MXPA06005394A

MXPA06005394A - N-acylsulfonamide apoptosis promoters

Info

Publication number: MXPA06005394A
Application number: MXPA/A/2006/005394A
Authority: MX
Inventors: Bruncko Milan; Ding Hong; Elmore Steven; R Kunzer Aaron; L Lynch Christopher; Mcclellan William; Park Cheolmin; Petros Andrew; Song Xiaohong; Wang Xilu; Tu Noah; D Wendt Michael
Original assignee: Abbott Laboratories; Bruncko Milan; Ding Hong; Elmore Steven; R Kunzer Aaron; L Lynch Christopher; Mcclellan William; Park Cheolmin; Petros Andrew; Song Xiaohong; Tu Noah; Wang Xilu; D Wendt Michael
Priority date: 2003-11-13
Filing date: 2006-05-12
Publication date: 2006-10-17

Abstract

Disclosed are N-acylsulfonamide compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression of one or more than one anti-apoptotic protein family member.

Description

N-ACILSULFONAMIDE APOPTOSIS PROMOTERS FIELD OF THE INVENTION This invention pertains to compounds that inhibit the activity of members of the anti-apoptotic protein family, to compositions containing the compounds, and to the uses of the compounds for preparing medicaments for treating diseases during which one or more than one is expressed. of members of the anti-apoptotic protein family.

BACKGROUND OF THE INVENTION Members of the anti-apoptotic protein family are associated with a number of diseases. Therefore, there is a need in therapeutic techniques for compounds that inhibit the activity of one or more of one of the members of the anti-apoptotic protein family.

BRIEF DESCRIPTION OF THE INVENTION One embodiment of this invention, therefore, pertains to therapeutically acceptable compounds or salts, prodrugs or prodrug salts thereof, which are useful as inhibitors of one or more of one of the members of the anti-apoptotic protein family. , the compounds have the formula (I) (l), wherein A1 is N or C (A2); one or two or three or each of A2, B1, D1 and E1 are independently selected from R \ OR1, SR1, S (0) R \ SO2R1, C (O) R \ C (O) OR1, OC (0) R1, NHR1, N (R1) 2, C (O) NHR1, C (0) N (R1) 2l NHC (O) R1, NHC (O) OR1, NR1C (0) NHR1, NR1C (0) N (R1) 2, SO2NHR1, S02N (R1) 2, NHS02R, NHS02NHR1 or N (CH3) S02N (CH3) R1, and the remainder are independently selected from H, F, Cl, Br , I, CN, CF3, C (0) OH, C (0) NH2 or C (0) OR1A; and Y1 is H, CN, N02, C (0) OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R17, OR17, C (0) R17, C (0) OR17, SR17, NH2, NHR17, N (R17) 2, NHC (0) R17, C (0) NH2I C (0) NHR17, C (0) N (R17) 2l NHS (O) R17 or NHS02R17; or B1 and Y1, together with the atoms to which they are attached, are imidazole or triazole; and one or two or each of A2, D1 and E1 are independently selected from R1, OR1, SR1, S (0) R1, S02R1, C (O) R \ C (O) OR1, OC (O ) R1, NHR1, N (R1) 2, C (O) NHR1, C (O) N (R1) 2, NHC (O) R1, NHC (O) OR1, NHC (O) NHR1, N (CH3) C (O) N (CH3) R1, SO2NHR1, S02N (R1) 2, NHS02R1, NHS02NHR1 or N (CH3) S? 2N (CH3) R1, and the remaining ones are independently selected from H, F, Cl, Br, I, CF3, C (0) OH, C (0) NH2 or C (O ) OR1 A; R1 is R2, R3, R4 or R5; R1 A is C6-C6 alkyl, C3-C6 alkenyl or C3-Ce alkynyl; R2 is phenyl which is not fused or fused with arene, heteroarene or R2A; R2A is cycloalkane or heterocycloalkane; R3 is heteroaryl which is not fused or fused with benzene, heteroarene or R3A; R3A is cycloalkane or heterocycloalkane; R 4 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is not fused or fused with arene, heteroarene or R 4A; R 4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R5 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or is substituted with one or two or three substituents that are independently selected from R6, NC (R6A) (R6B), R7, OR7, SR7 , S (0) R7, S02R7, NHR7, N (R7) 2, C (0) R7, C (0) NH2, C (O) NHR7, NHC (0) R7, NHS02R7, NHC (0) OR7, S02NH2 , S02NHR7, S02N (R7) 2, NHC (0) NH2, NHC (0) NHR7, NHC (O) CH (CH3) NHC (O) CH (CH3) NH2, NHC (O) CH (CH3) NHC (O CH (CH3) NHR \ OH, (O), C (O) OH, (O), N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R6 is C2-C5 spiroalkyl, each of which is unsubstituted or substituted by OH, (O), N3, CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH (CH3) or N (CH3) 2; R6A and R6B are independently selected from alkyl or, together with the N to which they are attached, R6C; R6C is aziridin-1-yl, azetidin-1-yl, pyrrolidin-1-yl or piperidin-1-yl, each having a CH portion not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH; R7 is R8, R9, R10 or R1 1; R8 is phenyl which is not fused or fused with arene, heteroarene or R8A; R8A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R9 is heteroaryl which is not fused or fused with arene, heteroarene or R9A; R9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R10 is C3-C10 cycloalkyl or C4-C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R 0A; R 0A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R1 1 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R12, OR12, NHR12, N (R12) 2, C ( O) NH 2 l C (O) NHR 12, C (0) N (R 12) 2, OH, (O), C (O) OH, N3, CN, NH2, CF3, CF2CF3I F, Cl, Br or I; R1 is R13, R14, R15 or R16; R13 is phenyl which is not fused or fused with arene, heteroarene or R13A; R13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R14 is heteroaryl, each of which is not fused or fused to arene, heteroarene or R14A; R14A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R15 is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene, each of which is not fused or fused with arene, heteroarene or R15A; R1 5A is cycloaican, cycloalkene, heterocycloalkane or heterocycloalkene; R16 is alkyl, alkenyl or alkynyl; R17 is R18, R19, R20 or R21; R18 is phenyl which is not fused or fused with arene, heteroarene or R18A; R18A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R19 is heteroaryl which is not fused or fused with arene, heteroarene or R19A; R19A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R20 is C3-C10 cycloalkyl or C4-C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), SO2 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R20A; R20A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R21 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or is substituted with one or two or three substituents that are independently selected from R22, OR22, NHR22, N (R22) 2, C (0) ) NH2, C (0) NHR22, C (O) N (R22) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R22 is R23, R24 or R25; R23 is phenyl which is not fused or fused with arene, heteroarene or R23A; R23A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R24 is heteroarene which is not fused or fused with arene, heteroarene or R24A; R24A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R25 is C3-C6 cycloalkyl or C4-C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R25A; R25A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; Z is R26 or R27, each of which is substituted with R28, R29 or R30, each of which is substituted with F, Cl, Br, I, CH2R37, CH (R31) (R37), C (R31) (R31A) (R37), C (O) R37, OR37, SR37, S (O) R37, SO2R37, NHR37 or N (R32) R37; R26 is phenyl which is not fused or fused with arene or heteroarene; R27 is heteroarene which is not fused or is fused with arene or heteroarene; R28 is phenyl which is not fused or fused to arene, heteroarene or R28A; R28A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R29 is heteroaryl or R29A; R29A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R30 is cycloalkyl or cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH independently selected and one or two CH portions not replaced or replaced with N, and each of which is not fused or is fused with arene, heteroarene or R30A; R30A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R31 and R31 A are independently F, Cl, Br or alkyl or are taken together and are spiroalkyl of C-C5; R32 is R33) C (O) R33 O C (O) OR33; R33 is R34 or R35; R34 is phenyl which is not fused or fused with aryl, heteroaryl or R3A; R3 A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R35 is alkyl which is unsubstituted or substituted with R36; R36 is phenyl which is not fused or fused with arene, heteroarene or R36A; R36A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R37 is R38, R39 or R40, each of which is substituted with F, Cl, Br, I, R4 \ OR41, NHR41, N (R41) 2, NHC (0) OR41, SR41, S (0) R41 or S02R41; R38 is phenyl which is not fused or fused with arene, heteroarene or R38A; R38A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R39 is heteroaryl which is not fused or fused to arene, heteroarene or R39A; R39A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R40 is C3-C8 cycloalkyl or C4-C8 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R40A; R40A cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R41 is R42, R43, R44 or R45; R42 is phenyl which is not fused or fused with arene, heteroarene or R42A; R42A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R43 is heteroaryl which is not fused or fused to arene, heteroarene or R43A; R43A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R44 is C3-C6 cycloalkyl or C4-C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), SO2 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R44A; R44A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R 45 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted by one or two substituents that are independently selected from R46, OR46, NHR46, N (R46) 2, C (0) NH2 , C (0) NHR46, C (0) N (R46) 2, OH, (O), C (0) OH, N3, CN, NH2I CF3, CF2CF3, F, Cl, Br or I; R46 is R47, R4d or R49; R47 is phenyl which is not fused or fused with arene, heteroarene or R47A; R47A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R48 is heteroaryl or R48A; R48A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R49 is C3-C3 cycloalkyl or C4-C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R49A; R49A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; wherein each preceding cyclic portion, independently, is not substituted, not further substituted, substituted or further substituted with one or two or three or four or five substituents that are independently selected from R50, OR50, SR50, S (O) R50, S02R5 °, C (O) R50, CO (O) R50, OC (0) R50, OC (0) OR50, NH2, NHR50, N (R50) 2, C (0) NH2, C (0) NHR50, C (O) N (R50) 2, C (0) NHOH, C (O) NHOR50, C (0) NHS02R5 °, C (0) NR55S02R50, S02NH2, SO2NHR50, SO2N (R50) 2, CF3, CF2CF3) C (0) H, C (0) OH, C (N) NH2, C (N) NHR50, C (N) N (R50) 2, OH, (O), N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I; R50 is R51, R52, R53 or R54; R51 is phenyl which is not fused or fused with arene, heteroarene or R51A; R51A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R52 is heteroaryl or R52A; R52A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R53 is C3-C6 cycloalkyl or C4-C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R53A; R53A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R54 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R55, OR55, SR55, S (0) R55, S02R55, NHR55 , N (R55) 2, C (0) R55, C (0) NH2, C (0) NHR55, NHC (0) R55, NHS02R55, NHC (0) OR55, S02NH2, S02NHR55, S02N (R55) 2, NHC (0) NH2, NHC (0) NHR55, OH, (O), C (0) OH, (O), N3, CN, NH2, CF3I OCF3, CF2CF3, OCF2CF3, F, Cl, Br or I; R55 is alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R56; R56 is C3-C6 cycloalkyl or C4-C6 cycloalkyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N. Even another modality belongs to compounds having the formula (l) -a (the, or prodrug salts, prodrugs or prodrug salts thereof, wherein R5a is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted by one or two or three substituents which are independently selected from from R6, NC (R6A) (R6B), R7, OR7, SR7, S (0) R7, S02R7, NHR7, N (R7) 2, C (0) R7, C (0) NH2, C (0) NHR7, NHC (0) R7, NHS02R7, NHC (0) OR7, S02NH2, S02NHR7, S02N (R7) 2, NHC (0) NH2, NHC (0) NHR7, NHC (0) CH (CH3) NHC (0) CH (CH3) NH2 l NHC (0) CH (CH3) NHC (0) CH (CH3) NHR1, OH, (O), C (0) OH, (O ), N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, wherein A1 is N or C (A2); A2 is H, F, CN, C (0) OH, C (0) NH2 or C (0) OR1A; B1 is R1, OR1, SR1, S (0) R1, S02R1, C (0) R1, C (0) OR1, OC (0) R1, NHR1, N (R1) 2, C (0) NHR1, C ( 0) N (R1) 2, NHC (0) R1, NHC (0) OR1, NR1C (0) NHR1, NR1C (O) N (R1) 2, S02NHR1, S02N (R1) 2, NHS02R1, NHS02NHR1 or N ( CH3) S02N (CH3) R; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, C (0) OH, F, Cl, Br, l, CF3, OCF3, CF2CF3, OCF2CF3lR17, OR17, C (0) R17, C (0) OR17, SR17, NH2, NHR17 , N (R17) 2, NHC (0) R17, C (0) NH2, C (0) NHR17, C (0) N (R17) 2, NHS (0) R17 or NHS02R17; or B1 and Y1, together with the atoms to which they are attached, are imidazole or triazole; R1 is R2, R3, R4 or R5; R1A is Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, Ce alkyl; R2 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R3 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazoI, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R4 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or Ce cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R5 is C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, C alkyl, C2 alkenyl, C3 alkenyl, C alkenyl, C5 alkenyl, C &alkenyl, C3 alkynyl, , C alkynyl, C5 alkynyl or Ce alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R6, R7, OR7, SR7, S ( 0) R7, S02R7, NHR7, N (R7) 2, C (0) R7, C (0) NH2, C (0) NHR7, NHC (0) R7, NHS02R7, NHC (0) OR7, S02NH2, S02NHR7, S02N (R7) 2, NHC (0) NH2, NHC (0) NHR7, NHC (0) CH (CH3) NHC (0) CH (CH3) NH2, OH, (O), C (0) OH, (O), N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R6 is spiroalkyl of C2, spiroalkyl of C3, spiroalkyl of C4 or spiroalkyl of C5, each of which is unsubstituted or substituted by OH, (O), N3, CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH (CH3) or N (CH3) 2; R7 is R8, R9, R10 or R1 1; R8 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R8A; R8A is C-cycloalkane, C5-cycloalkane, C6-cycloalkane, C4-cycloalkene, C5-cycloalkene or C6-cycloalkene, each having one or two CH2-portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R9 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R10 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, Ce cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, Cg cycloalkyl, C10 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl, Ce cycloalkenyl, C7 cycloalkenyl, C8 cycloalkenyl, Cg cycloalkenyl, C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R1 1 is Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, C6 alkyl, C2 alkenyl, C3 alkenyl, C alkenyl, C5 alkenyl, Ce alkenyl, C2 alkynyl , C3 alkynyl, C4 alkynyl, C5 alkynyl or Ce alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R12, OR12, NHR12, N (R12) 2, C (0) NH2, C (0) NHR12, C (0) N (R12) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R12 is R13, R14, R15 or R16; R13 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1, 2,3-triazoI or R13A; R 3A is cycloalkane of C4, cycloalkane of C5, cycloalkane of Ce, cycloalkene of C, cycloalkene of C5 or cycloalkene of C6, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3 , S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R 14 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl, 1,2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R15 is C3 cycloalkyl, C cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R1 d is C alkyl? , C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl) C6 alkyl, C2 alkenyl, C3 alkenyl, C4 alkenyl, C5 alkenyl, Ce alkenyl, C3 alkynyl, C4 alkynyl, alkynyl of C5 or alkynyl of Ce, 'R17 is R18, R19, R20 or R21; R18 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R19 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R20 is C3 cycloalkyl, C cycloalkyl, C5 cycloalkyl, Ce cycloalkyl, C cycloalkyl, Ce cycloalkyl, Cg cycloalkyl, C cycloalkyl, C cycloalkenyl, C5 cycloalkenyl, CT cycloalkenyl, C7 cycloalkenyl, C8 cycloalkenyl, Cg cycloalkenyl, Cio cycloalkenyl, each have one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R21 is Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, Cs alkyl, Ce alkyl, C2 alkenyl, C3 alkenyl, C4 alkenyl, C5 alkenyl, C6 alkenyl, C2 alkynyl, C3 alkynyl, C alkynyl, C5 alkynyl or Ce alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R22, OR22, NHR22, N (R22) 2, C (0) NH2, C (0) NHR22, C (0) N (R22) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F , Cl, Br or I; R22 is R23, R24 or R25; R23 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 24 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl, 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R25 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH independently selected and one or two CH portions not replaced or replaced with N; Z1 is R26 or R27, each of which is substituted with R28, R29 or R30, each of which is substituted with F, Cl, Br, I, CH2R37, CH (R31) (R37), C (R31) (R31A) (R37), C (0) R37, OR37, SR37, S (0) R37, S02R37, NHR37 or N (R32) R37; R26 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, soxazole, 1,2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine , pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 27 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R28 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R29 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazoi, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R30 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, Cg cycloalkyl, C10 cycloalkyl, Cu cycloalkyl, C12 cycloalkyl, C13 cycloalkyl, Cu cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl, C6 cycloalkenyl, C cycloalkenyl, C8 cycloalkenyl, C9 cycloalkenyl or C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R31 and R31 A are independently F, Cl, Br, Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl or are taken together and are C2 spiroalkyl, C3 spiroalkyl , C4 spiroalkyl or C5 spiroalkyl; R32 is R33, C (0) R33 or C (0) OR33; R33 is R34 or R35; R34 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 35 is C 1 alkyl, C 2 alkyl, C 3 alkyl, C alkyl, C 5 alkyl or C 6 alkyl, each of which is unsubstituted or substituted by R 36; R36 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R37 is R38, R39 or R40, each of which is substituted with F, Cl, Br, I, R41, OR41, NHR41, N (R41) 2, NHC (0) OR41, SR41, S (0) R41 or S02R41; R38 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, soxazole, 1,2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine , pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R39 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R40 is C3 cycloalkyl, C) cycloalkyl C5 cycloalkyl, Ce cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C cycloalkenyl, C5 cycloalkenyl, C6 cycloalkenyl, C-cycloalkenyl or C8 cycloalkenyl, each have a or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R41 is R42, R43, R44 or R45; R42 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R42A; R42A is C-cycloalkane, C5-cycloalkane, Ce-cycloalkane, C4-cycloalkene, C5-cycloalkene or C6-cycloalkene, each having one or two CH2-portions not replaced or replaced with O, C (O), S, S ( O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R43 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R44 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, Cs cycloalkylene or C6 cycloalkenyl, each having one or two CH portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH independently selected and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 45 is C 1 alkyl, C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, C 6 alkyl, C 2 alkenyl, C 3 alkenyl, C 4 alkenyl, C 5 alkenyl, C 6 alkenyl, C 2 alkynyl, C3 alkynyl, C4 alkynyl, C5 alkynyl or C6 alkynyl, each of which is unsubstituted or substituted by one or two substituents that are independently selected from R46, OR46, NHR46, N (R46 ) 2, C (0) NH2, C (0) NHR46, C (0) N (R46) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl , Br or I; R46 is R47, R48 or R49; R47 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R48 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R49 is C3 cycloalkyl, C4 cycloalkyl, Cs cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or Ce cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; in which the portions represented by B1 and Y1 together are substituted with Ci alkyl, C2 alkyl, C3 alkyl, C-alkyl, C5-alkyl or C6-alkyl, each of which is substituted with one or two substituents that are independently selected from SR55 or N (R55) 2, in which R55 is selected in a manner independent from phenyl, Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or Ce 'alkyl, the portions represented by R2, R3 and R4 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, S02R50, CO (0) R50 or OCF3, in which R50 is phenyl, Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, alkyl of C5 or Ce alkyl, the portions represented by R8, R9 and R10 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, C (0) NHS02R5 °, CO ( 0) R5 °, C (0) R50, C (0) OH, C (0) NHOH, OH, NH2, F, Cl, Br or I, in which R50 is phenyl, tetrazolyl or R54, wherein R54 is C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl, each of which is unsubstituted or substituted by phenyl; the portions represented by R26 and R27 are also not substituted or substituted with one or two substituents that are independently selected from F, Br, Cl or I; the portions represented by R28, R29 and R30 are also unsubstituted or substituted with OR54, in which R54 is Ci alkyl, C2 alkyl, C3 alkyl, C alkyl, C5 alkyl or C6 alkyl, each of which is unsubstituted or substituted with R56, in which R56 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl or C6 cycloalkyl, each having one or two CH2 portions replaced with independently selected O or NH and a CH portion not replaced or replaced with N; the portions represented by R38, R39 and R40 are unsubstituted or substituted with one or two substituents that are independently selected from R54, F, Br, Cl or I, in which R54 is Ci alkyl, C, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl; and the portions represented by R42, R43, R44 and R45 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, N (R50) 2, S02R5 °, CN, CF3 , F, Cl, Br or I, in which R50 is phenyl or R54, in which R54 is Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl, each of which is unsubstituted or substituted by N (R55) 2 or R56, in which R55 is Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or Ce alkyl and R56 is cycloalkyl C3, C4 cycloalkyl, C5 cycloalkyl or Ce cycloalkyl, each has a CH2 portion not replaced or replaced with O, C (O), S, S (0), S02 or NH independently selected and one or two CH portions not replaced or replaced with N. Even another embodiment pertains to compounds having the formula (I), or salts, prodrugs or salts of prodrugs thereof. pharmaceutically acceptable, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) NH2 or C (0) OR1 A; B1 is R \ OR1, SR1, S (0) R1, S02R1, C (0) R1, C (0) OR1, OC (0) R1, NHR1, N (R1) 2, C (0) NHR1, C ( 0) N (R1) 2, NHC (0) R1, NHC (0) OR1, NR1C (0) NHR1, NR1C (0) N (R1) 2, S02NHR1, S02N (R1) 2, NHS02R1, NHS02NHR1 or N ( CH3) S02N (CH3) R1; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, C (0) OH, F, Cl, Br, CF3, OCF3, NH2, C (0) NH2 or B1 and Y1, together with the atoms to which they are attached, are imidazole or triazole; R1 is R2, R3, R4 or R5; R 1 A is C 2 alkyl C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, C 6 alkyl; R2 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R3 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene; R4 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, Ce cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R5 is Ci alkyl, C2 alkyl, C3 alkyl, C alkyl, C5 alkyl, Ce alkyl, C2 alkenyl, C3 alkenyl, C4 alkenyl, C5 alkenyl, C6 alkenyl, C3 alkynyl, C5 alkynyl, C5 alkynyl or C6 alkynyl, each of which is unsubstituted or substituted by one or two or three substituents which are independently selected from R6, R7, OR7, SR7, S ( ) R7, S02R7, NHR7, N (R7) 2, C (0) R7, C (0) NH2, C (0) NHR7, NHC (0) R7, NHS02R7, NHC (0) OR7, S02NH2, S02NHR7, S02N (R7) 2, NHC (0) NH2, NHC (0) NHR7, NHC (0) CH (CH3) NHC (0) CH (CH3) NH2, OH, (O), C (0) OH, (O) , N3, CN, NH2) CF3, CF2CF3, F, Cl, Br or I; R6 is spiroalkyl of C2, spiroalkyl of C3, spiroalkyl of C4 or spiroalkyl of C5, each of which is unsubstituted or substituted by OH, (O), N3, CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH (CH3) or N (CH3) 2; R7 is R8, R9, R10 or R1 1; R8 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R8A; R8A is C4 cycloalkane, C5 cycloalkane, C6 cycloalkane, C4 cycloalkene, C5 cycloalkene or Ce cycloalkene, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S ( O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R9 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinium, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene; R 10 is C 3 cycloalkyl, C cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, C 7 cycloalkyl, C 8 cycloalkyl, Cg cycloalkyl, C cycloalkyl, C cycloalkenyl, C 5 cycloalkenyl, C 6 cycloalkenyl) C cycloalkenyl, C8 cycloalkenyl, Cg cycloalkenyl, C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R1 1 is Ci alkyl, C2 alkyl, C3 alkyl, C alkyl, C5 alkyl, C6 alkyl, C2 alkenyl, C3 alkenyl, C4 alkenyl, C5 alkenyl, C6 alkenyl, C2 alkynyl , C3 alkynyl, C alkynyl, C5 alkynyl or C6 alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R12, OR12, NHR12, N (R12) 2, C (0) NH2, C (0) NHR12, C (0) N (R12) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R12 is R13, R14, R15 or R16; R13 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R13A; R13A is C4 cycloalkane, C5 cycloalkane, Ce cycloalkane, C cycloalkene, C5 cycloalkene or C6 cycloalkene, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S ( O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R 14 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl, 1, 2,3-triazolyl, each of which is not fused or is fused with benzene; R15 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R 16 is C 1 alkyl, C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, C 6 alkyl, C 2 alkenyl, C 3 alkenyl, C 4 alkenyl, C 5 alkenyl, C 6 alkenyl, C 3 alkynyl, C4 alkynyl, C5 alkynyl or C6 alkynyl; Z1 is R26 or R27, each of which is substituted with R28, R29 or R30, each of which is substituted with Cl, Br, CH2R37, C (R31) (R31A) (R37), C (0) R37, OR37, SR37, S (0) R37, S02R37, or NHR37; R26 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 27 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene; R28 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R29 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene; R30 is C3 cycloalkyl, C cycloalkyl, C5 cycloalkyl, Ce cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C9 cycloalkyl, C10 cycloalkyl, Cu cycloalkyl, C2 cycloalkyl, C3 cycloalkyl, C- cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl, C6 cycloalkenyl, C7 cycloalkenyl, C8 cycloalkenyl, Cg cycloalkenyl or C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C ( O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R31 and R31 A are independently F, Cl, Br, Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl or are taken together and are C2 spiroalkyl, C3 spiroalkyl , C4 spiroalkyl or Cs spiroalkyl; R37 is R38, R39 or R40, each of which is substituted with F, Cl, Br, I, R41, OR41, NHR41, N (R41) 2, NHC (0) OR41, SR41, S (0) R41 or S02R41; R38 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R39 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene; R40 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl, Ce cycloalkenyl, C7 cycloalicynyl or C8 cycloalkenyl, each having a or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R41 is R42, R43, R44 or R45; R42 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazoI, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R42A; R42A is cycloalkane of C4, cycloalkane of C5, cycloalkane of C6, cycloalkene of C, cycloalkene of C5 or cycloalkene of C6, each having one or two portions CH2 not replaced or replaced with O, C (O), S, S ( O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R43 is furanyl, midazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene; R44 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, C cycloalkenyl or C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH independently selected and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 45 is Ci alkyl, C 2 alkyl, C 3 alkyl, C alkyl, C 5 alkyl, C 6 alkyl, C 2 alkenyl, C 3 alkenyl, C 4 alkenyl, C 5 alkenyl, C 6 alkenyl, C 2 alkynyl, C3 alkynyl, C alkynyl, C5 alkynyl or C6 alkynyl, each of which is unsubstituted or substituted by one or two substituents that are independently selected from R46, OR46, NHR46, N (R46 ) 2, C (0) NH2, C (0) NHR46, C (0) N (R46) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl , Br or I; R46 is R47, R48 or R49; R47 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R48 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene; R49 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, Ce cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; in which the portions represented by B1 and Y1 together are substituted with C2 alkyl, C3 alkyl or C4 alkyl, each of which is substituted with one or two substituents that are independently selected from SR55 or N (R55) 2, in which R55 is independently selected from phenyl or C alquilo alkyl, the portions represented by R 2, R 3 and R 4 are unsubstituted or substituted with one or two substituents which are independently selected from from R50, OR50, SR50, S02R5 °, CO (0) R5 ° or OCF3, in which R50 is phenyl, Ci alkyl, C2 alkyl, C3 alkyl or C4 alkyl; the portions represented by R8, R9 and R10 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, C (0) NHS02R5 °, CO (0) R5 °, C (0) ) R5 °, C (0) OH, C (0) NHOH, OH, NH2, F, Cl, Br or I, in which R50 is phenyl, tetrazolyl or R54, in which R54 is Ci-alkyl, C2 or C3 alkyl, each of which is unsubstituted or substituted by phenyl; the portions represented by R26 and R27 are also unsubstituted or substituted with one or two substituents that are independently selected from F, Br, Cl or I; the portions represented by R28, R29 and R30 are also unsubstituted or substituted with OR54, in which R54 is Ci alkyl or C2 alkyl, each of which is unsubstituted or substituted by N (R55) 2 or R56 , wherein R55 is Ci alkyl, C2 alkyl, C3 alkyl, C alkyl, Cs alkyl or C6 alkyl, and R56 is C or C6 cycloalkyl, each having one or two CH2 portions replaced with O or NH selected independently and a CH portion not replaced or replaced with N; the portions represented by R38, R39 and R40 are unsubstituted or are substituted with one or two substituents that are independently selected from alkyl of C-i, F, Br, Cl or I; and the portions represented by R42, R43, R44 and R45 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, N (R50) 2, S02R50, CN, CF3, F, Cl, Br or I, in which R50 is phenyl or R54, in which R54 is Ci-alkyl, C2-alkyl or C3-alkyl, each of which is unsubstituted or substituted by N (alkyl) C?) 2 or C6 cycloalkyl having a CH portion replaced with O and a CH portion replaced with N. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A1 is H, F, CN, C (0) OH, C (0) NH2 or C (0) OCH3; B1 is R1, OR1, NHR1, N (R1) 2 or NR1 C (0) N (R1) 2; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2, C (0) NH2, or B1 and Y1, together with the atoms to which they are attached, are imidazole or triazole; R1 is phenyl, pyrrolyl, cyclopentyl, cyclohexyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl or R5; R5 is Ci alkyl, C2 alkyl, C3 alkyl, C alkyl, C5 alkyl or CT alkyl, each of which is unsubstituted or substituted with one or two or three substituents which are independently selected from spiroalkyl of C4, spiroalkyl of C5, R7, OR7, SR7, S02R7, NHR7, N (R7) 2, C (0) R7, C (0) NH2, C (0) NHR7, NHC (0) R7 , NHS02R7, NHC (0) OR7, NHC (0) NH2, NHC (0) CH (CH3) NHC (0) CH (CH3) NH2, OH, C (0) OH or NH2; R7 is phenyl, furanyl, imidazolyl, pyridinyl, tetrazolyl, thiazolyl, thienyl, 1,3-benzoxazolyl, 1,3-benzodioxoyl, 1,3-benzothiazole, cyclopropyl, cyclobutyl, cyclohexyl, azetidinyl, morpholinyl, piperazinyl, piperidinyl, thiomorpholinyl, thiomorpholinyl sulfone 7-azabicyclo [2.2.1] heptanyl, 8-azabicyclo [3.2.1] octanyl, 4,5-dihydro-1 H-imidazolyl 2-oxa-5-azabicyclo [2.2.1] heptanyl, 1, 4,5,6-tetrahydropyrimidinyl or R 1 1; R1 1 is Ci alkyl, C2 alkyl, C3 alkyl or C4 alkyl, each of which is unsubstituted or substituted by one or two or three substituents which are independently selected from R12, OR12, N (R12) 2, C (0) N (R12) 2, OH, C (0) OH, NH2, CF3, F, Cl, Br or I; R 12 is 1, 3-benzodioxoly, pyridinyl, morpholinyl or alkyl of d; Z1 is phenyl or pyridinyl, each of which is substituted with cyclohexenyl, piperazinyl, piperidinyl, 1, 2,3,6-tetrahydropyridinyl or octahydropyrrolo [3,4-c] pyrrolyl, each of which is substituted with CH2R37, C (Spiroalkyl of C2) (R37) or C (0) R37; R37 is phenyl, naphthyl, imidazolyl, pyrazolyl, pyridinyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclo-octenyl or 3,6-dihydro-2H-pyranyl, each of which is substituted with F, Cl, Br, I, R41, NHR41, N (R41) 2, NHC (0) OR41 or SR41; R41 is phenyl, naphthyl, cyclohexyl, morpholinyl, piperidinyl, thienyl, pyridinyl, quinolinyl, benzofuranyl, 1,3-benzodioxolyl, isoindolinyl, 1,3-oxazolidin-2-onyl or R45; R 45 is C 1 alkyl, C 2 alkyl, C 3 alkyl or C 4 alkyl, each of which is unsubstituted or substituted by phenyl; in which the portions represented by B1 and Y1 together are substituted with C-alkyl, C3-alkyl or C4-alkyl, each of which is substituted with one or two substituents that are independently selected from SR55 or N (R55) 2, in which R55 is independently selected from phenyl or C1-alkyl; the portions represented by R are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, S02R5 °, CO (0) R5 ° or OCF3, in which R50 is phenyl, alkyl of d, C2 alkyl, C3 alkyl or C4 alkyl; the portions represented by R7 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, C (0) NHS02R50, CO (0) R5 °, C (0) R5 °, C (0) OH, C (0) NHOH, OH, NH2, F, Cl, Br or I, in which R50 is phenyl, tetrazolyl or R54, in which R54 is Ci alkyl, C2 alkyl or C3 alkyl , each of which is unsubstituted or substituted by phenyl; the phenyl and pyridinyl portions of Z1 are unsubstituted or are further substituted with one or two substituents that are independently selected from F, Br, Cl or I; The cyclohexenyl, piperazinyl, piperidinyl, 1, 2,3,6-tetrahydropyridinyl and octahydropyrrolo [3,4-c] pyrrolyl portions of Z1 are unsubstituted or are further substituted with OR54, in which R54 is Ci alkyl or alkyl. C2, each of which is unsubstituted or substituted by N (C ^ alkyl, morpholinyl, piperidinyl or piperidinyl; the portions represented by R37 are unsubstituted or substituted by one or two substituents which are independently selected from from Ci, F, Br, Cl or I alkyl, and the portions represented by R41 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, N (R50) 2, S02R5 °, CN, CF3) F, Cl, Br or I, in which R50 is phenyl or R54, in which R54 is Ci-alkyl, C2-alkyl or C3-alkyl, each of which is not substituted or is substituted with N (C-?) alkyl or morpholinyl.

Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1R) -2- (diethylamino) -1 - ((phenylsulfanyl) -methyl) ethylamino, (1R) -3- (diethylamino) -1 - ((phenylsulfanyl) -methyl) -propylamino, (1R) -3 - ((2,2-difluoro-ethyl) amino) -1 - ((phenyl-sulfanyl) methyl) propylamino, (1R) -3- (5,6-dihydro-1 (4H) -pyrimidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (di-isopropylamine) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -2 - ((2- (dimethylamino) ethyl) ( methyl) amino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1R) -2- (2- (dimethylamino) ethoxy) -1 - ((phenylsulfanyl) methyl) ethylamino, (3R) -5- (N - ((dimethylamino) methylcarbonyl) amino) -1- ((phenylsulfanyl) methyl) ) pentylamino, (1R) -3- (dimethylamino) -1- ((phenylisulfanyl) methyl) propoxy, (1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1S) -3- ( dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1- ((pyrimidin-2-ylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazol-2-yl) methyl) propylamino, (1R) -3- (dimethylamino) -1 - ((thien-2-ylsulfanyl) methyl) -propylamino, (1R ) -3- (dimethylamino) -1 - (((4- (trifluoromethoxy) -phenyl) sulfanyl) methyl) propylamino, (1 R) -3- (2,4-dimethyl-4,5-dihydro-1H-imidazole) -1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -3- (4,4-dimethyl-4,5-dihydro-1 H-imidazol-1-yl) -1- ( (phenylsulfanyl) methyl) propylamino, (1R) -5 - ((1,1-dimethylethoxy) carbonylamino) -1 - ((phenylsulfanyl) methyl) -pentylamino, 1- (1,1-dimethylethoxycarbonyl) piperidin-4-yloxy, 1,1-dimethyl-2- (phenylsulfonyl) etilamino, (1,1-dimethyl-2- (phenylsulfanyl) ethyl) a mino, 1,1-dimethyl-2- (phenylsulfanyl) ethyl, 4,4-dimethylpiperidin-1-yl, (1R) -3- (2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) - methyl) propylamino, (1R) -3 - ((2R, 6S) -2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, 1,1-dimethyl-2- (pyrimidin- 2-ylsulfanyl) ethylamino, (1R) -4 - ((2 R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((f-enylsulfanyl) methyl) -butylamino, (1R) -3- ((2R, 5R) -2,5-Dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (2,5-dimethyl-pyrrolidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) -methyl) propylamino, (1R) -3- ( (2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1,1-dimethyl-2- (thien-2-ylsulfanyl) ethylamino, (1R) -3 - (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ( dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (ethyl (2,2,2-trifluoroethyl) am ino) -1 - ((phenylsulfanyl) -methyl) propylamino, 1- (ethoxycarbonyl) piperidin-4-yloxy, (1R) -3 - ((2-fluoroethyl) amino) -1- ((phenylsulfanyl) methyl) -propylamino, (1R) -1 - (((4-fluorophenyl) sulfanil) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (1,3-benzodioxol-5-yl) phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (benzofuran-2-ylphenyl) -phenylmethyl) ) piperazin-1-yl) phenylcarbonyl, 4- (2-bromocyclohex-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2-bromocyclopent-1-en-1-ylmethyl) piperazine- 1 -yl) -phenylcarbonyl, 4- (2- (4-bromophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclohepta-1-en-1- ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (1 - (2- (4-chlorophenyl) cyclohex-1-en-1-ylmethyl) -1, 2,3,6-tetrahydropyridin-4-yl) - phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclohex-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclopent-1 -in-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cycloo-oct-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((4- (4-chlorophenyl) -5,6-dihydro-2 H -pyran-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((4- ( 4-chlorophenyl) -5,6-dihydro-2H-pyran-3-yl) methyl) -piperazin-1-yl) -phenylcarbonyl, 4- (1 - ((2- (4-chlorophenyl) -5,5- dimethyl-1 -ci clohex-1-en-1 -iI) methyl) -1, 2,3,6-tetrahydropyridin-4-yl) -phenylmethyl, 4- (4- (2- (4-chlorophenyl) naphth-3-ylmethyl) piperazine -1 -yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) pyridin-3-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (3- (4-chlorophenyl) pyridine -4-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((4- (4-chlorophenyl) pyridin-5-yl) methyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4 - (2- (4-chlorophenyl) -phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (1 - (2- (4-chlorophenyl) -phenyl-cycloprop-1-yl) -piperazin-1-yl) -phenylcarbonyl or 4- (4- (2- (4-chlorophenyl) -phenylmethyl) cyclohex-1-en-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -2- (diethylamino) -1 - ((phenylsulfanyl) -methyl) ethylamino, (1 R) -3- (diethylamino) -1 - ((phenylsulfanyl) -methyl) propylamino, (1R) - 3 - ((2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (5,6-dihydro-1 (4H) -pyrimidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (di-isopropylamino) -1- (phenylsulfanyl) methyl) -propylamino, (1R) -2 - ((2- (dimethylamino) etiI) (methyl) amino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1R) -2- (2- (dimethylamino) -ethoxy) -1 - ((phenylsulfanyl) methyl) ethylamino, (3R) -5- (N - ((dimethylamino) methylcarbonyl) amino) -1 - ((phenylsulfanyl) -methyl) pentylamino, (1R) -3- (dimethylamino) -1- ((phenylisulfanyl) methyl) propoxy, (1R) -3- (dimethylamino) -1- ( (phenylsulfanyl) methyl) propylamino, (1S) -3- (dimethylamine) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1- ((pyrimidin-2-ylsulfanil ) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazol-2-yl) methyl) propylamino, (1R) -3- (dimethylamino) -1- ((thien-2-ylsulfanyl) methyl) -propylamino, (1R) -3- (dimethylamino) -1 - (((4- (trifluoromethoxy) -fe nyl) -sulfanyl) methyl) propylamino, (1 R) -3- (2,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R ) -3- (4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -5 - ((1,1-dimethylethoxy) carbonylamino) -1 - ((phenylsulfanyl) methyl) -pentylamino, 1- (1,1-dimethylethoxycarbonyl) piperidin-4-yloxy, 1,1-dimethyl-2- (phenylsulfonyl) ethylamino, (1,1-dimethyl-2) - (phenylsulfanyl) ethyl) amino, 1,1-dimethyl-2- (phenylsulfanyl) -ethyl, 4,4-dimethylpiperidin-1-yl, (1 R) -3- (2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ((2R, 6S) -2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1,1-dimethyl -2- (pyrimidin-2-ylsulfanyl) ethylamino, (1R) -4 - ((2R, 5S) -2,5- dimethyl-pyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -butylamino, ( 1 R) -3- ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (2,5-dimethyl-pyrrolidin- 1 -yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) - methyl) propylamino, (1 R) -3- ((2S, 5S) -2,5-dimethyl-1-pyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1,1-dimethyl-2- (thienyl) 2-ylsulfanyl) ethylamino, (1 R) -3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (d-propylamino) - 1 - ((f-enylsulfanyl) methyl) propylammon, (1 R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (ethyl (2,2,2- trifluoroethyl) amino) -1 - ((phenylsulfanyl) -methyl) propylamino, 1- (ethoxycarbonyl) piperidin-4-yloxy, (1 R) -3 - ((2-fluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) ) -propylamino, (1 R) -1 - (((4-fluorophenyl) -sulfanyl) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (5- (2- (4-chlorophenyl) -phenylmethyl) -hexahydropyrrolo [3,4-c] -pyrrol-2 (1 H) -yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) -4-methoxypiperidin-1-l) -phenylcarbonyl, 4- (4 - (2- (4-chlorophenyl) -phenylmethyl) -piperazin-1-yl) -3,5-difluorophenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -2 -fluorophenyl-carbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -3-fluorophenylcarbonyl, 2- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazine- 1 -yl) pyridin-5-ylcarbonyl, 4- (1 - (2- (4-chlorophenyl) -phenylmethyl) piperidin-4-yl) -phenylcarbonyl, 5- (4- (2- (4-chlorophenyl) -phenylmethyl) ) -piperazin-1-yl) pyridin-2-ylcarbonyl, 4- (1 - (2- (4-chlorophenyl) -phenylmethyl) -1, 2,3,6-tetrahydropyridin-4-yl) -phenylcarbonyl, 4- (4- (2- (cyclohex-1-ylamino) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl-4- (2-cyclohex-1-phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - (2- (3-cyanophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2,4-dichloro phenyl) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3,4-dichlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2,4-difluorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (1,3-dihydro-2H-isoindol-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl 4- (4- (3- (1,1-dimethylethoxycarbonyl-amino) -phenyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (4- (2- (dimethylamino) ethoxy) -pheni) - phenylmethyl) piperazin-1-yl) -phenylcarbonyl or 4- (4- (3- (dimethylamino) -phenyl) piperazin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -2- (diethylamino) -1 - ((phenylsulfanyl) -methyl) ethylamino, (1 R) -3- (diethylamino) -1 - ((phenylsulfanyl) -methyl) propylamino, (1 R) -3 - ((2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (5,6-dihydro-1 (4H) -pyrimidin-1-yl) - 1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -2 - ((2- (dimethylamino) ethyl) (methyl) amino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1 R) -2- (2- (dimethylamino) -ethoxy) -1 - ((phenylsulfanyl) methyl) ethylamino, (3R) -5- ( N - ((dimethylamino) methylcarbonyl) amino) -1 - ((phenylsulfanyl) -methyl) pentylamino, (1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propoxy, (1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1S) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1- ((pyrimidin-2-ylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazol-2-yl) methyl) propylamine, (1 R) -3 - (dimethylamine) -1 - ((thien-2-yisulfanyl) methyl) -propylamino, (1R) -3- (dimethylamino) -1 - (((4 - (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino, (1R) -3- (2,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -5 - ((1 , 1-d-imethylethoxy) carbon-lamino) -1- ((phenylsulfanyl) methyl) -pentylamino, 1- (1,1-dimethylethoxycarbonyl) piperidin-4-yloxy, 1,1-dimethyl-2- (phenylsulfonyl) ethylamino, (1,1-dimethyl-2- (phenylsulfanyl) -ethyl) amino, 1,1-dimethyl-2- (phenylsulfanyl) ethyl, 4,4-dimethylpiperidin-1-yl, (1 R) -3- ( 2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ((2R, 6S) -2,6-dimethylpiperidin-1-yl) -1 - (( phenylsulfanyl) methyl) propylamino, 1,1-dimethyl-2- (pyrimidin-2-ylsulfanyl) ethylamino, (1 R) -4 - ((2R, 5S) -2,5-dimethyl-pyrrolidin-1-yl) - 1 - ((phenylsulfanyl) methyl) -butylamino, (1R) -3- ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylisulfanyl) methy1) -propylamino, (1R) -3- (2,5-Dimethylpyrrolidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3- ((2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1,1-dimethyl-2 - (thien-2-ylsulfanyl) ethylamino, (1R) -3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dipropylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (ethyl (2,2,2-trifluoroethyl) amino ) -1- (phenylsulfanyl) -methyl) propylamino, 1 - (ethoxycarbonyl) piperidin-4-yloxy, (1 R) -3 - ((2-fluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) - propylamino, (1 R) -1 - (((4-fluorophenyl) -sulfaniI) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (2- (4- (dimethylamino) -phenyl) -phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (dimethylamino) -phenyl) -phenylmethyl) piperazine -1-yl) -phenylcarbonyl, 4- (4 - ((2- (4- (dimethylamino) -phenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2 ~ (5,5-dimethyI-2-oxo-1,3-oxazolidin-3-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-fluorophenyl) cyclopent-1 in-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-fluorophenyl) -3-fluorophenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2 - (4-fluorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4-fluorophenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, - (2- (isopropylamino) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (isopropylsulfanyl) -phene) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methoxyphenyl) cyclopent-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3-methoxyphenyl) -phenylmethyl) piperazine-1- il) -phenylcarbonyl, 4- (4- (2- (4-methoxyphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarb onyl, 4- (4 - ((2- (4-methoxyphenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4-methoxy-4- (2- (pyridin-3-) il) -phenylmethyl) piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (2-methyl-4-dichlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2 - (2-methylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (methylsulfonyl) -phenyl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - (2- (4-methylsulfonylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl or 4- (4 - ((2- (4-methylsulfonylphenyl) pyridin-3-yl) methyl) piperazin-1-yl) - phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -2- (diethylamino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1 R) -3- (diethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) - 3 - ((2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) metii) propylamino, (1 R) -3- (5,6-dihydro-1 (4H) -pyrimidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -2 - ((2- (dimethylamine) ethyl) (methyl) ) amino) -1 - ((phenylsulfanyl) -methyl) ethylamino, (1 R) -2- (2- (dimethylamino) ethoxy) -1 - ((phenylsulfanyl) methyl) ethylamino, (3R) -5- (N- ((dimethylamino) -methylcarbonyl) amino) -1 - ((phenylsulfanyl) methyl) pentylamino, (1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propoxy, (1 R) -3- (dimethylamino ) -1 - ((phenylsulfanyl) methyl) propylamino, (1 S) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (dimethylamino) -3-oxo-1 - ((pyrimidin-2-ylsulfanyl) -methyl) propylamino, (1 R) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazol-2-yl) methyl) propylamine, ( 1 R) -3- (dimethylamino) -1 - ((thien-2-ylsulfanyl) methyl) propylamino, (1 R) -3- (dimethylamino) o) -1 - (((4- (trifluoromethoxy) -phenyl) -sulfanyl) -methyl) propylamino, (1 R) -3- (2,4-dimetii-4,5-dihydro-1 H-imidazole-1 -yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -5 - ((1,1-dimethylethoxy) carbonylamino) -1 - ((phenylsulfanyl) methyl) -pentylamino, 1- (1,1-dimethylethoxycarbonyl) piperidin-4-yloxy, 1,1-dimethyl -2- (phenylsulfonyl) ethylamino, (1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino, 1,1-dimethyl-2- (phenylsulfanyl) -ethyl, 4,4-dimethylpiperidin-1-yl, (1R ) -3- (2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ((2R, 6S) -2,6-dimethylpiperidin-1-yl) - 1 - ((phenylsulfanyl) methyl) propylamino, 1,1-dimethyl-2- (pyrimidin-2-ylsulfanyl) ethylamino, (1R) -4 - ((2R, 5S) -2,5-dimethyl-pyrrolidin-1- il) -1 - ((phenylsulfanyl) methyl) -butylamino, (1R) -3- ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R ) -3- (2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -3 - ((2R, 5S) -2,5-dimethylpyrrolidin-1- il) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3 - ((2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, 1, 1-dimethyl-2- (thien-2-ylsulfanyl) ethylamino, (1R) -3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) -methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (ethyl (2,2,2-trifluoroethyl) ) amino) -1 - ((phenylsulfanyl) methyl) propylamino, 1- (ethoxycarbonyl) piperidin-4-yloxy, (1R) -3 - ((2-fluoroethyl) amino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -1 - (((4-fluorophenyl) sulfanyl) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (5-methylthien-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsufanylphenyl) cyclohex-1-in -1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) -phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4 -met.sulfanylphenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, - (4- (2- (4- (2- (morpholin-1-yl) ethoxy) -phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (morpholin-1 - il) -phenylmethyl) piperazin-1-phenylcarbonyl, 4- (4- (2- (naphth-1-yl) -phenylmethyl) piperazin-1-phenylcarbonyl, 4- (4- (2- (naphth-2-yl) phenylmethyl) -piperazin-1-phenylcarbonyl or 4- (4- (2- (4-phenoxyphenyl) -phenylmethyl) -piperazin-1-phenylcarbonyl, 4- (4 - ((1-phenyl-1H-imidazole-2- il) methyl) piperazin-1-phenylcarbonyl, 4- (4 - ((1-phenyl-1 H -imidazol-5-yl) methyl) piperazin-1-phenylcarbonyl, 4- (2 - ((phenylmethyl) amino) -phenylmethyl) piperazin-1-phenylcarbonyl, 4- (4- (2- (phenyl) -phenylmethyl) -4- (2 (dimethylamine no) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4 - ((2- (phenyl-phenylmethyl) -4-methoxy-piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (phenyl-phenylmethyl) -4) - (2- (morpholin-1-yl) ethoxy)) - piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - (3- (phenyl-phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (phenyl) -phenyl-phenylmethyl) -piperazin-1-yl) -phenylcarbonyl or 4- (4- ( 2- (phenyl) -phenylmethyl) -4- (2- (piperidin-1-yl) ethoxy)) - piperidin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -2- (diethylamino) -1 - ((phenylsulfanyl) methyl) etilamino, (1R) -3- (diethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ((2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (5,6-dihydro-1 (4H) -pyrimidin-1-yl) -1 - (( phenylsulfanyl) methyl) propylamino, (1R) -3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -2 - ((2- (dimethylamino) ethyl) (methyl) amino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1R) -2- (2- (dimethylamino) ethoxy) -1 - ((phenylsulfanyl) methyl) ethylamino, (3R) -5- (N - ((dimethylamino) methylcarbonyl) amino ) -1 - ((phenylsulfanyl) methyl) pentylamino, (1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propoxy, (1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) ) propylamino, (1S) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1- ((pyrimidin-2-ylsulfanyl) methyl) prop Lamino, (1R) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazol-2-yl) methyI) propylamino, (1R) -3- (dimethylamino) -1 - ((thien) -2-ylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -1 - (((4- (trifluoromethoxy) -phenyl) ) -sulfanyl) methyl) propylamino, (1R) -3- (2,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (4,4-dimethyl-4,5-dihydro-1 H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -5 - ((1,1-dimethylethoxy) carbon (lamino) - 1 - ((phenylsulfanyl) methyl) -pentylammono, 1- (1,1-dimethylethoxycarbonyl) piperidin-4-yloxy, 1,1-dimethyl-2- (phenylsulfonyl) ethylamino, (1,1- dimethyl-2- (phenylsulfanyl) ethyl) amino, 1,1-dimethyl-2- (phenylsulfanyl) -ethyl, 4,4-dimethylpiperidin-1-yl, (1R) -3- (2,6-dimethylpiperidin-1-) il) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3 - ((2R, 6S) -2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1, 1 -dimethyl-2- (pyrimidin-2-ylsulfanyl) ethylammon, (1 R) -4 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) - butylamino, (1R) -3- ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (2,5-dimethylpyrrolidin-1) -yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-iI) -1 - ((phenylfluoryl) meti I) p ropylamino, (1R) -3- ((2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, 1,1-dimethyl-2- (thien-2) -ylsulfanyl) ethylamino, (1R) -3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) -methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (ethyl (2,2,2-trifluoroethyl) amino) -1 - ((phenylsulfanil ) methyl) propylamino, 1- (ethoxycarbonyl) piperidin-4-yloxy, (1R) -3 - ((2-fluoroethyl) amino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -1 - ((( 4-fluorophenyl) -sulfanyl) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (phenyl) -phenylmethyl) -4- (2- (pyrrolidin-1-yl) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4- (4 - ((2 - (phenyl) pyridin-3-yl) methyl) piperazine-1-phenylcarbonyl, 4- (4 - ((1-phenyl-1H-pyrazol-5-yl) methyl) piperazine-1-phenylcarbonyl, 4- ( 4- (2- (piperidin-1-yl) -phenylmethyl) piperazine-1-phenylcarbonyl, 4- (4- (2- (pyrid-3-yl) -phenyl) -phenylmethyl) piperazine-1-phenylcarbonyl, 4- (4- (2- (quinolin-3-ylphenyl) -phenylmethyl) piperazine-1-phenylcarbonyl, 4- (4- (2- (quinolin-8-ylphenyl) -phenylmethyl) piperazine-1-phenylcarbonyl, 4- (4- (2- (thien-2-yl) -phenylmethyl) -4-methoxypiperazin-1-yl) phenylcarbonyl, 4- (4- (2- (thien-2-yl) -phenylmethyl) -piperazine- 1-yl) phenylcarbonyl, 4- (4- (2- (4-trifluoromethoxyphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl or 4- (4- (2- (4-trifluoromethylphenyl) -phenylmethyl) piperazine-1 -yl) -phenylcarbonyl Even another embodiment belongs to compounds having the formula (I), or salts, prodrugs or prodrug salts thereof therapeutically acceptable, wherein A1 is C (A2); A2 is H, F, CN, C (0 ) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -2- (diethylamino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1 R) -3- (diethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3 - ((2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (5,6-dihydro-1 (4H) -pyrim id in-1 -il) - 1 - ((phenylsulfanyl) methyl) prop lamino, (1 R) -3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -2 - ((2- (dimethylamino) ethyl) (methyl) amino) -1 - ( (phenylsulfanyl) methyl) ethylamino, (1 R) -2- (2- (dimethylamino) -ethoxy) -1 - ((phenylsulfanyl) methyl) ethylamino, (3R) -5- (N - ((dimethylamino) methylcarbonyl) amino ) -1 - ((f-enylsulfanyl) -methyl) -pentylamino, (1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propoxy, (1 R) -3- (dimethylamino) -1 - ( (f-enylsulf indigo) methyl) propylamino, (1 S) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (dimethylamino) -3-oxo-1 - ((pyrimidine -2-ylsulfanyl) methyl) propylamino, (1 R) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazoI-2-yl) methyl) propylamino, (1 R) -3- ( dimethylamino) -1 - ((thien-2-ylsulfanyl) methyl) -propylamino, (1R) -3- (dimethylamino) -1 - (((4- (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino, ( 1 R) -3- (2,4-dimethyl-4,5-dihydro-1 H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (4.4 -dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -5 - ((1,1-dimethylethoxy) carb) onylamino) -1 - ((phenylsulfanyl) methyl) pentylamino, 1- (1,1-dimethylethoxycarbonyl) piperidin-4-yloxy, 1,1-dimethyl-2- (phenylsulfonyl) -ethylamino, (1,1-dimethyl) -2- (phenylsulfanyl) ethyl) amino, 1,1-dimethyl-2- (phenylsulfanyl) ethyl, 4,4-dimethylpiperidin-1-yl, (1R) -3- (2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) -methyl) propylamino, (1R) -3- ((2R, 6S) -2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1, 1- dimethyl-2- (pyrimidin-2-ylsulfanyl) ethylamino, (1 R) -4 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -butylamino, ( 1R) -3 - ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1- ((phenylisulfanyl) methyl) propylamino, (1R) -3- (2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) - 3- ((2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, 1,1-dimethyl-2- (thien-2-ylsulfanyl) ethylamino, (1R ) -3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) -methyl) propylamine, (1R) -3- (dipropylamino) -1 - ((fe n-sulphonyl) methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (ethyl (2,2,2-trifluoroethyl) amino) -1- ((phenylsulfanyl) methyl) propylamino, 1- (ethoxycarbonyl) piperidin-4-yloxy, (1R) -3 - ((2-fluoroethyl) amino) -1- ((phenylsulfanyl) methyl) propylamino, (1 R) -1 - (((4-fluorophenyl) -sulfanyl) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (1,3-benzodioxol-5-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (benzofuran-2-ylphenyl) - phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2-bromocyclohex-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2-bromocyclopent-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (4-bromophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclohepta-1-en- 1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (1- (2- (4-chlorophenyl) cyclohex-1-en-1-ylmethyl) -1,2,3,6-tetrahydropyridin-4-yl ) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclohex-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclopentyl) -1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclo-oct-1-en-1-ylmethyl) piperazin-1-yl) - phenylcarbonyl, 4- (4 - ((4- (4-chlorophenyl) -5,6-dihydro-2H-pyran-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((4 - (4-chlorophenyl) -5,6-dihydro-2H-pyran-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (1 - ((2- (4-chlorophenyl) -5,5 -dimethyl-1-cyclohex-1-en-1-yl) met il) -1,2,3,6-tetrahydropyridin-4-yl) -phenylmethyl, 4- (4- (2- (4-chlorophenyl) -naphth-3-ylmethyl) piperazin-1-yl) -phenylcarbonyl, - (4- (2- (4-chlorophenyl) pyridin-3-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (3- (4-chlorophenyl) pyridin-4-ylmethyl) piperazin-1- il) -phenylcarbonyl, 4- (4 - ((4- (4-chlorophenyl) pyridin-5-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) - phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (1- (2- (4-chlorophenyl) -phenyl-cycloprop-1-yl) -piperazin-1-yl) -phenylcarbonyl or 4- (4- (2- (4 -chlorophenyl) -phenylmethyl) cyclohex-1-en-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1R) -2- (diethylamino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1R) -3- (diethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3 - (( 2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (5,6-dihydro-1 (4H) -pyrimidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -2 - ((2- (dimethylamino) ethyl) (methyl) amino) -1- ( (phenylsulfanyl) methyl) ethylamino, (1R) -2- (2- (dimethylamino) ethoxy) -1 - ((phenylsulfanyl) methyl) ethylamino, (3R) -5- (N - ((dimethylamino) methylcarbonyl) amino) - 1 - ((phenylsulfanyl) methyl) pentylamino, (1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propoxy, (1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1S) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1- ((pyrimidin-2-ylsulfanyl) methyl) propylamino, (1R) ) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazol-2-yl) methyl) propylamino, (1 R) -3- (dimethylamino) -1 - ((thien-2-ylsulfanil ) methyl) propylamino, (1R) -3- (dimethylamino) -1 - (((4- (trifluoromethoxy) -phenyl) - sulfanyl) methyl) propylamino, (1R) -3- (2,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -5 - ((1,1-dimethylethoxy) carbonylamino) - 1 - ((phenylsulfanyl) methyl) -pentylamino, 1- (1,1-dimethylethoxycarbonyl) piperidin-4-yloxy, 1,1-dimethyl-2- (phenylsulfonyl) -ethylamino, (1,1-dimethyl-2) - (phenylsulfanyl) ethyl) amine, 1,1-dimethyl-2- (phenylsulfanyl) ethyl, 4,4-dimethylpiperidin-1-yl, (1 R) -3- (2,6-dimethylpiperidin-1-yl) - 1 - ((phenylsulfanyl) -methyl) propylamino, (1R) -3 - ((2R, 6S) -2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1,1-dimethyl -2- (Pyrimidin-2-ylsulfanyl) ethylamino, (1R) -4 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -butylamino, ( 1R) -3- ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (2,5-dimethyl-pyrrolidin-1- il) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) -methyl) propi lamino, (1R) -3- ((2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((f-enylsulfanyl) methyl) propylamino, 1,1-dimethyl-2- (thien-2) -ylsulfanyl) ethylamino, (1 R) -3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (ethyl (2,2,2-trifluoroethyl) amino) -1 - ((phenylisulfanyl) methyl) propylamino, 1- (ethoxycarbonyl) piperidin-4-yloxy, (1R) -3 - ((2-fluoroethyl) amino) -1- ((phenylsulfanyl) methyl) -propylamino, (1R) -1 - (( (4-fluorophenyl) -sulfanyl) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (5- (2- (4-chlorophenyl) -phenylmethyl) -hexahydropyrrolo [3,4-c] -pyrrol-2 (1H) -yl) -phenylcarbonyl, 4- (4- (2- ( 4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) -4-methoxy-piperidin-1-yl) -phenylcarbonyl, 4- (4- ( 2- (4-chlorophenyl) -phenylmethyl) -piperazin-1-yl) -3,5-difluoro-phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -2-fluorophenylcarbonyl 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -3-fluorophenylcarbonyl, 2- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) pyridin-5-ylcarbonyl, 4- (1- (2- (4-chlorophenyl) -phenylmethyl) piperidin-4-yl) -phenylcarbonyl, 5- (4- (2- (4-chlorophenyl) -phenylmethyl) -piperazine- 1 -yl) pyridin-2-ylcarbonyl, 4- (1 - (2- (4-chlorophenyl) -phenylmethyl) -1,2,3,6-tetrahydropyridin-4-yl) -phenylcarbonyl, 4- (4 - (2- (cyclohex-1-ylamino) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl-4- (2-cyclohex-1-phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3-cyanophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2,4-dichlorophenyl) - phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3,4-dichlorophenyl) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2, 4-difluorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (1,3-dihydro-2H-isoindol-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (3- (1,1-dimethylethoxycarbonyl-amino) -phenyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (4- (2- (dimethylamino) ethoxy) -pheni) -phenylmethyl) piperazine -1-yl) -phenylcarbonyl or 4- (4- (3- (dimethylamino) -phenyl) piperazin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -2- (diethylamino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1 R) -3- (diethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3 - ((2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (5,6-dihydro-1 (4H) -pyrimidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (di-isopropylamine) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -2 - ((2- (dimethylamino) ethyl) (methyl) amino) -1 - ((phenylsulfanyl) -methyl) ethylamino, (1 R) -2- (2- (d imethylamino) ethoxy) -1 - ((f-enylsulfanyl) methyl) ethylamido, (3R) -5 - (N - ((dimethylamino) -methylcarbonyl) amino) -1 - ((phenylsulfanyl) methyl) pentylamino, (1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propoxy, (1R) -3 - (dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1S) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1 - ((pyrimidin-2-ylsulfanyl) -methyl) propylamino, (1 R) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazol-2-yl) methyl) propylamino, (1R) -3- (dimethylamino) -1 - ((thien-2-ylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -1 - (((4 - (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino, (1R) -3- (2,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -3- (4,4-dimethyl-4,5-dihydro-1 H -imidazol-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -5- ( (1,1-d-imethylethoxy) carbon-lamino) -1- ((phenylsulfanyl) methyl) -pentylamine, 1- (1,1-dimethylethoxycarbonyl) pyrimid-4-xi, 1, 1-dimethyl-2- (phenylsulfonyl) ethalamino, (1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino, 1,1-dimethyl-2- (phenylsulfanyl) -ethyl, 4,4-dimethylpiperidine -1-yl, (1R) -3- (2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ((2R, 6S) -2.6- dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1,1-dimethyl-2- (pyrimidin-2-ylsulfanyl) ethylamino, (1 R) -4 - ((2R, 5S) -2, 5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -butylamino, (1R) -3 - ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3 - ((2R , 5S) -2,5-dimethylpyrroli din-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ((2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) - propylamino, 1,1-dimethyl-2- (thien-2-ylsulfanyl) ethylamino, (1R) -3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) -methyl) propylamino, (1 R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- ( ethyl (2,2,2-trifluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, 1- (ethoxycarbonyl) piperidin-4-yloxy, (1 R) -3 - ((2-fluoroetiI) -amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -1 - (((4-fluorophenyl) -sulfanyl) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (2- (4- (dimethylamino) -phenyl) -phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (dimethylamino) -phenyl) -phenylmethyl) piperazine -1-yl) -phenylcarbonyl, 4- (4 - ((2- (4- (dimethylamino) -phenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2 - (5, 5-dimethyl-2-oxo-1,3-oxazolidin-3-yl) -phene-methyl) piperazin-1-l) -phenylenecarbonyl, 4- (4- (2- (4-fluorophenyl) cyclopent- 1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-fluorophenyl) -3-fluorophenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- ( 2- (4-fluorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4-fluorophenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (isopropylamino) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (isopropylsulfanyl) -phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methoxyphenyl) cyclopent-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3-methoxyphenyl) -phenylmethyl) piperazine- 1-yl) -phenylcarbonyl, 4- (4- (2- (4-methoxyphenyl) -phenylmethyl) piperazin-1-yl) -phen ylcarbonyl, 4- (4 - ((2- (4-methoxyphenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4-methoxy-4- (2- (pyridin-3-) il) -phenylmethyl) piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (2-methyl-4-dichlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2 - (2-methylphenyl) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (methylsulfonyl) -phenyl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- ( 4- (2- (4-Methylsulfonylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl or 4- (4 - ((2- (4-methylsulfonylphenyl) pyridin-3-yl) methyl) piperazin-1-yl) phenylcarbonium. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -2- (diethylamino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1 R) -3- (diethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3 - ((2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (5,6-dihydro-1 (4H) -pyrimidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -2 - ((2- (dimethylamino) ethyl) (methyl) amino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1 R) -2- (2- (dimethylamino) ethoxy) -1 - ((phenylsulfanyl) methyl) ethylamino, (3R) -5- (N - ((dimethylamino) methylcarbonyl) amino) -1 - ((phenylsulfanyl) methyI) pentylamino, (1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propoxy, (1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1S) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (dimethylamino) -3-oxo-1 - ((pyrimidin-2-ylsulfanyl) methyl) propylamino, (1 R) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazol-2-yl) methyl) propylamino, (1 R) -3- (dimethylamino) -1 - ((thien-2-ylsulfanyl) methyl) propylamino, (1 R) -3- (dimethylamino) -1 - (((4- (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino, (1 R) -3- (2,4-dimethyl-4) , 5-dihydro-1H-imidazol-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl ) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -5 - ((1,1-dimethylethoxy) carbonylamino) -1 - ((phenylsulfanyl) methyl) -pentylamino, 1- (1,1-dimethylethoxycarbonyl) piperidine -4-iioxy, 1,1-dimethyl-2- (phenylsulfonyl) ethylamino, (1,1-dimethyl-2- (phenylsulf anil) ethyl) amino, 1,1-dimethyl-2- (phenylsulfanyl) -ethyl, 4,4-dimethylpiperidin-1-yl, (1 R) -3- (2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ((2R, 6S) -2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methy1) propylamino, 1,1-dimethyl-2 - (pyrimidin-2-ylsulfanyl) ethylamino, (1R) -4 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -butylamino, ( 1R) -3- ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3 - ((2R, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) - 3- ((2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1,1-dimethyl-2- (thien-2-ylsuiphenyl) ethylamino, (1R) -3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylisulfanyl) methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3 - (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (ethyl (2,2,2-trifluoroethyl) amino) -1 - ((phenylsulfanyl) -methyl) propylamino no, 1- (ethoxycarbonyl) piperidin-4-yloxy, (1R) -3 - ((2-fluoroethyl) amino) -1- ((phenylsulfanyl) methyl) -propylamino, (1R) -1 - (((4- fluorophenyl) -sulfanyl) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (5-methylthien-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) cyclohex-1-in -1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) -phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4 -methylsulfanylphenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonium, 4- (4- (2- (4-methylsulfanylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (2- (morpholin-1-yl) ethoxy) -phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (morpholin-1-yl) -phenyl) l) piperazin-1-phenylcarbonyl, 4- (4- (2- (naphth-1-yl) -phenylmethyl) piperazin-1-phenylcarbonyl, 4- (4- (2- (naphth-2-yl) -phenyl) l) piperazin-1-phenylcarbonyl or 4- (4- (2- (4-phenoxyphenyl) -phenylmethyl) piperazin-1-phenylcarbonyl, 4- (4 - ((1-phenyl-1H-imidazol-2-yl) ) met l) piperazin-1-phenylcarbonyl, 4- (4 - ((1-phenyl-1 H-imidazol-5-yl) met l) piperazin-1-phenylcarbonyl, 4- (2 - ((phenylmethyl) amino) phenylmet l) piperazin-1-phenylcarbonyl, 4- (4- (2- (phenyl) -phenylmethyl) -4- (2 (dimethylamino) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4 - ((2- (phenyl-phenylmethyl) -4-methoxy-piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (phenyl-phenylmethyl) -4- (2- ( morpholin-1-yl) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (3- (phenyl) phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (phenyl) -phenyl-phenylmethyl) -piperazin-1-yl) -phenylcarbonyl or 4- (4- (2- (phenyl) - phenylmethyl) -4- (2- (piperidin-1-yl) ethoxy)) piperidin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, wherein A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1R) -2- (diethylamino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1R) -3- (diethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3 - ((2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R ) -3- (5,6-Dihydro-1 (4H) -pyrimidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (di-isopropylamino) -1 - ((phenylsulfanil ) methyl) propylamino, (1R) -2 - ((2- (dimethylamino) ethyl) (methyl) amino) -1 - ((phenylsulfanyl) methyl) ethylamino, (1R) -2- (2- (dimethylamino) ethoxy) -1 - ((phenylsulfanyl) methyl) ethylamino, (3R) -5- (N - ((dimethylamino) methylcarbonyl) amino) -1 - ((phenylsulfanyl) methyl) pentylamino, (1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propoxy, (1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1S) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propylamino, ( 1R) -3- (dimethylamino) -3-oxo-1- ((pyrimidin-2-ylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -3-oxo-1 - ((1,3-thiazole) -2-yl) methyl) propylamino, (1 R) -3- (dimethylamino) -1 - ((thien-2-ylsulfanyl) methyl) propylamino, (1R) -3- (dimethylamino) -1 - (((4 - (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino, (1R) -3- (2,4-dimethyl-4,5-dihydrate o-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -5 - ((1,1-dimethylethoxy) carbonylamino) -1 - ((phenylsulfanyl) methyl) -pentylamino, 1- (1,1-dimethylethoxycarbonyl) piperidin-4- Ioxy, 1,1-dimethyl-2- (phenylsulfonyl) ethylamino, (1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino, 1,1-dimethyl-2- (phenylsulfanyl) ethyl, 4,4-dimethylpiperidine- 1-yl, (1R) -3- (2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3- ((2R, 6S) -2.6- dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1,1-dimethyl-2- (pyrimidin-2-ylsulfanyl) ethylamino, (1 R) -4 - ((2R, 5S) -2, 5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) butylamino, (1 R) -3 - ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsufanyl)) methyl) propylamino, (1R) -3- (2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3 - ((2R, 5S) -2.5 -dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ((2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfa nil) methyl) -propylamino, 1,1-dimethyl-2- (thien-2-ylsulfanyl) ethylamino, (1R) -3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ( ethyl (2,2,2-trifluoroethyl) amino) -1 - ((phenylsulfanyl) -methyl) propylamino, 1- (ethoxycarbonyl) piperidin-4-yloxy, (1R) -3 - ((2-fluoroethyl) amino) - 1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -1 - (((4-fluorophenyl) -sulfanyl) methyl) -3- (morpholin-4-yl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (phenyl) -phenylmethyl) -4- (2- (pyrrolidin-1-yl) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4- (4 - ((2 - (phenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((1-phenyl-1H-pyrazol-5-yl) methyl) piperazin-1-yl) -phenylcarbonyl 4- (4- (2- (piperidin-1-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (pyrid-3-yl) -phenyl) -phenylmethyl) piperazine -1-iI) -phenylcarbonyl, 4- (4- (2- (quinolin-3-ylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (quinolin-8-ylphenyl)) phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (thien-2-yl) -phenylmethyl) -4-methoxy-piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (thien-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-trifluoromethoxyphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl or 4- (4- ( 2- (4-trifluoromethylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -3- (4- (hydroxyaminocarbonyl) piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (2-hydroxy-2-methylpropyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (4-hydroxypiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (3R) -3- (3-hydroxypyrrolidin- 1 -yl) -1 - ((phenylsulfanyl) methyl) propylamino, isopropylamino, (1 R) -3- (isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (1 H-imidazole -1 -yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (isopropyl (methyl) amino) -1 - ((phenylsulfanyl) methyl) -propylamino, (4-methoxycyclohex-1-y) ) methyl) amino, (1 R) -3- (4- (methoxy-imino) piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -3- (N-methyl- N-carboxymethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (methyl) (cyclohexyl) amino, (methyl) (cyclohexylmethyl) amino, (1 R) -3- (2-methyl-4,5-dihydro-1 H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (3R) - 3- (N-Methyl-N- (dimethylcarbonylmethyl)) - 1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -3- (N-methyl-N- (1,1-dimethylethyl) amino) -1 - ((phenylsulfanii) methyl) propylamino, (N-methyl-N- (1, 2-diphenyl) amino) carbonyl) -N-methylamino, (N-methyl-N- ((diphenylmethyl) amino) carbonyl) -N- methylamino, (2-methylfuran-3-yl) -sulfanyl) (1,1-spirobutyl) ethylamino, (1R) -3- (N-methyl-N- (2-hydroxyethyl)) amino) -1 - ((phenylsulfanil ) methyl) propylamino, (1R) -3- (N-methyl-N-isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (N-methyl-N- (4-methoxyphenyl) amino) carbonyl) -N -methylamino, 1-methyl-4- (phenylsulfanyl) pyrrolidin-3-ylamino, (N-methyl-N- (4-methylphenyl) amino) carbonyl) -N-methylamino, (N-methyl-N- (2-methylphenyl) ) amino) carbonyl) -N-methylamino, (1R) -3- (4-methylpiperazin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1-methylpiperidin-4-yloxy, (N-methyl-N) - ((S) -1-phenylethyl) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (4-methyl) iperazin-4-yl)) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (morpholin-1-yl)) amino) carbonyl) -N-methylamino, (N- methyl-N- (1-phenyl-2- (N, N-dimethylamino) amino) carbonyl) -N-methylamino, (1R) -1-methyl-2 - ((phenylsulfanyl) methyl) ethylamino, (1S) -1 -methyl-2 - ((phenylsulfanyl) methyl) ethylamino, (1R) -4- (4-methylpiperazin-1-yl) -1- ((phenylsulfanyl) methyl) -butylamino, (1R) -3- (methyl- ( pyridin-4-yl) amino) -1 - ((phenylsulfanyl) methi I) propylamino, (1R) -5 - ((methylsulfonylamino) -1- ((phenylsulfanyl) methyl) -pentylamino, (1R) -3- (4 - (Methylsulfonyl-aminocarbonyl) -piperidin-1-yl) -1 - ((f-enylsulfanyl) methyl) -propylamino, 2 - ((4-methyl-1,3-thiazol-2-yl) -sulfanyl) -ethylamino, ( N-methyl-N- (4-trifluoromethoxyphenyl) amino) carbonyl) -N-methylamino, (1R) -3- (morpholin-4-ylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ((2- (morpholin-4-yl) ethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (morpholin-4-yl) -3-oxo-1 - ((2- thienylsulfanyl) methyl) -propylamino, (1R) -3- (morpholin-4-yl) -1 - ((1,3-thiazol-2-ylsulfanyl) methyl) propylamino, (1R) -3- (morpholine- 4-yl) -1 - ((thien-2-ylsulfanyl) methyl) propylamino, (1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- ( morpholin-4-yl) -1 - (((4- (methoxy) -phenyl) -sulfanyl) methyl) propylamino, (1R) -3- (morpholin-4-yl) -1 - (((4- (methyl) ) -phenyl) -sulfanyl) methyl) propylamino, (1R) -3- (morpholin-4-yl) -1 - ((phenylsulfonyl) methyl) propylamino, (1R) -3- (morpholin-4-yl) -1 - (((4- (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (1,3-benzodioxol-5-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (benzofuran-2-ylphenyl) - phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2-bromocyclohex-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2-bromocyclopent-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (4-bromophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -cyclohept-1-en- 1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (1- (2- (4-chlorophenyl) cyclohex-1-en-1-ylmethyl) -1,2,3,6-tetrahydropyridin-4-yl ) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclohex-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclopentyl) -1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cycloocta-1-en-1-ylmethyl) piperazin-1-yl) - phenylcarbonyl, 4- (4 - ((4- (4-chlorophenyl) -5,6-dihydro-2H-pyran-3-yl) methyl) piperazin-1-yl) phenylcarbonyl, 4- (4 - ((4- (4-chlorophenyl) -5,6-dihydro-2H-pyran-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (1 - ((2- (4-chlorophenyl) -5,5- dimethyl-1-cyclohex-1-en-1-yl) met il) -1,2,3,6-tetrahydropyridin-4-yl) -phenylmethyl, 4- (4- (2- (4-chlorophenyl) -naphth-3-ylmethyl) piperazin-1-yl) -phenylcarbonyl, - (4- (2- (4-chlorophenyl) pyridin-3-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (3- (4-chlorophenyl) pyridin-4-ylmethyl) piperazin-1 - il) -phenylcarbonyl, 4- (4 - ((4- (4-chlorophenyl) pyridin-5-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) - phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (1 - (2- (4-chlorophenyl) -phenyl-cycloprop-1-yl) -piperazin-1-yl) -phenylcarbonyl or 4- (4- (2- (4 chlorophenyl) -phenylmethyl) cyclohex-1-en-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B is (1 R) -3- (4- (hydroxyaminocarbonyl) piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (2-hydroxy-2-methylpropyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (4-hydroxypiperidin-1-y) -1 - ((phenylsulfanyl) methyl) -propylamino, (3R) -3- (3-hydroxypyrrolidin- 1 -yl) -1 - ((phenylsulfanyl) methyl) propylamino, isopropylamino, (1 R) -3- (isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (1 H-imidazole -1 -yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (isopropyl (methyl) amino) -1 - ((phenylsulfanyl) methyl) -propylamino, (4-methoxycyclohex-1 - il) methyl) amino, (1 R) -3- (4- (methoxy-imino) piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -3- (N-methyl) -N-carboxymethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (methyl) (cyclohexyl) amino, (methyl) (cyclohexylmethyl) amino, (1 R) -3- (2-methyl-4,5-dihydro-1 H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (3R) - 3- (N-Methyl-N- (dimethylcarbonylmethyl)) - 1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (N-methyl-N- (1,1-dimethylethyl) amino) -1- ((phenylsulfanyl) methyl) propylamino, (N-methyl-N- (1,2-diphenyl) amino) carbonyl) -N-methylamino, (N-methyl-N - ((diphenylmethyl) amino) carbonyl) -N-methylamino , (2-methyl-furan-3-yl) -sulfanyl) - (1,1-spirobutyl) ethylamino, (1R) -3- (N-methyl-N- (2-hydroxyethyl)) amino) -1 - ((phenylsulfanil ) methyl) propylamino, (1 R) -3- (N-methyl-N-isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (N-methyl-N- (4-methoxyphenyl) amino) carbonyl) -N -methylamino, 1-methyI-4- (phenylsulfanyl) pyrrolidin-3-ylamino, (N-methyl-N- (4-methylphenyl) amino) carbonyl) -N-methylamino, (N-methyl-N- (2-methylphenyl) ) amino) carbonyl) -N-methylamino, (1R) -3- (4-methylpiperazin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1-methylpiperidin-4-yloxy, (N-methyl-N) - ((S) -1-phenylethyl) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (4-methylpiper azin-4-yl)) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (morpholin-1-yl)) amino) carbonyl) -N-methylamino, (N- methyI-N- (1-phenyl-2- (N, N-dimethylamino)) amino) carbonyl) -N-methylamino, (1R) -1-methyl-2 - ((phenylsulfanyl) methyl) ethylamino, (1S) - 1-Methyl-2- ((phenylsulfanyl) methyl) ethylamino, (1R) -4- (4-methylpiperazin-1-yl) -1- ((phenylsulfanyl) methyl) -butylamino, (1R) -3- (methyl-) (pyridin-4-yl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -5 - ((methylsulfonylamino) -1 - ((phenylsulfanyl) methyl) pentylamino, (1R) -3- (4- (methylsulfonylaminocarbonyl) pyridin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, 2 - ((4-methyl-1,3-thiazol-2-yl) -sulfanyl) ethylamino, (N-methyl) -N- (4-trifluoromethoxyphenyl) amino) carbonyl) -N-methylamino, (1R) -3- (morpholin-4-ylami) -1 - ((f-enyl-sulfanyl) -methyl) -propylamino, (1R) -3- ((2- (morpholin-4-yl) ethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -3-oxo-1 - ( (2-thienylsulfanyl) methyl) -propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((1,3-thiazol-2-ylsulfanyl) methyl) propylamino, (1 R) -3- (morpho lin-4-yl) -1 - ((thien-2-ylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - (((4- (methoxy) -phenyl) -sulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - (( (4- (methyl) -phenyl) -sulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfonyl) -methyl) propylamino, (1 R) -3- ( morpholin-4-yl) -1 - (((4- (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (5- (2- (4-chlorophenyl) -phenylmethyl) -hexahydropyrrolo [3,4-c] -pyrrol-2 (1 H) -yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) -4-methoxypiperidin-1-yl) -phenylcarbonyl, 4- (4 - (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -3,5-difluorophenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -2- fluorophenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -3-fluorophenylcarbonyl, 2- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl ) pyridin-5-ylcarbonyl, 4- (1 - (2- (4-chlorophenyl) -phenylmethyl) piperidin-4-yl) -phenylcarbonyl, 5- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazine- 1-yl) pyridin-2-ylcarbonyl, 4- (1 - (2- (4-chlorophenyl) -phenylmethyl) -1,2,3,6-tetrahydropyridin-4-yl) -phenylcarbonyl, 4- (4- ( 2- (cyclohex-1-ylamino) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl 4- (4- (2-cyclohex-1-phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3-cyanophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2,4-dichlorophenyl) ) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3,4-dichlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2 , 4- difluorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (1,3-dihydro-2H-isoindol-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, - (4- (3- (1,1-dimethylethoxycarbonylamino) -phenyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (4- (2- (dimethylamino) ethoxy) -phenyl) -phenylmethyl) piperazine- 1-yl) -phenylcarbonyl or 4- (4- (3- (dimethylamino) -phenyl) piperazin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1R) -3- (4- (hydroxyaminocarbonyl) piperidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (2-hydroxy-2-methylpropyl) amino) - 1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (4-hydroxypiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (3R) -3- (3-hydroxypyrrolidin-1-yl) ) -1 - ((phenylsulfanyl) methyl) propylamino, isopropylamino, (1R) -3- (isopropylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (1H-imidazol-1-yl) - 1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (isopropyl (methyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (4-methoxycyclohex-1-yl) methyl) amino, (1R) -3- (4- (methoxy-imino) piperidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (N-methyl-N-carboxymethyl) amino) -1 - (( phenylsulfanyl) methyl) propylamino, (methyl) (cyclohexyl) amino, (methyl) (cyclohexylmethyl) amino, (1 R) -3- (2-methyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (3R) -3- (N-methyl-N- (dimethylcarbonylmethyl)) - 1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3- (N-methyl-N - (1,1-dimethylethyl) amino) -1 - ((phenylsulfanyl) methyl) pro Pilamino, (N-methyl-N- (1,2-diphenyl) amino) carbonyl) -N-methylamino, (N-methyl-N - ((diphenylmethyl) amino) carbonyl) -N-methylamino, (2-methylfuran- 3-yl) -sulfanyl) - (1,1-spirobutyl) ethylamino, (1R) -3- (N-methyl-N- (2-hydroxyethyl)) amino) -1 - ((phenylsulfanyl) methyl) propylamino, ( 1R) -3- (N-methyI-N-isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (N-methyl-N- (4-methoxyphenyl) amino) carbonyl) -N-methylamino, 1-methyl- 4- (phenylsulfanyl) pyrrolidin-3-ylamino, (N-methyl-N- (4-methylphenyl) amino) carbonyl) -N-methylamino, (N-methyl-N- (2-methylphenyl) amino) carbonyl) -N -methylamino, (1R) -3- (4-methylpiperazin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1-methylpiperidin-4-yloxy, (N-methyl-N - ((S) -1 phenylethyl) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (4-methylpiperazin-4-yl)) amino) carbonyl) -N-methylamino, (N-methyl- N- (1-phenyl-2- (morpholin-1-yl)) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (N, N-dimethylamino)) amino) carbonyl) -N-methylamino, (1R) -1-methyl-2 - ((phenylsulfanyl) methyl) ethylamino, (1S) -1-methyl-2- ((phenylsulfanyl) methyl) ethylamine ino, (1R) -4- (4-methylpiperazin-1-yl) -1- ((phenylsulfanyl) methyl) -butylamino, (1R) -3- (methyl- (pyridin-4-yl) amino) -1- ((phenylsulfanyl) methyl) propylamino, (1 R) -5 - ((methylsulfonylamino) -1- ((phenylsulfanyl) methyl) pentylamino, (1R) -3- (4- (methylsulfonylaminocarbonyl) piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 2 - ((4-methyl-1,3-thiazol-2-yl) -sulfanyl) ethylamino, (N-methyl-N- (4-trifluoromethoxyphenyl) amino) carbonyl) -N -methylamino, (1 R) -3- (morpholin-4-ylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3 - ((2- (morpholin-4-yl) ethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -3-oxo-1 - ((2-thienylsulfanyl) methyl) propylamino, (1 R) -3 - (morpholin-4-yl) -1 - ((1,3-thiazol-2-ylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((thien-2- ilsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (morfoin-4-yl) -1 - (( (4- (methoxy) -phenyl) -sulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - (((4- (methyl) -phenyl) -sulfanyl) methyl) propylamino , (1 R) -3 - (morpholin-4-yl) -1 - ((phenylsulfonyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - (((4- (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02) F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (2- (4- (dimethylamino) -phenyl) -phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (dimethylamino) -phenyl) -phenylmethyl) piperazine -1-yl) -phenylcarbonyl, 4- (4 - ((2- (4- (dimethylamino) -phenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2 - (5,5-dimethyl-2-oxo-1,3-oxazolidin-3-yl) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-fluorophenyl) cyclopent- 1-en-1-ylmethyl) piperazin-1-l) -phenylcarbonyl, 4- (4- (2- (4-fluorophenyl) -3-fluorophenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-fluorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4-fluorophenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl 4- (2- (isopropylamino) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (isopropylsulfanyl) -phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl4- (4- (2- (4-methoxyphenyl) cyclopent-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3-methoxyphenyl) -phenylmethyl) piperazine -1 -yl) - phenylcarbonyl, 4- (4- (2- (4-methoxyphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4-methoxyphenyl) pyridine-3 -yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4-methoxy-4- (2- (pyridin-3-yl) -phenylmethyl) piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (2-methyl-4-dichlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2-methylphenyl) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (methylsulfonyl) -phenyl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfonylphenyl) -phenylmethyl) piperazin-1-yl) phenylcarbonyl or 4- (4 - ((2- (4-methylsulfonylphenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -3- (4- (hydroxyaminocarbonyl) piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (2-hydroxy-2-methylpropyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (4-hydroxypiperidin-1-yl) -1 - ((phenylsuifanyl) methyl) propylamino, (3R) -3- (3-hydroxypyrrolidin-1) -yl) -1 - ((phenylsulfanyl) methyl) propylamino, isopropylamino, (1 R) -3- (isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (1 H-imidazole- 1 -yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (isopropyl (methyl) amino) -1 - ((f-enylsulfanyl) methyl) -propylamino, (4-methoxycyclohex-1 - il) methyl) amino, (1 R) -3- (4- (methoxy-imino) piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -3- (N-methyl) -N-carboxymethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (methyl) (cyclohexyl) amino, (methyl) (cyclohexylmethyl) amino, (1R) -3- (2-methyl-4,5-dihydro -1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (3R) -3- (N-methyl-N- (dimethylcarbonylmethyl)) - 1 - ((phenylsulfanyl) methyl) -propylamino, ( 1R) -3- (N-methyl-N- (1,1-dimethylethyl) amino) -1 - (( phenylsulfanyl) methyl) propylamino, (N-methyl-N- (1, 2-diphenyl) amino) carbonyl) -N-methylamino, (N-methyl-N- ((diphenylmethyl) amino) carbonyl) -N-methylamino, ( 2-methyl-furan-3-yl) -sulfanyl) - (1,1-spirobutyl) ethylamino, (1R) -3- (N-methyl-N- (2-hydroxyethyl)) amino) -1 - ((phenylsulfanyl) methyl) ) propylamino, (1R) -3- (N-methyl-N-isopropylamino) -1 - ((phenylsulfanyl) methy1) propylamino, (N-methyl-N- (4-methoxyphenyl) amino) carbonyl) -N-methylamino, 1-methyl-4- (phenylsulfanyl) pyrrolidin-3-ylamino, (N-methyl-N- (4-methylphenyl) amino) carbonyl) -N-methylamino, (N-methyl-N- (2-methylphenyl) amino) carbonyl) -N-methylamino, (1R) -3- (4-methyl-piperazin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 1-methylpiperidin-4-yloxy, (N-methyl-N- ((S) -1-phenylethyl) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (4-methylpiperazin-4-yl)) amino) carbonyl) -N- methylamino, (N-methyl-N- (1-phenyl-2- (morpholin-1-yl)) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (N, N-dimethylamino)) amino) carboniI) -N-methylamino, (1R) -1-methyl-2 - ((phenylsulfanyl) methyl) ethylamino, (1S) -1-methyl-2 - (( phenylsulfanyl) methyl) ethylamino, (1R) -4- (4-methylpiperazin-1-yl) -1- ((phenylsulfanyl) methyl) -butylamino, (1R) -3- (methyl- (pyridin-4-yl) amino) ) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -5 - ((methylsulfonylamino) -1- ((phenylsulfanyl) methyl) pentylamino, (1R) -3- (4- (methylsulfonylaminocarbonyl) piperidin-1-yl) ) -1 - ((phenylsulfanyl) methyl) propylamino, 2 - ((4-methiI-1,3-thiazol-2-yl) -sulfanyl) eti! Amino, (N-methyl-N- (4-trifluoromethoxyphenyl) amino ) carbonyl) -N-methylamino, (1 R) -3- (morpholin-4-ylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3 - ((2- (morpholin-4-yl) ) ethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -3-oxo-1 - ((2-thienylsulfanyl) methyl) propylamino, (1 R) ) -3- (morpholin-4-yl) -1 - ((1,3-thiazol-2-ylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((thien) -2-ylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamine, (1 R) -3- (morpholin-4-yl) -1 - (((4- (methoxy) -phenyl) -sulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-iI) -1 - (((4- (methyl) -phenyl) -sulfanyl) meti l-propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfonyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - (((4- ( trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (5-methylthien-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) cyclohex-1-in -1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) -phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4 -methylsulfanylphenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (2- (morpholin-1-yl) ethoxy) -phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (morpholin-1-yl) -pheni) ! met l) piperazin-1-phenylcarbonyl, 4- (4- (2- (naphth-1-yl) -phenylmethyl) piperazin-1-phenylcarbonyl, 4- (4- (2- (naphth-2-yl) phenylmet l) piperazin-1-phenylcarbonyl or 4- (4- (2- (4-phenoxyphenyl) -phenylmethyl) piperazine-1-phenylcarbonyl, 4- (4 - ((1-phenyl-1 H-imidazol-2-yl) met l) piperazin-1-phenylcarbonyl, 4-4 - ((1-phenyl-1H-imidazol-5-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (2 - ((phenylmethyl) amino) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (phenyl) -phenylmethyl) -4- ( 2- (dimethylamino) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4 - ((2- (phenyl) -phenylmethyl) -4-methoxy-piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- ( phenyl) phenylmethyl) -4- (2- (morpholin-1-yl) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (phenyl) -phenylmethyl) piperazin-1-yl) - phenylcarbonyl, 4- (4- (3- (phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (phenyl) -phenyl) -phenylmethyl) piperazin-1-yl ) -phenylcarbonyl or 4- (4- (2- (phenyl) -phenylmethyl) -4- (2- (piperidin-1-yl) ethoxy)) piperidin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1R) -3- (4- (hydroxyaminocarbonyl) piperidin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (2-hydroxy-2-methylpropyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (4-hydroxypiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (3R) -3- (3-hydroxypyrrolidin-1-yl) ) -1 - ((phenylsulfanyl) methyl) propylamino, isopropylamino, (1R) -3- (isopropylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (1H-imidazol-1-yl) - 1- ((phenylsulfanyl) methyl) propylamino, (1R) -3- (isopropyl (methyl) amino) -1 - ((phenylsulfanyl) methyl) -propylamino, (4-methoxycyclohex-1-yl) methyl) amino, (1R ) -3- (4- (methoxy-imino) piperidin-1-yl) -1 - ((f-enylsulfanyl) methyl) -propylamino, (1R) -3- (N-methyl-N-carboxymethyl) amino) - 1- ((phenylsulfanyl) methyl) propylamino, (methyl) (cyclohexyl) amino, (methyl) (cyclohexylmethyl) amino, (1 R) -3- (2-methyl-4,5-dihydro-1 H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (3R) - 3- (N-Methyl-N- (dimethylcarbonylmethyl)) - 1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -3- (N-methyl-N- (1,1-dimethylethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (N-methyl-N- (1, 2-diphenyl) amino) carbonyl) -N-methylamino, (N-methyl-N - ((diphenylmethyl) amino) carbonyl) -N- methylamino, (2-methylfuran-3-yl) -sulfanyl) - (1,1-spirobutyl) ethylamino, (1R) -3- (N-methyl-N- (2-hydroxyethyl)) amino) -1 - ( (phenylsulfanyl) methyl) -prop-lamino, (1 R) -3- (N-methyl-N-isopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (N-methyl-N- (4- methoxyphenyl) amino) carbonyl) -N-methylamino, 1-methyl-4- (phenylsulfanyl) pyrrolidin-3-ylamino, (N-methyl-N- (4-methylphenyl) amino) carbonyl) -N-methylamino, (N- methyl-N- (2-methylphenyl) amino) carbonyl) -N-methylamino, (1R) -3- (4-methylpiperazin-1 -iI) -1 - ((phenylisulfanyl) methyl) propylamino, 1-methylpiperidin-4 -iloxy, (N-methyl-N - ((S) -1-phenylethyl) amino) carbonyl) -N-methylamino, (N-methyl-N- (1 phenyl-2- (4-methylpiperazin-4-yl)) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (morpholin-1-yl)) amino) carbonyl) -N-methylamino, (N-methyl-N- (1-phenyl-2- (N, N-dimethylamino)) amino) carbonyl) -N-methylamino, (1 R) -1-methyl-2 - ((phenylsulfanil ) methyl) ethylamino, (1 S) -1-methyl-2- ((phenylsulfanyl) methyl) ethylamino, (1 R) -4- (4-methylpiperazin-1-yl) -1 - ((phenylsulfanyl) methyl) - butylamino, (1 R) -3- (methyl- (pyridin-4-yl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -5 - ((methylsulfonylamino) -1 - ((phenylsulfanyl) methyl) -pentylamino, (1 R) -3- (4- (methylsulfonylaminocarbonyl) -piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, 2 - ((4-methyl-1,3-thiazoyl) 2-yl) -sulfanyl) ethylamino, (N-methyl-N- (4-trifluoromethoxyphenyl) amino) carbonyl) -N-methylamino, (1 R) -3- (morpholin-4-ylamino) -1 - ((phenylsulfanil ) methyl) propylamino, (1 R) -3 - ((2- (morpholin-4-yl) ethyl) amino) -1 - ((phenylisulfaniI) methyl) propylamino, (1 R) -3- (morpholine-4-) il) -3-oxo-1 - ((2-thienylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((1,3-thiazol-2-ylsulfa) nil) methyl) -propylamino, (1 R) -3- (morpholin-4-yl) -1 - ((thien-2-ylsulfanyl) -methyl) propylamino, (1 R) -3- (morpholin-4-yl) ) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - (((4- (methoxy) -phenyl) -sulfanyl) methyl) propylamino, (1 R) ) -3- (morfoin-4-yl) -1 - (((4- (methyl) -phenyl) -sulfanyl) methyl) -propylamino, (1 R) -3- (morpholin-4-iI) -1 - ((phenylsulfonyl) methyl) propylamino, (1 R) -3- (morpholin-4-yl) -1 - (((4- (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (phenyl) -phenylmethyl) -4- (2- (pyrrolidin-1-yl) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4- (4 - ((2 - (phenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((1-phenyl-1 H -pyrazol-5-yl) methyl) piperazin-1-yl) - phenylcarbonyl, 4- (4- (2- (piperidin-1-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (pyrid-3-yl) -phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (quinolin-3-ylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (quinolin-8-ylphenyl) ) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (thien-2-yl) -phenylmethyl) -4-methoxy-piperazin-1-yl) -phenylcarbonyl, 4- (4- (2 - (thien-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-trifluoromethoxyphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl or 4- (4- (2- (4-trifluoromethyl-phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1R) -3 - ((1S, 4S) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3 - ((1R, 4R) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (azetidin -1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (cyclobutylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (cyclopropylamino) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- ( d-methylamino) -1 - ((phenylsulfonylmethyl) methyl) propylamino, (1R) -3-oxo-3- (d-methylamino) -1 - ((pyrimidin-1-ylsulfan-1) -methyl) propylamino, ( 1R) -3-oxo-3 - ((1,1-d-methylethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamine, (1R) -3-oxo-3- (N-methyl-N- (1,1-dimethylethyl) amino) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3-amino-1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (methylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (4-methylpiperazin-1-yl) -1 - ((phenylsulfanyl) methyl) - propylamino, (1R) -3-oxo-3- (morpholin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (2- (morpholin-1-yl) ethyl) -1 - ((phenylsulfanyl) methyl) propylamino, (2-phenoxyethyl) amino, 4- (1- (phenylmethyl) piperidin-4-yl) amino, 4- (1 - (phenylmethyl) piperidin-4-yl) methylamino, (4-phenyl-1,3-thiazol-2-ylsulfanyl) ethylamino, (1 R, 2S) -2- (phenylsulfanyl) cyclohex-1-ylamino, (1 S, 2R) -2- (phenylsulfanyl) cyclohex -1-amino, 2- (phenylsulfanyl) cyclo-pentylamino, 2- (phenylsulfanyl) ethoxy, 2- (phenylsulfanyl) -ethylamino, 2- (phenylsulfonyl) ethylamino, ( 1 R) -1 - ((phenylsulfanyl) methyl) -3- (morpholin-4-yl) propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3 - ((2,2,2-trifluoroetiI) amino) -propylamino, 4- (phenylsulfonyl) -tetrahydrofuran-3-ylamino, 4- (phenylsulfanyl) -tetrahydrofuran-3-ylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3 - ((2,2 , 2-trifluoroethyl) amino) -propylamino, (1 S) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-4-ylsulfanyl) -propylamino , (1 R) -1 - ((phenylsulfanyl) methyl) -3- (thiomorpholin-4-yl) propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3- (piperazin-1-yl) prop ilamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3 - ((2- (pyridin-2-yl) ethyl) amino) propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-4-ylmethyl) amino) -propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-3-ylamino) propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3- (pyrrolidin-1-ylamino) propylamino), (1 R) -1 - ((phenylsulfanyl) methyl) -3- (2H-tetrazol-5-yl) propylamino, (1 R) -1 - ( (phenylsulfanyl) methyl) -3- (pyrrolidin-1-yl) propylamino, (1 R) -1 - ((phenylsulfanyl) m ethyl) -3 - ((pyridin-2-ylmethyl) amino) propylamino, (1 S) -2- (phenylsulfanI) -1 - (pyridin-3-ylmethyl) eti lamino, (3S, 4R) - (phenylsulfanil ) pyrrolidin-4-ylamino, 2- (phenylsulfanyl) -l, 1-spirobutylethylamino, 2- (phen ylsulfonyl) -1,1-spiroethylethyl-amino, 2- (f-enylsulfanyl) -1, 1 -spiropentylethylamino, piperidin 4-yloxy, (1-propylpiperidin-4-yl) methylamino, pyran-4-ylamino, 2- (pi lid in -4 - i I its If an [I) et the mino, 2- (pyrimidin-2 -ylsulfanyl) ethylamino, 1,1-spirobutyl-2- (phenylsulfanyl) ethyl, 2- (thien-2-ylsulfanyl) ethylamino, sulfanylpyran-4-ylamino, (1R) -3- (2- (2H-tetrazole-3 -yl) pyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3- (3- (2H-tetrazol-3-yl) -azetidin-1-yl) -1 - (( phenylsulfanyl) methyl) propylamino or 2- (1,3-thiazol-2-ylsulfanyl) ethylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (1,3-benzodioxol-5-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (benzofuran-2-ylphenyl) - phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2-bromocyclohex-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2-bromocyclopent-1-en-1-ylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (2- (4-bromophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclohepty-1-en -1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (1- (2- (4-chlorophenyl) cyclohex-1-en-1-ylmethyl) -1,2,3,6-tetrahydropyridin-4- il) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclohex-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl)) cyclopent-1-en-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) cyclo-oct-1-en-1-ylmethyl) piperazin-1-yl) phenylcarbonyl, 4- (4 - ((4- (4-chlorophenyl) -5,6-dihydro-2H-pyran-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((4 - (4-chlorophenyl) -5,6-dihydro-2H-pyran-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (1 - ((2- (4-chlorophenyl) -5,5 -dimethyl-1-cyclohex-1-en-1-yl) me tyl) -1,2,3,6-tetrahydropyridin-4-yl) -phenylmethyl, 4- (4- (2- (4-chlorophenyl) -naphth-3-ylmethyl) piperazin-1-yl) -phenylcarbonyl, - (4- (2- (4-chlorophenyl) pyridin-3-ylmethyl) piperazin-1-yl) -phenylcarbonyl4- (4- (3- (4-chlorophenyl) pyridin-4-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((4- (4-chlorophenyl) pyridin-5-yl) met L) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylcarbonyl) -piperazin-1-yl) -phenylcarbonyl, 4- (1- (2- (4-chlorophenyl) ) -phenyl-cycloprop-1-yl) piperazin-1-yl) -phenylcarbonyl or 4- (4- (2- (4-chlorophenyl) -phenylmethyl) -cyclohex-1-en-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1R) -3 - ((1S, 4S) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1- ((phenylsulfanyl) methyl) -ropylamino, (1R) - 3 - ((1R, 4R) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- ( azetidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (cyclobutylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3 - (cyclopropylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- ( dimethylamino) -1 - ((phenylsulfonylmethyl) methyl) -propylamino, (1R) -3-oxo-3- (dimethylamino) -1 - ((pyrimidin-1-ylsulfanyl) methyl) propylamino, (1R) -3-oxo -3 - ((1,1-dimethylethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3-oxo-3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) - propylamino, (1R) -3-oxo-3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (N-methyl-N) - (1,1-dimethyIethyl) amino) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3-amino-1- ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (methylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (4-methylpiperazin-1-yl) ) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (morpholin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3 - (2- (morpholin-1-yl) ethyl) -1 - ((phenylisulfanyl) methyl) propylamino, (2-phenoxyethi) amino, 4- (1- (phenylmethyl) piperidin-4-yl) amino, 4- ( 1- (phenylmethyl) piperidin-4-yl) methylamino, (4-phenyl-1,3-thiazol-2-ylsulfanyl) ethylamino, (1R, 2S) -2- (phenylsulfanyl) -cyclohex-1-ylamino, ( 1S, 2R) -2- (phenylsulfanyl) cyclohex-1-ylamino, 2- (phenylsulfanyl) cyclopentylamino, 2- (phenylsulfanyl) ethoxy, 2- (phenylsulfanyl) ethylamino, 2- (phenylsulfonyl) ethylamino, (1R) -1- ((phenylsulfanyl) methyl) -3- (morpholin-4-yl) propylamino, (1R) -1- ((phenylsulfanyl) methyl) -3 - ((2,2,2-trifluoroethyl) amino) propylamino, 4- (phenylsulfonyl) -tetrahydrofuran-3-ylamino, 4- (phenylsulfanyl) -tetrahydrofuran-3-ylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((2,2,2-trifluoroethyl) -amino) propylamino, (1S) -1 - ((phenylsulfanyl) me til) -propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-4-ylsulfanyl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (thiomorpholin-4-yl) ) propylamino, (1R) -1 - ((phenylsulfanyl) -methyl) -3- (piperazin-1-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((2- (pyridine- 2-yl) ethyl) amino) -propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-4-ylmethyl) amino) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) ) -3- (pyridin-3-ylamino) propylamino, (1R) -1 - ((phenylsulfanyl) -methyl) -3- (pyrrolidin-1-ylamino) propylamino), (1R) -1 - ((phenylsulfanyl) methyl) ) -3- (2H-tetrazol-5-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (pyrrolidin-1-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) ) -3 - ((pyridin-2-ylmethyl) amino) propylamino, (1 S) -2- (phenylsulfanyl) -1 - (pyridin-3-ylmethyl) ethylamino, (3S, 4R) - (phenylsulfanyl) -pyrrolidin- 4-ylamino, 2- (phenylsulfanyl) -l, 1-spirobutyl-ethylamino, 2- (phenylsulfanyl) -1, 1-spiroethylethyl lactam, 2- (phenylsulfanyl) -1, 1-spiropentylethylamino, piperidin-4-yloxy, ( 1-propylpiperidin-4-yl) methylamino, pyran-4-yl mino, 2- (pyridin-4-ylsulfanyl) ethylamino, 2- (pyrimidin-2-ylsulfanyl) ethylamino, 1,1-spirobutyl-2- (f-enylsulfanyl) -ethyl, 2- (thien-2-ylsulfanyl) ethylamino , sulfanylpyran-4-ylamino, (1 R) -3- (2- (2H-tetrazol-3-yl) pyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (3- (2H-tetrazol-3-yl) -azetidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino or 2- (1,3-thiazol-2-ylsulfanyl) ethylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (5- (2- (4-chlorophenyl) -phenylmethyl) -hexahydropyrrolo [3,4-c] -pyrrol-2 (1 H) -yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) -4-methoxypiperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) -piperazin-1-yl) -3,5-difluorophenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -2- fluorophenylcarbonyl, 4- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) -3-fluorophenylcarbonyl, 2- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl pyridin-5-ylcarbonyl4- (1 - (2- (4-chlorophenyl) -phenylmethyl) piperidin-4-yl) -phenylcarbonyl, 5- (4- (2- (4-chlorophenyl) -phenylmethyl) piperazin-1-yl) pyridine- 2-ylcarbonyl, 4- (1- (2- (4-chlorophenyl) -phenylmethyl) -1,2,3,6-tetrahydropyridin-4-yl) -phenylcarbonyl, 4- (4- (2- (cyclohex-1) -ylamino) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl 4- (4- (2-cyclohex-1-phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3-cyanophenyl) - phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2,4-dichlorophenyl) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3, 4-dichlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2,4-difluorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (2- (1 , 3-dihydro-2H-isoindol-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (3- (1,1-dimethylethoxycarbonyl-amino) -phenyl) piperazin-1-yl ) -phenylcarbonyl, 4- (2- (4- (2- (dimethylamino) ethoxy) -phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl or 4- (4- (3- (dimethylamino) -phenyl) piperazine -1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1R) -3 - ((1S, 4S) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3 - ((1R, 4R) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) -propylamine, (1R) -3-oxo-3- ( azetidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (cyclobutylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo- 3- (cyclopropylamino) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo- 3- (dimethylamino) -1 - ((phenylsulfonylmethyl) methyl) propylamino, (1R) -3-oxo-3- (d -methyl-im) -1 - ((pyrimidin-1-ylsulfanyl) -methyl) -propylamino, (1R) -3-oxo-3 - ((1,1-dimethylethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3-di-isopropylamino) -1 - ((phenylsulfanyl) methyl) ) -propylamino, (1R) -3-oxo-3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) -methyl) propylamino, (1R) -3-oxo-3- (N- methi-N- (1,1-dimethylethi) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (piperidin-1-yl) -1- ((phenylsulfanyl) methyl) -prop-ilamino, (1R) -3-oxo-3- amino-1- ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (methylamino) -1 - ((phenylsulfanyl) -methyl) propylamino, (1R) -3-oxo-3- ( 4-methyl-piperazin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (morpholin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (2- (morpholin-1-yl) ethyl) -1 - ((phenylsulfanyl) methyl) propylamino, (2-phenoxyethyl) amino, 4- (1- (phenylmethyl) piperidin-4-yl ) amino, 4- (1- (phenylmethyl) piperidin-4-yl) methylamino, (4-phenyl-1,3-thiazol-2-ylsulfanyl) ethylamino, (1R, 2S) -2- (phenylsulfanyl) -cyclohex- l -ylamino, (1S, 2R) -2- (phenylsulfanyl) -cyclohex-1-ylamino, 2- (phenylsulfanyl) cyclopentylamino, 2- (phenylsulfanyl) ethoxy, 2- (phenylsulfanyl) ethylamino, 2- (phenylsulfonyl) ethylamino, (1R) -1- ((phenylsulfanyl) methyl) -3- (morpholin-4-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((2, 2, 2-trif luoroethyl) amino) propylamino, 4- (phenylsulfonyl) -tetrahydrofuran-3-ylamino, 4- (phenylsulfanyl) -tetrahydrofuran-3-ylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((2,2,2 -trifluoroethyl) amino) propylamino, (1S) -1- ((phenyl ulphanyl) methyl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-4-ylsulfanyl) propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3- (thiomorpholin-4) -yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (piperazin-1-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((2- (pyridine -2-yl) ethyl) amino) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-4-ylmethyl) amino) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-3-ylamino) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (pyrrolidin-1-ylamino) propylamino), (1 R) -1 - ((phenylsulfanyl) methyl) -3- (2H-tetrazol-5-yl) propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3- (pyrrolidin-1-yl) propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-2-ylmethyl) amino) -propylamino, (1 S) -2- (phenylsulfanyl) -1 - (pyridin-3-ylmethyl) etiiamino, (3S, 4R) - (phenylsulfanyl) pyrrolidine 4-ylamino, 2- (phenylsulfanyl) -1, 1-spirobutylethylamino, 2- (phenylsulfanyl) -1, 1-spiroethylethyl-lamino, 2- (phenylsulfanyl) -1, 1-spiropentylethylamino, piperidin-4-yloxy, (1 -propylpiperidin-4-yl) methylated mino, pyran-4-ylamino, 2- (pyridin-4-ylsulfanyl) ethylamino, 2- (pyrimidin-2-ylsulfanyl) ethylamino, 1,1-spirobutyl-2- (phenylsulfanyl) ethyl, 2- (thien-2-) ilsulfaniI) ethylamino, sulfanylpyran-4-ylamino, (1 R) -3- (2- (2H-tetrazol-3-yl) pyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3- (3- (2H-tetrazol-3-yl) -azetidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino or 2- (1,3-thiazol-2-ylsulfanyl) ethylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (2- (4- (dimethylamino) -phenyl) -phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (dimethylamino) -phenyl) -phenylmethyl) piperazine -1-yl) -phenylcarbonyl, 4- (4 - ((2- (4- (dimethylamino) -phenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2 - (5,5-dimethyl-2-oxo-1,3-oxazolidin-3-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-fluorophenyl) cyclopent-1 -in-1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-fluorophenyl) -3-fluorophenylmethyl) piperazin-1-yl) -phenylcarbonyl4- (4- (2- (4-fluorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4-fluorophenyl) pyridin-3-yl) methyl) piperazin- 1 -yl) -phenylcarbonyl, 4- (2- (isopropylamino) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (isopropylsulfanyl) -phenyl) -phenylmethyl) piperazine-1 -yl) -phenylcarbonyl, 4- (4- (2- (4-methoxyphenyl) cyclopent-1-en-1-methylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (3-methoxyphenyl) ) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methoxyphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4- methoxypheni) pyridin-3-yl) methyl) pperazin-1-yl) -phenylcarbonyl, 4- (4-methoxy-4- (2- (pyridin-3-yl) -phenylmethyl) piperidin-1-yl) - phenylcarbonyl, 4- (4- (2- (2-methyl-4-dichlorophenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (2-methylphenyl) -phenylmethyl) piperazine-1 -iI) -phenylcarbonyl, 4- (4- (2- (4- (methylsulfonyl) -phenyl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfonylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl or 4- (4 - ((2- (4-methylsulfonylphenyl) pyridin-3-) il) methyl) piperazin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -3 - ((1 S, 4S) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) ) -3 - ((1 R, 4R) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1) -3-oxo- 3- (Azetidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3-oxo-3- (cyclobutylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) - 3-Oxo-3- (cyclopropylamino) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (dimethylamido) -1 - ((f-enylsulfanyl) methyl) propylamino, ( 1R) -3-Oxo-3- (dimethylamino) -1 - ((phenylsulfonylmethyl) methyl) propylamino, (1R) -3-oxo-3- (dimethylamino) -1 - ((pyrimidin-1-ylsulfanyl) - methyl) propylamino, (1R) -3-oxo-3 - ((1,1-dimethylethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (di-isopropylamino ) -1 - ((f-enylsulfanyl) methyl) propylamine, (1R) -3-oxo-3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) -methyl) propylamino, (1R) -3-oxo-3- (N-methyl-N- (1,1-dimethylethyl) amino) -1 - ((phenylsulfan? ') Methyl) propylamine, (1R) -3-oxo-3- (piperidine) 1-yl) -1- ((phenylsulfanyl) methyl) propyl mino, (1 R) -3-oxo-3-amino-1- ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (methylamino) -1- ((phenylsulfanyl) methyl) propylamino, ( 1R) -3-oxo-3- (4-methyl-piperazin-1-yl) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (morpholin-1-yl) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (2- (morfoin-1-yl) ethyl) -1 - ((phenylsulfanyl) methyl) propylamino, (2-phenoxyethyl) amino, 4- (1- (phenylmethyl) piperidin-4-yl) amino, 4- (1- (phenylmethyl) piperidin-4-yl) methylamino, (4-phenyl-1,3-thiazol-2-ylsulfanyl) ethylamino, (1 R , 2S) -2- (phenylsulfanyl) -cyclohex-1-ylamino, (1S, 2R) -2- (phenylsulfanyl) cyclohex-1-ylamino, 2- (phenylsulfanyl) cyclopentylamino, 2- (phenylsulfanyl) ethoxy, 2- ( phenylsulfanyl) ethylamino, 2- (phenylsulfonyl) ethylamino, (1R) -1- ((phenylsulfanyl) methyl) -3- (morpholin-4-yl) propylamino, (1R) -1- ((phenylsulfanyl) methyl) -3- ((2, 2, 2-trifluoroethyl) amino) propylamino, 4- (phenylsulfonyl) -tetrahydrofuran-3-ylamino, 4- (phenylsulfanyl) -tetrahydrofuran-3-ylamino, (1R) -1 - ((phenylsulfanyl) methyl) ) -3 - ((2,2,2-trifluoroethyl) -amino) propyl mino, (1S) -1 - ((phenylsulfanyl) methyl) -propylamino, (1 R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-4-ylsulfanyl) propylamino, (1R) -1 - (( phenylsulfanyl) methyl) -3- (thiomorpholin-4-yl) propylamino, (1R) -1 - ((phenylsulfanyl) -methyl) -3- (piperazin-1-yl) propylamino, (1R) -1- ( (phenylsulfanyl) methyl) -3 - ((2- (pyridin-2-yl) ethyl) amino) -propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-4-ylmethyl) amino] ) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-3-ylamino) propylamino, (1R) -1 - ((phenylsuifanyl) -methyl) -3- (pyrrolidin-1-ylamino) ) propylamino), (1R) -1 - ((phenylsulfanyl) methyl) -3- (2H-tetrazol-5-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (pyrrolidin-1) -iI) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-2-ylmethyl) amino) propylamino, (1S) -2- (phenylsulfanyl) -1- (pyridin-3-ylmethyl) ) ethylamino, (3S, 4R) - (phenylsulfanyl) -pyrrolidin-4-ylamino, 2- (phenylsulfanyl) -1,1-spirobutyl-ethylamino, 2- (phenylsulfanyl) -1,1-spiroethylethylamino, 2- (phenylsulfanil) -1,1-Spiropentylethylamino, piperidin-4-yloxy, (1-propyl-piperidin-4-yl) methylamino, pyran-4-ylamino, 2- (pyridin-4-ylsulfanyl) ethylamino, 2- (pyrimidin-2-ylsulfanyl) ethylamino, 1,1-spirobutyl-2- (phenylsulfanyl) ethyl, 2- (thien-2- ilsulfanyl) ethylamino, sulfanylpyran-4-ylamino, (1R) -3- (2- (2H-tetrazol-3-yl) pyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) - 3- (3- (2H-tetrazoI-3-yl) -azetidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino or 2- (1,3-thiazol-2-ylsulfanyl) ethylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2; and Z1 is 4- (4- (2- (5-methylthien-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) cyclohex-1-en -1-ylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) -phenylcarbonyl) piperazin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (4 -methylsulfanylphenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-methylsulfanylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (2- (morpholin-1-yl) ethoxy) -phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl4- (4- (2- (morpholin-1-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (naphth-1-yl) -phenylmethyl) piperazine-1- il) -phenylcarbonyl, 4- (4- (2- (naphth-2-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4-phenoxyphenyl) -phenylmethyl) piperazine- 1 -yl) -phenylcarbonyl, 4- (4 - ((1-phenyl-1 H -imidazoi-2-yl) methyl) piperazin-1-yl) -phenocarbonyl, 4- (4 - ((1-phenyl-1) H-imidazol-5-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (2 - ((phenylmethyl) amino) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (phenyl) -phenylmethyl) -4- (2- (dimethylamino) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4 - ((2- (phenyl) -phenylmethyl) -4-methoxy-piperidin-1-yl) -phenylcarbonyl 4- (4- (2- (phenyl) -phenylmethyl) -4- (2- (morpholin-1-yl) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4- (4- (2- (phenyl) ) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (3- (phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (4- (phenyl)) phenyl) -phenylmethyl) -piperazin-1-yl) -phenylcarbonyl or 4- (4- (2- (phenyl) -phenylmethyl) -4- (2- (piperidin-1-yl) ethoxy)) piperidin-1 - il) -phenyl arboniIo. Even another embodiment belongs to compounds having the formula (I), or therapeutically acceptable salts, prodrugs or prodrug salts thereof, in which A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) OCH3 or C (0) NH2; B1 is (1 R) -3 - ((1 S, 4S) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) ) -3 - ((1 R, 4R) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3-oxo -3- (azetidin-1 -yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3-oxo-3- (cyclobutylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1 R) -3-oxo-3- (cyclopropylamino) -1 - ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) ) -3-oxo-3- (dimethylamino) -1 - ((phenylsulfonylmethyl) methyl) propylamino, (1R) -3-oxo-3- (dimethylamino) -1 - ((pyrimidin-1-ylsulfanyl) -methyl) propylamino , (1R) -3-oxo-3 - ((1,1-dimethylethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (di-isopropylamino) -1- ((phenylsulfanyl) methyl) propylamino, (1 R) -3-oxo-3- (1,1-dioxothiomorpholin-4-yl) -1 - ((phenylsulfanyl) -methyl) propylamino, (1 R) -3-oxo -3- (N-Methyl-N- (1,1-dimethylethyl) amino) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (piperidin-1-yl) -1- ((phenylsulfanyl) methyl) -propylamino , (1 R) -3-oxo-3-amino-1- ((phenylsulfanyl) methyl) -propylamino, (1R) -3-oxo-3- (methylamino) -1 - ((phenylsulfanyl) -methyl) propylamino, (1 R) -3-oxo-3- (4-methyl-piperazin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (morpholin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R) -3-oxo-3- (2- (morpholin-1-yl) ethyl) -1 - ((phenylsulfanyl) methyl) propylamino, (2-phenoxyethyl) amino, - (1- (phenylmethyl) piperidin-4-yl) amino, 4- (1- (phenylmethyl) piperidin-4-yl) methylamino, (4-phenyl-1,3-thiazol-2-ylsulfanyl) ethylamino, (1R , 2S) -2- (phenylsulfanyl) -cyclohex-1-ylamino, (1S, 2R) -2- (phenylsulfanyl) cyclohex-1-ylamino, 2- (phenylsulfanyl) cyclopentylamino, 2- (phenylsulfanyl) ethoxy, 2 - (phenylsulfanyl) ethylamino, 2- (phenylsulfonyl) ethylamino, (1R) -1- ((f-enylsulfanyl) methyl) -3- (morpholin-4-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) ) -3 - ((2, 2, 2-trifluoroethyl) amino) propylammonium, 4- (phenylsulfonyl) -tetrahydrofuran-3-ylamino, 4- (phenylsulfanyl) -tetrahydrofuran-3-ylamino, (1R) -1- ((phenylsulfanyl) methyl) -3 - ((2,2,2-trifluoroethyl) amino) -propylamin or, (1S) -1- ((phenylsulfanyl) methyl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-4-ylsulfanyl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (thiomorpholin-4-yl) propylamino, (1R) -1 - ((phenylsufinanyl) -methyl) -3- (piperazin-1-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) ) -3 - ((2- (pyridin-2-yl) ethyl) amino) -propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-4-ylmethyl) amino) propylamino, ( 1R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-S-ylamino-jopropylamino, (1R) -1 - ((phenylsulfanyl) -methyl) -3- (pyrrolidin-1-ylamino) propylamino), (1R) -1 - ((phenylsulfanyl) methyl) -3- (2H-tetrazol-5-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3- (pyrrolidin-1-yl) propylamino, (1R) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-2-ylmethyl) amino) propylamino, (1S) -2- (phenylsulfanyl) -1- (pyridin-3-ylmethyl) ethylamino, (3S, 4R) - (phenylsulfanyl) -pyrrolidin-4-ylamino, 2- (phenylsulfanyl) -l, 1-spirobutyl-ethylamino, 2- (phenylsulfani) -1, 1-spiroethylethylamino, 2- (phenylsulfanyl) -1,1-spiropentylamino, piperidine -4-Ioxy, (1-propylpipepdin-4-yl) meti lamino, pyran-4-ylamino, 2- (pyridin-4-ylsulfanyl) ethylamino, 2- (pyrimidin-2-ylsulfanyl) ethylamino, 1,1-spirobutyl-2- (phenylsulfanyl) -ethyl, 2- (thien) -2-ylsulfanyl) ethylamino, sulfanylpyran-4-ylamino, (1R) -3- (2- (2H-tetrazol-3-yl) pyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino, (1R ) -3- (3- (2H-tetrazoI-3-yl) -azetidin-1-yl) -1 - ((phenylsulfanyl) methyl) propylamino or 2- (1,3-thiazol-2-ylsulfanyl) ethylamino; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2 or C (0) NH2 and Z1 is 4- (4- (2- (phenyl) -phenylmethyl) -4- (2- (pyrrolidin-1) -yl) ethoxy)) piperidin-1-yl) -phenylcarbonyl, 4- (4 - ((2- (phenyl) pyridin-3-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- ( (1-phenyl-1H-pyrazol-5-yl) methyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (piperidin-1-yl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl 4- (4- (2- (pyrid-3-yl) -phenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (quinolin-3-ylphenyl) -phenylmethyl) piperazine -1-yl) -phenylcarbonium, 4- (4- (2- (quinolin-8-ylphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl4- (4- (2- (thien-2-yl) -phenylmethyl) -4-methoxy-piperazin-1-yl) -phenylcarbonyl, 4- (4- (2- (thien-2-yl) -phenylmethyl) piperazine -1-yl) -phenylcarbonyl, 4- (4- (2- (4-trifluoromethoxyphenyl) -phenylmethyl) piperazin-1-yl) -phenylcarbonyl or 4- (4- (2- (4-trifluoromethyl-phenyl) -phen Methyl) piperazin-1-yl) -phenylcarbonyl. Even another embodiment belongs to compounds having the formula (I) which are N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) -methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'- biphenyl) -2-yl) methyl) -piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzene -sulfonamide, 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) -methyl) propyl) amino) -N- (4- (4 - ((4'-methoxy- (1,1 '-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) -methyl) propyl) amino) -N- (4- (4 - ((4'-fluoro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (( (1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) -methyl) propyl) amino) -N- (4- (4 - ((4 '- (methylsulfanyl) (1,1'-biphenyl) -2 -yl) methyl) piperazin-1-ÍI) -benzoyl) -3-nitrobenzenesulfonamide, N - ((4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) -methyl) propyl) amino) -3-nitrophenyl) -sulfonyl) -4- (4- (4 '-phenyl-1,1'-biphenyl-2-ylmethyl) piperazin-1-yl) -benzamide, 4 - (((1R) -3- (dimethylamino) -1 - ((phenylanesulfanyl) -methyl) propii ) amino) -3-nitro-N- (4- (4 - ((4'-phenoxy- (1, 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) - benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- ((1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoii) -4 - (((1R) -3- (morpholin-4-yl) - 1 - ((phenylsulfanyl) -methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) - 3-Nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) -piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) -ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) -piperazin-1-yl) -benzoyl) -4 - (((1 R) -3 - (morpholin-4-yl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) - 2-yl) metii) -piperazin-1-yl) -benzoyl) -4 - ((1,1-dimethyl-2- (phenylsulfanyl) -ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4- ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -4- (dimethylamino) -1 - (( phenylsufinyl) methyl) -butyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) - benzoyl) -4 - (((1R) -5- (dimethylamino) -1 - ((phenylsulfanyl) methyl) pentyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-fluoro (1 , 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1- ((phenylsulfanyl) methyl) propyl ) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro-4-fluoro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1 '-biphenil) -2-il) m ethyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- ( 4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholine-4 -yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2 -yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1 - ((phenylsulfanyl) methyl) -3- (pyrrolidin-1-yl) propyl) amino) - benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-ii) -benzoyl) -4 - ((1,1-dimethyl) -2- (1,3-thiazol-2-ylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) ) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((1,3-thiazol-2-ylsulfanyl) methyl) propyl) amino) -3 -nitrobencenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) - 3- (dimethylamino) -1 - ((thien-2-ylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) - 2-il) me til) piperazin-1-yl) -benzoyl) -4 - (((1R) -2- (2- (dimethylamino) ethoxy) -1 - ((phenylsulfanyl) methyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1S) -3- (dimethylamino ) -1-methyl-1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) ) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (methylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, Acid (3R) -3 - (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyI) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2- nitroanilino) -4- (phenylsulfanyl) -butanoic, (3R) -3- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin -1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N-isopropyl-4- (phenylsulfanyl) -butanamide, N- (4- (4 - ((4'-chloro- (1,1 '-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) - 3-nitrobenzenesulfonamide, 4 - (((1R) -3- (azetidin-1-yl) -1- ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4- ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro) - (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((4- (phenylsulfanyl) -tetrahydro-3-furanyl) amino) -benzenesulfonamide , N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) -4-methoxy-piperidin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2- il) methyl) -4-methoxypiperidin-1-yl) -benzoyl) -4 - (((1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3 -Nitrobenzenesulfonamide N- (4- (4 - ((4'-chloro- (1, 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3-hydroxy-1 - ((phenylsulfanyl) methyl) propyl) amino) -3- nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) - 3- (isopropylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) - N- (4- (4- (2- (2-naphthyl) -benzyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4- (2- (1-naphthyl) -benzyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- ( 4 - ((3'-cyano- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((3'-methoxy- (1,1, -biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((3'- chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (tell me tilamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide N- (4- (4 - ((2'-chloro- (1,1'-biphenol) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4 - (4- (2- (1, 3-benzodioxol-5-yl) -benzyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - (( phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4- (2- (3-thienyl) -benzyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl ) amino) -3-nitro-N- (4- (4- (2- (pyridin-3-yl) -benzyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 4 - (((1 R) - 3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4- (2- (quinolin-8-yl) -benzyl) piperazin-1-yl) benzoyl) -benzenesulfonamide, N- (4- (4- (2- (1-benzofuran-2-yl) -benzyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3 - (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-ni trobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((2'-methyl- (1, 1 ' -biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl ) amino) -3-nitro-N- (4- (4- (2- (quinolin-3-yl) -benzyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, N- (4- (4- ( (1- (4-chlorophenyl) -2-naphthyl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1- (4-chlorophenyl) -2-naphthyl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1- (4-chlorophenyl) -2-naphthyl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- ( 1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) cyclopentyl) amino) -benzenesulfonamide, N- (4- ( 4 - ((1,1'-biphenyl) -2-ylmethyl) -4-methoxypiperidin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) cyclopentyl) amino) -benzenesulfonamide, N - (4- (4 - ((4'-fluoro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- ( phenylsulfanyl) etiI) amino) -benzenesulfonamide, N- (4- (4 - ((3 ', 4'-dichloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (( 2- (f-enylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((3 ', 4'-dichloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1 -yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((3 ' , 4'-dichloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -N- (4- (4 - ((4 '- (trifluoromethyl)) ( 1, -biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino ) -3-nitro-N- (4- (4 - ((4'- (trifluoromethyl) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, - (((1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4 - ((4'- (trifluoromethyl) ) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) - N- (4- (4 - ((4 '- (trifluoromethoxy) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 3-nitro-4- ( (2- (phenylsulfanyl) ethyl) amino) -N- (4- (4 - ((4 '- (trifluoromethoxy) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl ) -benzenesulfonamide, 4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4 - ((4 , - (trifluoromethoxy) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 3-nitro-N- (4- (4 - ((4'-phenoxy) - (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, 4 - (((1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4 - ((4'-phenoxy- (1,1'-biphenyl) ) -2-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazine -1-yl) benzoyl) -4 - (((1S) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 '-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((1,1-dimethyl-2- (phenylsulfonyl) ethyl) amino) -3- nitrobenc ensulfonamide, N- (4- (4 - ((2 \ 4'-dichloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (( (1R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) ) propyl) amino) -3-nitro-N- (4- (4- (2- (2-thienyl) -benzyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, N- (4- (4- ( (4'-Chloro-2'-methyl- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) - 1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2 ', 4'-difluoro- (1,1'-biphenyl) -2-ii) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1- ((phenylsulanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4- ( (1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfonyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfonyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((4- (phenylsu L-phenyl) -tetrahydro-3-furanyl) amino) -benzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -N- (4- ( 4- (2- (5-methyl-2-thienyl) -benzyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4, -chloro (1,1 ' -biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((4- (phenylsulfonyl) -tetrahydro-3-furanyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((4- (phenylsulfonyl) -tetrahydro-3 -furanyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) benzoyl) -4- ((1-methyl-4- (phenylsulani) pyrrolidin-3-yl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzene sulfonamide, N- ( 4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholine-4-) il) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-bromo (1,1'-biphenyl) -2-yl) methyl) piperazine -1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1- ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4- (1- (4'-chloro- (1,1'-biphenyl) -2- yl) cyclopropyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) ) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -2- (dimethylamino) -1 - ((phenylsulfanyl) methyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- ( 4 - ((4'-Chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -2- (dimethylamino) -1- ((phenylsulfanyl) methyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1 -iI) -benzoyl) -4 - (((1R) -2- (diethylamino) -1 - ((phenylsulfanyl) methyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 '-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -2- (morpholin-4-yl) -1 - (( phenylsulfanyl) methyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -2- (diethylamino) -1 - ((phenylsulfanyl) methyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) - 1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -2- (morpholin-4-yl) -1 - ((phenylsulanyl) methyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4- (((1R) -3- (cyclopropyl- (methyl) amino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzene sulfonamide, N- (4- (4 - ((1,1'-biphenyl) ) -2-ylmethyl) -4-methoxypiperidin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide , 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4-methoxy-4- (2- (pyridin-3-yl) ) -benzyl) piperidin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -N- (4 - (4-methoxy-4- (2- (pyridin-4-yl) -benzyl) piperidin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) - 1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4-methoxy-4- (2- (2-thienyl) -benzyl) piperidin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4-methoxy-4- (2- (3-thienyl) -benzyl) ) piperidin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (azetidin-1 -yl) -1 - ((phenylisulfanyl) methyl) propyl) amino) -N- ( 4- (4 - ((4'-chloro- (1,1 '-biphenyl) ) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1 R) -1 - ((phenylsulfanyl) methyl) -3 - ((2,2,2-trifluoroethyl) amino) propiI) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((( 1 R) -3- (Methyl- (2,2,2-trifluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 ' -chloro- (1,1 '-biphenyl) -2-yl) methyl) -4-methoxypiperidin-1-yl) -benzoyl) -4 - (((1 R) -3- (morpholin-4-yl) - 1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) -4-methoxypiperidine -1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'- biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (ethyl- (2,2,2-trifluoroethyl) amino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) - 4 - (((1R) -3 - ((2-fluoroethyl) amino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- ((2,2-difluoroethyl) amino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl)) -2-yl) methyl) piperazin-1-yl) -benzoyl) -1 - ((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) -1H-benzimidazole-5-sulfonamide, N - (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -1 - ((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) -1H-1,2,3-benzotriazole-5-sulfonamide, 5 - (((4- (4 - ((4'-chloro- (1,1'-biphenyl) ) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) - benzamide, N- (4- (4 - ((4 '- (dimethylamino) (1,1'-biphenyl) -2-yl) carbonyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (dimethylamino) -1- ((f-enylsulfonyl) methyl) propyl) amino) -N- (4- (4 - ((4 '- (methylsulfanyl) (1,1'-biphenyl) -2-yl) carbonyl) piperazin-1-yl) -benzoyl) -3-nitrobenzene lfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4 '- (methylsulfanyl) (1, - biphenyl) -2-yl) carbonyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-; l) methyl) piperazin-1-yl) -benzoyl) -3-cyano-4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -benzenesulfonamide, N- ( 4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) - 1 - ((phenylsulfanyl) methyl) propyl) -oxi) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1 -yl) -benzoyl) -4 - (((1 R) -3- (4,4-dimethyl-4,5-dihydro-1 H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propyl ) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4- ( ((1R) -3- (5,6-Dihydro-1 (4H) -pyrimidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (2-methyl-4 , 5-dihydro-1 H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1- il) -benzoyl) -4 - (((1R) -3- (5,6-dihydro-1 (4H) -pyrimidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((( 1R) -3- (2,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (2- methyl-4,5-dihydro-1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4 ' -chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (4,4-dimethyl-4,5-dihydro- 1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1- cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) -oxy) -3- (tri fluoromethyl) -benzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) cyclohepty-1-en-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R ) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, 4 - (((1R) -3- (bis- (2-methoxyethyl) amino) - 1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) - benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (bis- (2-methoxyethyl) amino) -1- ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4- ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3- (trifluoromethyl) -benzenesulfonamide, 4 - (((1R) -5-amino-1 - ((phenylsulfanyl) methyl) pentyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -4 -yl) methyl) -1-piperazinyl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) - 4 - (((1R) -4-methyl-1 - ((phenylsulfanyl) methyl) pentyl) amino) -3-nitrobenzenesulfonamide, (5R) -5- (4 - (((4- (4 - ((4 ' -chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -6- (phenylsulfanyl) -hexylcarbamate tert -butyl, 4 - (((1R) -5-amino-1 - ((phenylsulfanyl) methyl) pentyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2 -yl) methyl) pperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-b-phenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -5 - ((methylsulfonyl) amino) -1 - ((phenylsulfanyl) methyl) pentyl) amino) -3-nitrobenzenesulfonamide, 4 - (( (1R) -5 - ((aminocarbonyl) amino) -1 - ((phenylsulfanyl) methyl) pentyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) - 2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) prop il) amino) -N- (4- (4- (2- (methylsulfanyl) -benzyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (dimethylamino) - 1 - ((phenylsulfanyl) methyl) propyI) amino) -N- (4- (4- (2- (methylsulfonyl) -benzyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4- (2- (5,5-dimethyl-2-oxo-1,3-oxazolidin- 3-yl) -benzyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4- (2-cyclohexylbenzyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (d imeti lamino) -1 - ((phenylsulfanyl) methyl) propyI) amino) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) ) propyl) amino) -N- (4- (4- (2- (morpholin-4-yl) -benzyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) - 3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -N- (4- (4- (2- (isopropylsulfanyl) -benzyl) piperazin-1-yl) -benzoyl) -3- Nitrobencenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3 - (isopropyl- (methyl) ami no) -1 ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1 -yl) -benzoyl) -4 - (((1 R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzene sulfonamide, N- (4- (4 - (4 '-chloro- (1, 1' -biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dipropylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (diethylamino) -1-O ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzene sulfonamide, N- (4- (4 - ((4'-chloro- (1, 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (diethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3 -nitrobencenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -3-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -3-ylmethyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenc ensulfonamide, N- (4- (4 - ((1,1'-biphenyl) -3-ylmethyl) piperazin-1-yl) -benzoyl) -4- (((1R) -3- (morpholin-4-yl) ) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -3- fluorobenzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) ) -2-ylmethyl) piperazin-1-yl) -3-fluorobenzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -3-f! Uorobenzoyl) -4 - (((1R) -3- (morpholine-4 -yl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) - 3,5-difluorobenzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide N- (4- (4 - ((1,1 '-biphenyl) -2-ylmethyl) piperazin-1-yl) -3,5-difluorobenzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -3,5-difluorobenzoyl) -4 - (((1 R) -3- (morfoIin-4-yl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 3-Nitro-N- (4- (4 - ((1-phenyl-1H-imidazol-2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, 4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4 - (( 1-phenyl-1H-imidazol-2-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 3-nitro-N- (4- (4 - ((1-phenyl-1H-pyrazole-5- il) methyl) piperazin-1-yl) -benzoyl) -4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, 4 - (((1R) -3- (morpholin-4-yl) -1- ((f-enylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4 - ((1-phenyl-1H-pyrazol-5-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4 - ((1 - phenyl-1H-pyrazol-5-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide 4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl ) -amino) -3-nitro-N- (4- (4 - ((1-phenyl-1H-imidazol-5-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, Acid 1 - (( 3R) -3- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-ii) -benzoyl) amino) -sulfonyl ) -2-nitroanilino) -4- (phenylsulfanyl) -butyl) -3-azetidine-carboxylic acid, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) met L) piperazin-1-yl) -benzoyl) -4 - (((1R) -3 - ((2-hydroxy-2-methylpropyl) amino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3 -nitrobenzenesulfonamide, Acid (((3R) -3- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) benzoyl) amino) -sulfonyl) -2-nitroanilino) -4- (phenylsulfanyl) -butyl) (methyl) amino) -acetic acid, (2R) -1 - ((3R) -3- (4 - ((( 4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -4- (phenylsulfanil) ) -butyl) -2-pyrrolidine-carboxylic acid, Acid 1 - ((3R) -3- (4 - (((4- (4 - ((4'-chloro- (1,1'-biphenyl) -2- il) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -4- (phenylsulfanyl) -butyl) -4-piperidinecarboxylic acid, N- (4- (4 - ((4 '-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3 - ((2-hydroxyethyl) (methyl) amino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, Acid (2S) -1 - ((3R) -3- (4 - (((4- (4 - ((4'-chloro ( 1,1'-biphenyl) - 2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -4- (phenylsulfanyl) -butyl) -2-pyrrolidinecarboxylic acid, N- ( 4- (4 - ((4, -chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1- ((phenylsulfanyl) methyl) -3- (3- (2H-tetrazol-5-yl) -azetidin-1-yl) propyl) amino) -benzenesulfonamide, (2S) -2-amino-N - ((1S ) -2 - (((3R) -3- (4 - (((4- (4 - ((4'-chloro- (1, r-biphenyl) -2-yl) methyl) piperazin-1-yl) benzoyl) amino) -sulfonyl) -2-nitroanilino) -4- (phenylsulfanyl) -butyl) amino) -1-methyl-2-oxoethyl) propanamide, N- (4- (4 - ((4'-chloro ( 1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1 - ((phenylsulfanyl) methyl) -3- (2- (2H-tetrazol-5-yl) pyrrolidin-1-yl) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) ) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (4 - (((methylsulfonyl) amino) carbonyl) piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) pperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfani l) methyl) propyl) amino) -benzenesulfonamide, 1 - ((3R) -3- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -4- (phenylsulfanyl) -butyl) -N-hydroxy-4-pperidinecarboxamide, 2-chloro-N- ( 4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) - 1 - ((phenylsulfanyl) methyl) propyl) amino) -benzenesulfonamide, 2,6-dichloro-N- (4- (4 - ((4'-chloro- (1,1, -biphenyl) -2-yl) methyl) ) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -benzenesulfonamide, 4 - (((1R) -3- ((1R, 5S) -8-azabicyclo [3.2.1] -oct-8-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4'-chloro) - (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (7-azabicyclo [2.2.1] - hept-7-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) - benzoyl) -3-nitro-4- (2- (phenylsul fanil) ethoxy) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4- (2- (phenylsulfanyl) ethoxy ) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3 -nitro-4 - (((1R) -3 - ((1S, 4S) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4- (((1R) -3 - ((RI, 4R) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) - 3 - ((1S, 4S) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -benzenesulfonamide, N- (4- ( 4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -3 - ((1R, 4R) -2-oxa-5-azabicyclo [2.2.1] -hept-5-yl) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -benzenesulfonamide, 4 - (((1R) -3- (7-azabicyclo [2.2.1] -hept-7-yl) -1 - ((phenylsulfanyl) methyl) propyl) am ino) -N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3 - ((2R, 5S) - 2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -3 - ((1R, 4R) -2-oxa-5-azabicyclo [2.2. 1] -hept-5-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1 -yl) -benzoyl) -4- (cyclohexyloxy) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - (cyclohexylmethoxy) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- (2-cyclohexylethoxy) -3 -nitrobencenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4- (tetrahydro-2H-pyran-4-) ilamino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - ((2-cic lohexylethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- (cyclohexyl (methyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- (4,4-dimethylpiperidin-1-yl) -3-nitrobenzenesulfonamide, 4- (4 - (((4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitrophenoxy ) -1-piperidine-tert-butyl carboxylate, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4- (piperidin-4-yloxy) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - ((1-methylpiperidin- 4-yl) -oxi) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((cyclohexylmethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-cioro (1,1'-biphenyl) -2-y)) methyl) piperazin-1-yl) -benzoyl) -4 - ((cyclohexylmethyl) (propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1-benzylpiperidin-4-yl) methyl) amino) -N- (4- (4 - ((1, Bifenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - ((cyclohexylmethyl) (methyl) amino) -3-nitrobenzenesulfonamide, 4- ((1-benzylpiperidin-4-yl) amino) -N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N - (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4- (tetrahydro-2H-sulfanylpyran-4-ylamino) -benzenesulfonamide , 4- (4 - (((4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -1-piperidine ethyl-carboxylate, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1-propylpiperidin- 4-yl) methyI) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- (isopropylamino) -3 -nitrobencenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (1,3- thiazol-2-ylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2 - ((4-phenyl-1,3-thiazol-2-yl) -sulfanyl) ethyl) amino) -benzenesulfonamide, 4 - ((2- (1,3-benzothiazol-2-ylsulfanyl) ethyl) amino) -N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 '-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (1,3-thiazol-2-ylsulfanyl) ethyl) ) amino) -benzenesulfonamide, 4 - ((2- (1,3-benzoxazol-2-ylsulfanyl) ethyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) ) -2-il) met il) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - ((2- (1,3-benzothiazol-2-ylsulfanyl) ethyl) amino) -N- (4- (4- (( 4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1 , 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (pyrimidin-2-ylsulfanyl) ethyl) amino) -benzenesulfonamide, 4- ( ((1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4 - ((1-phenyl-1H-pyrazole -5-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 4 - (((1-benzylpiperidin-4-yl) methyl) amino) -N- (4- (4 - ((4'- chloro- (1, 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2 -ylmethyl) piperazin-1-yl) -benzoyl) -4 - ((2-bromoethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl)) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((2 - ((4-methyl-1,3-thiazol-2-yl) -sulfanyl) ethyl) amino) -3- nitrobenzenesulfonamide , N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((4-methoxycyclohexyl) methyl) )to mino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- ( 2-thienylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) - 4 - ((1,1-dimethyl-2- (2-thienylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2 -yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((1,3-thiazol-2-ylsulfanyl) methyl) propyl ) amino) -3-nitrobenzenesulfonamide, (3R) -3- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin- 1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N, N-dimethyl-4- (pyrimidin-2-ylsulfanyl) -butanamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -3-oxo-1- ( (2-thienylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl ) -benzoyl) -4 - ((1,1-dimethyl-2- (pyrimidin-2-ylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, (3R) -3- (4 - (((4- (4- ((4'-chloro- (1,1'-biphenyl) -2 -yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N, N-dimethyl-4- (1,3-thiazol-2-ylsulfanyl) -butanamide, N- ( 4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4 -yl) -1 - ((2-thienylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) ) metl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - (((4- (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propyl) amino ) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3- Nitro-4 - ((2-phenoxyethyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - (((4- (trifluoromethoxy) -phenyl) -sulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -1- (((4-methoxyphenyl) -sulfanyl) methyl) -3- (morpholin-4-yl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1 ' -biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -1 - (((4-methylphenyl) -sulfanyl) methyl) -3- (morpholine-4-) il) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((2-thienylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4 ' -chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -1 - (((4-chlorophenyl) -sulfanyl) methyl) - 3- (morpholin-4-yl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1 -yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - (((4-fluorophenyl) -sulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -1 - (((4- fluorophenyl) -sulfanyl) methyl) -3- (morpholin-4-yl) pr opyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -2-fluorobenzoyl) - 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (1 - ((4'-chloro- (1, 1'-biphenyl) -2-yl) methyl) -1,2,3,6-tetrahydropyridin-4-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanil ) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (1 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) -1,2,3,6 -tetrahydropyridin-4-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4 - (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -2-fluorobenzoyl) -4 - (((1 R) -3- (dimethylamino ) -1- ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N - ((6- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) ) methyl) piperazin-1-yl) pyridin-3-yl) carbonyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N - (4- (1 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperidin-4-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (1 - ((4'-chloro (1,1'-biphenyl) -2 -yl) methyl) piperidin-4-ii) -benzoyl) -4 - (((1 R) -3- (morpholin-4-yl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide , N- (4- (1 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) -1,2,3,6-tetrahydropyridin-4-yl) -benzoyl) - 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N - ((6- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) pyridin-3-yl) carbonyl) -4 - (((1R) -3- (morpholin-4-yl) - 1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N - ((6- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1 -yl) pyridin-3-yl) carbonyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyI) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1, -biphenyl) -2-yl) methyl) piperidin-1-yl) -benzoyl) -4 - (((1R) -3- ( dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-i l) methyl) piperidin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N - ((5- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) pyridin-2-yl) carbonyl) -4 - (((1R ) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N - ((5- (4 - ((4'-chloro (1,1'-biphenyl) -2 -yl) methyl) piperazin-1-yl) pyridin-2-yl) carbonyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsuifanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (1 - ((2- (4-chlorophenyl) -5,5-dimethyl-1-cyclohexen-1-yl) methyl) -1,2,3,6-tetrahydropyridin- 4-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (1 - (( 2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) -1, 2,3,6-tetrahydropyridin-4-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (1 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) -1,2 , 3,6-tetrahydropyridin-4-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) me propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (1 - ((2- (4-chlorophenyl) -5,5-dimethyl-1-cyclohexen-1-yl) methyl) -1,2,3,6-tetrahydropyridin-4-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) -1-cyclohexen-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2- il) methyl) -1-cyclohexen-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- Nitrobencenesulfonamide, N- (4 - ((3aR, 6aS) -5 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) -hexahydropyrrolo [3,4-c] -pyrrole-2 (1 H) -yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-n itrobenze n sulfone measure, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- (methyl - ((methyl-4- (trifluoromethoxy) -anilino) carbonyl) amino ) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - (((2-dimethylanilino) carbonyl) ( methyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - (((4-methoxy- (methyl) -anilino) carbonyl) ( methyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - (((4-dimethylanilino)) carbonyl) (methyl) amino) -3-nitrobenzenesulfonamide, 4 - (((benzhydryl- (methyl) amino) carbonyl) (methyl) amino) -N- (4- (4 - ((1,1'-biphenyl) -2-ylmethi) piperazin-1-yl) -benzoyl ) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-ii) -benzoyl) -4- (methyl - ((methyl - ((1S ) -1-phenylethyl) amino) carbonyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - (methyl - ((methyl- (2- (4-methylpiperazin-1-yl) -1-phenylethyl) amino) carbonyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1 ' -biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- (methyl - ((methyl- (2- (morpholin-4-yl) -1-phenylethyl) amino) carbonyl) amino) -3 -nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- ((((1,2-diphenylethyl) (methyl) amino) carbonyl) (methyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - (( ((2- (dimethylamino) -1-phenylethyl) (methyl) amino) carbonyl) (methyl) amino) -3-nitrobenzenesulfonamide, 3-amino-N- (4- (4 - ((4'-chloro (1, 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((2- (phenylsulfani l) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -1- (2- (phenylsulfanyl) ethyl) -1 H-1, 2,3-benzotriazole-5-sulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2- il) methyl) piperazin-1-yl) -benzoyl) -1- (2- (phenylsulfanyl) ethyl) -1H-benzimidazole-5-sulfonamide, N- (4- (4 - ((1,1'-biphenyl)) -2-ylmethyl) -4-methoxy-piperidin-1-yl) -benzoyl) -4 - ((cyclohexylmethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2 -ylmethyl) -4-methoxy-piperidin-1-yl) -benzoyl) -4- (cyclohexylamino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4 -methoxypiperidin-1-yl) -benzoyl) -4 - ((1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'- biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((1 - ((phenylsulfanyl) methyl) cyclopentyl) amino) -benzenesulfonamide, N- (4- (4- ((1, r-biphenyl) -2-ylmethyl) -4-methoxypiperidin-1-yl) -benzoyl) -3-nitro-4 - ((1 - ((phenylsulfanyl) methyl) cyclopentyl) amino) -benzenesulfonamide , N- (4- (4 - ((4'-chloro (1,1'-biphenl) -2-yl) methyl) pip erazin-1-yl) -benzoyl) -3-nitro-4 - ((1 - ((phenylsulfanyl) methyl) cyclopentyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro ( 1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1S) -1 - ((phenylsulfanyl) methyl) propyl) amino) -benzenesulfonamide , N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4-methoxypiperidin-1-yl) -benzoyl) -3-nitro-4 - (((1S) -1- ((phenylsulfanyl) methyl) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl ) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'- chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1S) -3-methyl-1 - ((phenylsulfanyl) methyl) -butyl) amino ) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4-methoxypiperidin-1-yl) -benzoyl) -4 - (((1S) -3 -methyl-1 - ((phenylsulfanyl) methyl) -butyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((1 - ((f-enylsulfanyl) methyl) cyclopropyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((1- ((phenylsulfanyl) methyl) cyclohexyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -1-methyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2- ylmethyl) piperazin-1-yl) -benzoyl) -4 - (((1S) -1-methyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1, 1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R, 2S) -2- (phenylsulfanyl) cyclohexyl) amino) -benzenesulfonamide, N- (4 - (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) - 1- ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, 4 - (((1R) -5-amino-1 - ((phenylsulfanyl) methyl) pentyl) amino) -N- (4_ (4 _ ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1 '-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1S) -2- (phenylsulfanyl) -1- (pyridin-3-ylmethyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4-methoxypiperidin-1-yl) -benzoyl) -3-nitro-4 - (( (1S) -2- (phenylsulfanyl) -1- (pyridin-3-ylmethyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2- ilmethyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1S, 2R) -2- (phenylsulfanyl) cyclohexyl) amino) -benzenesulfonamide, N- (4- (4 - ((1, 1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4- ((1 - (((2-methyl-3-furyl) -sulfanyl) methyl) cyclopentyl) amino) -3-nitrobenzenesulfonamide , N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((1 - ((( 2-methyl-3-furyl) -sulfanyl) methyl) cyclopentyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1 S) -2- (phenylsulfanyl) -1 - (pyridin-3-ylmethyl) ethyl) amino) -benzenesulfonamide, N- ( 4- (4 - ((2- (4-chlorophenyl) -3-pyridin-3-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) - (dimethylamino) -1- ((phenylsuifanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) pyridin-3-yl) met il) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) pyridin-3-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (morpholine-4 -yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 3-nitro-N- (4- (4 - ((2-phenylpyridin-3-yl) methyl) piperazin-1-yl ) -benzoyl) -4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, 4 - (((1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4 - ((2-phenylpyridin-3-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4- (4 - ((2-phenylpyridin-3-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((2- (4- (methylsulfanyl) - phenyl) pyridin-3-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino ) -N- (4- (4 - ((2- (4-methoxyphenyl) pyridin-3-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4- ( (2- (4- (dimethylamino) -phenyl) pyridin-3-yl) methyl) pi perazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1R) -3 - (dimethylamine) -1- ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((2- (4-fluorophenyl) pyridin-3-yl) methyl) piperazin-1-yl) - benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((2- (4- (methylsulfonyl) -phenyl) pyridin-3-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) ) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (pyridin-4-ylsulfanyl) ethyl) amino) -benzenesulfonamide, 4 - (((1R) - 3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4 '- (methylsulfonyl) (1,1'-biphenyl) -2-yl) methyl ) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 '- (methylsulfonyl) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3 - (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) - 2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1- ((f-enylsulfonyl) methyl) propyl) amino) -3 -nitrobencenesulfonamide, N- (4- (4 - ((4 '- (dimethylamino) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R ) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, (3R) -3- (4 - (((4- (4 - ((4'-chloro)) , 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N, N-dimethyl-4- (phenylsulfonyl) -butanamide, N- ( 4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((3S, 4R) - (phenylsulfanyl) pyrrolidin-4-yl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl ) -benzoyl) -3-nitro-4 - (((1R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-4-ylsulfanyl) propyl) amino) -benzenesulfonamide, N- (4- (4- ((3- (4-chlorophene) nil) pyridin-4-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide , N- (4- (4 - ((3- (4-chlorophenyl) pyridin-4-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclopenten-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino ) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1 -yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- bromo-1-cyclopenten-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3 -nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3 - (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1- il) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) benzenesulfonamide, N- (4- (4 - ((2-bromo-1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1- (( phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4- (4-chlorophenyl) -5,6-dihydro-2 H -pyran-3-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((( 1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl ) amino) -N- (4- (4 - ((2- (4-methoxyphenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (( (1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((2- (4-fluorophenyl) -1-cyclohexen-1-yl) methyl ) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-N- (4 - (4 - ((2-phenyl-1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl)) - 1-cyclo-octen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3 -nitrobencenesulfonamide, 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((2- (4- (methylsulfanyl) -phenyl) ) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -3-ní trobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohepten-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohepten-1-yl) methyl) piperazine -1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- ( 4 - ((2- (4-chlorophenyl) -5,5-dimethyl-1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino ) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -5,5-dimethyl-1-cyclohexen-1-yl) ) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4- (2- (morpholin-4-yl) ethoxy) piperidin-1-yl) -benzoyl) -4 - ((1 , 1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4- (2- (morpholine- 4-yl) ethoxy) piperidin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) ami no) -benzenesulfonamide, N- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4- (2- (pyrrolidin-1-yl) ethoxy) piperidin-1-yl) -benzoyl) -4 - ((1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4- (2 - (pyrroidin-1-yl) ethoxy) piperidin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - (( 1,1'-biphenyl) -2-ylmethyl) -4- (2- (pyrrolidin-1-yl) ethoxy) piperidin-1-yl) -benzoyl) -3-nitro-4 - ((1 - ((phenylsulfanil ) methyl) cyclopentyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4- (2- (dimethylamino) ethoxy) piperidin-1-yl ) -benzoyl) -4 - ((1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) ) -4- (2- (dimethylamino) ethoxy) piperidin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4- ((1,1'-biphenyl) -2-ylmethyl) -4- (2- (dimethylamino) ethoxy) piperidin-1-yl) -benzoyl) -3-nitro-4 - ((1 - ((phenylsulfanyl) methyl) cyclopentyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4- (2- (pyrrolidin-1-yl) ethoxy) piperidin-1-yl) -benzoyl) -4 - ((1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4- (2- (pyrrolidin-1-yl) ethoxy) piperidin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4- (2- (pyrrolidin-1-yl) ethoxy) piperidin-1 -yl) -benzoyl) -3-nitro-4 - ((1 - ((phenylsulfanyl) methyl) cyclopentyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) - 2-methylmethyl) piperazin-1-yl) -benzoyl) -4 - (((1S) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 '- (2- (dimethylamino) ethoxy) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (( (1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 '- (2- (dimethylamino) ethoxy) (1 , 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl ) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 '- (2- (dimethylamino) ethoxy) (1,1'-biphenyl) -2-yl) me til) piperazin-1-yl) -benzoyl) -4 - ((1, 1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 '- (2- (dimethylamino) ethoxy) (1,1'-biphenyl) -2 -yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) - 1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4 '- (2- (morpholin-4-yl) ethoxy) (1, r-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 '- (2- (morpholin-4-yl) ethoxy) (1,1'-biphenyl) - 2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide , 4 - ((1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -N- (4- (4 - ((4 '- (2- (morpholin-4-yl) ethoxy) (1.1 '-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4' - (2- (morpholin-4-yl) ethoxy) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (1H-imidazole- 1-il) -1- ((phenylsulfani l) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - ((( 1R) -3- (1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) - 2-ylmethyl) -4-methoxy-piperidin-1-yl) -benzoyl) -4 - (((1R) -3- (1H-imidazol-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino ) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (( (1R) -4- (4-Methylpiperazin-1-yl) -1 - ((phenylsulfanyl) methyl) -butyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1 , 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -2 - ((2- (dimethylamino) ethyl) (methyl) amino) -1- ((phenylsulfanyl) methyl) ethyl) amino) -3-nitrobenzenesulfonamide, (4R) -4- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-il ) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N, N-dimethyl-5- (phenylsulfanyl) -pentanamide, N- (4- (4 - ((4'- chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -4- (dimethylamino) -1 - ((phenylsulfonyl) methyl) -butyl )to mino) -3-nitrobenzenesulfonamide, 2 - (((3R) -4- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2- yl) methyl) piperazin -1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -4- (f-enylsulfanyl) -butyl) (methyl) amino) -N, N-dimethylacetamide, (3R) -N- (tert- butyl) -3- (4 - (((4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) - sulfonyl) -2-nitroanilino) -4- (phenylsulfanyl) -butanamide, (3R) -3- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2- il) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N, N-di-isopropyl-4- (phenylsulfanyl) -butanamide, (3R) -N- (tert-butyl) ) -3- (4 - (((4- (4 - ((4'-chloro- (1,1'-bifeniI) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl ) -2-nitroanilino) -N-methyl-4- (phenylisulfanyl) -butanamide, (3R) -3- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl)) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N-isopropyl-N-methyl-4- (phenylsulfanyl) -butanamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -3-oxo-1- ((phenylsulfanyl) methyl) -3- (piperidin-1-yl) propyl) am ino) -benzenesulfonamide, N - ((5R) -5- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1- il) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -6- (phenylsulfanyl) hexyl) -2- (dimethylamino) -acetamide, (3R) -3- (4 - (((4- (4- ( (4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N, N-dimethyl-4- (phenylsulfanil) ) -butanamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R ) -3- (1, 1-dioxidothiomorpholin-4-yl) -3-oxo-1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, (3R) -3- (4 - (( (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -4- ( phenylsulfanyl) -butanamide, (3R) -3- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) - benzoyl) amino) -sulfonyl) -2-nitroanilino) -N-cyclopropyl-4- (phenylsulfanyl) -butanamide, (3R) -3- (4 - (((4- (4 - ((4'-chloro (1 , 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N-cyclobutyl-4- (phenylsulfanyl) -butanamide, N- (4- (4 - ((4'- chlorine- (1, 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (4-methylpiperazin-1-yl) -3-oxo-1- ( (phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (morpholin-4-yl) -3-oxo-1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1R ) -3- (azetidin-1-yl) -3-oxo-1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'- biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, (3R) -3- (4 - (((4- (4 - ((4'-chloro (1 , 1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2-nitroanilino) -N- (2- (morpholin-4-yl) ethyl) -4- (phenylsulfanyl) -butanamide, (3R) -3- (4 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) benzoyl) amino) -sulfonyl) -2-nitroanilino) -N-methyl-4- (phenylsulfanyl) -butanamide, 4 - (((1R) -3-amino-1 - ((phenylsulfanyl) methyI) propyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-i l) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3-cyano-1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - ((( 1 R) -3- (tert-butylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4'-chloro- (1, r-bifeniI) -2- il) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1 -yl) -benzoyl) -4 - (((1R) -3- (cyclopropylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 ' -chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (cyclobutylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4- ((1R) -3- (diethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl)) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (isopropyl- (methyl) amino) -1- ((phenylsulfanyl) methyl) propyl) amino) - 3-Nitrobenzenesulfonamide, 4 - (((1R) -3- (tert-butyl- (methyl) amino) -1 - ((phenylsulfanyl) methyl) p ropil) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N - (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) - 1 - ((phenylsulfanyl) methyl) -3- (piperidin-1-yl) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2 -yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (4-hydroxypiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- Nitrobencenesulfonamide, 4 - (((1R) -3- (4-acetylpiperazin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4'-chloro- (1, r-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) ) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1 - ((phenylsulfanyl) methyl) -3- (thiomorpholin-4-yl) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R ) -3 - ((2- (morpholin-4-yl) ethyl) amino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'- chlorine (1,1'-biphenyl) -2-yl) meti l) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1 - ((phenylsulfanyl) methyl) -3- (piperazin-1-yl) propyl) amino) -benzenesulfonamide, N - (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3 - (( 3R) -3-hydroxypyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1R) -3 - ((3R) -3-aminopyrrolidin-1- il) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1- il) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (3-hydroxyazetidin-1-yl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro) (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (4-methylpiperazin-1-yl) -1 - ((phenylsulfanil ) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (1,1-dioxidothiomorpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (1, 3-benzodioxol-5-ylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-il ) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3 - ((1,3-benzodioxol-4-ylmethyl) amino) -1 - ((phenylsulfanyl) methyl) ) propyl) amino) -N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R ) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-2-ylmethyl) amino) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1 ' -biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1 - ((phenylsulfanyl) methyl) -3 - ((2- (pyridine- 2-yl) ethyl) amino) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1 - ((phenylsulfanyl) methyl) -3 - ((pyridin-4-ylmethyl) amino) propyl) amino) -benzenesulfonamide, N- (4- ( 4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (morpholin-4-ylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4- (((1R) -3- (methyl- (pyridin-4-yl) amino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4 ' -chloro- (1,1'-biphenyl) -2-yl) methy1) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1 - ((phenylsulfanyl) methyl) -3- (pyridin-3-ylamino) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1- il) -benzoyl) -4 - (((1R) -3- (2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3 - ((2R, 6S) -2,6-dimethylpiperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'- biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1 - ((f-enylsulfanyl) methyl) -3- (pyrrolidin-1- ilamino) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4- (((1R) -3- (4- (methoxy-imin o) piperidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) - 2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitro-4 - (((1R) -1 - ((phenylsulfanyl) methyl) -3- (2H-tetrazol-5-yl) propyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R ) -3- (di-isopropylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1 '-biphenyl) -2 ~ il) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (isopropylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, 4 - (((1 R) -3- (bis- (2-hydroxyethyl) amino) -1- ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4- ( (4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino ) -4- (trifluoromethoxy) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piper azin-1-yl) -benzoyl) -4 - (((1R) -3- (isopropyl) (methyl) amino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) - benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) - 3- (diethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl)) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino ) -3-nitrobenzenesulfonamide, 4 - (((1R) -3-amino-1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4 - ((4'-chloro- (1,1 '-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) ) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -2- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) - 3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-fluorobenzenesulfonamide, N- (4- (4 - ((4'-chloro ( 1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -2- (trifluoromethoxy) -benzenesulfon amide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -2,5-difluorobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) ) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-methylbenzenesulfonamide, N- (4 - (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (di-isopropylamino) - 1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1 -yl) -benzoyl) -4 - (((1R) -3 - ((2R, 5R) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- Nitrobencenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3 - ((2S, 5S) -2,5-dimethylpyrrolidin-1-yl) -1- ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - (( 4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3 - ((2R, 5S) -2.5 -dimethylpyrrolidin-1-yl) -1 - ((phenyl) sulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl ) -4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitro-5- (trifluoromethyl) -benzenesulfonamide, N- (4- (4- ( (2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) ) methyl) propyl) amino) -3-nitro-5- (trifluoromethyl) -benzenesulfonamide, N- (4- (4 - ((2- (4-chlorophenyl) -1-cyclohepten-1-yl) methyl) piperazine- 1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamine) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitro-5- (trifluoromethyl) -benzenesulfonamide, N - (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -3 - (((1R) -3- (dimethylamino ) -1- ((phenylsulfanyl) methyl) propyl) amino) -4-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin- 1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3,5-difluorobenzenesulfonamide, 5 - (((4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazi n-1-yl) -benzoyl) amino) -sulfonyl) -2 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzoate methyl, Acid 5 - (((4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-ii) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2 - (( (1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzoic acid, 5 - (((4- (4 - ((4'-chloro (1,1'- biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzoic, - (((4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2 - (( (1R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzoic acid, 5 - (((4- (4 - ((2- (4-chlorophenyl) -1-cyclohexen -1-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3 -nitrobenzamide, 5 - (((4- (4 - ((4'-chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzamide, 5 _ (((4- (4 - ((2- (4-chlorophenyl) -1 -cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) amino) -sulfonyl) -2 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (Methyl trifluoromethyl) -benzoate, 5 - (((4- (4 - ((4- (4-chlorophenyl) -5,6-dihydro-2H-pyran-3-yl) methyl) piperazin-1 -yl) -benzoyl) amino) -sulfonyl) -2 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzoic acid methyl ester; - (((4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) - ben zoil) amino) -sulfonyl) -2 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- (trifluoromethyl) -benzoic acid methyl ester, N- (4 - (4 - ((2- (4-chlorophenyl) -1-cyclohexen-1-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -4 - ((2R, 5S ) -2,5-dimethylpyrrolidin-1-yl) -1 - ((phenylsulfanyl) methyl) -butyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4- (4-chlorophenyl)) -5,6-dihydro-2H-pyran-3-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -4 - ((2R, 5S) -2,5-dimethylpyrrolidine -1 -yl) -1 - ((phenylsulfanyl) methyl) -butyl) amino) -3-nitrobenzenesulfonamide, 3 - ((4- (4 - ((((4 - (((1 R) -3- (dimethylamino ) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrophenyl) -sulfonyl) amino) carbonyl) -phenyl) piperazin-1-yl) carbonyl) -phenyl-tert-butylcarbamate, N- (4 - (4- (3- (dimethylamino) -benzoyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) benzoyl) -4 - (((1 R) -3- (dimethylamino) -1-methyl-1 - ((phenylsulfanyl) methyl) propyl) am ino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - (((1 S) -3- (dimethylamine No) -1-methyl-1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4- (2- (1,3-dihydro-2H-isoindole-2 -yl) -benzyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N ~ (4- (4- (2- (cyclohexylamino) -benzyl) piperazin-1-yl) -benzoyl) -4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -N- (4- (4- (2- (isopropylamino) -benzyl) ) piperazin-1-yl) -benzoyl) -3-nitrobenzenesulfonamide, N- (4- (4- (2- (benzylamino) -benzyl) piperazin-1-yl) -benzoyl) -4 - (((1R) - 3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-Nitro-N- (4- (4- (2- (piperidin-1-yl) -benzyl) piperazin-1-yl) -benzoyl) -benzenesulfonamide, N- (4- (4 - ((1, 1'-biphenyl) -2-ilmet il) piperazin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((1,1, -biphenyl) - 2-ylmethyl) piperazin-1-yl) -benzoyl) -4 - ((cyclohexylmethyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) - 4-methoxy-piperidin-1-yl) -benzoyl) -4 - (((1 R) -3- (morpholin-4-yl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((1,1'-biphenyl) -2-ylmethyl) -4-methoxy-piperidin-1-yl) -benzoyl) -3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1S) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl ) piperazin-1-yl) -benzoyl) -4 - (((1 R) -1 - ((phenylsulfanyl) methyl) -3- (pyrrolidin-1-yl) propyl) amino) -3- (trifluoromethyl) -benzenesulfonamide , N- (4- (4 - ((4- (4-chlorophenyl) pyridin-3-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, N- (4- (4 - ((4- (4-chlorophenyl) pyridin-3-yl) methyl) piperazin-1-yl) - benzoyl) -4 - (((1 R) -3- (morpholin-4-yl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, and N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -2-f-luoro-3- (trifluoromethyl) -benzenesulfonamide, or therapeutically acceptable salts, prodrugs or prodrug salts thereof. Even another embodiment pertains to compositions for treating diseases during which one or more than one of anti-apoptotic Bcl-X protein, anti-apoptotic Bcl-2 protein or anti-apoptotic Bcl-w protein is expressed, said compositions comprise an excipient and a therapeutically effective amount of the compound having the formula (I). Even another embodiment pertains to methods of treating a disease in a patient during which one or more than one of anti-apoptotic BCI-XL protein, anti-apoptotic Bcl-2 protein or anti-apoptotic Bcl-w protein is expressed, said methods they comprise administering to the patient a therapeutically effective amount of a compound having the formula (I). Even another embodiment pertains to compositions for treating bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, tumors Malignant lymphoid originating in T cell or B cell, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or splenic cancer, said compositions comprise a excipient and a therapeutically effective amount of the compound having the formula (I). Even another modality belongs to methods to treat bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, tumors malignant lymphoid originating in T cell or B cell, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer in a patient, said methods comprise administering to the patient a therapeutically effective amount of a compound having the formula (I).

