substituent methyl, ethyl, hydroxy, cyano, carbarnoyl, N-methylaminomethyl, carboxy, fluoro, methoxy, triptoreline, methylthio, methylsulphonyl, acetylamino, acetyl, trifluoromethyl or methylsulfonylamino.

9. The compound according to claim 1, which is selected from the group consisting of
(1)N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}-amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide,
(2)N-[4-(4-{[4-(butyl{[(6-methyl-3-pyridinyl)amino]-carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]-methanesulfonamide,
(3)N-[4-(4-{[4-(butyl{[(2,4-differenl)amino]carbonyl}-amino)piperidine-1-yl]methyl} - for 3,5-dimethyl-1H-pyrazole-1-yl)phenyl]methanesulfonamide,
(4)N-[4-(4-{[4-(butyl{[(1-methyl-1H-pyrazole-4-yl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide,
(5)3-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]benzamide,
(6)N-{4-[4-({4-[{[(4-forfinal)aminocarbonyl}(phenyl)-amino]piperidine-1-yl}methyl)phenoxy]phenyl}methanesulfonamide,
(7)5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]-2-fermentated,
(8)5-[({butyl[1-(4-{4-[(methylsulphonyl)amino]phenoxy}-benzyl)piperidine-4-yl]amino}carbonyl)amino]-2,4-differentated,
(9)N-[4-(4-{[4-(butyl{[(3-cyano-4-forfinal)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide and
(10)N-[4-(4-{[4-(butyl{[(3-hydroxycyclohexyl)amino]-carbonyl}amino)piperidine-1-yl]methyl}phenoxy)phenyl]-methanesulfonamide, and
(11)N-{4-[4-({4-[{[(4-forfinal)amino]carbonyl}(1,3-thiazol-4-ylmethyl)amino]piperidine-1-yl} methyl)phenoxy]phenyl}-methanesulfonamide.

10. The CCR5 regulator containing a compound according to claim 1, its salt or its MES.

11. The CCR5 regulator of claim 10, which is a CCR5 antagonist.

12. The CCR5 regulator under item 10, which is an agent for treatment and/or prevention of diseases mediated CCR5.

13. The regulator CCR5 indicated in paragraph 12, where the disease is mediated by CCR5, is the infection of the human immunodeficiency virus.

14. The CCR5 regulator according to item 13, where the infection of the human immunodeficiency virus is acquired immunodeficiency syndrome.

15. The regulator CCR5 indicated in paragraph 12, where the disease is mediated by CCR5, is immunological diseases.

16. The regulator CCR5 indicated in paragraph 15, where the immunological disease is the rejection of organs after transplantation.

17. The regulator CR5 indicated in paragraph 12, where a disease mediated by CCR5, is inflammatory diseases.

18. The regulator CCR5 on 17, where the inflammatory disease is asthma.

19. Agent for prevention and/or treatment of infection with human immunodeficiency virus, sexually transmitted diseases or inflammatory diseases, which contains a compound represented by formula (I)according to claim 1, its salt or its MES.

20. Pharmaceutical composition having activity against CCR5 receptor, which contains a compound represented by formula (I)according to claim 1, its salt or its MES.

21. Medicinal product, which contains a compound represented by formula (I) according to claim 1, its salt or its MES in combination with one or at least two nucleoside reverse transferase, protease inhibitor, CCR2 antagonist, CCR3 antagonist, CCR4 antagonist, CCR5 antagonist, CXCR4 antagonist, inhibitor of fusion, antibody against surface antigen of HIV-1 vaccines in HIV-1.

22. Method for the treatment or prevention of diseases mediated by CCR5, in a mammal which comprises the administration to a mammal an effective amount of a compound according to claim 1 or its salt or its MES.

23. The use of compounds according to claim 1 or its salt or its MES for production of an agent for prevention and/or treatment of diseases mediated CC5.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 1,4-diazabicyclo[3,2,1]octanecarboxamide with general formula (1) , in which X is a nitrogen atom, P and W each independently represent a nitrogen atom or a group with general formula C-R3, Q and R each independently represent a group with general formula C-R3, R1 is a hydrogen atom, R3 is a hydrogen atom or halogen or C1-C6-alkyl, C1-C6-alkoxy, O-Ms. The invention also relates to a medicinal preparation and pharmaceutical composition based on these compounds for treating or preventing disorders, related to malfunction of nicotinic receptors.