Even another embodiment pertains to compositions for treating diseases during which one or more than one of anti-apoptotic BCI-XL protein, anti-apoptotic Bcl-2 protein or anti-apoptotic Bcl-w protein are expressed, said compositions comprise a excipient and a therapeutically effective amount of N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4- ( ((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, or a therapeutically acceptable salt, prodrug or salt of a prodrug thereof. Even another embodiment pertains to methods of treating a disease in a patient during which one or more than one of anti-apoptotic BCI-XL protein, anti-apoptotic Bcl-2 protein or anti-apoptotic Bcl-w protein is expressed, said methods comprising administering to the patient a therapeutically effective amount of N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, or a therapeutically acceptable salt, prodrug or salt of a prodrug thereof. Even another embodiment pertains to compositions for treating bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, tumors Malignant lymphoid originating in T cell or B cell, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or splenic cancer, said compositions comprise a excipient and a therapeutically effective amount of N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4- ( ((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, or a therapeutically acceptable salt, prodrug or salt of a prodrug thereof. Even another modality belongs to methods to treat bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, tumors malignant lymphoid originating in T cell or B cell, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer in a patient, said methods comprise administering to the patient a therapeutically effective amount of N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) - 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide, or a therapeutically acceptable salt, prodrug or salt of a prodrug thereof.

Even another embodiment pertains to compositions for treating diseases during which one or more than one of anti-apoptotic Bcl-XL protein, anti-apoptotic Bcl-2 protein or anti-apoptotic Bcl-w protein are expressed, said compositions comprise an excipient and a therapeutically effective amount of the compound having the formula (I) and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent. Even another embodiment pertains to methods of treating a disease in a patient during which one or more than one of anti-apoptotic BCI-XL protein, anti-apoptotic Bcl-2 protein or anti-apoptotic Bcl-w protein is expressed, said methods comprising administering to the patient a therapeutically effective amount of a compound having the formula (I) and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent. Even another embodiment pertains to compositions for treating bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, cancer of the esophagus, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, malignant lymphoid tumors of T cell or B cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, Non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer, said compositions comprise an excipient and a therapeutically effective amount of the compound having the formula (I) and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent. Even another modality belongs to methods to treat bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, cancer of the esophagus, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, tumors malignant lymphoid originating in T cell or B cell, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer in a patient, said methods comprise administering to the patient a therapeutically effective amount of the compound having the formula (I) and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent. Even another embodiment pertains to compositions for treating diseases during which one or more than one of anti-apoptotic Bcl-X protein, anti-apoptotic Bcl-2 protein or anti-apoptotic Bcl-w protein is expressed, said compositions comprise an excipient and a therapeutically effective amount of N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - ((( 1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, or a therapeutically acceptable salt, pro-drug or salt thereof, and a therapeutically effective amount of an agent additional therapeutic or more than one additional therapeutic agent. Even another embodiment pertains to methods of treating a disease in a patient during which one or more than one of anti-apoptotic Bcl-X protein, anti-apoptotic Bcl-2 protein or anti-apoptotic Bcl-w protein is expressed, said methods They comprise administering to the patient a therapeutically effective amount of N- (4- (4 - ((4'-chloro- (1, 1'-bifeni ^ -i-methyl piperazin-1-y-benzoyl-1-RJ-S-1-dimethylamino) - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, or a therapeutically effective amount, a prodrug or salt of a prodrug thereof thereof, and a therapeutically effective amount * of an additional therapeutic agent or more than one additional therapeutic agent. Even another embodiment pertains to compositions for treating bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, lymphoma follicular, malignant lymphoid tumors of T cell or B cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or splenic cancer, compositions comprise an excipient and a therapeutically effective amount of N- (4- (4 - ((4'-chloro- (1, -biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4- (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, or a therapeutically acceptable salt, prodrug or prodrug thereof, and an amount Therapeutically effective of an additional therapeutic agent or more than one additional therapeutic agent. Even another modality belongs to methods to treat bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, cancer of the esophagus, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, malignant lymphoid tumors of T cell or B cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer , small cell lung cancer or splenic cancer in a patient, said methods comprise administering to the patient a therapeutically effective amount of N- (4- (4 - ((4'-chloro- (1, 1'-biphenyl) -2 -yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, or a salt, prodrug or salt of a therapeutically acceptable prodrug thereof, and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent.

DETAILED DESCRIPTION OF THE INVENTION The variable portions in the present invention are represented by identifiers (uppercase letters with numerical and / or alphabetic superscripts) and can be modalized specifically. It is intended that it be understood that appropriate valences are maintained for all portions and combinations thereof, that monovalent portions having more than one atom are drawn from left to right and are joined through their left ends, and that Divalent portions are also drawn from left to right. It is also intended to be understood that a specific embodiment of a variable portion in the present invention may be the same or different from another specific embodiment having the same identifier. The term "cyclic portion", as used in the present invention, means arene, aryl, cycloalkane, cycloalkyl, cycloalkene, cycloalkenyl, heteroarene, heteroaryl, heterocycloalkane, heterocycloalkyl, heterocycloalkene, heterocycloalkenyl, spiroalkyl, spiroalkenyl, spiroheteroalkyl and spiroheteroalkenyl. The term "arene", as used in the present invention, means benzene. The term "aryl", as used in the present invention, means phenyl. The term "cycloalkane", as used in the present invention, means cycloalkane of C3, cycloalkane of C4, cycloalkane of C5, cycloalkane of C6, cycloalkane of C7, cycloalkane of C8, cycloalkane of Cg, cycloalkane of C10, cycloalkane of Cu, C 2 cycloalkane, C 13 cycloalkane and C 14 cycloalkane. The term "cycloalkyl", as used in the present invention, means C3 cycloalkyl, C-cycloalkyl, C5-cycloalkyl, C6-cycloalkyl, C-cycloalkyl, C8-cycloalkyl, Cg-cycloalkyl, C10-cycloalkyl, C-cycloalkyl. Cu, C 2 cycloalkyl, C 13 cycloalkyl and C 1 cycloalkyl. The term "cycloalkene", as used in the present invention, means C4 cycloalkene, cycloalkene C5, cycloalkene of C6, cycloalkene of C7, cycloalkene of Cs, cycloalkene of Cg, cycloalkene of C10, cycloalkene of Cu, cycloalkene of C? 2, cycloalkene of C13 and cycloalkene of C14. The term "cycloalkenyl", as used in the present invention, means cycloalkenyl of C3, cycloalkenyl of C4, cycloalkenyl of C5, cycloalkenyl of C6, cycloalkenyl of C7, cycloalkenyl of C8, cycloalkenyl of Cg, cycloalkenyl of C10, cycloalkenyl of Cu, cycloalkenyl of C 2, cycloalkenyl of C 13 and cycloalkenyl of C? . The term "heteroarene", as used in the present invention, means furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazole. The term "heteroaryl," as used in the present invention, means furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl. The term "heterocycloalkane", as used in the present invention, means cycloalkane having one or two or three CH2 portions replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N and also means cycloalkane having one or two or three CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O) , S02 or NH and one or two CH portions replaced with N. The term "heterocycloalkyl", as used in the present invention, means cycloalkyl having one or two or three CH2 portions replaced with O, C (O), CNOH , CNOCH3, S, S (O), S02 or NH independently selected and one or two CH portions not replaced or replaced with N and also means cycloalkyl having one or two or three portions CH2 not replaced or replaced with which are selected independently from O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH and one or two CH portions replaced with N. The term "heterocycloalkene", as used in the present invention, means cycloalkene having a or two or three CH2 portions replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH independently selected and one or two CH portions not replaced or replaced with N and also means cycloalkene which has one or two or three CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH and one or two CH portions replaced with N. The term "heterocycloalkenyl", as used in the present invention, it means cycloalkenyl having one or two or three CH2 portions replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N and also means cycloalkenyl having one or two or three CH2 portions not replaced or replaced with which are independently selected from O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH and one or two CH portions replaced with N. The term "spiroalkyl", as used in the present invention, it means spiroalkyl of C2, spiroalkyl of C3, spiroalkyl of C4, spiroalkyl of C5, spiroalkyl of CT, spiroalkyl of C, spiroalkyl of C8 and spiroalkyl of Cg. The term "spiroalkenyl", as used in the present invention, means spiroalkenyl of C2, spiroalkenyl of C3, spiroalkenyl of C, spiroalkenyl of C5, spiroalkenyl of Ce, spiroalkenyl of C7, spiroalkenyl of C8 and spiroalkenyl of C9.