EFFECT: obtaining new compounds and a pharmaceutical composition based on the said compounds, which can be used for treating cognition failure and attention failure, or for treating motor, neurological or alerting symptoms related to dependency on different addictive substances.

5 cl, 2 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to quinobenzoxazin analogues with general formula (1) where V represents H, halo-, or NR1R2; NH2, or NR1-(CR12)n-NR3R4; A represents H, fluoro-, or NR12; Z represents O, S, NR1 or CH2; U represents NR1R2; X represents NR1R2 or halo-; n=1-6; where in NR1R2, R1 and R2 can form 5-7-member heterocyclic ring which is optionally substituted and has 1-2 heteroatoms, selected from group consisting of N, O and S; R1 represents H or C1-6alkyl; R2 represents C1-10alkyl optionally including one or more non-adjacent heteroatoms N or O and is optionally substituted with if necessary substituted 3-6-member carbocyclic or 5-14-member heterocyclic ring; or R2 is 5-14-member heterocyclic ring, which has 1-2 heteroatoms, selected from group consisting of N, O or S, 6-member aryl or 5-7member heteroaryl ring, which contains 1-3 heteroatoms, selected from group consisting of N, O and S, each of which can be, if necessary, substituted; R3 represents H or C1-6alkyl; R4 represents H, C1-6alkyl, optionally substituted with 3-6 carbocyclic or 5-14-member heterocyclic ring, or 6-member aryl, R4 and R3, if necessary, can form optionally 5-7-member substituted heterocyclic ring, which contains 1-2 heteroatoms selected from N and O; W represents substituent, such as described in i.1 of invention formula, where Q, Q1, Q2, and Q3 represents independently CH or N; Y represents independently O or CH; R5 represents substituent in any position of closed ring in form of H or OR2; on condition that U is not morpholinyl or 2,4-difluoroaniline, when X represents F or pyrrolidinyl, A is F, Z represents O, and W represents phenylene; each obligatorily substituted fragment being substituted with one or more halogen, C1-6-alkoxy, amino, carbamate, C1-10alkyl, C2-10alkenyl, each of which is optionally substituted with halogen, =O, 6-member aryl or one or more heteroatom, selected from N and O; 6-member aryl, 3-6-member carbocyclic ring or 5-7-member heterocyclic ring containing 1-2 heteroatoms, selected from group, consisting of N and O; or its pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition based on formula (1) compound and to method of treatment of proliferative cell diseases using formula (1) compounds.

EFFECT: obtaining novel quinobenzoxazin analogues possessing useful biological properties.

48 cl, 3 tbl, 50 ex

FIELD: chemistry.

SUBSTANCE: compounds of the invention have chemokine antagonistic properties and can be applied in treatment of immunoinflammatory diseases, such as atherosclerosis, allergy diseases. In general formula (I) R1 is hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxyl, cyclopropylmethoxy group, (C1-C4)-alkylthio group; R2 is halogen atom, (C1-C8)-alkyl, perfluoro-(C1-C4)-alkyl, (C3-C10)-cycloalkyl, phenyl, (C1-C8)-alkoxyl, values of the other radicals are indicated in the claim of the invention.

EFFECT: improved properties.

14 cl, 7 tbl, 20 dwg, 17 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new macrocyclic compounds with formula (I): (where R3, R6, R7 and R21 can be identical or different from each other, and each of them assume values given in the description), their salts used in pharmacology and their hydrate. Compounds with formula (I) are capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, and can be used as therapeutic means of treating solid malignant tumours. The invention also relates to medicinal agents based on these compounds, prevention and treatment method and use of these compounds in making preparations for preventing and treating cancerous diseases.

EFFECT: obtaining compounds, capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, which can be used as therapeutic means of treating solid malignant tumours.