The term "spiroheteroalkyl", as used in the present invention, means spiroalkyl having one or two CH2 portions replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected in a manner Independent. The term "spiroheteroalkenyl", as used in the present invention, means spiroalkenyl having one or two CH2 portions replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected in a manner independent and one or two CH portions not replaced or replaced with N and also means spiroalkenyl having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH and one or two CH portions replaced with N. The term "alkenyl", as used in the present invention, means C alkenyl, C3 alkenyl, C4 alkenyl, C5 alkenyl and C6 alkenyl. The term "alkyl", as used in the present invention, means C 1 alkyl, C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl and C 6 alkyl. The term "alkynyl", as used in the present invention, means C2 alkynyl, C3 alkynyl, C4 alkynyl, C5 alkynyl and C6 alkynyl. The term "C2 alkenyl", as used in the present invention, means ethenyl (vinyl). The term "C3 alkenyl", as used in the present invention, means 1-propen-1-yl, 1-propen-2-yl (isopropenyl) and 1-propen-3-yl (allyl). The term "C4 alkenyl", as used in the present invention, means 1-buten-1-yl, 1-buten-2-yl, 1,3-butadien-1-yl, 1,3-butadiene 2-yl, 2-buten-1-yl, 2-buten-2-yl, 3-buten-1-yl, 3-buten-2-yl, 2-methyl-1-propen-1-yl and 2- methyl-2-propen-1-yl. The term "C5 alkenyl", as used in the present invention, means 2-methylene-3-buten-1-yl, 2-methylenebut-1-yl, 2-methyl-1-buten-1-yl, 2-methyl-1,3-butadien-1-yl, 2-methyl-2-buten-1-yl, 2-methyl-3-buten-1-yl, 2-methyl-3-buten-2-yl, 3-methyl-1-buten-1-yl, 3-methyl-1-buten-2-yl, 3-methyl-1,3-butadien-1-yl, 3-methyl-1,3-butadiene-2- ilo, 3-methyl-2-buten-1-yl, 3-methyl-2-buten-2-yl, 3-methyl-3-buten-1-yl, 3-methyl-3-buten-2-yl, 1-penten-1-yl, 1-penten-2-yl, 1-penten-3-yl, 1,3-pentadien-1-yl, 1,3-penta-dien-2-yl, 1,3- pentadien-3-yl, 1,4-pentadien-1-yl, 1,4-pentadien-2-yl, 1,4-pentadien-3-yl, 2-penten-1-yl, 2-penten-2- ilo, 2-penten-3-yl, 2,4-pentadien-1-yl, 2,4-pentadien-2-yl, 3-penten-1-yl, 3-penten-2-yl, 4-penten- 1-yl and 4-penten-2-yl. The term "C6 alkenyl", as used in the present invention, means 2,2-dimethyl-3-buten-1-yl, 2,3-dimethyl-1-buten-1-yl, 2,3- dimethyl-1,3-butadien-1-yl, 2,3-dimethyl-2-buten-1-yl, 2,3-dimethyl-3-buten-1-yl, 2,3-dimethyl-3-buten- 2-yl, 3,3-dimethyl-1-buten-1-yl, 3,3-dimethyl-1-buten-2-yl, 2-ethenyl-1,3-butadien-1-yl, 2-ethenyl- 2-buten-1-yl, 2-ethyl-1-buten-1-yl, 2-ethyl-1,3-butadien-1-yl, 2-ethyl-2-buten-1-yl, 2-ethyl- 3-buten-1-yl, 1-hexen-1-yl, 1-hexen-2-yl, 1-hexen-3-yl, 1,3-hexadien-1-yl, 1,3-hexadien-2- ilo, 1,3-hexadien-3-yl, 1,3,5-hexatrien-1-yl, 1, 3,5-hexatrien-2-yl, 1,3,5-hexatrien-3-yl, 1, 4-hexadien-1-yl, 1,4-hexadien-2-yl, 1,4-hexadien-3-yl, 1,5-hexadien-1-yl, 1,5-hexadien-2-yl, 1, 5-hexadien-3-yl, 2-hexen-1-yl, 2-hexen-2-yl, 2-hexen-3-yl, 2,4-hexadien-1-yl, 2,4-hexadien-2- iio, 2,4-hexadien-3-yl, 2,5-hexadien-1-yl, 2,5-hexadien-2-yl, 2,5-hexadien-3-yl, 3-hexen-1-yl, 3-hexen-2-yl, 3-hexen-3-yl, 3,5-hexadien-1-yl, 3,5-hexadien-2-y it, 3,5-hexadien-3-yl, 4-hexen-1-yl, 4-hexen-2-yl, 4-hexen-3-yl, 5-hexen-1-yl, 5-hexen-2- ilo, 5-hexen-3-yl, 2-methylene-3-methyl-3-buten-1-yl, 2-methylene-3-methylbut-1-yl, 2-methylene-3-penten-1-yl, 2-methylene-4-penten-1-yl, 2-methylenepent-1-yl, 2-methylenepent-3-yl, 3-methylene-1-penten-1-yl, 3-methylene-1-penten-2 ilo, 3-methylenepent-1-yl, 3-methylene-1,4-pentadien-1-yl, 3-methylene-1,4-pentadien-2-yl, 3-methylene-pent-2-yl, 2- methyl-1-penten-1-yl, 2-methyl-1-penten-3-yl, 2-methyl-1,3-pentadien-1-yl, 2-methyl-1,3-pentadien-3-yl, 2-methyl-1,4-pentadien-1-yl, 2-methyl-1, 4 -pentadien-3-yl, 2-methyl-2-penten-1-yl, 2-methyl-2-penten-3-yl, 2-methyl-2,4-pentadien-1-yl, 2-methyl-2 , 4-pentadien-3-yl, 2-methyl-3-penten-1-yl, 2-methyl-3-penten-2-yl, 2-methyl-3-penten-3-yl, 2-methyl-4 -penten-1-yl, 2-methyl-4-penten-2-yl, 2-methyl-4-penten-3-yl, 3-methyl-1-penten-1-yl, 3-methyl-1-penten -2-yl, 3-methyl-1,3-pentadien-1-yl, 3-methyl-1,3-pentadien-2-yl, 3-methyl-1,4-pentadien-1-yl, 3-methyl -1,4-pentadien-2-yl, 3-methyl-2-penten-1-yl, 3-methyl-2-penten-2-yl, 3-methyl-2,4-pentadien-1-yl , 3-methyl-3-penten-1-yl, 3-methyl-3-penten-2-yl, 3-methyl-4-penten-1-yl, 3-methyl-4-penten-2-yl, 3 -methyl-4-penten-3-yl, 4-methyl-1-penten-1-yl, 4-methyl-1-penten-2-yl, 4-methyl-1-penten-3-yl, 4-methyl -1, 3-pentadien-1-yl, 4-methyl-1,3-pentadien-2-yl, 4-methyl-1,3-pentadien-3-yl, 4-methyl-1,4-pentadien -1-yl, 4-methyl-1,4-pentadien-2-yl, 4-methyl-1,4-pentadien-3-yl, 4-methyl n-2-penten-3-yl, 4-methyl-2-penten-1-yl, 4-methyl-2-penten-2-yl, 4-methyl-2-penten-3-yl, 4-methyl- 2,4-pentadien-1-yl, 4-methyl-2,4-pentadien-2-yl, 4-methyl-3-penten-1-yl, 4-methyl-3-penten-2-yl, 4- methyl-3-penten-3-yl, 4-methyl-4-penten-1-yl and 4-methyl-4-penten-2-yl. The term "Ci alkyl", as used in the present invention, means methyl. The term "C2 alkyl", as used in the present invention, means ethyl. The term "C3 alkyl", as used in the present invention, means prop-1-yl and prop-2-yl (isopropyl). The term "C4 alkyl", as used in the present invention, means but-1-yl, but-2-yl, 2-methylprop-1-yl and 2-methylprop-2-yl (tert-butyl) . The term "C5 alkyl", as used in the present invention, means 2,2-dimethylprop-1-yl (neo-pentyl), 2-methylbut-1-yl, 2-methylbut-2-yl, 3 -methylbut-1-yl, 3-methylbut-2-yl, pent-1-yl, pent-2-yl and pent-3-yl. The term "Ce alkyl", as used in the present invention, means 2,2-dimethylbut-1-yl, 2,3-dimethylbut-1-yl, 2,3-dimethylbut-2-yl, 3, 3-dimethylbut-1-yl, 3,3-dimethylbut-2-yl, 2-ethylbut-1-yl, hex-1-yl, hex-2-yl, hex-3-yl, 2-methylpent-1- ilo, 2-methylpent-2-yl, 2-methylpent-3-yl, 3-methylpent-1-yl, 3-methylpent-2-yl, 3-methylpent-3-yl, 4-methylpent-1-yl and 4-methylpent-2-yl. The term "C2 alkynyl", as used in the present invention, means ethynyl (acetylenyl). The term "C3 alkynyl", as used in the present invention, means 1-propin-1-yl and 2-propin-1-yl (propargyl). The term "C4 alkynyl", as used in the present invention, means 1-butin-1-yl, 1,3-butadi-1-yl, 2-butyn-1-yl, 3-butin- 1 -yl and 3-butin-2-yl. The term "C5 alkynyl", as used in the present invention, means 2-methyl-3-butin-1-yl, 2-methyl-3-butin-2-yl, 3-methyl-1-butin- 1-yl, 1,3-pentadi-in-1-yl, 1,4-pentadi-in-1-yl, 1,4-pentadi-yn-3-yl, 2,4-pentadi-in-1- ilo, 1-pentyne-1-yl, 1-pentyne-3-yl, 2-pentyne-1-yl, 3-pentyne-1-yl, 3-pentyne-2-yl, 4-pentyne-1-yl and 4-pentin-2-yl. The term "C6 alkynyl", as used in the present invention, means 2,2-dimethyl-3-butin-1-yl, 3,3-dimethyl-1-butin-1-yl, 2-ethyl- 3-butin-1-yl, 2-ethynyl-3-butin-1-yl, 1-hexin-1-yl, 1-hexin-3-yl, 1,3-hexadis-1-yl, 1, 3,5-hexatriin-1-yl, 1,4-hexadi-in-1-yl, 1,4-hexadi-in-3-yl, 1,5-hexadi-in-1-yl, 1,5- hexadi-in-3-yl, 2-hexin-1-yl, 2,5-hexadin-1-yl, 3-hexin-1-yl, 3-hexin-2-yl, 3,5-hexadi- in-2-yl, 4-hexin-1-yl, 4-hexin-2-yl, 4-hexin-3-yl, 5-hexin-1-yl, 5-hexin-2-yl, 5-hexin- 3-yl, 2-methyl-3-pentin-1-yl, 2-methyl-3-pentin-2-yl, 2-methyl-4-pentin-1-yl, 2-methyl-4-pentin-2- ilo, 2-methyl-4-pentin-3-yl, 3-methyl-1 -pentin-1-yl, 3-methyl-4-pentin-1-yl, 3-methyl-4-pentin-2-yl, 3-methyl-1,4-pentadi-in-1-yl, 3-methyl-1,4-pentadi-in-3-yl, 3-methyl-4-pentin-1-yl, 3-methyl-4- pentin-3-yl, 4-methyl-1 -pentin-1-yl and 4-methyl-2-pentin-1-yl. The term "C4 cycloalkane", as used in the present invention, means cyclobutane. The term "C5 cycloalkane", as used in the present invention, means cyclopentane. The term "C6 cycloalkane", as used in the present invention, means cyclohexane. The term "C-cycloalkane", as used in the present invention, means cycloheptane. The term "C8 cycloalkane", as used in the present invention, means cyclo-octane. The term "Cg cycloalkane", as used in the present invention, means cyclononane. The term "Cio cycloalkane", as used in the present invention, means cyclodecane. The term "Cu cycloalkane", as used in the present invention, means cycloundecane. The term "C? 2 cycloalkane", as used in the present invention, means cyclododecane. The term "C13 cycloalkane", as used in the present invention, means cyclotridecane.

The term "C 14 cycloalkane", as used in the present invention, means cyclootetradecane. The term "C-cycloalkene", as used in the present invention, means cyclobutene and 1,3-cyclobutadiene. The term "C5 cycloalkene", as used in the present invention, means cyclopentene and 1,3-cyclopentadiene. The term "Ce cycloalkene", as used in the present invention, means cyclohexene, 1,3-cyclohexadiene and 1,4-cyclohexadiene. The term "C-cycloalkene", as used in the present invention, means cycloheptene and 1,3-cycloheptadiene. The term "C8 cycloalkene", as used in the present invention, means cyclo-octene, 1,3-cyclo-octadiene, 1,4-cyclo-octadiene, 1,5-cyclo-octadiene, 1, 3, 5-cyclo-octatriene and 1, 3,6-cyclo-octatriene. The term "Cg cycloalkene", as used in the present invention, means cyclononene, 1,3-cyclononadiene, 1,4-cyclononadiene, 1,5-cyclononadiene, 1, 3,5-cyclononatriene, 1,3, 6-cyclononatriene, 1, 3,7-cyclononatriene and 1, 3,5,7-cyclononatetraene. The term "C10 cycloalkene", as used in the present invention, means cyclodecene, 1,3-cyclodecadiene, 1,4-cyclodecadiene, 1,5-cyclodecadiene, 1,6-cyclodecadiene, 1, 3,5- cyclodecatriene, 1, 3,6-cyclodecatriene, 1, 3,5,7-cyclodecatetraene, 1, 3,5,8-cyclodecatetraene and 1, 3,6,8-cyclodecatetraene. The term "Cu cycloalkene", as used in the present invention, means cycloundecene, 1,3-cycloundecadiene, 1,4-cycloundecadiene, 1,5-cycloundecadiene, 1,6-cycloundecadiene, 1, 3,5- cycloundecatriene, 1, 3,6-cycloundecatriene, 1,3,7-cycloundecatriene, 1,4,7-cycloundecatriene, 1,4,8-cycloundecatriene; 1,3,5,7-cycloundecatetraene, 1,3,5,8-cycloundecatetraene, 1,3,6,8-cycloundecatetraene and 1,3,5,7,9-cycloundecapentane. The term "C12 cycloalkene", as used in the present invention, means cyclododecene, 1,3-cyclododecadiene, 1,4-cyclododecadiene, 1,5-cyclododecadiene, 1,6-cyclododecadiene, 1,7-cyclododecadiene, 1, 3,5-cyclododecatriene, 1,3,6-cyclododecatriene, 1,3,7-cyclododecatriene, 1,3,8-cyclododecatriene, 1,4,7-cyclododecatriene, 1,4,8-cyclododecatriene, 1 5,9-cyclododecatriene, 1,3,5,7-cyclododecatetraene, 1,3,5,8-cyclododecatetraene, 1,3,5,9-cyclododecatetraene, 1,3,6,8-cyclododecatetraene, 1,3, 6,9-cyclododecatetraene, 1,3,6,10-cyclododecatetraene, 1,3,7,9-cyclododecatetraene, 1,4,7,10-cyclododecatetraene, 1,3,5,7,9-cyclododecapentane, 1 3,5,7,10-cyclododecapentane and 1,3,5,8,10-cyclododecapentane. The term "C13 cycloalkene", as used in the present invention, means 1,3-cyclotridecadiene, 1,4-cyclotridecadiene, 1,5-cyclotridecadiene, 1,6-cyclotridecadiene, 1,7-cyclotridecadiene, 1, 3,5-cyclotridecatriene, 1, 3,6-cyclotridecatriene, 1,3,7-cyclotridecatriene, 1,3,8-cyclotridecatriene, 1,4,7-cyclotridecatriene, 1,4,8-cyclotridecatriene, 1,4, 9-cyclotridecatriene, 1, 5,9-cyclotridecatriene, 1, 3,5,7-cyclotridecatetraene, 1,3,5,8-cyclotridecatetraene, 1, 3,5,9-cyclotridecatetrane, 1,3,6,8- cyclotridecatetraene, 1, 3,6,9-cyclotridecatetraene, 1,3,6,10-cyclotridecatetrane, 1,3,6,11-cyclotridecatetraene, 1,3,7,9-cyclotridecatetraene, 1, 3,7,10- cyctridecatecatene, 1,4,7,10-cyclotridecatetrane, 1,3,6,11-cyclotridecatetraene, 1,3,5,7,9-cyclotridecapentane, 1,3,5,7,10-cyclotridecapentane, 1,3, 5,8,10-cyclotridecapentane, 1,3,5,8,11-cyclotridecapentane, 1,3,6,8,11-cyclotridecapentane and 1,3,5,7,9,11-cyclotridecahexaeno. The term "C? 4 cycloalkene", as used in the present invention, means cyclotetradecene, 1,3-cyclotetradecadiene, 1,4-cyclotetradecadiene, 1,5-cyclotetradecadiene, 1,6-cycotetradecadiene, 1,7- cycotetradecadiene, 1,8-cyclotetradecadiene, 1,3,5-cyclotetradecatriene, 1, 3,6-cyclotetradecatriene, 1, 3,7-cyclotetradecatriene, 1, 3,8-cyclootetradecatriene, 1, 3, 3-cyclotetradecatriene, 1, 4,7-cyclotetradecatriene, 1, 4,8-cyclotetradecatriene, 1, 4,9-cyclotetradecatriene, 1,5,9-cycotetradecatriene, 1, 5,10-cyclotetradecatriene, 1, 3,5,7-cyclootetradecatetraene, 1, 3,5,8-cyclootetradecatetraene , 1,3,5,9-cyclootetradecatetraene, 1, 3,5,10-cyclootetradecatetraene, 1, 3,6,8-cyclootetradecatetraene, 1,3,6,9-cyclootetradecatetraene, 1,3,6,10-cyclootetradecatetraene , 1,3,6,11-cyclootetradecatetraene, 1,3,6,12-cyclootetradecatetraene, 1, 3,7,9-cyclootetradecatetraene, 1, 3, 7,10-cyclootetradecatetraene, 1,3,7,11-cyclicotetradecatetraene , 1,3,8,10- cycotetradecatetraene, 1,4,7,10-cyclootetradecatetraene, 1,4,7,11-cyclootetradecatetraene, 1,4,8,11-cyclic tetradecatetraene, 1,3,5,7,9 -Cyclotetradecapentane, 1, 3,5,7,10-cyclootetradecapentane, 1,3,5,7,11-cyclootetradecapentane, 1,3,5,8,10-cyclootetradecapentane, 1,3,5,8,11-cyclootetradecapentane, 1,3,5,8,12-cyclootetradecapentane, 1,3,5,9,11-cyclootetradecapentane, 1,3,5,8,11-cyclootetradecapentane, 1,3,6,8,11-cyclootetradecapentane, 1,3,6,9,11-cyclootetradecapentane, 1, 3,6,9,12-cyclootetradecapentane, 1,3,5,8,11-cyclootetradecapentane, 1, 3,5,8,12-cyclootetradecapentane, 1,3,5,7,9,11-cyclootetradecahexaeno, 1,3,5,7,9,12-cyclootetradecahexaeno, 1,3,5,7,10,12-cyclootetradecahexaeno, 1,3,5,8,10,12-cyclootetradecahexaeno and 1, 3,5,7, 9,11,13-cycotetradecaheptaene. The term "C3 cycloalkenyl", as used in the present invention, means cycloprop-1-en-1-yl and cycloprop-2-en-1-yl. The term "C4 cycloalkenyl", as used in the present invention, means cyclobut-1-en-1-yl and cyclobut-2-en-1-yl. The term "C5 cycloalkenyl", as used in the present invention, means cyclopent-1-en-1-yl, cyclopent-2-en-1-yl, cyclopent-3-en-1-yl and cyclopenta- 1,3-dien-1-yl. The term "C6 cycloalkenyl", as used in the present invention, means cyclohex-1-en-1-yl, cyclohex-2-en-1-yl, cyclohex-3-en-1-yl, cyclohexa- 1,3-dien-1-yl, cyclohexa-1,4-dien-1-yl, cyclohexa-1, 5-dien-1-yl, cyclohexa-2,4-dien-1-yl and cyclohexa-2, 5-dien-1-yl. The term "C7 cycloalkenyl", as used in the present invention, means bicyclo [2.2.1] -hept-2-en-1-yl, bicyclo [2.2.1] -hept-2-en-2 ilo, bicyclo [2.2.1] -hept-2-en-5-yl, bicyclo [2.2.1] -hept-2-en-7-yl, bicyclo [2.2.1] -hepta-2,5-dien -1-iOo, bicyclo [2.2.1] -hepta-2,5-dien-2-yl, bicyclo [2.2.1] -hepta-2,5-dien-7-yl, cyclohepta-1-en-1 -yl, cyclohepta-2-en-1-yl, cyclohepta-3-en-1-yl, cyclohepta-4-en-1-yl, cyclohepta-1,3-diene-1-yl, cyclohepta-1,4 -dien-1-yl, cyclohepta-1,5-dien-1-yl, cyclohepta-1,6-dien-1-yl, cyclohepta-2,4-dien-1-yl, cyclohepta-2,5-dien -1-yl, cyclohepta-2,6-dien-1-yl, cyclohepta-3,5-dien-1-yl, cyclohepta-1,3,5-trien-1-yl, cyclohepta-1,3,6 -trien-1-yl, cyclohepta-1,4,6-trien-1-yl and cyclohepta-2,4,6-trien-1-yl. The term "C8 cycloalkenyl", as used in the present invention, means bicyclo [2.2.2] -oct-2-en-1-yl, bicyclo [2.2.2] -oct-2-en-2 ilo, bicyclo [2.2.2] -oct-2-en-5-yl, bicyclo [2.2.2] -oct-2-en-7-yl, bicyclo [2.2.2] -octa-2,5-dien -1-yl, bicyclo [2.2.2] -octa-2,5-dien-2-yl, bicyclo [2.2.2] -octa-2,5-dien-7-yl, bicyclo [2.2.2] - octa-2,5,7-trien-1-yl, bicyclo [2.2.2] -octa-2,5,7-trien-2-yl, cyclo-oct-1-en-1-yl, cyclo-oct -2-en-1-yl, cyclo-oct-3-en-1-yl, cyclo-oct-4-en-1-yl, cyclo-octa-1,3-dien-1-yl, cyclo-octa -1, 4-dien-1-yl, cyclo-octa-1,5-dien-1-yl, cyclo-octa-1,6-dien-1-yl, cyclo-octa-1,7-dien-1 -yl, cyclo-octa-2,4-dien-1-yl, cyclo-octa-2,5-dien-1-yl, cyclo-octa-2,6-dien-1-yl, cyclo-octa-2 , 7-dien-1-yl, cyclo-octa-3,5-dien-1-yl, cyclo-octa-3,6-dien-1-yl, cyclo-octa-1, 3,5-trien-1 -yl, cyclo-octa-1, 3,6-trien-1-yl, cyclo-octa-1, 3,7-trien-1-yl, cyclo-octa-1,4,6-trien-1-yl , cyclo-octa-1,4,7-trien-1-yl, cyclo-octa-1,5,7-trien-1-yl, cyclo-octa-2,4,6-trien-1-y lo, cyclo-octa-2,4,7-trien-1-yl, cyclo-octa-2,5,7-trien-1-yl and cyclo-octa-1,3,5,7-tetraen-1- ilo. The term "Cg cycloalkenyl", as used in the present invention, means cyclonon-1-en-1-yl, cyclonon-2-en-1-yl, cyclonon-3-en-1-yl, cyclonon- 4-en-1-yl, cyclonon-5-en-1-yl, cyclonone-1,3-dien-1-yl, cyclonone-1,4-dien-1-yl, cyclonone-1,5-dien- 1-yl, cyclonone-1, 6-dien-1-yl, cyclonone-1, 7-dien-1-yl, cyclonone-1, 8-dien-1-yl, cyclonone-2,4-dien-1- ilo, cyclonone-2,5-dien-1-yl, cyclonone-2,6-dien-1-yl, cyclonone-2,7-dien-1-yl, cyclonone-2,8-dien-1-yl, cyclonone-3,5-dien-1-yl, cyclonone-3,6-dien-1-yl, cyclonone-3,7-dien-1-yl, cyclonone-4,6-dien-1-yl, cyclonone- 1, 3,5-trien-1-yl, cyclonone-1, 3,6-trien-1-yl, cyclonone-1,3,7-trien-1-yl, cyclonone-1,3,8-trien- 1-yl, cyclonone-1,4,6-trien-1-yl, cyclonone-1,4,7-trien-1-yl, cyclonone-1,4,8-trien-1-yl, cyclonone-1, 5,7-trien-1-yl, cyclonone-1, 5,8-trien-1-yl, cyclonone-1,6,8-trien-1-yl, cyclonone-2,4,8-trien-1- ilo, cyclonone-2,4,6-trien-1-yl, cyclonone-2,4,7-trien-1-yl, cyclonone-2,4,8-trien-1-yl , cyclonone-2,5,7-trien-1-yl, cyclonone-2,5,8-trien-1-yl, cyclonone-1, 3,5,7-tetraen-1-yl, cyclonone-1, 3 , 5,8-tetraen-1-yl, cyclonone-1,3,6,8-tetraen-1-yl, cyclonone-1,4,6,8-tetraen-1-yl and cyclonone-2,4,6 , 8-tetraen-1-yl.