35 cl, 3 tbl, 147 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to a new piperidine derivative, with the following general formula (I) where R1 - R4 each stands for any of the univalent groups, indicated below: R1 stands for a hydrogen atom, halogen atom, inferior alkyl, which can be substituted with a halogen atom or OH; -O-inferior alkyl, which can be substituted with a halogen atom; -O-aryl, aryl, -C(=O)-inferior alkyl, COOH, -C(=O)-O-inferior alkyl, -C(=O)-NH2, -C(=O)NH-inferior alkyl, -C(=O)N-(inferior alkyl)2, OH, -O-C(=O)-inferior alkyl, NH2, -NH-inferior alkyl, -N-(inferior alkyl)2, NH-C(=O)- inferior alkyl, CN or NO2; R2 and R3 each stands for a hydrogen atom; and R4 stands for any of the univalent groups (a), (b) and (c), shown below in formula 2 where in the above indicated groups (a), (b) and (c), A stands for a pyrrolidine, piperidine, morpholine, piperizine or oxazepane ring; B stands for a pyrrolidine or piperidine ring; R5 and R8-R11 can be identical or different from each other and each stands for a hydrogen atom, -C(=O)-O-inferior alkyl, cycloalkyl or tetrahydropyrane; R6 stands for a hydrogen atom, -C(=O)-O-inferior alkyl, OH, -inferior alkylene-OH or -C(=O)-pyridine; and R7 stands for a hydrogen atom. The invention also pertains to pharmaceutical salts of the piperidine derivative, as well as medicinal compositions.

EFFECT: obtaining new biologically active compounds and a medicinal composition, based on these compounds, which is a sodium channel inhibitor.

10 cl, 91 ex, 22 tbl

FIELD: chemistry.

SUBSTANCE: invention claims compound of the general formula (I) , where R is hydrogen atom or vinyl group; n is 1, X is a group of the formula CH or nitrogen atom, R1 is either phenyl or naphthyl group, or cyclohexyl group, or heteroaryl group, R2 is either hydrogen atom or one or more substitutes selected out of halogen atoms and trifluoromethyl, alkyl, alkoxyl phenyloxy, hydroxyl groups or group of the general formula -NR4R5, SO2NR4R5, or group of the formula -OCF2O-, each of R4 and R5 groups is hydrogen atom or alkyl group; and method of obtaining compound of the general formula (I), medicine, pharmaceutical composition. Compounds display special effect as specific inhibitors of glycine GlyT1 and/or GlyT2 transmitters and thus are applied in treatment of various diseases.

EFFECT: obtaining compounds with high specific inhibition effect.

13 cl, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: derivatives of 7-aryl-3,9-diazabicyclo(3.3.1)non-6-ene of general formula I , general formula I, where X and W or both represent -CH-, or one of them represents -CH-, and the other -N. V represents -A-(CH2)s-, -(CH2)s-A-, -A-(CH2)v-B- or -CH2-A-(CH2)3-B-; A and B represent-O- U -phenyl, possibly 1-3 substituted with halogen, alkyl, alkoxy, CF3, CF3O - or alkylcarbonyl, or pyridyl, monosubstituted with cyanogroup. T represents -CONR1-, -(CH2)pOCO- or -(CH2)pN(R1)CO- Q-alkylene; M - hydrogen, phenyl, possibly substituted, benzo[1,3]dioxol, possibly substituted, or pyridyl; L represents -R3, -COR3, -COOR3, -CONR2R3 or -SO2R3; R1 - hydrogen, alkyl, C3-7 cycloalkyl, pyrrolidinyl, benzo[b]thienyl, chinoxalinyl, phenylalkyl, thienylalkyl or tetrazolylalkyl, possibly substituted. m=1, n=0 or m=0, n=1, p - integer 1-4, s - integer 2-5, v - integer 2-4, optically pure enantiomers, mixtures of enantiomers, pharmaceutically acceptable salts and complexes with solvents, possessing activity of phenin inhibitors.

EFFECT: efficient application in medicine for treatment of cardio-vascular diseases and renal failure.

8 cl, 743 ex

FIELD: chemistry.