The term "C10 cycloalkenyl", as used in the present invention, means cyclodec-1-en-1-yl, cyclodec-2-en-1-yl, cyclodec-3-en-1-yl, cyclodec 4-en-1-yl, cyclodec-5-en-1-yl, cyclodeca-1,3-dien-1-yl, cyclodeca-1,4-dien-1-yl, cyclodeca-1, 5-dien- 1-yl, cyclodeca-1,6-dien-1-yl, cyclodeca-1,7-dien-1-yl, cyclodeca-1, 8-dien-1-yl, cyclodeca-1, 9-dien-1- ilo, cyclodeca-2,4-dien-1-yl, cyclodeca-2,5-dien-1-yl, cyclodeca-2,6-dien-1-yl, cyclodeca-2,7-dien-1-yl, cyclodeca-2,8-dien-1-yl, cyclodeca-2,9-dien-1-yl, cyclodeca-3,5-dien-1-yl, cyclodeca-3,6-dien-1-yl, cyclodeca- 3,7-dien-1-yl, cyclodeca-3,8-dien-1-yl, cyclodeca-4,6-dien-1-yl, cyclodeca-4,7-dien-1-yl, cyclodeca-1, 3,5-trien-1-yl, cyclodeca-1, 3,6-trien-1-yl, cyclodeca-1, 3,7-trien-1-yl, cyclodeca-1,3,8-trien-1- ilo, cyclodeca-1,3,9-trien-1-yl, cyclodeca-1,4,6-trien-1-yl, cyclodeca-1,4,7-trien-1-yl, cyclodeca-1,4, 8-trien-1-yl, cyclodeca-1,4,9-trien-1-yl, cyclodeca-1,5,7-trien-1-yl, cyclodeca- 1,5,8-trien-1-yl, cyclodeca-1,5,9-trien-1-yl, cyclodeca-1,6,8-trien-1-yl, cyclodeca-1,6,9-trien- 1-yl, cyclodeca-1,7,9-trien-1-yl, cyclodeca-2,4,6-trien-1-yl, cyclodeca-2,4,7-trien-1-yl, cyclodeca-2, 4,8-trien-1-yl, cyclodeca-2,4,9-trien-1-yl, cyclodeca-2,5,7-trien-1-yl, cyclodeca-2,5,8-trien-1- ilo, cyclodeca-2,5,9-trien-1-yl, cyclodeca-2,6,8-trien-1-yl, cyclodeca-3,5,7-trien-1-yl, cyclodeca-3,5, 8-trien-1-yl, cyclodeca-1, 3,5,7-tetraen-1-yl, cyclodeca-1, 3,5,8-tetraen-1-yl, cyclodeca-1,3,5,9- tetraen-1-yl, cyclodeca-1, 3,6,8-tetraen-1-yl, cyclodeca-1,3,6,9-tetraen-1-yl, cyclodeca-1, 3,7,9-tetra- 1-yl, cyclodeca-1,4,6,8-tetraen-1-yl, cyclodeca-1,4,6,9-tetraen-1-yl, cyclodeca-1,4,7,9-tetraen-1- ilo, cyclodeca-1, 5,7,9-tetraen-1-yl, cyclodeca-2,4,6,8-tetraen-1-yl, cyclodeca-2, 4,6,9-tetraen-1-yl, Cyclodeca-2,4,7,9-tetraen-1-yl and cyclodeca-1,3,5,7,9-pentaen-1-yl. The term "Cu cycloalkenyl", as used in the present invention, means cycloundec-1-en-1-yl, cycloundec-2-en-1-yl, cycloundec-3-en-1-yl, cycloundec- 4-en-1-yl, cycloundec-5-en-1-yl, cycloundec-6-en-1-yl, cycloundeca-1,3-dien-1-yl, cycloundeca-1,4-dien-1 ilo, cycloundeca-1, 5-dien-1-yl, cycloundeca-1,6-dien-1-yl, cycloundeca-1,7-dien-1-yl, cycloundeca-1,8-dien-1-yl, cycloundeca-1,9-dien-1-yl, cycloundeca-1,10-dien-1-yl, cycloundeca-2,4-dien-1-yl, cycloundeca-2,5-dien-1-yl, cycloundeca- 2,6-dien-1-yl, cycloundeca-2,7-dien-1-yl, cycloundeca-2,8-dien-1-yl, cycloundeca-2,9-dien-1-yl, cycloundeca-2, 10-dien-1-yl, cycloundeca-3,5-dien-1-yl, cycloundeca-3,6-dien-1-yl, cycloundeca-3,7-dien-1-yl, cycloundeca-3,8- dien-1-yl, cycloundeca-3,9-dien-1-yl, cycloundeca-4,6-dien-1-yl, cycloundeca-4,7-dien-1-yl, cycloundeca-4,8-dien 1-yl, cycloundeca-5,7-dien-1-yl, cycloundeca-1, 3,5-trien-1-yl, cycloundeca-1, 3,6-trien-1-yl, cycloundeca-1, 3, 7-trien-1-il or, cycloundeca-1,3,8-trien-1-yl, cycloundeca-1,3,9-trien-1-yl, cycloundeca-1, 3, 10-trien-1-yl, cycloundeca-1,4, 6-trien-1-yl, cycloundeca-1, 4,7-tri-en-1-yl, cycloundeca-1, 4,8-trien-1-yl, cycloundeca-1, 4,9-trien-1- ilo, cycloundeca-1, 4,10-trien-1-yl, cycloundeca-1, 5,7-trien-1-yl, cycloundeca-1, 5,8-trien-1-yl, cycloundeca-1, 5, 9-trien-1-yl, cycloundeca-1, 5,10-trien-1-yl, cycloundeca-1, 6,8-trien-l-yl, cycloundeca-1, 6,9-trien-yl, cycloundeca -1,6,10-trien-1-yl, cycloundeca-1, 7,9-trien-yl, cycloundeca-1,7,10-trien-1-yl, cycloundeca-1, 8,10-trien- -yl, cycloundeca-2,4,6-trien-1-yl, cycloundeca-2,4,7-trien-yl, cycloundeca-2,4,8-trien-1-yl, cycloundeca-2, 4,9-trien-yl, cycloundeca-2,4,10-trien-1-yl, cycloundeca-2,5,7-trien-yl, cycloundeca-2,5,8-trien-1-yl, cycloundeca-2,5,9-trien-yl, cycloundeca-2,5,10-tri-en-1-yl, cycloundeca-2,6,8-trien-yl, cycloundeca-2,6,9- trien-1-yl, cycloundeca-2,6,10-trien-yl, cycloundeca-2,7,9-trien-1-yl, cycloun deca-3,5,7-trienyl, cycloundeca-3,5,8-trien-1-yl, cycloundeca-3,5,9-trienyl, cycloundeca-3,6,8-trien- 1-lilo, cycloundeca-3,6,9-trien-yl, cycloundeca-4,6,8-trien-1-yl, cycloundeca-1, 3,5,7-tetraen-'-yl, cycloundeca-1, 3, 5,8-tetraen-1-yl, cycloundeca-1, 3,5,9-tetraen-'-yl, cycloundeca-1,3,5,10-tetraen-1-yl, cycloundeca-1, 3,6, 8-tetraen-l-yl, cycloundeca-1, 3,6,9-tetraen-1-yl, cycloundeca-1, 3,6,10-tetraen-1-yl, cycloundeca-1,3,7,9- tetraen-1-yl, cycloundeca-1,3,7,10-tetraen-1-yl, cycloundeca-1,3,8,10-tetraen-1-yl, cycloundeca-1,4,6,8-tetraen- 1-yl, cycloundeca-1,4,6,9-tetraen-1-yl, cycloundeca-1,4,6,10-tetraen-1-yl, cycloundeca-1,4,8,10-tetraen-1- ilo, cycloundeca-1, 5,7,9-tetraen-1-yl, cycloundeca-1, 5,7,10-tetraen-1-yl, cycloundeca-1,5,8,10-tetraen-1-yl, cycloundeca-1,6,8,10-tetraen-1-yl, cycloundeca-2,4,6,8-tetraen-1-yl, cycloundeca-2, 4,6,9-tetraen-1-yl, cycloundeca- 2,4,6,10-tetraen-1-yl, cycloundeca-2,4,7,9-tetraen-1-yl, cycloundeca-2,5,7,9-tetraen-1-yl, cycloundeca-3, 5,7,9-tetraen-1-yl, cycloundeca-1, 3,5,7,9-pentaenyl, cycloundeca-1,3,5,7,10-pentaenyl, cic loundeca-1,3,5,8,10-pentaenyl, cycloundeca-1,3,6,8,10-pentaenyl, cycloundeca-1,4,6,8,10-pentaenyl and cycloundeca-2,4,6, 8,10-pentaenyl. The term "C? 2cycloalkenyl", as used in the present invention, means cyclododec-1-en-1-yl, cyclododec-2-en-1-yl, cyclododec-3-en-1-yl, cyclododec-4-en-1-yl, cyclododec-5-en-1-yl, cyclododec-6-en-1-yl, cyclododeca-1,3-dien-1-yl, cyclododeca-1,4-dien 1-yl, cyclododeca-1,5-dien-1-yl, cyclododeca-1,6-dien-1-yl, cyclododeca-1,7-dien-1-yl, cyclododeca-1,8-dien-1- ilo, cyclododeca-1, 9-dien-1-yl, cyclododeca-1,10-dien-1-yl, cyclododeca-1,11-dien-1-yl, cyclododeca-2,4-dien-1-yl, cyclododeca-2,5-dien-1-yl, cyclododeca-2,6-dien-1-yl, cyclododeca-2,7-dien-1-yl, cyclododeca-2,8-dien-1-yl, cyclododeca- 2,9-dien-1-yl, cyclododeca-2,10-dien-1-yl, cyclododeca-2,11-dien-1-yl, cyclododeca-3,5-dien-1-yl, cyclododeca-3, 6-dien-1-yl, cyclododeca-3,7-dien-1-yl, cyclododeca-3,8-dien-1-yl, cyclododeca-3,9-dien-1-yl, cyclododeca-3,10- dien-1-yl, cyclododeca-3,11-dien-1-yl, cyclododeca-4,6-dien-1-yl, cyclododeca-4,7-dien-1-yl, cyclododeca-4,8-dien 1-ilri cyclone ododeca-4,9-dien-1-yl, cyclododeca-5,7-dien-1-yl, cyclododeca-5,8-dien-1-yl, cyclododeca-1,3,5-trien-1-yl, cyclododeca-1,3,6-trien-1-yl, cyclododeca-1,3,7-trien-1-yl, cyclododeca-1,3,8-trien-1-yl, cyclododeca-1, 3,9- trien-1-yl, cyclododeca-1, 3, 10-trien-1-yl, cyclododeca-1,3,11-trien-1-yl, cyclododeca-1,4,6-trien-1-yl, cyclododeca- 1, 4,7-trien-1-yl, cyclododeca-1, 4,8-trien-1-yl, cyclododeca-1, 4,9-trien-yl, cyclododeca-1, 4,10-trien-1 -yl, cyclododeca-1, 4,11-trien-yl, cyclododeca-1, 5,7-trien-1-yl, cyclododeca-1, 5,8-trien-yl, cyclododeca-1, 5,9-trien -1-yl, cyclododeca-1, 5,10-trien-yl, cyclododeca-1 5,11 -trien-1-yl, cyclododeca-1,6,8-trienyl, cyclododeca-6,9 -trien-1-yl, cyclododeca-1, 6, 10-trien-yl, cyclododeca-1 6, 1 -trien-1-yl, cyclododeca-1, 7,9-trien-yl, cyclododeca-1 7 , 10-trien-1-yl, cyclododeca-1,7,11-trien-yl, cyclododeca-1 8,10-trien-1-yl, cyclododeca-1,8,11-trien-yl, cyclododeca- 1 9,11-trien-1-yl, cyclododeca-2,4, 6-trien-yl, cyclododeca-2, 4,7-trien-1-yl, cyclododeca-2,4,8-trien-yl, cyclododeca-2, 4,9-trien-1-yl, cyclododeca-2, 4,10-trien-yl, cyclododeca-2 4,11-trien-1-yle, cyclododeca-2,5,7-trien-yl, cyclododeca-2 5,8-trien-1-yl, cyclododeca -2,5,9-trien-yl, cyclododeca-2 5, 10-trien-1-yl, cyclododeca-2,5,11-trien-yl, cyclododeca-2 6,8-trien-1-yl , cyclododeca-2,6,9-trien-yl, cyclododeca-2 6,10-trien-1-yl, cyclododeca-2,6,11-trien-yl, cyclododeca-2 7,9-trien-1 -yl, cyclododeca-2,7,10-trien-yl, cyclododeca-2 8,10-trien-1-yl, cyclododeca-3,5,7-trien-yl, cyclododeca-3, 5,8- trien-1-yl, cyclododeca-3,5,9-trien-yl, cyclododeca-3 5,10-trien-1-yl, cyclododeca-3,6,8-trien-yl, cyclododeca-3 6, 9-trien-1-yl, cyclododeca-3,6,10-trien-yl, cyclododeca-3, 7,9-trien-1-yl, cyclododeca-4,6,8-trien-yl, cyclododeca- 4, 6,9-trien-1-yl, cyclododeca-1, 3,5,7-tetraen-yl, cyclododeca-1, 3,5,8-tetraen-1-yl, cyclododeca-1, 3,5,9-tetraen-yl, cyclododeca-1 , 3,5,10-tetraen-1-yl, cyclododeca-1,3,5,11-tetraen-1-yl, cyclododeca-1, 3,6,8-tetraen-1-yl, cyclododeca-1, 3 , 6,9-tetraen-1-yl, cyclododeca-1,3,6,10-tetraen-1-yl, cyclododeca-1,3,6,11-tetraen-1-yl, cyclododeca-1,3,7 , 9-tetraen-1-yl, cyclododeca-1,3,7,10-tetraen-1-yl, cyclododeca-1,3,7,11-tetraen-1-yl, cyclododeca-1,3,8,10 -tetraen-1-yl, cyclododeca-1,3, 8,11-tetra-1-yl, cyclododeca-1,3,9,11-tetraen-1-yl, cyclododeca-1,4,6,8-tetraen -1-yl, cyclododeca-1,4,6,9-tetraen-1-yl, cyclododeca-1,4,6,10-tetraen-1-yl, cyclododeca-1,4,6,11-tetraen-1 -yl, cyclododeca-1,4,7,9-tetraen-1-yl, cyclododeca-1,4,7,10-tetraen-1-yl, cyclododeca-1, 4,7,11-tetraen-1-yl , cyclododeca-1, 4,8,10-tetraen-1-yl, cyclododeca-1,4,8,11-tetraen-1-yl, cyclododeca-1,4,9,11-tetraen-1-yl, cyclododeca -1,5,7,9-tetraen-1-yl, cyclododeca-1,5,7,10-tetraen-1-yl, cyclododeca- 1,5, 7,11- tetraen-1-yl, cyclododeca-1, 5,8,10-tetraen-1-yl, cyclododeca-1, 5,8,11-tetraen-1-yl, cyclododeca-1,5,9,11-tetraen- 1-yl, cyclododeca-1,6,8,10-tetraen-1-yl, cyclododeca-1,6,8,11-tetraen-1-yl, cyclododeca-1,6,9,11-tetraen-1 - ilo, cyclododeca-1,7, 9, 11-tetraen-1-yl, cyclododeca-2,4,6,8-tetraen-1-yl, cyclododeca-2,4,6,9-tetraen-1-yl, cyclododeca-2,4,6,10-tetraen-1-yl, cyclododeca-2,4,6,11-tetraen-1-yl, cyclododeca-2,4,7,9-tetraen-1-yl, cyclododeca- 2,4,7,10-tetraen-1-yl, cyclododeca-2,4,7,11-tetraen-1-yl, cyclododeca-2,4,8,10-tetraen-1-yl, cyclododeca-2, 4,8,11-tetraen-1-yl, cyclododeca-2,4,9,11-tetraen-1-yl, cyclododeca-2,5,7,9-tetraen-1-yl, cyclododeca-2,5, 7,10-tetraen-1-yl, cyclododeca-2,5,7,11-tetraen-1-yl, cyclododeca-2,5,8,10-tetraen-1-yl, cyclododeca-2,5,8, 11-tetraen-1-yl, cyclododeca-2,6,8,10-tetraen-1-yl, cyclododeca-3,5,7,9-tetraen-1-yl, cyclododeca-3,5,7,10- tetraen-1-yl, cyclododeca-3,5,8,10-tetraen-1-yl, cyclododeca-1,3, 5,7, 9-pentaen-1-yl, cyclo ododeca-1,3,5,7,10-pentaen-1-yl, cyclododeca-1,3,5,7,11-pentaen-1-yl, cyclododeca- 1,3, 5, 8, 10-pentaen- 1 -yl, cyclododeca-1,3,5,8,11-pentaen-1-yl, cyclododeca-1, 3,5,9,11-pentaen-1-yl, cyclododeca-1,3,6,8, 10-pentaen-1-yl, cyclododeca-1,3,6,8,11-pentaen-1-yl, cyclododeca-1,3,6,9,11-pentaen-1-yl, cyclododeca-1,3, 7,9,11-pentaen-1-yl, cyclododeca-1,4,6,8,10-pentaen-1-yl, cyclododeca-1,4,6,8,11-pentaen-1-yl, cyclododeca- 1,4,6,9,11-pentaen-1-yl, cyclododeca-1, 4,7,9,11-pentaen-1-yl, cyclododeca-1,5,7,9,11-pentaen-1- ilo, cyclododeca-2,4,6,8,10-pentaen-1-yl, cyclododeca-2,4,6,8,11-pentaen-1-yl, cyclododeca-2,4,6,9,11- pentaen-1-yl and cyclododeca-1,3,5,7,9,11-hexaen-1-yl. The term "C13 cycloalkenyl", as used in the present invention, means cyclotridec-1-en-1-yl, cyclotridec-2-en-1-yl, cyclotridec-3-en-1-yl, cyclotridec- 4-en-1-yl, cyclotridec-5-en-1-yl, cyclotridec-6-en-1-yl, cyclotridec-7-en-1-yl, cyclotrideca-1,3-dien-1-yl, cyclotrideca-1,4-dien-1-yl, cyclotrideca-1,5-dien-1-yl, cyclotridade-1,6-dien-1-yl, cyclotrideca-1,7-dien-1-yl, cyclotrideca- 1, 8-dien-1-yl, cyclotrideca-1,9-dien-1-yl, cyclotrideca-1, 10-dien-1-yl, cyclotrideca-1, 11-di-1-yl, cyclotrideca-1, 12-dien-1-yl, cyclotrideca-2,4-dien-1-yl, cyclotrideca-2,5-dien-1-yl, cyclotrideca-2,6-dien-1-yl, cyclotrideca-2,7- dien-1-yl, cyclotrideca-2,8-dien-1-yl, cyclotrideca-2,9-dien-1-yl, cyclotrideca-2,10-dien-1-yl, cyclotrideca-2,11-d? en-1-yl, cyclotrideca-2,12-dien-1-yl, cyclotrideca-3,5-dien-1-yl, cyclotrideca-3,6-dien-1-yl, cyclotrideca-3,7-dien- 1-yl, cyclotrideca-3,8-dien-1-yl, cyclotrideca-3,9-dien-1-yl, cyclotrideca-3,10-dien-1 -yl, cyclotrideca-3,11-dien-1-yl, cyclotrideca-4,6-dien-1-yl, cyclotrideca-4,7-dien-1-yl, cyclotrideca-4,8-dien-1-yl , cyclotrideca-4,9-dien-1-yl, cyclotrideca-4,10-dien-1-yl, cyclotrideca-5,7-dien-1-yl, cyclotrideca-5,8-dien-1-yl, cyclotrideca -5,9-dien-1-yl, cyclotrideca-6,8-dien-1-yl, cyclotrideca-1,3, 5-trien-1-yl, cyclotrideca-1,3,6-trien-1-yl, cyclotrideca-1,3,7-trien-1-yl, cyclotrideca-1,3, d-trien-1-yl , cyclotrideca-1,3,9-trien-1-yl, cyclotrideca-1, 3, 10-trien-1-yl, cyclotrideca-1, 3,11-trien-yl, ciclotrideca-1,3,12- trien-1-yl, cyclotrideca-1, 4,6-trien-yl, cyclotrideca-1, 4,7-trien-1-yl, cyclotrideca-1, 4,8-trien-yl, cyclotrideca-1, 4,9-trien-1-yl, cyclotrideca-1,4,10-trien-yl, cyclotrideca-1,4,11-trien-1-yl, cyclotrideca-1,4,12-trien-yl, cyclotrideca-1, 5,7-trien-1-yl, cyclotrideca-1, 5,8-trien-yl, cyclotrideca-1, 5,9-trien-1-yl, cyclotrideca-1, 5,10-trien - -yl, cyclotrideca-1,5,11-trien-1-yl, cyclotrideca-1,5,12-trien-yl, cyclotrideca-1, 6,8-trien-1-yl, cyclotrideca-1, 6 , 9-trien-yl, cyclotrideca-1,6,10-tri-en-1-yl, cidotrideca-1,6,11-trien-yl, cyclotrideca-1,6,12-trien-1-yl , cyclotrideca-1, 7,9-trien-yl, cyclotrideca-1,7,10-trien-1-yl, cyclotrideca-1,7,11-tri-en-yl, cyclotrideca- 1, 7, 12 -trien-1 -yl, cyclotrideca-1 , 8,10-trien-yl, cyclotrideca-1,8,11-trien-1-yl, cyclotrideca-1,8,12-trien-yl, cyclotrideca-1, 9, 11-trien-1-yl , cyclotrideca- 1, 9, 12-trien-1-yl, cyclotrideca-1,10,12-trien-1-yl, cyclotrideca-2,4,6-trien-1-yl, cyclotrideca-2,4,7 -trien-1-yl, cyclotrideca-2,4,8-trien-1-yl, cyclotrideca-2,4,9-trien-1-yl, cyclotrideca-2,4,10-trien-1-yl, cyclotrideca -2,4,11 -trien-1 -yl, cyclotrideca-2,4,12-trien-1-yl, cyclotrideca-2,5,7-trien-1-yl, cyclotrideca-2,5,8-trien -1-yl, cyclotri-deca-2,5,9-trien-1-yl, cyclotri-deca-2,5,10-trien-1-yl, cyclotrideca-2,5,11-trien-1-yl , cyclotrideca-2,5,12-trien-1-yl, cyclotrideca-2,6,8-trien-1-yl, cyclotrideca-2,6,9-trien-1-yl, cyclotrideca-2,6,10 -trien-1-yl, cyclotrideca-2,6,11 -trien-1-yl, cyclotrideca-2,6,12-trien-yl, otrideca-2,7,9-trien-1-yl, cyclotrideca- 2,7,10-trien-yl, otrideca-2,7,11-trien-1-yl, cyclotrideca-2,7,12-trien-yl, otrideca-2,8,10-trien-1- ilo, cyclotrideca-2,8,11-trien-yl, otrideca-2,8,12-trien-1-yl, c iclotrideca-2,9,11-trien-yl, otrideca-2,9,12-trien-1-yl, cyclotri-deca-2, 10, 12-trien-yl, otrideca-3,5,7- trien-1-yl, cyclotrideca-3,5,8-trien-yl, otrideca-3,5,9-trien-1-yl, cyclotrideca-3,5,10-trien-yl, otrideca-3, 5,11 -trien-1-yl, cyclotrideca-3,6,8-trien-yl, otrideca-3,6,9-trien-1-yl, cyclotrideca-3,6,10-trien-yl, otrideca-3,6,11 -trien-1-yl, cyclotrideca-3,7,9-trien-yl, otrideca-3,7,10-trien-1-yl, cyclotrideca-3,7,11-tri -in- -yl, otrideca-3,8,10-trien-1-yl, cyclotrideca-4,6,8-trien-yl, otrideca-4,6,9-trien-1-yl, cyclotri-deca -4,6,10-trien-yl, otrideca-4,7,9-trien-1-yl, cyclotrideca-4,7,10-trien-yl, otrideca-1,3,5,7-tetraen -1-yl, cyclotrideca-1,3,5,8-tetraen-yl, cyclotrideca-1, 3,5,9-tetraen-1-yl, cyclotrideca-1, 3,5,10-tetraen-1- ilo, cyclotrideca-1, 3,5,11-tetraen-1-yl, cyclotrideca-1, 3,5,12-tetraen-1-yl, cyclotrideca-1, 3,6,8-tetraen-1-yl, cyclotrideca-1, 3,6,9-tetraen-1-yl, cyclotrideca-1, 3,6,10-tetraen-1-yl, cyclotrideca-1 , 3,6,11-tetraen-1-yl, cyclotrideca-1,3,6,12-tetraen-1-yl, cyclotrideca-1, 3,7,9-tetraen-1-yl, cyclotrideca-1, 3 , 7,10-tetraen-1-yl, cyclotrideca-1,3,7,11-tetraen-1-yl, cyclotrideca-1,3,7,12-tetraen-1-yl, cyclotri-deca-1, 3 , 8,10-tetraen-1-yl, cyclotrideca-1, 3,8,11-tetraen-1-yl, cyclotrideca-1, 3,8,12-tetraen-1-yl, cyclotrideca-1, 3,9 , 11-tetraen-1-yl, cyclotrideca-1,3,9,12-tetraen-1-yl, cyclotrideca-1,3,10,12-tetraen-1-yl, cyclotrideca-1,4,6,8 -tetraen-1-yl, cyclotrideca-1, 4,6,9-tetraen-1-yl, cyclotri-deca-1, 4,6,10-tetraen-1-yl, cyclotrideca-1,4,6,11 -tetraen-1-yl, cyclotrideca-1,4,6,12-tetraen-1-yl, cyclotrideca-1,4,7,9-tetraen-1-yl, cyclotrideca-1,4,7,10-tetraen -1-yl, cyclotrideca-1,4,7,11-tetraen-1-yl, cyclotrideca-1,4, 7,12-tetraen-1-yl, cyclotri-deca-1, 4,8,10-tetraen -1-yl, cyclotri-deca-1, 4,8,11-tetraen-1-yl, cyclotrideca-1, 4,8,12-tetraen-1-yl, cyclotrideca-1, 4,9,11-tetraen -1-yl, cyclotrideca-1, 4,9,12-tetraen-1-yl, cyclotrideca-1,4,10,12-tetraen-1- ilo, cyclotrideca-1,5,7,9-tetraen-1-yl, cyclotrideca-1,5,7,10-tetraen-1-yl, cyclotri-deca-1,5,7,11-tetraen-1-yl , cyclotri-deca-1, 5,7,12-tetraen-1-yl, cyclotrideca-1,5,8,10-tetraen-1-yl, cyclotrideca-1,5,8,11-tetraen-1-yl , cyclotrideca-1, 5,8,12-tetraen-1-yl, cyclotrideca-1, 5,9,11-tetraen-1-yl, cyclotrideca-1, 5,9,12-tetraen-1-yl, cyclotrideca -1, 5,10,12-tetraen-1-yl, cyclotrideca-1,6,8,10-tetraen-1-yl, cyclotri-deca-1,6,8,11-tetraen-1-yl, cyclotrideca -1,6,8,12-tetraen-1-yl, cyclotrideca-1,6,9,11-tetraen-1-yl, cyctrotrideca-1,6,9,12-tetraen-1-yl, cyclotrideca- 1 , 6,10, 12-tetraen-1-yl, cyclotrideca-1,7,9,11-tetraen-1-yl, cyclotrideca-1, 7,9,12-tetraen-1-yl, cyclotri-deca-1 , 7,10,12-tetraen-1-yl, cyclotrideca-1,8,10,12-tetraen-1-yl, cyclotrideca-2,4,6,8-tetraen-1-yl, cyclotrideca-2,4 , 6,9-tetraen-1-yl, cyclotri-deca-2,4,6,10-tetraen-1-yl, cyclotrideca-2, 4,6,11-tetraen-1-yl, cyclotrideca-2,4 , 6,12-tetraen-1-yl, cyclotrideca-2,4,7,9-tetraen-1-yl, cyclotri-deca-2,4,7 , 10-tetraen-1-yl, cyclotrideca-2,4,7,11-tetraen-1-yl, cyclotrideca-2,4,7,12-tetraen-1-yl, cyclotrideca- 2,4,8,10 -tetraen-1-yl, cyclotri-deca-2,4,8,11-tetraen-1-yl, cyclotrideca-2,4,8,12-tetraen-1-yl, cyclotrideca-2,4,9,11 -tetraen-1-yl, cyclotrideca-2,4,9,12-tetraen-1-yl, cyclotrideca-2,4,10,12-tetraen-1-yl, cyclotrideca-2,5,7,9-tetraen -1-yl, cyclotrideca-2,5,7,10-tetraen-1-yl, cyclotrideca-2,5,7,11-tetraen-1-yl, cyclotrideca-2,5,7,12-tetraen-1 -yl, cyclotrideca-2,5,8,10-tetraen-1-yl, cyclotrideca-2,5,8,11-tetraen-1-yl, cyclotrideca-2,5,8,12-tetraen-1-yl , cyclotri-deca-2,5,9,11-tetraen-1-yl, cyclotrideca-2,5,9,12-tetraen-1-yl, cyclotrideca-2,5,10,12-tetraen-1-yl , cyclo-trideca-2,6,8,10-tetraen-1-yl, cyclotri-deca-2,6,8,11-tetraen-1-yl, cyclotrideca-2,6,8,12-tetraen-1-yl , cyclotrideca-2,6,9,11-tetraen-1-yl, cyclotrideca-2,6,9,12-tetraen-1-yl, cyclotri-deca-2,6,10,12-tetraen-1-yl , cyclotrideca-2,7,9,11-tetraen-1-yl, cyclotrideca-2,7,9, 12-tetraen-1-yl, cyclotrid eca-2,7,10, 2-tetraen-1-yl, cyclotri-deca-3,5,7,9-tetraen-1-yl, cyclotrideca-3,5,7,10-tetraen-1-yl, cyclotrideca-3,5,7,11-tetraen-1-yl, cyclotrideca-3, 5,8,10-tetraen-1-yl, cyclotri-deca-3,5,8,11-tetraen-1-yl, cyclotrideca-3,5,9,11-tetraen-1-yl, cyclotrideca-3,6,8,10-tetraen-1-yl, cyclotrideca-3,6,8,11-tetraen-1-yl, cyclotrideca- 3,7,9,11-tetraen-1-yl, cyclotrideca-1, 3,5,7,9-pentaen-1-yl, cyclotrideca-1, 3,5,7,10-pentaen-1-yl, cyclotrideca-1,3,5,7,11-pentaen-1-yl, cyclotrideca-1,3,5,7,12-pentaen-1-yl, cyclotrideca-1,3,5,8,10-pentaen- 1-yl, cyclotrideca-1, 3,5,8,11-pentaen-1-yl, cyclotrideca-1,3,5,8,12-pentaen-1-yl, cyclotrideca-1,3,5,9, 11-pentaen-1-yl, cyclotrideca-1,3,5,9,12-pentaen-1-yl, cyclotrideca-1,3,6,8,10-pentaen-1-yl, cyclotrideca-1,3, 6, 8, 11-pentaen-1-yl, cyclotrideca-1,3,6,8,12-pentaen-1-yl, cyclotrideca-1,3, 6, 9, 11-pentaen-1-yl, cyclotrideca- 1,3,6,9,12-pentaen-1-yl, cyclotrideca-1,3, 7, 9,11-pentaen-1-yl, cyclotrideca-1,3,7,9,12-pentaen-1- ilo, cyclotrideca-1, 4,6,8,10-pentaen-1-yl, cyclotrideca-1,4,6,8,11-pentaen-1-yl, cyclotrideca-1,4,6,8,12- pentaen-1-yl, cyclotrideca-1,4,6,9,11-pentaen-1-yl, cyclotrideca-1,4,6,9,12-pentaen-1-yl, cyclotrideca-1,4,7, 9,11-pentaen-1-yl, cyclotrideca-1,4, 7, 9, 12-pentaen-1-yl, cyclotrideca-1,5,7,9,11-pentaen-1-yl, cyclotrideca-1, 5,7,9,12-pentaen-1-yl, cyclotrideca-2,4,6,8,10-pentaen-1-yl, cyclotrideca-2,4,6,8,11-pentaen-1-yl, cyclotrideca-2,4,6,8,12-pentaen-1-yl, cyclotrideca-2,4,6,9,11-pentaen-1-yl, cyclotrideca-2,5,7,9,11-pentaen- 1-yl, cyclotrideca-2,5,7,9,12-pentaen-1-yl, cyclotrideca-1,3,5,7,9,11-hexaen-1-yl and cyclotrideca-2,4,6, 8,10,12-hexaen-1-yl. The term "C1-cycloalkenyl", as used in the present invention, means cyclootetradec-1-en-1-yl, cyclootetradec-2-en-1-yl, cyclootetradec-3-en-1-yl, cyclotetradec 4-en-1-yl, cyclotetradec-5-en-1-yl, cyclotetradec-6-en-1-yl, cyclotetradec-7-en-1-yl, cyclotetradec-8-en-1-yl, cyclotetradeca- 1,3-dien-1-yl, cyclotetradeca-1,4-dien-1-yl, cyclotetradeca-1,5-dien-1-yl, cyclotetradeca-1,6-dien-1-yl, cyclotetradeca-1,7-dien-yl, cycloteti radeca -1, 8-dien-1-yl, cyclotetradeca-1, 9-dien-yl, cycloteti radeca-1,10-dien-1-yl, cyclotetradeca-1, 11 -di-en-yl, cycloteti radeca -1, 12-dien-1-yl, cyclotetradeca-1, 13-d en-yllo, cycloteti radeca-2,4-dien-1-yl, cyclotetradeca-2,5-d en-yllo, cycloteti radeca -2,6-dien-1-yl, cyclotetradeca-2,7-d en- -lo, cycloteti radeca-2,8-dien-1-yl, cyclotetradeca-2,9-d en-yl, cycloteti radeca-2,10-dien-1-yl, cyclotetradeca-2, 11-d en--iio, cycloteti radeca-2,12-dien-1-yl, cyclotetradeca-2,13-d en-yl, cycloteti radeca-3,5-dien-1-yl, cyclotetradeca-3,6-d en-yllo, cycloteti radeca-3,7-dien-1-yl, cyclotetradeca-3,8-d en-yllo, cyclotet radeca-3,9-dien-1-yl, cidotetradeca-3, 10-d en-yllo, cyclotet radeca-3,11-dien-1-yl, cyclotetradeca-3, 12-d en-yl, cyclotet ! radeca-4,6-dien-1-yl, cyclotetradeca-4,7-d en-yllo, cycletet radeca-4,8-dien-1-yl, cyclotetradeca-4,9-d en-yl, cyclotet radeca-4,10-dien-1-yl, cyclo-tetradeca-4, 11-d en-yl, cyclo-treet-radeca-5,7-dien-1-yl, cyclo-tetradeca-5,8-d en-yl, cyclotet radeca-5,9-dien-1-yl, cyclotetradeca-5, 10-d en-yl, cyclo-treet-radeca-6,8-dien-1-yl, cyclotetra-deca-6,9-d en-yl , radeca-1,3,5-tetraen-1-yl cyclotet, cyclo-tetradeca-1,3,6-tetraen-yl, cyclotetradeca-1, 3,7-tetraen-1-yl, cyclotetradeca-1, 3,8 -tetraen-1-yl, cyclotetradeca-1, 3,9-tetraen-1-yl, cyclotetradeca-1, 3,10-tetraen-l-yl, cyclotetradeca-1, 3,11-tetraen-1-yl, cyclotetradeca -1, 3,12-tetraen-1-yl, cyclo-tetradeca-1, 3,13-tetraen-1-yl, cyclo-tetradeca-1,4,6-tetraen-1-yl, cyclo-tetradeca-1, 4,7-tetraen -1-yl, cyclo-tetradeca-1, 4,8-tetraen-1-yl, cyclo-tetradeca-1, 4,9-tetraen-1-yl, cyclotetradeca-1, 4,10-tetraen-1-yl, cyclotetradeca-1 , 4,11-tetraen-1-yl, cyclo-tetradeca-1,4,12-tetraen-1-yl, cyclo-tetradeca-1,4,13-tetra en-1-yl, cyclotetradeca-1, 5,7-tetraen-1-yl, cyclo-tetradeca-1,5,8-tetraen-1-yl, cyclo-tetradeca-1,5,9-tetraen-1-yl, cyclotetradeca- 1, 5,10-tetraen-1-yl, cyclo-tetradeca-1, 5,11-tetraen-1-yl, cyclo-tetradeca-1,5,12-tetraen-1-yl, cyclotetradeca-1,5,13-tetraen- 1-yl, cyclotetradeca-1, 6,8-tetraen-1-yl, cyclo-tetradeca-1,6,9-tetraen-1-yl, cyclo-tetradeca-1,6,10-tetraen-1-yl, cyclotetradeca-1, 6,11-tetraen-1-yl, cyclo-tetradeca-1,6,12-tetraen-1-yl, cyclo-tetradeca-1,6,13-tetraen-1-yl, cyclo-tetradeca-1,7,9-tetraen-1 - ilo, cyclotetradeca-1, 7,10-tetraen-1-yl, cyclotetradeca-1, 7,11-tetraen-1-yl, cyclotetradeca-1, 7,12-tetraen-1-yl, cyclotetradeca-1,7, 13-tetraen-1-yl, cyclo-tetradeca-1,8,10-tetraen-1-yl, cyclotetradeca-1, 8,11-tetra-1-yl, cyclotetradeca-1, 8, 12-tetraen-1-yl, cyclo-tetradeca-1, 8,13-tetraen-1-yl, cyclo-tetradeca-1, 9,11-tetraen-1-yl, cyclo-tetradeca-1,9,12-tetraen-1-yl, cyclo-tetradeca-1,9,13- tetraen-1-yl, cyclo-tetradeca-1,10,12-tetraen-1-yl, cyclotetradeca-1 , 10,13-tetraen-1-yl, cyclotetradeca-1, 11,13-tetraen-1-yl, cyclotetradeca-2,4,6-tetraen-1-yl, cyclotetradeca-2,4,7-tetraen-1 -yl, cyclo-tetradeca-2,4,8-tetraen-1-yl, cyclo-tetradeca-2,4,9-tetraen-1-yl, cyclo-tetradeca-2,4,10-tetraen-1-yl, cyclo-tetradeca-2,4 , 11-tetra-1-yl, cyclo-tetradeca-2,4, 12-tetraen-1-yl, cyclo-tetradeca-2,4,13-tetraen-1-yl, cyclo-tetradeca-2,5,7-tetraen-1-yl , cyclotetradeca-2,5,8-tetraen-1-yl, cyclotetradeca-2,5,9-tetraen-1-ylo, cyclotetradeca-2,5,10-tetraen-1-yl, cyclotetradeca-2,5,11 -tetraen-1-yl, cyclotetradeca-2,5,12-tetraen-1-yl, cyclotetradeca-2,5,13-tetraen-1-yl, cyclo-tetradeca-2,6,8-tetraen-1-yl, cyclotetradeca -2,6,9-tetraen-1-yl, cyclo-tetradeca-2,6,10-tetraen-1-yl, cyclo-tetradeca-2,6,11-tetraen-1-yl, cyclo-tetradeca-2,6,12-tetraen -1-yl cyclo-tetradeca-2,6,13-tetraen-1-yl, cyclo-tetradeca-2,7,9-tetraen-1-yl, cyclo-tetradeca-2,7,10-tetraen-1-yl, cyclotetradeca-2, 7,11-tetraen-1-yl, cyclotetradeca-2,7,12-tetraen-1-yl, cyclotetradeca- 2,7,13-tetraen-1-yl, cyclo-tetradeca-2,8,10-tetraen-1-yl, cyclotetradeca-2, 8,11-tetraen-1-yl, cyclotetradeca-2,8,12-tetraen-1-yl, cyclotetradeca-2,8,13-tetraen-1-yl, cyclotetradeca-2,9,11-tetraen-1 -yl, cyclotetradeca-2,9,12-tetraen-1-yl, cyclotetradeca-2,9,13-tetraen-1-yl, cyclotetradeca-2,10,12-tetraen-1-yl, cyclotetradeca-2,10 , 13-tetraen-1-yl, cyclotetradeca-2,11,13-tetraen-1-yl, cyclotetradeca-3,5,7-tetraen-1-yl, cyclotetradeca-3,5,8-tetraen-1-yl , cyclotetradeca-3,5,9-tetraen-1-yl, cyclotetradeca-3,5,10-tetraen-1-yl, cyclotetradeca-3,5,11-tetraen-1-yl, cyclotetradeca-3,5,12 -tetraen-1-yl, cyclo-tetradeca-3,6,8-tetraen-1-yl, cyclo-tetradeca-3,6,9-tetraen-1-yl, cyclo-tetradeca-3,6,10-tetraen-1-yl, cyclotetradeca -3,6,11-tetraen-1-yl, cyclo-tetradeca-3,6,12-tetraen-1-yl, cyclo-tetradeca-3,7,9-tetraen-1-yl, cyclo-tetradeca-3,7,10-tetraen -1-yl, cyclo-tetradeca-3,7,11-tetraen-1-yl, cyclo-tetradeca-3,7,12-tetraen-1-yl, cyclo-tetradeca-3,8,10-tetraen-1-yl, cyclotetradeca-3 , 8,11-tetraen-1-yl, cyclotetradeca-3,9,11-tetraen-1-yl, cyclo-tetradeca-4,6, 8-tetraen-1-yl, cyclo-tetradeca-4,6,9-tetraen-1-yl, cyclo-tetradeca-4,6,10-tetraen-1-yl, cyclo-tetradeca-4,6,11-tetraen-1-yl, cyclo-tetradeca-4,7,9-tetraen-1-yl, cyclotetradeca-4,7,10-tetraen-1-yl, cyclotetradeca-4,7,11-tetraen-1-yl, cyclotetradeca-4,8,10- tetraen-1-yl, cyclo-tetradeca-1,3,5,7-tetraen-1-yl, cyclo-tetradeca-1,3,5,8-tetraen-1-yl, cyclotetradeca-1, 3,5,9-tetraen- 1-yl, cyclotetradeca-1, 3,5,10-tetraen-1-ylo, cyclo-tetradeca-1,3,5,11-tetraen-1-yl, cyclotetradeca-1,3,5,12-tetraen-1 -yl, cyclo-tetradeca-1,3,5,13-tetraen-1-yl, cyclo-tetradeca-1,3,6,8-tetraen-1-yl, cyclo-tetradeca-1,3,6,9-tetraen-1-yl , cyclotetradeca-1, 3,6,10-tetraen-1-yl, cyclotetradeca-1, 3,6,11-tetraen-1-yl, cyclotetradeca-1, 3,6,12-tetraen-1-yl, cyclotetradeca -1,3,6,13-tetraen-1-yl, cyclo-tetradeca-1,3,7,9-tetraen-1-yl, cyclo-tetradeca-1,3,7,10-tetraen-1-yl, cyclotetradeca-1 , 3,7,11-tetraen-1-yl, cyclo-tetradeca-1,3,7,12-tetraen-1-yl, cyclo-tetradeca-1,3,7,13-tetraen-1-yl, cyclotetradeca-1,3 , 8,10 -tetraen-1-yl, cyclotetradeca-1, 3,8,11-tetraen-1-yl, cyclotetradeca-1, 3,8,12-tetraen-1-yl, cyclo-tetradeca-1,3,8,13-tetraen -1-yl, cyclotetradeca- 1, 3,9,11-tetraen-1-yl, cyclo-tetradeca-1, 3,9,12-tetraen-1-yl, cyclo-tetradeca-1, 3,9,13-tetraen-1 -yl, cyclo-tetradeca-1, 3,10,12-tetraen-1-yl, cyclo-tetradeca-1,3,10,13-tetraen-1-yl, cyclo-tetradeca-1,3,11,13-tetraen-1-yl , cyclo-tetradeca-1, 4,6,8-tetraen-1-yl, cyclo-tetradeca-1, 4,6,9-tetraen-1-yl, cyclotetradeca-1, 4,6,10-tetraen-1-yl, cyclo-tetradeca-1,4,6,11-tetraen-1-yl, cyclo-tetradeca-1,4,6,12-tetraen-1-yl, cyclo-tetradeca-1,4,6,13-tetraen-1-yl, cyclotetradeca- 1,4,7,9-tetraen-1-yl, cyclo-tetradeca-1,4,7,10-tetraen-1-yl, cyclo-tetradeca-1,4, 7,11-tetraen-1-yl, cyclotetradeca- 1, 4, 7, 12-tetraen-1-yl, cyclotetradeca-1, 4,7,13-tetraen-1-yl, cyclotetradeca-1, 4,8,10-tetraen-1-yl, cyclotetradeca-1, 4, 8,11-tetraen-1-yl, cyclotetradeca-1, 4,8,12-tetraen-1-yl, cyclotetradeca-1, 4,8,13-tetraen-1-yl, cyclo-tetradeca-1,4,9, eleven -tetraen-1-yl, cyclo-tetradeca-1,4,9,12-tetraen-1-yl, cyclo-tetradeca-1,4,9,13-tetraen-1-yl, cyclo-tetradeca-1,4,10,12-tetraen -1-yl, cyclo-tetradeca-1,4, 10,13-tetraen-1-yl, cyclo-tetradeca-1, 4,11, 13-tetraen-1-yl, cyclo-tetradeca-1, 5,7,9-tetraen-1 -yl, cyclotetradeca-1, 5,7,10-tetraen-1-yl, cyclo-tetradeca-1,5,7,11-tetraen-1-yl, cyclo-tetradeca-1,5,7,12-tetraen-1-yl , cyclo-tetradeca-1,5,7,13-tetraen-1-yl, cyclo-tetradeca-1, 5,8,10-tetraen-1-yl, cyclotetradeca-1, 5,8,11-tetraen-1-yl, cyclotetradeca -1,5,8,12-tetraen-1-yl, cyclo-tetradeca-1,5,8,13-tetraen-1-yl, cyclo-tetradeca-1, 5,9,11-tetraen-1-yl, cyclotetradeca-1 , 5,9,12-tetraen-1-yl, cyclotetradeca- 1,5, 9, 13-tetraen-1-yl, cyclo-tetradeca-1,5,10,12-tetraen-1-yl, cyclotetradeca-1,5 , 10,13-tetraen-1-yl, cyclo-tetradeca-1,5,11,13-tetraen-1-yl, cyclo-tetradeca-1,6,8,10-tetraen-1-yl, cyclo-tetradeca-1,6,8 , 11-tetraen-1-yl, cyclotetradeca-1, 6,8,12-tetraen-1-yl, cyclotetradeca-1, 6,8,13-tetraen-1-yl, cyclotetradeca-1,6,9,11 -tetr aen-1-ilo, cyclo-tetradeca-1,6,9,12-tetraen-1-yl, cyclo-tetradeca-1,6,9,13-tetraen-1-yl, cyclo-tetradeca-1,6,10,12-tetraen-1-yl, cyclotetradeca -1,6,10,13-tetraen-1-yl, cyclo-tetradeca-1, 6, 11, 13-tetraen-1-yl, cyclo-tetradeca-1,7,9,11-tetraen-1-yl, cyclotetradeca-1 , 7,9,12-tetraen-1-yl, cyclo-tetradeca-1,7,9,13-tetraen-1-yl, cyclo-tetradeca-1,7,10,12-tetraen-1-yl, cyclotetradeca-1,7 , 10,13-tetraen-1-yl, cyclo-tetradeca-1,7,11,13-tetraen-1-yl, cyclo-tetradeca-1,8,10,12-tetraen-1-yl, cyclotetradeca-1, 8,10 , 13-tetraen-1-yl, cyclotetradeca-1, 8,11,13-tetraen-1-yl, cyclotetradeca-2,4,6,8-tetraen-1-yl, cyclotetradeca-2,4,6,9 -tetraen-1-yl, cyclo-tetradeca-2,4,6,10-tetraen-1-yl, cyclo-tetradeca-2,4,6,11-tetraen-1-yl, cyclo-tetradeca-2,4,6,12-tetraen -1-yl, cyclo-tetradeca-2,4,6,13-tetraen-1-yl, cyclo-tetradeca-2,4,7,9-tetraen-1-yl, cyclo-tetradeca-2,4,7,10-tetraen-1 -yl, cyclo-tetradeca-2,4,7,11-tetraen-1-yl, cyclo-tetradeca-2,4,7,12-tetraen-1-yl, cyclo-tetradeca-2,4,7,13-tetraen-1-yl , cyclotet Radeca-2,4,8,10-tetraen-1-yl, cyclo-tetradeca-2,4,8,11-tetraen-1-yl, cyclo-tetradeca-2,4,8,12-tetraen-1-yl, cyclotetradeca- 2,4,8,13-tetraen-1-yl, cyclo-tetradeca-2,4,9,11-tetraen-1-yl, cyclo-tetradeca-2,4,9, 12-tetraen-1-yl, cyclotetradeca-2, 4,9,13-tetraen-1-yl, cyclo-tetradeca-2,4,10,12-tetraen-1-yl, cyclo-tetradeca-2,4,10,13-tetraen-1-yl, cyclo-tetradeca-2,4, 11,13-tetraen-1-yl, cyclotetradeca-2,5,7,9-tetraen-1-yl, cyclotetradeca-2,5,7,10-tetraen-1-yl, cyclotetradeca-2,5,7, 11-tetraen-1-yl, cyclotetradeca-2,5,7,12-tetraen-1-yl, cyclotetradeca-2,5,7,13-tetraen-1-yl, cyclotetradeca-2,5,8,10- tetraen-1-yl, cyclotetradeca-2,5,8,11-tetraen-1-yl, cyclo-tetradeca-2,5,8,12-tetraen-1-yl, cyclotetradeca-2,5,8,13-tetraen- 1-yl, cyclotetradeca-2,5,9,11-tetraen-1-yl, cyclo-tetradeca-2,5,9, 12-tetraen-1-yl, cyclotetradeca-2,5,9,13-tetraen-1- ilo, cyclotetradeca-2,5, 10, 12-tetraen-1-yl, cyclotetradeca-2,5, 10,13-tetraen-1-yl, cyclotetradeca-2,6,8,10-tetraen-1-yl, Cyclotetradeca-2,6,8 , 11-tetraen-1-yl, cyclo-tetradeca-2,6,8,12-tetraen-1-yl, cyclo-tetradeca-2,6,8,13-tetraen-1-yl, cyclo-tetradeca-2,6,9,11 -tetraen-1-yl, cyclo-tetradeca-2,6,9,12-tetraen-1-yl, cyclo-tetradeca-2,6,9, 13-tetraen-1-yl, cyclo-tetradeca-2,6,10,12-tetraen -1-yl, cyclo-tetradeca-2,6,10,13-tetraen-1-yl, cyclo-tetradeca-2, 6,11,13-tetraen-1-yl, cyclo-tetradeca-2,7,9,11-tetraen-1 -yl, cyclo-tetradeca-2,7,9, 12-tetraen-1-yl, cyclo-tetradeca-2,7,10,12-tetraen-1-yl, cyclo-tetradeca-3,5,7,9-tetraen-1-yl , cyclotetradeca-3,5,7,10-tetraen-1-yl, cyclotetradeca-3,5,7,11-tetraen-1-yl, cyclotetradeca-3,5,7,12-tetraen-1-yl, cyclotetradeca -3,5,8,10-tetraen-1-yl, cyclo-tetradeca-3,5,8,11-tetraen-1-yl, cyclo-tetradeca-3,5,8,12-tetraen-1-yl, cyclotetradeca-3 , 5,9,11-tetraen-1-yl, cyclotetradeca-3,5, 9,12-tetraen-1-yl, cyclotetradeca-3,5,10,12-tetraen-1-yl, cyclotetradeca-3,6 , 8,10-tetraen-1-yl, cyclotetradeca-3,6,8,11-tetraen-1-yl, cyclotetradeca-3,6,8,12-tetraen-1-yl, cyclotetradeca-3,7,9 , 11-tetraen-1- ilo, cyclotetradeca-1,3,5,7,9-pentaen-1-yl, cyclotetradeca-1,3,5,7,10-pentaen-1-yl, cyclotetradeca-1,3,5,7,11- pentaen-1-yl, cyclotetradeca-1, 3,5,7, 12-pentaen-1-yl, cyclotetradeca-1, 3,5,7,13-pentaen-1-yl, cyclotetra-deca-1,3, 5,8, 10-pentaen-1-yl, cyclotetradeca-1,3,5,8,11-pentaen-1-yl, cyclotetradeca- 1,3, 5, 8, 12-pentaen-1-yl, cyclotetradeca- 1,3,5,8,13-pentaen-1-yl, cyclotetradeca-1,3,5,9,11-pentaen-1-yl, cyclotetradeca- 1,3, 5, 9,12-pentaen-1- ilo, cyclotetradeca-1, 3,5,9,13-pentaen-1-yl, cyclotetradeca-1, 3,5,10,12-pentaen-1-yl, cyclotetradeca-1,3,5,10,13- pentaen-1-yl, cyclo-tetradeca-1,3, 5,11,13-pentaen-1-yl, cyclotetradeca-1, 3,6,8, 10-pentaen-1-yl, cyclo-tetradeca-1, 3,6, 8,11-pentaen-1-yl, cyclotetradeca-1,3,6,8,12-pentaen-1-yl, cyclotetradeca-1,3,6,8,13-pentaen-1-yl, cyclotetradeca-1, 3,6,9,11-pentaen-1-yl, cyclo-tetradeca-1,3, 6, 9, 12-pentaen-1-yl, cyclo-tetradeca-1,3, 6, 9, 13-pentaen-1-yl, cyclo-tetradeca-1,3,7,9,11-pentaen-1-yl, cyclo-tetradeca-1, 3 , 7, 9,12-pentaen-1-yl, cyclotetradeca-1,3, 7, 9, 13-pentaen-1-yl, cyclo-tetradeca-1,4,6,8,10-pentaen-1-yl, cyclotetradeca-1 , 4,6,8,11-pentaen-1-yl, cyclo-tetradeca- 1,4, 6, 8, 12-pentaen-1-yl, cidotetradeca-1,4,6,8,13-pentaen-1-yl , cycotetradeca-1,4,6,9,11-pentaen-1-iio, cyclotetradeca- 1,4, 6, 9, 12-pentaen-1-yl, cyclotetradeca-1,4,6,9,13-pentaen -1-yl, cyclotetradeca-1,4,7,9,11-pentaen-1-yl, cyclotetradeca-1, 4,7,9,12-pentaen-1-yl, cyclotetradeca-1, 4,7,9 , 13-pentaen-1-yl, cyclotetradeca-1,5,7,9,11-pentaen-1-yl, cyclotetradeca- 1,5, 7, 9, 12-pentaen-1-yl, cyclotetradeca- 1,5 , 7, 9,13-pentaen-1-yl, cyclotetradeca-2,4,6,8,10-pentaen-1-yl, cyclootetradeca-2,4,6,8,11-pentaen-1-yl, cyclotetradeca -2,4,6,8,12-pentaen-1-yl, cyclo-tetradeca-2,4,6,8,13-pentaen-1-yl, cyclo-tetradeca-2,4,6,9,11-pentaen-1 -yl, cyclo-tetradeca-2,4,6,9,12-pentaen-1-yl, cyclo-tetradeca-2,4,6,9,13-pentaen-1-yl, cyclotetradeca-2,4,6,10,12 -pentaen-1-yl, cyclotetradeca- 2,4,6, 10,13-pentaen-1-yl, cyclotet Radeca-2,4,6,11,13-pentaen-1-yl, cyclootetradeca-2,4,7,9,11-pentaen-1-yl, cyclotétradeca-2,4,7,9,12-pentaen- 1-yl, cyclo-tetradeca-2,4,7,9,13-pentaen-1-yl, cyclo-tetradeca-2,4,7,10,12-pentaen-1-yl, cyclo-tetradeca- 2,4,7, 10, 13-pentaen-1-yl, cyclo-tetradeca-2,4,7,11,13-pentaen-1-yl, cyclo-tetradeca-2,4,8,10,12-pentaen-1-yl, cyclo-tetradeca-2,4, 8, 10,13-pentaen-1-yl, cyclotetradeca-2,5,7,9,11-pentaen-1-yl, cyclotetradeca-2,5,7,9,12-pentaen-1-yl, cyclotetradeca- 2,5,7,9,13-pentaen-1-yl, cyclotetradeca-2,5,7,10,12-pentaen-1-yl, cyclotetradeca-2,5,7,10,13-pentaen-1- ilo, cyclotetradeca- 1,3,5,7,9,11-hexaen-1-yl, cyclotetradeca- 1,3, 5, 7, 9, 12-hexaen-1-yl, cyclotetradeca-1, 3,5, 7,9,13-hexaen-1-yl, cyclotetradeca- 2,4,6,8, 10,12-hexaen-1-yl, cyclootetradeca-2,4,6,8,10,13-hexaen-1- ilo, cyclotetradeca-2,4,6,8,11,13-hexaen-1-yl and cyclootetradeca-1,3,5,7,9,11,13-heptaen-1-yl. The term "C3 cycloalkyl", as used in the present invention, means cycloprop-1-yl. The term "C4 cycloalkyl", as used in the present invention, means cyclobut-1-yl. The term "C5 cycloalkyl", as used in the present invention, means cyclopent-1-yl. The term "Ce cycloalkyl", as used in the present invention, means cyclohex-1-yl. The term "C-cycloalkyl", as used in the present invention, means bicyclo [2.2.1] -hept-1-yl, bicyclo [2.2.1] -hept-2-yl, cycloheptyl-1-yl, bicyclo [2.2.1] -hept-7-yl and cyclohept-1-yl. The term "C8 cycloalkyl", as used in the present invention, means bicyclo [2.2.2] -oct-1-yl, bicyclo [2.2.2] -oct-2-yl, bicyclo [2.2.2] -oct-7-yl, cyclo-oct-1-yl. The term "Cg cycloalkyl", as used in the present invention, means cyclonon-1-yl. The term "C10 cycloalkyl", as used in the present invention, means adamant-1-yl, adamant-2-yl and cyclodec-1-yl. The term "Cu cycloalkyl", as used in the present invention, means cycloundec-1-yl, tricyclo [4.3.1.13,8] -undec-1-yl (homoadamant-1-yl), tricyclo [4.3. 1 .13 d] -undec-2-yl (homoadamant-2-yl), tricyclo [4.3.1. 13.8] -undec-3-yl (homoadamant-3-yl), tricycle [4.3.1.13,8 ] -undec-4-yl (homoadamant-4-yl), and tricyclo [4.3.1. 13.8] -undec-9-yl (homoadamant-9-yl). The term "C? 2 cycloalkyl", as used in the present invention, means cyclododec-1-yl. The term "C13 cycloalkyl", as used in the present invention, means cyclotridec-1-yl. The term "C? 4 cycloalkyl", as used in the present invention, means cyclootetradec-1-yl. The term "C2 spiroalkenyl", as used in the present invention, means ethen-1,2-ylene, of which both ends replace hydrogen atoms of the same CH2 portion.

The term "C3 spiroalkenyl", as used in the present invention, means prop-1-en-1,3-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C4 spiroalkenyl", as used in the present invention, means but-1-en-1,4-ylene, but-2-en-1,4-ylene and buta-1,3-diene. 1,4-ilene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C5 spiroalkenyl", as used in the present invention, means pent-1-en-1,5-yl-ene, pent-2-en-1,5-ylene, penta-1, 3- dien-1,5-ylene and penta-1,4-dien-1,5-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C6 spiroalkenyl", as used in the present invention, means hex-1-en-1,6-ylene, hex-2-en-1,6-ylene, hexa-1,3-diene. 1,6-ylene, hexa-1,4-di-en-1,6-ylene and hexa-1,3,5-trien-1,6-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C7 spiroalkenyl", as used in the present invention, means hept-1-en-1,7-yl-ene, hept-2-en-1,7-ylene, hept-3-en- 1,7-ylene, hepta-1,3-diene-1,7-ylene, hepta-1,4-diene-1,7-ylene, hepta-1,5-diene-1,7-ylene, hepta- 2,4-dien-1,7-ylene, hepta-2,5-dien-1,7-ylene, hepta-1,3,5-trie-1,7-ylene and hepta-1,3,6- trie-1,7-ileno, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C8 spiroalkenyl", as used in the present invention, means oct-1-en-1,8-ylene, oct-2-en-1,8-ylene, oct-3-en-1, 8-ylene, octa-1,3-diene-1,8-ylene, octa-1,4-diene-1,8-ylene, octa-1,5-diene-1,8-ylene, octa-1, 6-diene-1,8-ylene, octa-2,4-diene-1, 8-ylene, octa-2,5-diene-1, 8-ylene, octa-3,5-diene-1, 8- Ilene, octa-1,3,5-trie-1,8-ylene, octa-1,3,6-trie-1,8-ylene and octa-2,4,6-tri-en-1,8- ileno, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C9 spiroalkenyl", as used in the present invention, means nona-1-en-1,9-yl-ene, nona-2-en-1,9-ylene, nona-3-en- 1,9-ylene, nona-4-en-1,9-ylene, nona-1,3-diene-1,9-ylene, nona-1,4-dien-1,9-ylene, nona-1, 5-dien-1,9-ylene, nona-1,6-dien-1,9-ylene, nona-1,7-dien-1,9-ylene, nona-1,8-dien-1,9- Ilene, nona-2,4-dien-1, 9-ylene, nona-2,5-dien-1, 9-ylene, nona-2,6-diene-1,9-ylene, nona-2,7- dien-1,9-ylene, nona-3,5-diene-1,9-ylene, nona-3,6-diene-1,9-ylene, nona-4,6-diene-1,9-ylene, nona-1,3,5-trie-1,9-ylene, nona-1,3,6-trien-1,9-ylene, nona-1,3,7-trie-1, 9-ylene, nona- 1,3,8-trien-1,9-ylene, nona-1,4,6-trie-1,9-yl-ene, nona-1,4,7-trien-1, 9-ylene, nona- 1, 4,8-trie-1, 9-ylene, nona-1, 5,7-trien-1, 9-amino, nona-2,4,6-trie-1,9-ylene, nona-2, 4,7-trien-1, 9-ylene, nona-1, 3,5,7-tetraen-1,9-ylene, nona-1,3,5,8-tetraen-1,9-ylene and nona- 1, 3,6,9-tetraen-1,9-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C2 spiroalkyl", as used in the present invention, means et-1,2-ylene, of which both ends replace hydrogen atoms of the same CH2 portion.

The term "C3 spiroalkyl", as used in the present invention, means prop-1,3-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C4 spiroalkyl", as used in the present invention, means but-1,4-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C5 spiroalkyl", as used in the present invention, means pent-1, 5-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "Ce spiroalkyl", as used in the present invention, means hex-1,6-ylene, of which both ends replace hydrogen atoms of the same CH 2 portion. The term "C7 spiroalkyl", as used in the present invention, means hept-1, 7-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "C8 spiroalkyl", as used in the present invention, means oct-1, 8-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The term "Cg spiroalkyl", as used in the present invention, means non-1, 9-ylene, of which both ends replace hydrogen atoms of the same CH2 portion. The compounds of this invention contain asymmetrically substituted carbon atoms in the R or S configuration, in which the terms "R" and "S" are as defined by the IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Puree, Appl. Chem. (1976) 45, 13-10. Compounds having asymmetrically substituted carbon atoms with equal amounts of the R and S configurations are racemic at said carbon atoms. Atoms with an excess of one configuration with respect to the other are assigned the configuration present in the highest amount, preferably an excess of about 85% -90%, more preferred an excess of about 95% -99%, and even more preferred an excess greater than about 99%. Accordingly, this invention includes racemic mixtures, relative and absolute stereoisomers, and mixtures of relative and absolute stereoisomers. The compounds of this invention may also contain carbon-carbon double bonds or carbon-nitrogen double bonds in the Z or E configuration, in which the term "Z" represents the two largest substituents on the same side of a carbon-double bond. carbon or carbon-nitrogen and the term "E" represents the two largest substituents on opposite sides of a carbon-carbon or carbon-nitrogen double bond. The compounds may also exist in an equilibrium mixture of the Z or E configurations. The compounds of this invention which contain NH, C (0) OH, OH or SH portions may have attached to the same prodrug-forming portions. The prodrug forming portions are eliminated by metabolic processes and release the compounds having the hydroxyl, amino or carboxylic acid released in vivo. Prodrugs are useful for adjusting pharmacokinetic properties of compounds such as solubility and / or hydrophobicity, absorption in the gastrointestinal tract, bioavailability, tissue penetration and clearance rate. The metabolites of the compounds having the formula (I), which are produced by in vitro or in vivo metabolic procedures, may also have utility for treating diseases associated with the expression of a member of the anti-apoptotic protein family such as of the BCI-X protein, and the Bcl-2 protein or the Bcl-w protein. Some precursor compounds that can be metabolized in vitro or in vivo to form compounds having the formula (I) may also have utility for treating diseases associated with the expression of a member of the anti-apoptotic protein family such as the BC protein. I-XL, and the BcI-2 protein or the Bcl-w protein. The compounds having the formula (I) can exist as acid addition salts, basic addition salts or zwitterions. The salts of the compounds are prepared during their isolation or after their purification. The acid addition salts of the compounds are those which are obtained from the reaction of the compounds with an acid. For example, acetate, adipate, alginate, bicarbonate, citrate, aspartate, benzoate, benzene sulfonate, bisulfate, butyrate camphorate, camphor sulfonate, digluconate, formate, glycerophosphate fumarate, glutamate, hemisulfate, heptanoate, hexanoate hydrochloride, hydrobromide, and hydroiodide salts are contemplated , lactobionate, lactate, mesitylene sulphonate maleate, methanesulfonate, naphthylene sulfonate, nicotinate oxalate, pamoate, pectinate, persulfate, phosphate, picrate propionate, succinate, tartrate, thiocyanate, trichloroacetic trifluoroacetic, para-toluenesulfonate, and undecanoate of the compounds and prodrugs of the they are encompassed by this invention. The basic addition salts of the compounds are those that are obtained from the reaction of the compounds with the hydroxide, carbonate or bicarbonate of cations such as lithium, sodium, potassium, calcium, and magnesium. The compounds having the formula (I) can be administered, for example, orally, ophthalmicly, orally, osmotically, parenterally (intramuscularly, intraperitoneally, intra-sternum, intravenously, subcutaneously), rectally, topically, transdermally or vaginally. Therapeutically effective amounts of the compounds having the formula (I) depending on the treatment recipient, the disorder being treated and the severity thereof, the composition containing them, the time of administration, the route of administration, the duration of treatment, its potency, its rate of elimination and whether or not another drug is administered altogether. The amount of a compound of this invention having the formula (I) used to make a composition to be administered daily to a patient in a single dose or in divided doses is from about 0.03 to about 200 mg / kg of body weight. . Individual dose compositions contain these amounts or a combination of sub-multiples thereof. The compounds having the formula (I) can be administered with or without an excipient. The excipients include, for example, materials or additives for encapsulation such as absorption accelerators, antioxidants, binders, pH regulators, coating agents, coloring agents, diluents, disintegrating agents, emulsifiers, extenders, fillers, flavoring agents, humectants. , lubricants, perfumes, preservatives, propellants, release agents, sterilization agents, ulcorants, solubilizing agents, wetting agents and mixtures thereof. The excipients for the preparation of compositions comprising a compound having the formula (I) to be administered orally in solid dosage form include, for example, agar, alginic acid, aluminum hydroxide, benzyl alcohol, benzyl benzoate. , 1, 3-butylene glycol, carbomers, castor oil, cellulose, cellulose acetate, cocoa butter, corn starch, corn oil, cottonseed oil, cross-linked povidone, diglycerides, ethanol, ethylcellulose, laurel ethyl, ethyl oleate, fatty acid esters, gelatin, germ oil, glucose, glycerol, peanut oil, hydroxypropylmethylcellulose, isopropanol, isotonic saline, lactose, magnesium hydroxide, magnesium stearate, malt, mannitol, monoglycerides, olive oil, peanut oil, potassium phosphate salts, potato starch, povidone, propylene glycol, Ringer's solution, safflower oil, sesame oil, carboxymethylcell sodium sulphate, sodium phosphate salts, sodium lauryl sulfate, sodium sorbitol, soybean oil, stearic acids, stearyl fumarate, sucrose, surfactants, talc, tragacanth, tetrahydrofurfuryl alcohol, triglycerides, water, and mixtures thereof. The excipients for the preparation of compositions comprising a compound of this invention having the formula (I) to be administered ophthalmic or orally in liquid dosage forms include, for example, 1,3-butylene glycol, castor oil. , corn oil, cottonseed oil, ethanol, sorbitan fatty acid esters, germ oil, peanut oil, glycerol, isopropanol, olive oil, polyethylene glycols, propylene glycol, sesame oil, water and mixtures thereof . The excipients for the preparation of compositions comprising a compound of this invention having the formula (I) to be administered osmotically include, for example, chlorofluorohydrocarbons, ethanol, water and mixtures thereof. The excipients for the preparation of compositions comprising a compound of this invention having the formula (I) to be administered parenterally include, for example, 1,3-butanediol, castor oil, corn oil, cottonseed oil, dextrose, germ oil, peanut oil, liposomes, oleic acid, olive oil, peanut oil, Ringer's solution, safflower oil, sesame oil, soybean oil, sodium chloride solution U. S. P. or isotonic, water and mixtures thereof. The excipients for the preparation of compositions comprising a compound of this invention having the formula (I) to be administered rectally or vaginally include, for example, cocoa butter, polyethylene glycol, wax and mixtures thereof. Compounds having the formula (I) may also be administered with one or more than one additional therapeutic agents, in which the additional therapeutic agents include agents for radiation or chemotherapeutics, in which the chemotherapeutic agents include, but are not limit to, carboplatin, cisplatin, cyclophosphamide, dacarbazine, dexamethasone, docetaxel, doxorubicin, etoposide, fludarabine, irinotecan, CHOP (C: Cytoxan® (cyclophosphamide); H: Adiamycin® (hid roxidoxorrubicin); O: Vincristine (Oncovin®); P: prednisone), paclitaxel, rapamycin, Rituxin® (rituximab) and vincristine. To determine the utility of the compounds having the formula (I) as inhibitors of anti-apoptotic Bcl-XL activity, the representative examples in DMSO at concentrations between 1 00 μM and 1 pM are added to each well of a plaque of micro-titration of 96 cavities. A mixture that makes a total of 125 μl is agitated per cavity of buffer for testing (20 mM phosphate buffer, pH 7.4), 1 mM EDTA, 50 mM NaCl, 0.05% PF-68), 30 nM of Bcl-X protein (which is prepared as described in Science 1997, 275, 983-986), 15 nM of fluorescein-labeled BAD peptide (which is prepared in the laboratory itself), and the solution in DMSO of the example for 2 minutes then it is placed in an LJL Analyst device (LJL Bio Systems, CA). A negative control is used (DMSO, 15 nM of BAD peptide, regulatory solution for testing) and a positive control (DMSO, 15 nM of BAD peptide, 30 nM of Bcl-XL protein, buffer for testing) to determine the range of the proof. Polarization is measured at 25 ° C with a continuous fluorescein lamp (excitation 485 nm, emission 530 nm). The percent inhibition is determined by (1 - ((mP value of the negative control-cavity) / interval)) x100%. The IC50 values (concentration of the example required for 50% inhibition of BCI-XL) for the representative compounds having the formula (I), calculated using Microsoft Excel, are 3.7 nM, 5.8 nM, 6.1 nM, 6.2 nM, 6.9 nM, 7.1 nM, 7.1 nM, 7.4 nM, 7.7 nM, 7.8 nM, 7.9 nM, 8.3 nM, 8.3 nM, 8.3 nM, 8.4 nM, 8.4 nM, 8.5 nM, 8.5 nM, 8.7 nM, 8.8 nM, 9.1 nM , 9.1 nM, 9.1 nM, 9.2 nM, 9.5 nM, 9.6 nM, 9.7 nM, 9.8 nM, 9.8 nM, 9.9 nM, 9.9 nM, 9.9 nM, 10.0 nM, 10.0 nM, 10.0 nM, 10.0 nM, 10.1 nM, 10.1 nM, 10.2 nM, 10.2 nM, 10.3 nM, 10.3 nM, 10.3 nM, 10.3 nM, 10.3 nM, 10.3 nM, 10.3 nM 10.3 nM, 10.5 nM 10.6 nM, 10.6 nM, 10.6 nM 10.6 nM, . 6 nM 10.7 nM, 10.7 nM 10.7 nM, 10.7 nM, 10.8 nM 10.8 nM, . 8 nM 10.8 nM, 10.9 nM 10.9 nM, 10.9 nM, 10.9 nM 11.0 nM, 11. 0 nM 11.0 nM, 11.0 nM 11.0 nM, 11.1 nM, 11.1 nM 11.1 nM, 11. 1 nM 11.1 nM, 11.1 nM 11.1 nM, 11.1 nM, 11.1 nM 11.2 nM, 11. 2 nM 11.2 nM, 11.2 nM 11.2 nM, 11.2 nM, 11.2 nM 11.3 nM, 11. 3 nM 11.3 nM, 11.3 nM 11.4 nM, 11.5 nM, 11.5 nM 11.5 nM, 11. 5 nM 11.5 nM, 11.6 nM 11.6 nM, 11.6 nM, 11.6 nM 11.6 nM, 11. 6 nM 11.6 nM, 11.7 nM 11.7 nM, 11.8 nM, 11.8 nM 11.9 nM, 11. 9 nM 11.9 nM, 11.9 nM 11.9 nM, 12.1 nM, 12.1 nM 12.1 nM, 12. 2 nM 12.2 nM, 12.3 nM 12.3 nM, 12.3 nM, 12.3 nM 12.4 nM, 12. 4 nM 12.4 nM, 12.4 nM 12.5 nM, 12.5 nM, 12.5 nM 12.6 nM, 12. 6 nM 12.6 nM, 12.6 nM 12.6 nM, 12.7 nM, 12.7 nM 12.7 nM, 12.8 nM 12.8 nM, 12.8 nM 12.8 nM, 12.8 nM, 12.8 nM 12.8 nM, 12. 8 nM 12.9 nM, 12.9 nM 12.9 nM, 12.9 nM, 13.0 nM 13.0 nM, 13.1 nM 13.2 nM, 13.2 nM 13.2 nM, 13.3 nM, 13.3 nM 13.4 nM, 13.4 nM 13.5 nM, 13.5 nM 13.5 nM, 13.6 nM, 13.6 nM 13.6 nM, 13. 7 nM 13.7 nM, 13.7 nM 13.7 nM, 13.7 nM, 13.7 nM 13.8 nM, 13. 8 nM 13.8 nM, 13.8 nM 13.9 nM, 13.9 nM, 13.9 nM 13.9 nM, 13. 9 nM 13.9 nM, 13.9 nM 14.0 nM, 14.0 nM, 14.0 nM 14.0 nM, 14.1 nM 14.1 nM, 14.1 nM 14.1 nM, 14.2 nM, 14.2 nM 14.2 nM, 14. 3 nM 14.3 nM, 14.4 nM 14.4 nM, 14.4 nM, 14.5 nM 14.6 nM, 14. 6 nM 14.7 nM, 14.7 nM 14.7 nM, 14.7 nM, 14.7 nM 14.7 nM, 14. 7 nM 14.7 nM, 14.8 nM 14.8 nM, 14.8 nM, 14.9 nM 14.9 nM, 14. 9 nM 14.9 nM, 14.9 nM 15.0 nM, 15.0 nM, 15.1 nM 15.1 nM, 15.2 nM 15.2 nM 15.3 nM 15.3 nM 15.3 nM 15.3 nM 15.4 nM 15.4 nM, . 5 nM 15.5 nM 15.5 nM 15.5 nM 15.6 nM 15.6 nM 15.7 nM, 15.8 nM 15.9 nM 15.9 nM 15.9 nM 15.9 nM 15.9 nM 15.9 nM, 16. 0 nM 16.0 nM 16.0 nM 16.0 nM 16.0 nM 16.1 nM 16.1 nM, 16. 1 nM 16.1 nM 16.1 nM 16.2 nM 16.2 nM 16.4 nM 16.4 nM, 16.4 nM 16.4 nM 16.4 nM 16.5 nM 16.5 nM 16.5 nM 16.6 nM, 16. 6 nM 16.7 nM 16.8 nM 16.8 nM 16.9 nM 17.0 nM 17.0 nM, 17. 0 nM 17.1 nM 17.1 nM 17.2 nM 17.2 nM 17.3 nM 17.3 nM, 17. 3 nM 17.4 nM 17.4 nM 17.4 nM 17.5 nM 17.5 nM 17.6 nM, 17.8 nM 17.8 nM 17.8 nM 17.8 nM 17.9 nM 17.9 nM 18.1 nM, 18. 2 nM 18.2 nM 18.2 nM 18.3 nM 18.4 nM 18.4 nM 18.8 nM, 18.8 nM 18.8 nM 18.9 nM 18.9 nM 19.1 nM 19.2 nM 19.2 nM, 19. 3 nM 19.3 nM 19.4 nM 19.4 nM 19.6 nM 19.7 nM 19.7 nM, 19.8 nM 19.8 nM 19.9 nM 20.0 nM 20.2 nM 20.3 nM 20.3 nM, . 3 nM 20.3 nM 20.7 nM 20.7 nM 20.7 nM 20.8 nM 20.9 nM, 21. 4 nM 21.5 nM 21.7 nM 21.9 nM 22.0 nM 22.2 nM 22.3 nM, 22. 5 nM 22.6 nM 22.9 nM 23.2 nM 23.3 nM 23.5 nM 23.8 nM, 23.8 nM 24.4 nM 24.5 nM 25.0 nM 25.2 nM 25.6 nM 25.7, nM, . 8 nM 25.9 nM 26.1 nM 26.4 nM 26.4 nM 26.7 nM 27.7 nM, 27. 9 nM 28.3 nM 28.4 nM 28.9 nM 29.5 nM 29.6 nM 29.7 nM, 29.9 nM 30.3 nM 30.5 nM 30.9 nM 31.0 nM 31.1 nM 31.3 nM, 31. 8 nM 32.1 nM 32.2 nM 32.4 nM 33.2 nM 33.4 nM 33.7 nM, 37. 1 nM 39.3 nM 39.5 nM 40.8 nM 42.1 nM 44.6 nM 44.6 nM, 44. 9 nM 44.9 nM 45.2 nM 47.4 nM 47.5 nM 51.5 nM 51.6 nM, 53. 2 nM 55.6 nM 56.0 nM 58.3 nM 58.7 nM 58.9 nM 61.0 nM, 65.7 nM, 68.3 nM, 83.6 nM, 85.9 nM, 0.2 μM, 0.2 μM, 0.2 μM, 0.2 μM, 0.2 μM, 0.2 μM, 0.3 μM, 0.2 μM , 0.2 μM, 0.3 μM, 0.3 μM, 0.3 μM, 0.5 μM, 0.5 μM, 0.9 μM, 1.0 μM, 1.0 μM, 1.0 μM, 1.1 μM, 1.2 μM, 1.4 μM, 1.5 μM, 1.5 μM, 1.9 μM, 2.0 μM, 2.1 μM, 2.1 μM, 2.7 μM, 2.7 μM, 2.9 μM, 3.1 μM, 3.4 μM, 3.6 μM, 3.6 μM, 3.7 μM, 5.5 μM, 5.5 μM, 6.6 μM, 6.8 μM, 7.8 μM, 10.0 μM, 10.0 μM, 10.0 μM, 10.0 μM, 10.0 μM, 10.0 μM and 13.5 μM. The determination of the utility of the compounds having the formula (I) as inhibitors of anti-apoptotic Bcl-2 in 96-well micro-titration plates is also carried out. Representative examples are diluted in DMSO at concentrations between 10 μM and 10 pM and are added to each well of the plate. A mixture that makes a total of 125 μl is agitated per cavity of buffer for testing (20 mM phosphate buffer, pH 7.4), 1 mM EDTA, 50 mM NaCl, 0.05% PF-68), 10 nM of Bcl-2 protein (which is prepared as described in PNAS 2001, 98, 3012-3017), 1 nM of BAX peptide labeled with fluorescein (which is prepared in the laboratory itself), and the solution in DMSO of the example for 2 minutes and it is placed in an LJL Analyst device. Polarization is measured at 25 ° C with a continuous fluorescein lamp (excitation 485 nm; emission 530 nm). The values of K, for the representative compounds having the formula (I), calculated using Microsoft Excel, are < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < '.0 nM, < 1.0 nM; < '1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '.0 nM, < '.0 nM, < 1 .0 nM, < '1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '1.0 nM, < '.0 nM, < 1 .0 nM, < '1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '.0 nM, < '.0 nM, < 1 .0 nM, < '1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '.0 nM, < '.0 nM, < 1 .0 nM, < '1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '1.0 nM, < '.0 nM, < 1 .0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '1.0 nM, < '.0 nM, < 1 .0 nM, < - .0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '1.0 nM, < '.0 nM, < 1 .0 nM, < ".0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '1.0 nM, < '.0 nM, < 1 .0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '1.0 nM, < 'LO nM, < 1 .0 nM, < '.0 nM, < 1.0 nM; < 1.0 nM, < 1 .0 nM, < '1.0 nM, < '1.0 nM, < 1 .0 nM, < • 1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '1.0 nM, < '1.0 nM, < 1 .0 nM, < '1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < '1.0 nM, < '1.0 nM, < 1 .0 nM, < • 1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < • 1.0 nM, < '1.0 nM, < 1 .0 nM, < • 1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < • 1.0 nM, < • 1.0 nM, < 1 .0 nM, < • 1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < • 1.0 nM, < • 1.0 nM, < 1 .0 nM, < -1.0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < • 1.0 nM, < • 1.0 nM, < 1 .0 nM, < • 1.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < 1.0 nM, < '1.0 nM, < 1 .0 nM, < '1.0 nM, < 1.0 nM, < 1.0 nM, < ".0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < ".0 nM, < 1.0 nM, < 1.0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < J .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < '.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 10 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, < 0 nM, < 1 .0 nM, < 1.0 nM, < 1.0 nM, < 1.0 nM, 1.1 nM, 1.1 nM, 1.1 nM, 1.1 nM, 1.1 nM, 1.1 nM, 1. 1 nM, 1.1 nM, 1.2 nM, 1.2 nM, 1.3 nM, 1.3 nM, 1.3 nM, 1.3 nM, 1. 3 nM, 1.4 nM, 1.5 nM, 1.5 nM, 1.5 nM, 1.5 nM, 1.6 nM, 1.6 nM, 1.7 nM, 1.7 nM, 1.7 nM, 1.7 nM, 1.8 nM, 1. 8 nM, 1.8 nM, 1.8 nM, 1.9 nM, 2.0 nM, 2.0 nM, 2.2 nM, 2.3 nM, 2.4 nM, 2.5 nM, 2.5 nM, 2.6 nM, 2.6 nM, 2.9 nM, 3.0 nM, 3.1 nM, 3.5 nM, 3.7 nM, 3.9 nM, 4.0 nM , 4.0 nM, 4.0 nM, 4.2 nM, 4.4 nM, 4.5 nM, 4.6 nM, 4.7 nM, 5.8 nM, 5.9 nM, 6.0 nM, 6.2 nM, 6.5 nM, 6.7 nM, 7.0 nM, 7.2 nM, 7.7 nM, 7.8 nM, 8.0 nM, 8.1 nM, 8.4 nM, 9.4 nM, 10.4 nM, 10.4 nM, 13.1 nM, 13.6 nM, 13.8 nM, 15.2 nM, 15.7 nM, 15.9 nM, 16.2 nM, 16.9 nM, 19.7 nM, 22.5 nM , 24.4 nM, 25.4 nM, 26.9 nM, 28.9 nM, 29.1 nM, 32.4 nM, 33.0 nM, 36.5 nM, 38.0 nM, 39.7 nM, 41.7 nM, 42.9 nM, 45.7 nM, 53.9 nM, 56.2 nM, 56.6 nM, 62.3 nM, 71.6 nM, 72.9 nM, 80.4 nM, 82.4 nM, 83.4 nM, 0.09 μM, 0.09 μM, 1.0 μM, 0.12 μM, 0.12 μM, 0.15 μM and 0.30 μM.

These binding data and inhibitors demonstrate the utility of the compounds having the formula (I) as inhibitors of anti-apoptotic BCI-X protein and anti-apoptotic Bcl-2. It is expected that, because the compounds having the formula (I) bind to and inhibit the activity of BCI-X and Bcl-2, that these may also have utility as inhibitors of members of the anti-apoptotic protein family that they have close structural homology with BCI-XL and BcI-2, such as, for example, anti-apoptotic Bcl-w protein. Accordingly, it is expected that compounds having the formula (I) have utility in the treatment of diseases during which the apoptotic Bcl-X | _ protein is expressed, anti-apoptotic Bcl-2 protein, anti Bcl-w protein -Apoptotic or a combination thereof. Diseases during which members of the anti-apoptotic protein family such as Bcl-XL protein, Bcl-2 protein and Bcl-w protein are expressed include cancer and autoimmune disorders, in which cancer includes, but is not limited to, , bladder cancer, brain cancer, breast tissue cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, cancer of the esophagus, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, malignant lymphoid tumors of T cell or B cell origin, melanoma , myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer and small cell lung cancer (Cancer Res., 2000, 60, 61 01 -1 0); autoimmune disorders include, but are not limited to, acquired immunodeficiency disease syndrome, autoimmune lymphoproliferative syndrome, hemolytic anemia, inflammatory diseases, and thrombocytopenia (Current Allergy and Asthma Reports 2003,3: 378-384; Br. J. Haematol 2000 Sep; 1 1 0 (3): 584-90; Blood 2000 Feb 15; 95 (4): 1283-92 and New England Journal of Medicine 2004 Sep; 351 (14): 1409-1418). A representative compound having the formula (I), EJ EM PLO 2, presented therapeutic utility against human tumor cell lines derived from small cell lung carcinomas and malignant lymphoid tumors of both T cell and B cell origin The EJ EMPLO 2 also presented therapeutic utility against acute lymphoblastoid leukemia, small cell lung cancer, prostate cancer, non-small cell lung cancer, and follicular lymphoma tumors (RS 1 1 380, DoHH2 and SuDH L-4) in xenograft models. EJ EMPLO 2 also demonstrates anti-tumor activity in two murine models (xenograft H 146 and SCLC) from human-derived small cell lung cancer from smokers and non-smokers, defective with respect to the function of the Rb / p53 gene , and that can express moderately high levels of Bcl-2. in the H 146 model, treatment with EJ EMPLO 2 results in the complete regression of an established tumor with, in some cases, the disappearance of the tumor after prolonged therapy. EJ EMPLO 2 also prolongs survival in a systemic model of acute lymphoblastic leukemia and inhibits tumor growth in a follicular lymphoma model (DOHH-2). Therapeutic utility is also observed in a prostate cancer model. Without being limited to the theory, the genetic link between Bcl-2 and cancer comes from the observation that chromosomal transpositions t (14; 18) in B cell lymphomas lead to overexpression of the protein. The aberrant expression of Bcl-2 and BCI-XL is also seen in other malignant lymphoid tumors such as chronic lymphocytic leukemia and acute lymphocytic leukemia. EJ EM PLO 2 presents significant activity in a model of acute lymphoblastoid leukemia T-cell CCRF-CEM as well as in SuDH L4 and RS 1 1 380, two models of B-cell follicular lymphoma. CCRF-CEM which is a line of acute lymphoblastoid leukemia mutant of p53 of T-cell origin used as an animal model (mouse) of systemic leukemia involving intravenous inoculation of tumor cells. If left untreated, mice succumb to the disease within approximately 34 days after inoculation, at which time extensive tumor infiltration of the spleen, liver, and bone marrow has occurred. The administration of EJ EM P LO 2 increases the average survival of the mice and shows a significant decrease in the average weight of the spleen in relation to the vehicle controls (which indicate a lower tumor load in this organ). Subsequent histopathological evaluations reveal less tumor infiltration in both the liver and the spleen in relation to the controls. Table 1 shows the therapeutic effect of the EX EMPLO 2 on other human tumor cell lines for which the EC50 values are the effective concentrations that cause a 50% reduction in cell viability.

TABLE 1 TABLE 1 (cont.) to serum-free conditions, treatment of 48 hours b mean ± SEM (n) The therapeutic effect of paclitaxel on non-small cell lung carcinoma cells is approximately 4.4 times more effective when administered with the EJ EMPLO 2. A similar increase (4.7 fold) in efficacy against PC-3 prostate carcinoma cells is demonstrated . The enantiomer of EJ EM P LO 2 is less than effective, which indicates that the therapeutic effect of EXAMPLE 2 is the direct result of binding to anti-apoptotic Bcl-2 family proteins. The antitumor activity of EJ EMPLO 2 is equivalent to slightly better than paclitaxel near the maximum tolerated dose in a small cell lung cancer xenograft tumor model and superior to cisplatin and etoposide. In a murine model derived from PC3 of prostate cancer, EJ EMPLO 2 present approximately 40-50% inhibition of tumor growth rate. The studies pertaining to the efficacy of EJ EMPLO 2 in combination with etoposide, vincristine, modified CHOP, doxorubicin, rapamycin and Rituxin®; demonstrate that EXAMPLE 2 synergistically increases the efficacy of these cytotoxic agents during combination therapy. In particular, combinations comprising EJ EMPLO 2 and rapamycin and EJ EM PLO 2 and Rituxin® result in the complete regression of a significant percentage of follicular lymphoma tumors DoHH2 established during a sustained time interval. These data demonstrate the utility of the compounds having the formula (I) for the treatment of diseases that are caused or exaggerated by the expression of one or more than one of a member of the anti-apoptotic protein family. Also, experiments with representative Bcl-XL selective compounds demonstrate synergistic therapeutic effects with multiple chemotherapeutic agents against cell lines representative of various types of tumor. Accordingly, compounds having the formula (I) are expected to be useful as chemotherapeutic agents alone or in combination with additional therapeutic agents. The compounds having the formula (I) can be prepared using chemical synthesis methods, examples of which are shown in the present invention. It is intended that it be understood that the order of the steps in the procedures can be varied, that the reactants, solvents, and reaction conditions can be substituted for those specifically mentioned, and that the vulnerable portions can be protected and unprotected, as the case may be. necessary, by protective groups of NH, C (O) OH, OH, SH. The following abbreviations have the meanings indicated. ADDP means 1, 1 '- (azodicarbonyl) -dipiperidine; AD-mix-β means a mixture of (DHQD) 2P HAL, K3Fe (CN) 6, K2C03, and K2S04); 9-BBN means 9-borabicyclo [3.3.1] nonane; Boc means tert-butoxycarbonyl; (DHQD) 2PHAL means diethyl ether of hydroquinidin-1,4-phthalazindi-yl; DBU means 1,8-diaza-bicyclo [5.4.0] -undec-7-ene; DI BAL means di-isobutyl aluminum hydride; DI EA means di-isopropylethylamine; DMAP means N, N-dimethylaminopyridine; DM F means N, N-dimethylformamide; dmpe means 1,2-bis- (dimethylphosphino) ethane; DMSO means dimethyl sulfoxide; dppb means 1,4-bis- (diphenylphosphino) -butane; dppe means 1,2-bis- (d -iphenylphosphino) ethane; dppf means 1,1 '-bis- (diphenylphosphino) -ferrocene; dppm means 1,1-bis- (diphenylphosphino) methane; EDAC-HCl means 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride; Fmoc means fluorenylmethoxycarbonyl; HATU stands for O - ^ - azabenzotriazol-l -i-N ^ 'N'N'-tetramethyluronium hexafluorophosphate; HMPA means hexamethylphosphoramide; I PA means isopropyl alcohol; MP-BH3 means triethylammonium cyanoborohydide and macroporous methylpolystyrene; TEA means triethylamine; TFA means trifluoroacetic acid; TH F denotes tetrahydrofuran; NCS means N-chlorosuccinimide; NMM means N-methylmorpholine; N MP means N-methylpyrrolidine; PPh3 means triphenylphosphine. The term "protecting group NH", as used herein, means trichloroethoxycarbonyl, tribromoethoxycarbonyl, benzyloxycarbonyl, para-nitrobenzyl carbonyl, ortho-bromobenzyloxycarbonyl, chloroacetyl, d icloroacetilo, trichloroacetyl, trifluoroacetyl, phenylacetyl, formyl, acetyl, benzoyl, tert-amyloxycarbonyl, tert-butoxycarbonyl, para-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 4- (phenylazo) -benzyloxycarbonyl, 2-furfuryl-oxycarbonyl, diphenylmethoxycarbonyl, 1,1-dimethyl I-pro poxy- carbonyl, isopropoxycarbonyl, phthaloyl, succinyl, alanyl, leucyl, 1-adamantyloxycarbonyl, 8-quinolyloxycarbonyl, benzyl, diphenylmethyl, triphenylmethyl, 2-nitrophenylthio, methanesulfonyl, para-toluenesulfonyl, N, N-dimethylaminomethylene, benzylidene, 2-hydroxy-benzylidene, 2-hydroxy-5-chlorobenzylidene, 2-hydroxy-1-naphthyl-methylene, 3-hydroxy-4-pyridylmethylene, cyclohexylidene, 2-ethoxy-carbonyl-cyclohexylidene, 2-ethoxycarbonyl-cyclopentyl-lead, 2- acetyl-cyclohexylidene, 3,3-dimethyl-5-oxycyclohexylidene, diphenylphosphoryl, dibenzylphosphoryl, 5-methyl-2-oxo-2H-1, 3-dioxol-4-yl-methyl, trimethyl-silyl, triethylsilyl, and triphenylsilyl . The term "protecting group of C (0) OH", as used in the present invention, means methyl, ethyl, n-propyl, isopropyl, 1,1-dimethylpropyl, n-butyl, tert-butyl, phenyl, naphthyl. , benzyl, diphenylmethyl, triphenylmethyl, para-nitrobenzyl, para-methoxybenzyl, bis (p-methoxyphenyl) methyl, acetylmethyl, benzoyl-methyl, para-nitrobenzoylmethyl, para-bromobenzoylmethyl, para-metansulfonilbenzoilmetilo, 2-tetrahydropyranyl 2-Tetrah id roturan yl, 2,2,2-trichloro-ethyl, 2- (trimethylsilyl) ethyl, acetoxymethyl, propionyloxy-methyl, pivaloyloxymethyl, phthalimidomethyl, succinimidomethyl, cyclopropyl, cyclobutyl, cyclopentyl, ciciohexilo, methoxymethyl, methoxyethoxymethyl, 2- (trimethylsilyl) ethoxymethyl, benzyloxymethyl, methyl-thiomethyl, 2-methylthioethyl, phenylthiomethyl, 1,1-dimethyl-2-propenyl, 3-methyl-3-butenyl, allyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, diethylisopropylsilyl, tert-butyldimethylsilyl, tert-butyldifenylsilyl, diphenylmethylsilyl , and ter-butilm ethoxyphenylsilyl. The term "protecting group of OH or SH", as used in the present invention, means benzyloxycarbonyl, 4-nitro-benzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl , tert-butoxycarbonyl, 1,1-dimethylpropoxycarbonyl, isopropoxycarbonyl, isobutyloxycarbonyl, diphenylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2,2,2-tribromoethoxycarbonyl, 2- (trimethylsilyl) ethoxycarbonyl, 2- (phenylsulfonyl) ) ethoxycarbonyl, 2- (trifen Ifosfonio i) ethoxycarbonyl, 2-furfuryloxycarbonyl, 1 -adamantiloxicarbonilo, vinyloxycarbonyl, allyloxycarbonyl, S-benzylthiocarbonyl, 4-ethoxy-1 -naftiloxicarbonilo, 8-quinolyloxycarbonyl, acetyl, formyl, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, methoxyacetyl, phenoxyacetyl, pivaloyl, benzoyl, methyl, tert-butyl, 2,2,2-trichloroethyl, 2-trimethyl-silylethyl, 1,1-dimethyl-2-propenyl, 3-methyl-3-butenyl, allyl, benzyl (phenylmethyl), pa ra-methoxybenzyl, 3,4-dimethoxybenzyl, d ifenilmetilo, triphenylmethyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiopyranyl, methoxymethyl, methylthiomethyl, benzyloxymethyl, 2-metoxietoxim ethyl, 2,2,2-trichloro-ethoxymethyl, 2- (trimethylsilyl) ethoxymethyl 1 -etoxietilo, methanesulfonyl, para-toluenesulfonyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, dietiiisopropilsililo, tert-butyl-dimethylsilyl, tert-butild Ifen ilsililo, diphenylmethylsilyl, and tert-butylmethoxyphenylsilyl.

REACTION SCHEME 1 (i) (2) (I) Compounds having the formula (1) can be converted to compounds having the formula (2) by reacting the former, chlorosulfonic acid, and ammonia. The compounds having the formula (2) can be converted into compounds having the formula (!) By reacting the first and compounds having the formula Z1-C02H and an agent for coupling, with or without a first base. Examples of agents for coupling include EDCl, CDl, and PyBop. Examples of first bases include TEA, DI EA, DMAP, and mixtures thereof. The compounds having the formula (2) can be converted into compounds having the formula (I) by reacting the first and compounds having the formula Z1-COCI and the first base.

REACTION SCHEME 2 The compounds having the formula (4) can be converted into compounds having the formula (I), in which B1 and Y together are imidazole, the former reacting sodium nitrite, hydrochloric acid, and acetic acid. Compounds having the formula (I), in which B1 and Y together are imidazole, can be reacted with a second base and the appropriate electrophile to provide compounds having the formula (I), in which B1 and Y1 together they are substituted imidazole. Examples of second bases include sodium hydride, potassium hydride, lithium diisopropylamide and sodium bis- (trimethylsilyl) amide.

REACTION SCHEME 3 (3) (4) (I) (I) The compounds having the formula (3) can be converted into compounds having the formula (4) by reacting the first one, hydrogen and a catalyst for hydrogenation. Examples of catalysts for hydrogenation include Pd on carbon, platinum on carbon, and Raney nickel. The compounds having the formula (4) can be converted into compounds having the formula (I), in which B1 and Y1 together are triazole, the former reacting sodium nitrite, hydrochloric acid, and acetic acid. The compounds having the formula (I), in which B1 and Y1 together are triazole, can be reacted with the second base and the appropriate electrophile to provide compounds having the formula (I), in which B1 and Y1 together they are substituted triazole.

EXAMPLES EXAMPLE 1 A A mixture of piperazine (1 29.2 g), ethyl 4-fluorobenzoate (84 g), and K2C03 (1 03.65 g) in DMSO (200 ml) at 120 ° C is stirred for 6 hours, poured into water, stirred for 30 minutes, and filtered.

EXAMPLE 1 B Example 1 A (200 mg) is treated in dioxane at 40 ° C (4 mL) with 2- (bromomethyl) -1,1-biphenyl (232 mg) and DI EA (165 mg) and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20% ethyl acetate / hexanes.

EXAMPLE 1C Example 1B (340 mg) in 3: 1: 1 THF / methane / water (4 mL) at 25 ° C is treated with LiOH-water (143 mg), stirred for 16 hours, and treated with 4M HCl ( 850 μl) and dichloromethane. The extract is dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20% methanol / dichloromethane.

EXAMPLE 1D Example 1C (112 mg) in dichloromethane (2.5 ml) at 25 ° C is treated with 4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide , which is prepared as described in the International Joint Application No. PCT / US01 / 29432, published as WO 02/24636, (115 mg), EDAC-HCI (109 mg), and DMAP (49 mg), is stirred for 16 hours, and concentrates. The concentrated material is subjected to flash chromatography on silica gel with 20% methanol / dichloromethane. H NMR (300 MHz, DMSO-d6) d 8.45 (d, 1H), 8.28 (d, 1H), 7.78 (dd, 1H), 7.72 (d, 2H), 7.54 (dd, 1H), 7.45-7.41 ( m, 4H), 7.40-7.28 (m, 6H), 7.25 (td, 2H), 7.17 (tt, 1H), 6.88 (d, 1H), 6.78 (d, 2H), 4.10-4.01 (m, 1H) , 3.41 (s, 2H), 3.33 (d, 2H), 3.14 (m, 4H), 2.82-2.62 (m, 2H), 2.44-2.35 (m, 10 H), 2.09-1.91 (m, 2H).

EXAMPLE 1E Example 1C (112 mg) in dichloromethane (2.5 ml) a ° C is treated with example 1D (115 mg), EDAC-HCI (109 mg), and DMAP (49 mg), stirred for 16 hours, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20% methanol / dichloromethane. 1 H NMR (300 MHz, DMSO-d 6) d 8.45 (d, 1 H), 8.28 (d, 1H), 7.78 (dd, 1H), 7.72 (d, 2H), 7.54 (dd, 1H), 7.45-7.41 (m, 4H), 7.40-7.28 (m, 6H), 7.25 (td, 2H), 7.17 (tt, 1H), 6.88 (d, 1H), 6.78 (d, 2H), 4.10-4.01 (m, 1H), 3.41 (s, 2H), 3.33 (d, 2H), 3.14 (m, 4H), 2. 82-2.62 (m, 2H), 2.44-2.35 (m, 10H), 2.09-1.91 (m, 2H).

EXAMPLE 2A A mixture of example 1A (23.43 g), 2-bromobenzyl bromide (26.24 g), and DIEA (20.94 ml) in acetonitrile (200 ml) at 25 ° C is stirred for 2 hours and filtered.

EXAMPLE 2B A mixture of example 2A (13.83 g), 4-chlorophenyl boronic acid (7.04 g), bis- (triphenylphosphine) palladium dichloride (481 mg) and 2M sodium carbonate (22.5 ml) in DME / water / ethanol 7: 3: 2 (200 ml) at 90 ° C is stirred for 4.5 hours and extracted with ethyl acetate. The extract is dried (MgSO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% -40% ethyl acetate / hexanes.

EXAMPLE 2C A mixture of example 2B (13 g) and lithium hydroxide hydrate (3.78 g) in dioxane (250 ml) and water (100 ml) at 95 ° C is stirred for 16 hours and concentrated. The material concentrated in water is heated to 80 ° C and filtered. The filtered material is treated with HCl 1M (90 mL) and filtered. 2D EXAMPLE A mixture of example 2C (3683 g), 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide (3.53 g), EDAC-HCI (3.32) g) and DMAP (2.12 g) in dichloromethane (500 ml) at 25 ° C is stirred for 8 hours, washed with saturated NH 4 Cl (330 ml), and dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 1%, 2%, 5%, 10%, and 15% methanol / dichloromethane saturated with NH3. 1 H NMR (DMSO-de) d 12.10 (br s, 1 H), 11.18 (br s, 1 H), 10.40 (br s, 1 H), 8.54 (s, 1 H), 8.29 (d, 1 H), 8.10 (br s , 1H), 7.85 (d, 1H), 7.77 (d, 2H), 7.52 (d, 4H), 7.40-7.36 (m, 2H), 7.35-7.32 (m, 1H), 7.26-7.21 (m, 2H ), 7.16-7.09 (m, 3H), 6.93 (d, 2H), 4.34 (br s, 2H), 4.35-4.23 (m, 1H), 3.88 (br s, 2H), 3.42-3.36 (m, 4H) ), 3.17-3.07 (m, 2H), 2.90-2.78 (m, 2H), 2.50 (s, 6H), 2.20-2.15 (m, 2H).

EXAMPLE 3A This example is prepared by substituting 4-methoxyphenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 3B This example is prepared by substituting example 3A for example 2B in example 2C.

EXAMPLE 3C This example is prepared by substituting example 3B for example 2C in example 2D. H NMR (400 MHz, DMSO-d6) d 12.10 (br s, 1H), 9.9 (br s, 1H), 9.57 (s, 1H), 8.54 (d, 1H), 8.29 (d, 1H), 7.86 ( dd, 1H), 7.77 (d, 2H), 7.72 (m, 1H), 7.50 (m, 2H), 7.33 (m, 1H), 7.29 (d, 2H), 7.23 (dd, 2H), 7.18 (d , 1H), 7.11 (m, 2H), 7.03 (d, 2H), 6.93 (d, 3H), 4.36 (br s, 2H), 4.18 (m, 1H), 3.80 (br s, 2H), 3.79 ( s, 3H), 3.39 (d, 2H), 3.07 (m, 6H), 2.75 (s, 3H), 2.74 (s, 3H), 2.14 (q, 2H).

EXAMPLE 4A This example is prepared by substituting 4-fluorophenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 4B This example is prepared by substituting example 4A for example 2B in example 2C.

EXAMPLE 4C This example is prepared by substituting example 4B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (br s, 1 H), 10.00 (br s, 1 H), 9.65 (s, 1 H), 8.54 (d, 1 H), 8.29 (d, 1 H), 7.86 ( dd, 1H), 7.77 (d, 2H), 7.74 (m, 1H), 7.52 (m, 2H), 7.41 (m, 2H), 7.34 (m, 1H), 7.29 (t, 2H), 7.23 (dd) , 2H), 7.18 (d, 1H), 7.12 (m, 3H), 6.93 (d, 2H), 4.29 (br s, 4H), 4.19 (m, 1H), 3.84 (br s, 2H), 3.39 ( d, 2H), 3.13 (m, 4H), 2.92 (m, 2H), 2.74 (s, 6H), 2.15 (m, 2H).

EXAMPLE 5A This example is prepared by substituting 4- (methylsulfanyl) -phenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 5B This example is prepared by substituting example 5A for example 2B in example 2C.

EXAMPLE 5C This example is prepared by substituting example 5B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (s, 1 H), 9.9 (br s, 1 H), 9.54 (s, 1 H), 8.53 (d, 1 H), 8.27 (d, 1 H), 7.85 (dd) , 1H), 7.76 (d, 2H), 7.72 (m, 1H), 7.51 (dd, 2H), 7.33 (d, 2H), 7.31 (m, 1H), 7.29 (d, 2H), 7.21 (d, 2H), 7.16 (d, 1H), 7.10 (m, 3H), 6.92 (d, 2H), 4.32 (br s, 2H), 4.17 (m, 1H), 3.85 (br s, 4H), 3.38 (d , 2H), 3.11 (m, 5H), 2.90 (br s, 1H), 2.73 (s, 6H), 2.49 (s, 3H), 2.14 (m, 2H).