SUBSTANCE: description is given of new diazabicyclic aryl derivatives, with general formula I: its enantiomers, or mixture of enantiomers, or its adjoining pharmaceutical salt, where X and Y independently represent CR2, CR3 or N, where R2 is hydrogen, C1-6alkyl or halogen; and R3 is hydrogen or halogen; and R1 is hydrogen or halogen, CF3, NO2 or phenyl, possibly substituted, group with formula phenyl-Z-(C1-6alkyl)m-, phenyl -C≡C- or pyridyl -Z-(C1-6alkyl)m-, where m equals 0 or 1; Z - O or S, where phenyl and pyridyl are possibly substituted, or R1 and R3 , together with carbon atoms to which they are bonded, form a benzocondensed aromatic carbocyclic ring, which can be substituted. The new compounds are cholinergic ligands of nicotinic acetylcholine receptors.

EFFECT: compounds can be useful for treating such diseases or disorders related to the cholinergic system of the central nervous system, peripheral nervous system etc.

11 cl, 3 ex, 1 tbl

FIELD: organic chemistry.

SUBSTANCE: invention relates to novel individual compounds of series 2,5a-methano[1,4]diazepino[1,7-a]-quinoxaline-5-carboxylates, namely, to isopropyl-12-aroyl-2-hydroxy-1,6-dioxo-4-(3-pyridinyl)-7-phenyl-1,3,6,7-tetrahydro-2,5a-methano[1,4]diazepino[1,7-a]-quinoxaline-5-carboxylates of the formula (1) wherein Ar means phenyl or p-methoxyphenyl, and to a method for their synthesis. Method for synthesis of compound of the formula (1) involves interaction of 3-aroyl-5-phenylpyrrolo[1,2-a]-quinoxaline-1,2,4(5H)-triones with isopropyl-3-amino-3-(3-pyridinyl)-2-propenoate in an inert aprotonic solvent medium and the following isolation of end substances. The proposed method provides synthesis of novel compounds of the formula (1) possessing antibacterial effect with high yield and selectivity.

EFFECT: improved method of synthesis.

4 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: described are derivatives of 1,3,4-oxadiazol-2-on of formula (I) , where ARYL represents phenyl; Z represents -O(CH2)n- and n represents independent integer number from 1 to 5; X represents S; R1 represents C1-6alkyl; R2 represents phenyl, substituted with C1-6perfluoralkyl; or its pharmaceutically acceptable salt; based on it pharmaceutical composition; and method of disease treatment, where disease can be modulated by activity of PPAR-delta binding.

EFFECT: obtaining compounds which possess agonistic or antagonistic activity.

7 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: or its pharmacologically acceptable salts, where n equals 1, 2 or 3; and values of R1, R2, R3, R4, R3', R10, R11 are given in i.1 of formula.

EFFECT: compounds I have ability to inhibit release and/or synthesis of β-amyloid peptide, which allows to apply them in pharmaceutical composition.

25 cl, 3 dwg, 5 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new coumarin derivatives and their carboxamides, with general formula (I) , where R3 is chosen from a group consisting of H, carboxyl, alkyloxycarbonyl, 5'-(phenyloxadiazol-2')-yl, 5'-(pyridyl-4"-oxadiazol-2')-yl, , CONHR9, where R9 is chosen from a group consisting of fatty acids C2-C8, benzoxamido, isonicotinamido, unsubstituted, or mono-, or polysubstituted phenyl, in which the substitute can be hydroxy, C1-C8-alkoxy, CF3, carboxyl, alkyloxycarbonyl, OCH2CO2H, NO2, halogen, SO3H, SO2NHR11, where R11 is chosen from a group consisting of hydrogen, amidino, 2"-thizolyl, 3"-(511-methylisooxazolyl), 2"-pyrimidinyl, 2"-(4",6"-dimethylpyrimidinyl), 4"-(5",6"-dimethoxypyrimidinyl); R4 is chosen from a group consisting of hydrogen, CONHR10, where R10 is chosen from a group consisting of C2-C8 fatty acids, unsubstituted phenyl; R5 is chosen from a group consisting of H, C1-C4 alkyl; R6 is chosen from a group consisting of H, C1-C12-alkyl, halogen, NO2, CONHR13, where R13 is substituted phenyl; R7 is chosen from a group consisting of H, hydroxyl, C1-C4alkyl or alkoxyl, carboxyalkyleneoxyl, OCH2CONHR14, where R14 is chosen from a group consisting of unsubstituted, mono-, or polysubstituted phenyl, in which the substitute can be hydroxyl, OCH3, CF3, CO2H, CO2C2H5, NO2; R8 is chosen from a group consisting of H, C1-C4-alkyl or alkoxyl, NO2; under the condition that, when R3, R5 and R6 are H, and R7 is OH, R4 and R7 are not groups, chosen from H, C1-C6-alkyl or C1-C6-alkoxy. The invention also relates to pharmaceutical compositions based on formula I compounds and their use as medicinal preparations for protecting kidneys, for curing hypertonia, cardio-cerebrovascular diseases, non-achrestic diabetes, tumours, precancerous diseases and oedema.

EFFECT: enhanced effectiveness of the composition and treatment method.

17 cl, 6 tbl, 51 ex

FIELD: chemistry; medicine.

SUBSTANCE: invention relates to 3-phenylpropionic acid derivatives of formula (I) as ligand of peroxisome proliferator-activated gamma-receptor (PPARγ), to their pharmaceutically acceptable salts, as well as to their application, treatment method and based on them pharmaceutical composition. Compounds can be applied for treatment and prevention of diseases mediated by peroxisome proliferator-activated gamma-receptor (PPARγ), for instance type 2 diabetes, insulin-resistance, metabolic syndrome, complications resulting from or connected with diabetes, cardio-vascular dysfunctions, atherosclerosis, obesity, cognition disturbances and lipid metabolism derangements. In general formula (I): W represents COOH or -COO-C1 - C4-alkyl group; Y represents NH; Z represents S or O; X represents O; R1 - R8 each independently represents hydrogen atom or halogen atom; A represents mono-, bi- or tri-cyclic 5-13-member heteroaryl with 1 or 2 heteroatoms selected from N, S or O, aryl, selected from phenyl and naphtyl, or -N(C1-C4-alkyl)-CO-C3-C7-cycloalkyl, where heteroaryl is optionally substituted with 1-3 substituents, independently selected from group, consisting of C1-C4-alkyl, CN, phenyl halogen and phenyl, optionally substituted with 1-3 substituents, independently selected from C1-C4alkoxy, halogen and ethylenedioxy-group; and n represents integer number from 0 to 3 including; and their pharmaceutically acceptable salts.

EFFECT: increased efficiency of composition and treatment method.

20 cl, 14 dwg, 10 ex

FIELD: chemistry.

SUBSTANCE: invention is related to the compound of general formula 1 or its tautomer or pharmaceutically acceptable salt, where W selected from N and CR4; X is selected from CH(R8), O, S, N(R8), C(=O), C(=O)O, C(=O)N(R8), OC(=O), N(R8)C(=O), C(R8)-CH and C(=R8); G1 - bicyclic or tricyclic condensed derivative of azepin, selected from general formulas 2-9 , or derivative of aniline of common formula 10 , where A1, A4, A7 and A10 are independently selected from CH2, C=O, O and NR10; A2, A3, A9, A11, A13, A14, A15, A19 and A20 are independently selected from CH and N; or A5 stands for covalent connection, and A6 represents S; or A5 stands for N=CH, and A6 represents covalent connection; A8 , A12 , A18 and A21 are independently selected from CH=CH, NH, NCH3 and S; A16 and A17 both represent CH2, or one from A16 and A17 represents CH2, and the one another is selected from C=O, CH(OH), CF2, O, SOc and NR10; Y is selected from CH=CH or S; R1 and R2 are independently selected from H, F, Cl, Br, alkyl, CF3 and group O-alkyl; R3 is selected from H and alkyl; R4-R7 are independently selected from H, F, Cl, Br, alkyl, CF3, OH and group O-alkyl; R8 is selected from H, (CH2)bR9 and (C=O)(CH2)bR9; R9 is selected from H, alkyl, possibly substituted aryl, possibly substituted heteroaryl, OH, groups O-alkyl, OC(=O)alkyl, NH2, NHalkyl, N(alkyl)2, CHO, CO2H, CO2alkyl, CONH2, CONHalkyl, CON(alkyl)2 and CN; R10 is selected from H, alkyl, group COalkyl and (CH2)dOH; R11 is selected from alkyl, (CH2)dAr, (CH2)dOH, (CH2)dNH2, group (CH2)aCOOalkyl, (CH2)dCOOH and (CH2)dOAr; R12 and R13 are independently selected from H, alkyl, F, CI, Br, CH(OCH3)2, CHF2, CF3, groups COOalkyl, CONHalkyl, (CH2)dNHCH2Ar, CON(alkyl)2, CHO, COOH, (CH2)dOH, (CH2)dNH2, N(alkyl)2, CONH(CH2)dAr and Ar; Ar is selected from possibly substituted heterocycles or possibly substituted phenyl; a is selected from 1, 2 and 3; b is selected from 1, 2, 3 and 4; c is selected from 0, 1 and 2; and d is selected from 0, 1, 2 and 3. Besides, the invention is related to pharmaceutical compound and to method for activation of vasopressin receptors of type 2.

EFFECT: compounds according to invention represent agonists of receptor of vasopressin V2, which stipulates for their application (another object of invention) for preparation of medicine for treatment of condition selected from polyuria, including polyuria, which is due to central diabetes insipidus, nocturnal enuresis of nocturnal polyurea, for control of enuresis, to postpone bladder emptying and for treatment of disorders related to bleeds.

21 cl, 228 ex

FIELD: chemistry.

SUBSTANCE: invention can be applied in medicine and concerns inhibitors of MaR-kinase p38 of formula where W represents N or O, when Y represents C, and W represents C, when Y represents N; U represents CH or N; V represents C-E or N; X represents O, S, SO, SO2, NH, C=O,-C=NOR1 or CHOR1; B represents H or NH2; R1, E and A stands for H or various alkyl, heteroalkyl, aromatic and heteroaromatic substitutes.

EFFECT: production of new biologically active compounds.

48 cl, 138 ex, 54 dwg

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula (I) where R1 stands for hydrogen or linear, branched, saturated or unsaturated hydrocarbon radical; D stands for nitrogen atom or C-R2; E stands for nitrogen atom or C-R3; F stands for nitrogen atom or C-R4; G stands for nitrogen atom or C-R5; R2, R3, R4 and R5 are identical or different and individually represent hydrogen, halogen, alkoxy, linear or branched, saturated or unsaturated hydrocarbon radical; W stands for oxygen atom; X stands for radical of formula radical -(CH2)k-C(O)-(CH2)m-, -(CH2)n- or -(CH2)r-O-(CH2)s-, where k, m, r and s are equal to integers 0 to 6, and n is equal to an integer 1 to 6. Said radicals are optionally substituted with one or more substitutes independently chosen from the group consisting of R7; Y stands for radical of formula radical -(CH2)i-NH-C(O)-(CH2)j-, -(CH2)n-, -(CH2)r-O-(CH2)s-, -(CH2)t-NH-(CH2)u-, where i, j, n, r, s, t and u are equal to integers 0 to 6. Said radicals are optionally substituted C1-3alkyl, or C1-3alkyl-C1-3alkylsulphonylamino; radicals R7, B, R8, A, R9 are as it is presented in the patent claim. The invention also describes the pharmaceutical composition possessing inhibitory activity of receptor tyrosine kinase to KDR receptor including described compounds.

EFFECT: compounds possess inhibitory activity of receptor tyrosine kinase to KDR receptor and can be effective in therapy of the diseases associated uncontrolled angiogenesis.

29 cl, 746 ex, 6 tbl

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel 2,4-pyridindiamine compounds of formula (1). In structural formula (I) L1 is direct bond; L2 is direct bond; R2 is phenyl group, three times substituted with three groups R8; R4 is X represents N; Y is selected from group consisting of O, NH, S, SO and SO2; Z is selected from group consisting of O, NH; on condition that if Y is selected from group consisting of NH, S, SO and SO2, Z is not the same as Y; R5 is selected from group consisting from R6, halogen; each R6 is independently selected from group consisting of hydrogen, halogen; R8 is selected from group consisting from Ra, Rb, Ra substituted with one or several similar or different groups Ra or Rb, -ORa, -O-CHRaRb; each R35 independently on others is selected from group consisting of hydrogen and R35, or in alternative case, two groups R35, bound to one and the same carbon atom are taken together with formation of oxogroup (=O), and the remaining two groups R35 each independently on each other are selected from group consisting from hydrogen and R8; each Ra is independently selected from group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rb is suitable group which is independently selected from group consisting of -ORd, halogen, -CF3, -C(O)NRcRc, and -OC(O)ORd; each Rc is independently protective group or Ra; each Rd is independently protective group or Ra; each index m is independently integer number from 1 to 3.

EFFECT: novel compounds can be used for treatment or prevention of autoimmune diseases, for instance such as rheumatoid arthritis and/or related to it symptoms, systemic lupus erythematosus and/or related to it symptoms, as well as and/or related to it symptoms.

41 cl, 14 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: invention concerns novel compounds of formula I: , where M is macrolide subunit of substructure II: , L is chain of substructure III: -X1-(CH2)m-Q-(CH2)n-X2-, D is steroid or non-steroid subunit derived from steroid or non-steroid NSAID medicines (nonsteroid anti-inflammatory drug) with anti-inflammatory effect; pharmaceutically acceptable salts and solvates of claimed compounds; methods and intermediary compounds for obtainment of claimed compounds.

EFFECT: improved therapeutic effect, application in inflammatory disease and state treatment for humans and animals.

37 cl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazole derivatives of formula (I): and to its salts with acid, where: R1 and R2 represent hydrogen; Q represents (CH2)m-X-(CH2)n-A; A represents direct bond, O, SO2, NR5; X represents direct bond, O, SO2, C(O) or NR5; Z represents group selected from : m and n represent, each independently, 0, 1, 2, 3 or 4; p represents 1, 2, 3 or 4; q represents 0, 1 or 2; dotted line means that R8 and/or R9 can be situated in any position of benzothiophene ring; R3 and R8 represent, each independently, hydrogen or hydroxy, cyano, halogen, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylthio, (C1-C6)alkylsulfonyl, acyl, (C1-C6)alcoxycarbonyl, carboxamido, NR10R11, SO2NR10R11, OSO2NR10R11 or NR12SO2NR10R11, OSO2NR12SO2NR10R11, CO2R10; when Q-Z represents n 0, 1 or 2 and p represents 1, one of R3 and R8 represents hydroxy, nitro, NR10R11, OSO2NR10R11, NR12SO2NR10R11, OSO2NR12SO2NR10R11, CO2R10, CONR10R11, and the other represents hydrogen or hydroxy, cyano, halogen, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylsulfonyl, acyl, (C1-C6)alcoxycarbonyl, carboxamido, NR10R11, SO2NR10R11 OSO2NR10R11, NR12SO2NR10R11, CO2R10; R4 and R9 represent, each independently, hydrogen or hydroxy, cyano, halogen, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylthio, (C1-C6)alkylsulfonyl, acyl, (C1-C6)alcoxycarbonyl, carboxamido, NR10R11, SO2NR10R11, OSO2NR10R11, NR12SO2NR10R11, OSO2NR12SO2NR10R11, CO2R10, CHO; when p represents 2, 3 or 4, R9 can be similar or different; R6 and R7 represent hydrogen; each R5, R10, R11 and R12 represents hydrogen; when Z represents and p represents 1, then R8 and R9 can also together with phenyl ring form benzoxathiazine dioxide. Invention also relates to pharmaceutical composition and to application of derivatives by any of ii.1-25.

EFFECT: obtaining novel biologically active compounds which possess inhibiting activity with respect to aromatase and/or steroid-sulfatase and/or carboanhydrase.

36 cl, 67 ex, 5 tbl

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