EXAMPLE 6A This example is prepared by substituting 1, 1 '-biphenyl-4-ylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 6B This example is prepared by substituting example 6A for example 2B in example 2C.

EXAMPLE 6C This example is prepared by substituting example 6B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (br s, 1 H), 9.9 (br s, 1 H), 9.56 (s, 1 H), 8.54 (d, 1 H), 8.28 (d, 1 H), 7.86 ( dd, 1H), 7.75 (m, 7H), 7.56 (m, 2H), 7.48 (m, 4H), 7.39 (m, 2H), 7.22 (dd, 2H), 7.17 (d, 1H), 7.11 (m, 3H), 6.93 ( d, 2H), 4.42 (br s, 2H), 4.18 (m, 1H), 3.83 (br s, 2H), 3.39 (d, 2H), 3.25 (br s, 2H), 3.13 (m, 4H), 2. 91 (m, 2H), 2.74 (s, 6H), 2.14 (m, 2H).

EXAMPLE 7A This example is prepared by substituting 4-phenoxyphenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 7B This example is prepared by substituting example 7A for example 2B in example 2C.

EXAMPLE 7C This example is prepared by substituting example 7B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.09 (br s, 1 H), 10.10 (br s, 1 H), 9.64 (s, 1 H), 8.55 (d, 1 H), 8.29 (d, 1 H), 7.87 ( dd, 1H), 7.78 (d, 2H), 7.73 (m, 1H), 7.51 (m, 2H), 7.38 (m, 5H), 7.23 (m, 2H), 7.14 (m, 5H), 7.07 (d , 4H), 6.95 (d, 2H), 4.33 (br s, 2H), 4.20 (m, 1H), 3.86 (br s, 2H), 3.39 (d, 2H), 3.25 (br s, 2H), 3.12 (m, 4H), 2.92 (m, 2H), 2.74 (s, 6H), 2.15 (m, 2H).

EXAMPLE 8 This example is prepared by substituting 4 - ((1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1R ) -3- (di methylamino) -1 - ((f-enylsulfonyl) methyl) ptopyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (500 MHz, DMSO-d 6) d 12.05 (br s, 1 H), 9.8 (br s, 1 H), 8.53 (s, 1 H), 8.51 (d, 1 H), 7.83 (dd, 1 H), 7.79 ( d, 2H), 7.72 (br s, 1H), 7.52 (br s, 2H), 7.47 (t, 2H), 7.41 (t, 1H), 7.36 (d, 2H), 7.35 (m, 2H), 7.26 (d, 2H), 7.01 (t, 2H), 6.93 (d, 2H), 6.92 (d, 1H), 4.32 (br s, 2H), 3.79 (br s, 2H), 3.49 (br s, 4H) , 3.14 (br s, 2H), 2.80 (br s, 2H), 1.56 (s, 6H).

EXAMPLE 9 This example is prepared by substituting 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02 / 24636, by 4 - (((1 R) -3- (dimethylamine) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (500 MHz, DMSO-d6 ) d 8.60 (d, 1H), 8.40 (d, 1H), 7.89 (dd, 1H), 7.79 (d, 2H), 7.64 (m, 7H), 7.62 (d, 1H), 7.31 (d, 2H) , 7.30 (d, 1H), 7.24 (dd, 2H), 7.19 (dd, 2H), 6.94 (d, 2H), 4.24 (m, 1H), 3.71 (m, 4H), 3.55 (m, 2H), 3.41 (d, 2H), 3.31 (m, 4H), 2.80 (m, 4H), 2.48 (m, 4H), 2.16 (m, 1H), 2.06 (m, 1H).

EXAMPLE 10 This example is prepared by substituting 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide), which is prepared as described in WO 02/24636, by 4 - (((1R) -3 - (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (300 MHz, DMSO-d 6) d 11.87 (br s, 1 H), 8.74 (t, 1 H), 8.58 (d, 1 H), 7.89 (dd, 1 H), 7.72 (d, 2 H), 7.55 (m , 1H), 7.38 (m, 7H), 7.26 (m, 4H), 7.17 (m, 2H), 6.89 (d, 3H), 3.66 (m, 2H), 3.47 (m, 2H), 3.26 (m, 6H), 2.41 (m, 4H).

EXAMPLE 11 This example is prepared by substituting 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.93 (s, 1 H), 8.66 (t, 1 H), 8.56 (d, 1 H), 7.89 (dd, 1 H), 7.73 (d, 2 H), 7.51 (d, 1H), 7.47 (m, 4H), 7.37 (m, 4H), 7.28 (t, 2H), 7.24 (m, 1H), 7.18 (t, 1H), 7.11 (d, 1H), 6.86 (d, 2H) ), 3.64 (q, 2H), 3.40 (s, 2H), 3.27 (q, 2H), 3.21 (m, 4H), 2.40 (m, 4H).

EXAMPLE 12 This example is prepared by substituting 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02 / 24636, by 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.07 (s, 1H), 9.98 (s, 2H), 8.55 (d, 1H), 8.30 (d, 1H), 7.87 (dd, 1H), 7.77 (d, 2H), 7.72 (br s, 1H), 7.52 (d, 4H), 7.40 (d, 2H), 7.34 (m, 1H), 7.23 (d, 2H), 7.18 (d, 1H), 7.15 (t, 2H), 7.10 (m, 1H), 6.93 (d, 2H), 4.25 (br s, 2H), 4.19 (m, 1H), 3.95 (br s, 5H), 3.63 (br s, 4H), 3.40 ( m, 4H), 3.18 (m, 4H), 3.02 (br s, 3H), 2.18 (m, 2H).

EXAMPLE 13 This example is prepared by substituting 4 - ((1,1-dimethyl-2- (phenylsulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1R ) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzene-sulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.06 (br s, 1 H), 9.69 (br s, 1 H), 8.53 (s, 1 H), 8.51 (d, 1 H), 7.83 (dd, 1 H), 7.80 ( d, 2H), 7. 71 (br s, 1H), 7.52 (d, 4H), 7.40 (d, 2H), 7.37 (d, 1H), 7.33 (m, 1H), 7.26 (d, 2H), 7.01 (t, 2H), 6.93 (m, 3H), 4.33 (br s, 2H), 3.73 (br s, 4H), 3.12 (br s, 4H), 2.85 (br s, 2H), 1.56 (s, 6H).

EXAMPLE 14 This example is prepared by substituting 4 - (((1R) -4- (di methylamino) -1 - ((f-enylsulfonyl) methyl) -butyl) am i no) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.07 (br s, 1H), 9.75 (br s, 1H), 9.26 (s, 1H), 8.54 (d, 1H), 8.29 (d, 1H), 7.87 ( dd, 1H), 7.77 (d, 2H), 7.74 (m, 1H), 7.52 (d, 4H), 7.39 (d, 2H), 7.34 (m, 1H), 7.23 (m, 3H), 7.11 (m , 3H), 6.93 (d, 2H), 4.30 (br s, 2H), 4.14 (m, 1H), 3.73 (br s, 6H), 3.37 (m, 2H), 3.02 (m, 4H), 2.72 ( t, 6H), 1.77 (m, 4H).

EXAMPLE 15 This example is prepared by substituting 4 - (((1R) -5- (dimethylamino) -1 - ((phenylsulfanyl) methyl) pentyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1 R) -3- (dimethylamino) -1 - ((faith or Is or Ifa n il) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.11 (s, 1 H), 10.96 (m, 1 H), 9.99 (m, 1 H), 8.52 (d, 1 H), 8.32 (d, 1 H), 8.05 (m, 1H), 7.85 (dd, 1H), 7.75 (d, 2H), 7.53 (m, 4H), 7.36 (m, 4H), 7.23 (d, 2H), 7.11 (m, 3H), 6.93 (d, 2H) ), 4.35, (m, 1H), 4.12 (m, 1H), 3.92-3.87 (m, 2H), 3.53 (m, 8H), 3.27 (m, 2H), 2.94 (m 2H), 2.69 (s, 3H), 2.68 (s, 3H), 1.76 (m, 2H), 1.62 (m, 2H), 1.36 (m, 2H).

EXAMPLE 16 This example is prepared by substituting 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02 / 24636, and in Example 4B by 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide and Example 2C, respectively, in Example 2D . 1 H NMR (400 MHz, DMSO-d 6) d 12.09 (br s, 1H), 9.93 (br s, 2H), 8.55 (d, 1H), 8.30 (d, 1H), 7.87 (dd, 1H), 7.77 (d, 2H), 7.73 (br s, 1H), 7.52 (m, 2H), 7.41 (m, 2H), 7.34 (m, 1H), 7.29 (t, 2H), 7.23 (m, 2H), 7.18 (d, 1H), 7.12 (m, 3H), 6.93 (d, 2H), 4.28 (br s, 2H), 4.21 (m, 1H), 3.95 (br s, 5H), 3.63 (br s, 4H), 3.40 (br, 3H), 3.19 (br, 4H), 3.02 (Br, 3H) ), 2.18 (m, 2H).

EXAMPLE 17A A mixture of example 1A (703 mg), 2-bromo-5-fluorobenzaldehyde (914 mg), 2.47 mmol / g of MP-BH3CN (4.05 g), and acetic acid (340 μl) in methanol / dichloromethane 1: 1 ( 30 ml) is stirred for 1 day and filtered. The filtrate is concentrated, and the concentrated material is subjected to flash chromatography on silica gel with 5-50% ethyl acetate / hexanes.

EXAMPLE 17B This example is prepared by substituting example 17A for example 2A in example 2B.

EXAMPLE 17C This example is prepared by substituting example 17B for example 2B in example 2C.

EXAMPLE 17D This example is prepared by substituting example 17C for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.09 (br s, 1H), 9.61 (br s, 1H), 8.55 (d, 1H), 8.29 (d, 1H), 7.86 (dd, 1H), 7.77 (d, 2H), 7.60 (bd, 1H), 7.52 (d, 2H), 7.37 (m, 4H), 7.23 (m, 2H), 7.18 (d, 1H), 7.12 (m, 3H), 6.94 (d, 2H), 4.18 (m, 3H), 3.80 (br s, 4H), 3.39 (d, 2H), 3.14 (m, 3H), 2.89 (s, 3H), 2.75 (s, 6H), 2.15 (m, 2H).

EXAMPLE 18A The compound 3- (R) - ((carbobenzyloxy) amino) -? - butyrolactone, which is prepared as described in J. Am. Chem. Soc. 1986, 108, 4943-4952, (7.72 g) in THF (100 mi) at 25 ° C is saturated with dimethylamine, stirred for 16 hours, and concentrated. The concentrated material is filtered through a pad of silica gel with 50% acetone / hexanes.

EXAMPLE 18B Example 18A (8.45 g) in toluene (15 ml) at 25 ° C is treated with tributylphosphine (9.76 ml) and diphenyl disulfide (7.3 g), heated to 80 ° C for 16 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0-50% ethyl acetate / hexanes.

EXAMPLE 18C Example 18B (10.60 g) in 30% H Br / acetic acid (50 ml) at 25 ° C is stirred for 18 hours, concentrated, treated with water (200 ml) and 5% HCl (100 ml), washed with diethyl ether, adjusted to pH 8-9 with Na 2 CO 3. , and extracted with dichloromethane. The extract is dried (MgSO4), filtered, and concentrated.

EXAMPLE 18D Compound 1-fluoro-2- (trifluoromethyl) -benzene (1.5 g) in chlorosulfonic acid (50 ml) and 1,2-dichloroethane (50 ml) at 70 ° C is stirred for 2 hours, and concentrated. The material concentrated in TH F (200 ml) at 0 ° C is treated with concentrated ammonium hydroxide (20 ml), stirred for 10 minutes, and poured into ethyl diethyl ether (500 ml). The extract is washed with brine and dried (Na S04), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 30% ethyl acetate / hexanes.

EXAMPLE 18E A mixture of Example 1 8D (1.7 g) and Example 18C (1.67 g) in DMSO (17 ml) is treated with DIEA (1.22 ml), heated at 1 10 ° C for 24 hours, poured into ethyl acetate (400 ml), washed with water. ua and brine, and dried (Na S04), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 18F Example 1 8E (2.5 g) in TH F (20 ml) at 25 ° C is treated with 1 M borane-THF (22 ml), stirred for 24 hours, treated with methanol and concentrated. The methanol-concentrated material (20 ml) is treated with methanol saturated with HCl (75 ml), stirred at reflux for 24 hours, concentrated, poured into 1 M NaOH, and extracted with ethyl acetate. The extract is washed with brine and dried (Na 2 SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0-5% TEA / ethyl acetate.

EXAMPLE 18G This example is prepared by replacing Example 18F with 4 - (((R) -3- (dimethylamino) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 7.94 (d, 1 H), 7.80 (dd, 1H), 7.73 (d, 2H), 7.53 (dd, 1H), 7.47 (AB q, 4H), 7.41-7.33 (m, 5H), 7.36 (dd, 2H), 7.32 (d, 2H), 7.27 ( m, 4H), 7.19 (dd, 1H), 6.89 (d, 2H), 6.87 (d, 1H), 5.94 (d, 1H), 3.94 (m, 1H), 3.42 (m, 2H), 3.26 (m , 4H), 3.10 (m, 1H), 2.96 (m, 1H), 2.67 (s, 6H), 2.41 (m, 4H), 2.13 (m, 2H).

EXAMPLE 19A The compound 3- (R) - ((carbobenzyloxy) amino) -? - butyrolactone, which is prepared as described in J. Am. Chem. Soc. 1986, 108, 4943-4952, (62 g) in dioxane (700 mi) is treated with morpholine (46 ml), heated to 65 ° C for 24 hours, cooled and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10% methanol in ethyl acetate.

EXAMPLE 19B This example is prepared by substituting example 19A for example 1 8A in example 1 8B.

EXAMPLE 19C This example is prepared by substituting example 19B for example 18B in example 18C.

EXAMPLE 19D Example 19C (45.4 g) in THF (500 ml) at 55 ° C is treated with borane-THF 1 M in THF (650 ml), stirred for 24 hours, cooled to 0 ° C, treated with methanol, It is poured into methanol, and concentrated. The methanol-concentrated material (400 mL) is treated with HCl saturated in methanol (800 mL), refluxed for 24 hours, concentrated, poured into 2M NaOH, and extracted with ethyl acetate. The extract is washed with 1 M NaOH and brine and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with ethyl acetate, 10% methanol / ethyl acetate, and 10% methanol / 10% acetonitrile / 5% TEA / 75% ethyl acetate .

EXAMPLE 19E This example is prepared by substituting example 19D for example 18C in example 18E.

EXAMPLE 19F This example is prepared by replacing Example 19E with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 7.92 (d, 1H), 7.76 (dd, 1H), 7.72 (d, 2H), 7.50 (dd, 1H), 7.47 (s, 4H), 7.41-7.33 ( m, 5H), 7.30 (d, 2H), 7.24 (dd, 1H), 7.19 (dd, 1H), 6.88 (d, 2H), 6.79 (d, 1H), 5.98 (d, 1H), 3.94 (m , 1H), 3.51 (m, 4H), 3.31-3.23 (m, 8H), 2.43 (m, 2H), 2.39 (m, 4H), 2.28 (m, 2H), 1.96 (m, 1H), 1.83 ( m, 1H).

EXAMPLE 20A The compound 3- (R) - ((carbobenzyloxy) amino) -? - butyrolactone, which is prepared as described in J. Am. Chem. Soc. 1986, 108, 4943-4952, (1.8 g) in THF (20) mi) at 25 ° C is treated with pyrrolidine (3 ml), stirred for 3 days, and concentrated with an azeotrope of toluene.

EXAMPLE 20B This example is prepared by substituting example 20A for example 1 8A in example 18B.

EXAMPLE 20C This example is prepared by substituting example 20B for example 1 8B in example 1 8C.

EXAMPLE 20D Example 20C (1.8g) in DMF (30ml) at 25 ° C is treated with TEA (950μl) and 4-fluoro-3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, (1.5 g), heated at 60 ° C for 1 50 minutes, poured into water, and extracted with ethyl acetate. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, concentrated. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 20E Example 20D (2.35 g) in THF (30 ml) at 25 ° C is treated with borane-TH F 1 M in THF (20 ml), stirred for 24 hours, cooled to 0 ° C, treated with methanol , it is poured into 6M HCl, stirred for 24 hours, cooled to 0 ° C, brought to pH 12 with KOH, and extracted with ethyl acetate. The extract is washed with brine and dried (Na 2 SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with ethyl acetate, 10% methanol / ethyl acetate, and 10% methanol / 5% TEA / 85% ethyl acetate.

EXAMPLE 20F This example is prepared by substituting Example 20E for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.06 (br s, 1H), 9.73 (br s, 2H), 8.54 (d, 1H), 8.29 (d, 1H), 7.87 (dd, 1H), 7.77 (d, 2H), 7.74 (m, 1H), 7.52 (m, 4H), 7.39 (d, 2H), 7.34 (m, 1H), 7.23 (m, 2H), 7.18 (d, 1H), 7.12 (m, 3H), 6.92 (d, 2H), 4.22 (m, 3H), 3.86 ( s, 4H), 3.51 (m, 2H), 3.38 (m, 2H), 3.21 (m, 4H), 2.94 (m, 4H), 2.15 (m, 2H), 2.00 (m, 2H), 1.84 (m , 2H).

EXAMPLE 21 The compound 2-amino-2-methyl-1-propanol (5 g) in dichloromethane (200 ml) at 0 ° C is treated with di-tert-butyl dicarbonate (3.5 g), stirred for 8 hours at 25 ° C. C, washed with water, 5% aqueous citric acid, saturated NaHCO3, and brine, and dried (MgSO4), filtered, and concentrated.

EXAMPLE 21 B A mixture of example 21 A (980 mg), 2-mercaptothiazoI (610 mg), and triphenylphosphine (1.5 g) in THF (12 ml) at 25 ° C is stirred for 20 minutes, cooled to 0 ° C, treated with di-isopropyl dicarboxylate (1.1 mL) in THF (6 mL), stirred at 25 ° C for 3 days, treated with ethyl acetate, washed with water and brine, and dried (MgSO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 2% -10% ethyl acetate / hexanes.

EXAMPLE 21 C Example 21 B (410 mg) in diethyl ether (5 ml) at 25 ° C is treated with 4M HCl in 1,4-dioxane (5 ml), stirred for 2.5 hours, and filtered.

EXAMPLE 21 D A mixture of example 21 C (300 mg) and 4-phloro-3-nitrobenzenesulfonamide (300 mg), and DI EA (690 μl) in DMSO (2 ml) at 25 ° C is stirred for 18 hours, cooled to 15 ° C, treated with water (25 ml), acidified with 1 M HCl, cooled to 0 ° C, stirred for 1 hour, and filtered.

EXAMPLE 21E This example is prepared by substituting Example 21 D for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.59 (d, 1 H), 8.49, (s, 1H), 7.90 (dd, 1H), 7.80 (d, 2H), 7.77 (s, 1H), 7.52 (d, 3H), 7.48 (d, 2H), 7.45 (dd, 2H), 7.40 (d, 2H) ), 7.40 (d, 1H), 6.93 (d, 2H), 4.24 (s, 2H), 3.86, (s, 2H), 3.35 (m, 6H), 2.85 (s, 2H), 1.58 (s, 6H) ).

EXAMPLE 22A A mixture of 2-mercaptothiazole (4.6 g) and tetra-n-butylammonium persulfate, which is prepared as described in Tetrahedron Lett. 1993, 34, 3581-3584, (14.7 g) in water (460 ml) at 25 ° C, stirred for 18 hours and extracted with diethyl ether. The extract is washed with brine and dried (MgSO 4), filtered, and concentrated.

EXAMPLE 22B A mixture of Example 18A (720 mg) and Example 22A (770 mg) in toluene (9.1 ml) at 85 ° C is treated with tributylphosphine (830 μl), heated to 85 ° C, stirred for 5.5 hours, it is treated with ethyl acetate, washed with water and brine, and dried (MgSO.sub.4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 30% -66% ethyl acetate / hexanes.

EXAMPLE 22C This example is prepared by substituting example 22B for. Example 18B in Example 18C.

EXAMPLE 22D This example is prepared by substituting example 22C for example 1 9C in example 1 9D.

EXAMPLE 22E This example is prepared by substituting example 22D for example 21 C in example 21 D.

EXAMPLE 22F This example is prepared by substituting example 22E for 4 - (((1 R) -3- (d-methylamino) -1 - ((f-enylsulf a-n-yl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.50 (d, 1 H), 8.22 (d, 1H), 7.90 (dd, 1H), 7.72 (dd, 2H), 7.61 (d, 1H), 7.51 (m, 2H), 7.47 (s, 3H), 7.37 (m, 2H), 7.23, (m, 2H), 6.79 (d, 2H), 4.28 (m, 1H), 3. 60 (m, 2H), 3.39 (s, 2H), 3.14 (m, 4H), 3.00 (m, 2H), 2.62 (s, 6H), 2.40 (m, 4H), 2.10 (m, 2H).

EXAMPLE 23A This example is prepared by substituting 2-thienyl disulfide and THF for Example 22A and toluene, respectively, in Example 22B.

EXAMPLE 23B This example is prepared by substituting example 23A for example 18B in example 18C.

EXAMPLE 23C This example is prepared by substituting example 23B for example 19C in example 19D.

EXAMPLE 23D This example is prepared by substituting example 23C for example 21C in example 21D.

EXAMPLE 23E This example is prepared by replacing Example 23D with 4 - (((1R) -3- (dimethylamine) -1 - ((f-enylsulfonyl) methyl) propy!) Amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500MHz, DMSO-d 6) d 8.50 (d, 1H), 8.22 (d, 1H), 7.90 (dd, 1H), 7.82, (dd, 1H), 7.72 (d, 2H), 7.62 (dd, 1H), 7.51 (m, 1H), 7.47 (s, 3H), 7.37 (m, 2H), 7.25 (dd, 1H), 7.14 (dd, 1H), 7.02 (dd, 1H), 6.80 (m, 3H) ), 3.99 (m, 1H), 3.31 (m, 2H), 3.18 (m, 6H), 2.95 (m, 3H), 2.59 (s, 6H), 2.40 (t, 3H), 2.11 (m, 1H) , 2.02 (m, 1H).

EXAMPLE 24A Treat the methyl ester of N-tert-butoxycarbonyl-L-serine (30 g) in dichloromethane (300 ml) at 0 ° C with DIEA (59.7 ml) and methanesulfonyl chloride (11.65 ml), stir for 20 minutes, it is treated with thiophenol (15.5 ml), stirred at 25 ° C for 24 hours, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10-30% ethyl acetate / hexanes.

EXAMPLE 24B Example 24A (8.35 g) in dichloromethane (75 ml) is treated with DI BAL 1 M in dichloromethane (94 ml), stirred for 2 hours, treated with methanol, poured into saturated NaH2P0 (300 ml), stir for 30 minutes, and extract with ethyl acetate. The extract is washed with brine and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 24C 60% oily NaH (480 mg) in dioxane (30 ml) is treated at 25 ° C with example 24B (1.7 g) in dioxane (10 ml), stirred for 10 minutes, treated with N, N -dimethylchloroacetamide (1.23 ml), heated at 70 ° C for 24 hours, poured into water, and extracted with ethyl acetate. The extract is washed with brine and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 24D Example 24C (1.65 g) in THF (10 mL) at 25 ° C is treated with borane-THF 1M (20 mL), stirred for 24 hours, treated with 5M HCl (300 mL) and THF (300 mL). , it is stirred for 2 days, cooled to 0 ° C, adjusted to pH 12 with KOH and extracted with ethyl acetate. The extract is washed with brine and dried (Na 2 SO), filtered, and concentrated. The material concentrated in DMF (30 ml) is treated with 4-fluoro-3-nitrobenzenesulfonamide (1 g) and TEA (627 μl), heated at 55 ° C for 90 minutes, poured into water, and extracted with acetate of ethyl. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with ethyl acetate, 10% methanol / ethyl acetate, and 10% methanol / 10% acetonitrile / 80% ethyl acetate.

EXAMPLE 24E This example is prepared by replacing Example 24D with 4 - (((1R) -3- (d-methylamino) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-de) d 12.12 (s, 1 H), 10.90 (m, 1H), 9.90 (m, 1H), 8.56 (d, 1H), 8.52 (d, 1H), 8.04 (m, 1H), 7.86 (dd, 1H), 7.76 (d, 2H), 7.53 (m, 4H), 7.13-7.39 (m, 9H), 6.93 (d, 2H), 4.35 (m, 1H), 3.87-3.79 (m, 2H) ), 3.74 (m, 4H), 3.47 (m, 8H), 3.23 (m, 4H), 2.75 (m, 6H).

EXAMPLE 25A Treat diethylamine (4.15 mL) in THF (150 mL) at -78 ° C with 2.5M n-butyllithium in hexanes (1 5.4 mL), stir for 5 minutes at 0 ° C, cool to -78 ° C. C is treated with (2R, 4S) -3 - ((benzyloxy) carbonyl) -4-methyl-2-phenyl-1,3-oxazolidin-5-one, which is prepared as described in Helv. Chim. Acta 1991, 74, 800, (10 g) in THF (40 ml), stirred for 20 minutes, treated with allyl bromide (4.29 ml), stirred for 1 hour, stirred at 25 ° C for 18 hours , it is poured into buffer pH 7, and extracted with diethyl ether. The extract is washed with brine and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20% ethyl acetate / hexanes.

EXAMPLE 25B Example 25A (8.18 g) in methanol (200 ml) and water (20 ml) at 25 ° C is treated with LiOH-water (1.95 g), stirred for 30 minutes, poured into saturated NaH2P04 (200 ml). ), and extracted with ethyl acetate. The extract is washed with 1 M NaOH and brine and dried (Na S04), filtered, and concentrated. The base wash is acidified with 12M HCl and extracted with ethyl acetate. The extract is concentrated, and the material concentrated in ethyl acetate / methanol 1: 1 (50 ml) at 25 ° C is treated with 2M (trimethylsilyl) -diazomethane in THF (5 ml), stirred for 10 minutes, and It is concentrated. The concentrated materials are combined and subjected to flash chromatography on silica gel with 10% ethyl acetate / hexanes.

EXAMPLE 25C Example 25B (5.03 g) in TH F (75 ml) at 25 ° C is treated with LiBH (CH 2 CH 3) 3 1 M in THF (38 ml), stirred for 2 hours, treated with methanol (30 ml), It is poured into water, and extracted with ethyl acetate. The extract is washed with brine and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 30% ethyl acetate / hexanes.

EXAMPLE 25D This example is prepared by substituting example 25C for example 18A in example 18B.

EXAMPLE 25E Example 25D (2.9 g) in diethyl ether (45 ml) and tert-butanol (45 ml) at 25 ° C is treated with AD-mix-β (12.74 g), stirred for 18 hours, poured into saturated Na 2 CO 3, and extracted with ethyl acetate. The extract is washed with brine and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20-50% ethyl acetate / hexanes. The product in THF (30 ml) and water (30 ml) at 25 ° C is treated with Nal04 (2.75 g), stirred for 20 minutes, poured into water, and extracted with ethyl acetate. The extract is washed with brine and dried (Na2SO4), filtered, and concentrated.

EXAMPLE 25F Example 25E (1.92 g) in dichloromethane (30 ml) at 25 ° C is treated with dimethylamine hydrochloride (684 mg), sodium triacetoxyborohydride (1.9 g), and TEA (1.56 ml), stir for 24 hours, treat with methanol and water, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 25G This example is prepared by substituting example 25F for example 18B in example 18C.

EXAMPLE 25H A mixture of example 25G (600 mg) and 4-fluoro-3-nitrobenzenesulfonamide (554 mg) in DMSO (7 ml) at 25 ° C is treated with TEA (351 μl), heated at 60 ° C for 90 minutes, it is poured into water (30 ml), and extracted with ethyl acetate. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0-10% methanol / ethyl acetate.

EXAMPLE 251 This example is prepared by replacing Example 25H with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) -prop i) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.14 (s, 1 H), 10.90 (m, 1H), 10.22 (m, 1H), 8.50 (d, 1H), 8.32 (s, IH), 8.04 (m, 1H), 7.83 (m, 3H), 7.54 (m, 4H), 7.36 (m, 4H), 7.23 (d, 2H), 6.98-6.85 (m, 5H), 4.35 (m, 2H), 3.92-3.87 (m, 2H) ), 3.74 (m, 2H), 3.48 (m, 8H), 3. 23 (m, 2H), 2.70 (m, 6H), 1.56 (s, 3H).

EXAMPLE 26A This example is prepared by substituting methylamine for dimethylamine in Example 18A.

EXAMPLE 26B This is prepared by replacing Example 26A with Example 1 8A in Example 18B.

EXAMPLE 26C This example is prepared by substituting example 26B for example 18B in example 18C.

EXAMPLE 26D This example is prepared by substituting example 26C for example 21 C in example 21 D.

EXAMPLE 26E This example is prepared by substituting example 26D for example 18E in example 18F.

EXAMPLE 26F Example 26E (1.12 g) in TH F (7 ml) and acetonitrile (7 ml) at 25 ° C are treated with di-tert-butyl dicarbonate (572 mg) and TEA (276 mg), stirred for 16 hours, and concentrates. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 26G This example is prepared by substituting example 26F for 4 - (((1 R) -3- (di methylamino) -1 - ((phen i Isulf añil) methyl) -propyl) am i no) -3-nitrobenzenesulfonamide in the example 2D EXAMPLE 26H Example 26G is subjected to flash chromatography on silica gel with dichloromethane, dichloromethane / ethyl acetate 1: 1, and 10% (NH37M in methanol) in methanol. A mixture of the free base in dichloromethane at 25 ° C is treated with 2M HCl / diethyl ether 1: 1 (10 mL), stirred for 18 hours and concentrated. 1 H NMR (500 MHz, DMSO-d 6) d 12.11 (s, 1 H), 10.94 (m, 1H), 8.71 (m, 1H), 8.53 (d, 1H), 8.28 (d, 1H), 8.05 (m, 1H), 7.86. (dd, 1H), 7.77 (d, 2H), 7.53 (m, 4H), 7.37 (m, 4H), 7.23 (m, 2H), 7. 11 (m, 3H), 6.93 (d, 2H), 4.34 (m, 1H), 4.28 (m, 1H), 4.12 (m, 1H), 3.92-3.87 (m, 2H), 3.39 (m, 8H), 3.27 (m, 3H), 2.94 (m, 3H), 2.11 (m, 2H).

EXAMPLE 27A A mixture of Fmoc-D-Asp- (0-tert-butyl) -OH (10.25 g) and NMM (2.8 ml) in DME (30 ml) at -1 5 ° C is treated with isobutyl chloroformate (4.1 ml) , stir for 10 minutes, and filter. The filtrate is cooled to 0 ° C, treated with NaBH4 (2.84 g) in water (15 ml), stirred for 5 minutes, treated with water, stirred at 25 ° C for 3 hours, and filtered.

EXAMPLE 27B A mixture of example 27A (9.5 g), diphenyl disulfide (7.86 g) and tributylphosphine (7.28 g) in toluene (200 ml) at 80 ° C is stirred for 5 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% to 20% ethyl acetate / hexanes.

EXAMPLE 27C This example is prepared by substituting example 27B for example 21 C in example 21 D.

EXAMPLE 27D This example is prepared by replacing Example 27C with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 27E Example 27D (1 g) in dichloromethane (5 ml) at 25 ° C is treated with TFA (5 ml), stirred for 3 hours, and concentrated. 1 H NMR (500 MHz, DMSO-d 6) d 8.57 (d, 1H), 8.52 (d, 1H), 7.84 (dd, 1H), 7.75 (d, 2H), 7.55-7.35 (m, 7H), 7.27- 7.11 (m, 6H), 6.91 (d, 2H), 4.39 (m, 1H), 3.39 (2.2H), 3.31 (s, 8H), 3.26 (m, 2H), 2.81 (d, 2H).

EXAMPLE 28 A mixture of example 27E (160 mg) and N-methyl-morpholine (27 μl) in DMF (1 ml) at 25 ° C is treated with HATU (92 mg) and sopropylamine (50 μl), stirred for 5 hours , treated with ethyl acetate (200 ml), washed with 1% HCl, saturated NaHCO3, water, and brine, and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with dichloromethane, (1: 1) dichloromethane / ethyl acetate, and 5% methanol / dichloromethane. 1 H NMR (500 MHz, DMSO-d 6), d 8.73 (d, 1 H), 8.52 (d, 1 H), 7.93 (d, 1 H), 7.83 (dd, 1 H), 7.76 (d, 2 H), 7.52 (m , 2H), 7.38 (m, 3H), 7.23 (m, 2H), 7.18-7.10 (m, 6H), 6.92 (d, 2H), 4.39 (m, 1 H), 3.75 (m, 1 H), 3.40 (m, 10H), 3.34 (m, 2H), 2.54 (m, -2H), 0.98 (d, 3H), 0.91 (d, 3H).

EXAMPLE 29A Example 27B (500 mg) in dichloromethane (3 ml) at 25 ° C is treated with TFA (3 ml), stirred for 3 hours, and concentrated with an azeotrope of dichloromethane.

EXAMPLE 29B A mixture of Example 29A (450 mg) and NMM (140 μL) in DMF (3 mL) at 25 ° C is treated with HATU (464 mg) and di-isopropylamine (283 μL), stirred for 5 hours, treated With ethyl acetate, wash with 1% HCl, saturated NaHCO3, water, and brine, and dry (Na2SO4), filter, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with dichloromethane, dichloromethane / ethyl acetate 1: 1, 5% methanol / dichloromethane.

EXAMPLE 29C Example 29B (200 mg) in TH F (5 mL) at 25 ° C is treated with borane-TH F 2M in THF (1 mL), stirred for 4 hours, treated with methanol (3 mL) and HCl Concentrate (1 mL), stir for 2 hours, bring to pH 7 with saturated NaHCO 3, and extract with dichloromethane. The extract is washed with water and brine and dried (Na S04), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with dichloromethane and 5% methanol / dichloromethane.

EXAMPLE 29D This example is prepared by substituting example 29C for example 21C in example 21D.

EXAMPLE 29E This example is prepared by replacing Example 29D with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.88 (s, 1 H), 11.33 (s, 1 H), 10.13 (s, 1 H), 9.57 (s, 1 H), 8.30 (d, 1 H), 8.08 (d, 1H), 7.94 (m, 1H), 7.63 (dd, 1H), 7.55 (d, 2H), 7.30 (m, 4H), 7.15 (m, 2H), 7.09 (m, 1H), 6.99 (m, 3H) ), 6.89 (m, 3H), 6.71 (d, 2H), 4.11 (m, 1H), 3.61 (m, 8H), 3.19 (m, 1H), 3.17 (m, 2H), 2.94 (m, 1H) , 2.77 (m, 4H), 2.62 (m, 1H), 2.05 (m, 1H), 1.53 (m, 2H), 1.09-0.75 (m, 12H).

EXAMPLE 30A Example 27C (2.2 g) in dichloromethane (25 ml) at 0 ° C is treated with TFA (25 ml) and water (2.5 ml), stirred at 25 ° C for 2 hours, and concentrated with a toluene azeotrope. .

EXAMPLE 30B Example 30A (1 g) in DME (25 ml) at 25 ° C is treated with NMM (280 μl), cooled to -10 ° C, treated with isobutyl chloroformate (330 μl), shaken for 15 hours. minutes, treated with sodium borohydride (277 mg) in water (10 ml), stirred for 45 minutes, and concentrated. The concentrated material is treated with 0.5 M HCl and extracted with ethyl acetate. The extract is washed with brine and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 2% methanol / dichloromethane and 4% methane / dichloromethane.

EXAMPLE 30C A mixture of example 30B (705 mg) and TEA (740 μl) in dichloromethane (8 ml) at 0 ° C is treated with S03-pyridine (850 mg) in DMSO (6 ml), stirred at 25 ° C for 30 minutes, treated with 10% aqueous citric acid (w / v), and extracted with ethyl acetate.

The extract is washed with brine and dried (Na2SO4), filtered, and concentrated.

EXAMPLE 30D Example 30C (100 mg) and azetidine hydrochloride (20 mg) in acetonitrile (2 ml) at 25 ° C is treated with DIEA (44 μl) and sodium triacetoxyborohydride (67 mg), stirred for 16.5 hours, absorbed on silica gel, concentrated, and subjected to flash chromatography on silica gel with 5% methanol / dichloromethane and 10% methanol / dichloromethane saturated with NH3.

EXAMPLE 30E This example is prepared by substituting Example 30D for 4 - (((1 R) -3- (di methylamino) -1 - ((phen i Isulf indyl) methyl) -propyl) am i no) -3-nitrobenzenesulfonamide in the example 2D 1 H NMR (300MHz, DMSO-d 6) d 8.45 (d, 1H), 8.20 (d, 1H), 7.81 (dd, 1H), 7., 71 (d, 2H), 7.35 (m, 14H), 6.88 (d, 1H), 6.78 (d, 2H), 4.05 (m, 1H), 3.79 ( m, 4H), 3.33 (m, 5H), 3.13 (m, 5H), 2. 40 (m, 4H), 2.24 (m, 2H), 1.89 (m, 2H).

EXAMPLE 31A A mixture of 3,6-dioxa-bicyclo [3.1.0] -hexane (3.44 g) and sodium azide (5.2 g) in water (10 mL) at 60 ° C is stirred for 24 hours and extracted with ethyl acetate. of ethyl. The extract is dried (MgSO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0-40% ethyl acetate / hexanes.

EXAMPLE 31 B A mixture of example 31 A (3.23 g), di-tert-butyl dicarbonate (8.73 g), and palladium hydroxide on carbon at 20% by weight (200 mg) in ethanol (15 ml) at 25 ° C was added. treat with triethylsilane (4.651 g), stir at 50 ° C for 16 hours, filter, and concentrate. The concentrated material is recrystallized with ethyl acetate / hexanes.

EXAMPLE 31 C A mixture of Example 31 B (2.03 g) and diphenyl disulfide (2,401 g) in toluene (20 ml) at 25 ° C is treated with tributylphosphine (2.224 g), stirred for 16 hours at 80 ° C, and concentrate The concentrated material is subjected to flash chromatography on silica gel with 0% -40% ethyl acetate / hexanes.

EXAMPLE 31D Example 31C (590 mg) in dioxane / dichloromethane 1: 1 (8 ml) at 25 ° C is treated with 4M HCl in dioxane (5 ml), stirred for 16 hours, and concentrated. The concentrated material is triturated with diethyl ether and filtered.

EXAMPLE 31E This example is prepared by substituting example 31 D for example 21C in example 21D.

EXAMPLE 31F This example is prepared by substituting Example 31 E for 4 - (((1 R) -3- (di methylamino) -1 - ((f-enyl-sulfonyl) -methyl) -propi-1) -amino) -3-nitrobenzenesulfonamide in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 12.09 (s, 1H), 9.70 (s, 1H), 8.69 (d, 1H), 8.54 (d, 1H), 7.87 (dd, 1H), 7.78 (d, 2H), 7.74 (br s, 1H), 7.52 (d, 4H), 7.39 (d, 2H), 7.34 (bd, 1H), 7.27 (m, 3H), 7.08 (t, 2H), 6.98 (t, 1H), 6.93 (d, 2H), 4.74 (quintet, 1H), 4.45 (q, 1H), 4.33 (dd, 1H), 4.17 (dd, 1H), 3.86 (br s, 2H), 3.77 (t, 1H), 3.75 (t, 1H), 3.49 (br s, 4H), 3.12 (br s, 2H), 2.89 (s, 2H).

EXAMPLE 32A A mixture of magnesium chips (432 mg) and a crystal of iodine in diethyl ether (30 ml) at 25 ° C is treated with 2-bromobenzyl bromide (4.5 g), stirred for 3 hours, cooled to 0 °. C, treated with 4- (4-oxo-piperidin-1-yl) -benzoic acid ethyl ester, which is prepared as described in Synthesis 1981, 606-608, (3.7 g) in diethyl ether / TH F 1 : 1 (40 ml), stirred at 25 ° C for 18 hours, treated with aqueous NH 4 Cl and extracted with ethyl acetate. The extract is dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 32B Example 32A (1.6g) in THF (20 ml) at 25 ° C is treated with 60% oily sodium hydride (288 mg), heated at 50 ° C for 2 hours, treated with HMPA (3 ml). ) and methyl iodide (3.0 ml), stirred at reflux for 18 hours, cooled to 0 ° C, treated with aqueous NaHS04, and extracted with ethyl acetate. The extract is dried (Na2SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10% -15% ethyl acetate / hexanes.

EXAMPLE 32C (and 25% (w / w) of EXAMPLE 32B) A mixture of example 32B (640 mg), 4-chlorophenyl boronic acid (465 mg), Pd (dppf) CI2 (122 mg), and cesium carbonate (1.46 g) in DMF (15 ml) at 80 ° C is stirred for 2 days and treated with ethyl acetate and brine. The aqueous layer is extracted with ethyl acetate, and the extract is dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% -15% ethyl acetate / hexanes.

EXAMPLE 32D This example is obtained by substituting example 32C for example 2B in example 2C.

EXAMPLE 32E This example is prepared by substituting example 32D for example 2C in example 2D and purified by high pressure liquid chromatography on a C8 on Symmetry Waters column (25 mm x 100 mm, particle size 7 μm) with 10-1 00% acetonitrile / 0.1% aqueous TFA in a lapse of 8 minutes at a flow rate of 40 ml / minute. 1 H NMR (400MHz, DMSO-d6) d 9.38 (s, 1 H), 8.54 (d, 1H), 8.28 (d, 1H), 7.86 (dd, 1H), 7.69 (d, 2H), 7.46 (d , 2H), 7.28 (m, 7H), 7.15 (m, 4H), 6.82 (d, 2H), 4.18 (m, 1H), 3.40 (m, 4H), 3.13 (m, 2H), 3.04 (s, 3H), 2.86 (m, 4H), 2.74 (s, 6H), 2.14 (m, 2H), 1.47 (d, 2H.), 1.18 (t, 2H).

EXAMPLE 33 This example is prepared by substituting 4 - (((1R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02 / 24636, and Example 32D by 4 - (((1R) -3- (dimethylamino) -1- (phenylsulfanyl) methyl) propyl) -amino) -3-nitrobenzenesulfonamide and Example 2C, respectively, in Example 2D and purified by high pressure liquid chromatography on a Waters Symmetry C8 column (25 mm x 100 mm, particle size 7 μm) with 10-100% acetonitrile / 0.1% aqueous TFA in a span of 8 minutes at a time. flow rate of 40 ml / minute. 1 H NMR (400 MHz, DMSO-d 6) 6 9.71 (s, 1 H), 8.54 (d, 1H), 8.29 (d, 1H), 7.87 (dd, 1H), 7.69 (d, 2H), 7.46 (d, 2H), 7.30 (m, 7H), 7.14 (m, 4H), 6.82 (d, 2H), 4.18 (m, 1H), 3.95 (m, 2H), 3.67 (m, 4H), 3.39 (m, 4H), 3.19 (m, 2H) ), 3.03 (s, 3H), 3.00 (m, 2H), 2.85 (m, 4H), 2.17 (m, 2H), 1.47 (d, 2H), 1.17 (t, 2H).

EXAMPLE 34 Example 27E (6.7 g) in DME (50 ml) at -15 ° C is treated with NMM (920 μl) and isobutyl chloroformate (1.09 ml), stirred for 20 minutes, treated with sodium borohydride (1.59 g) ) in water (10 ml), stirred for 30 minutes, treated with water, and extracted with ethyl acetate. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with dichloromethane, dichloromethane / ethyl acetate 1: 1, and 10% methanol / dichloromethane. 1 H NMR (500 MHz, DMSO-d 6) d 8.53 (d, 1 H), 8.49 (d, 1H), 7.83 (dd, 1H), 7.74 (d, 2H), 7.47 (m, 4H), 7.53-7.36 (m, 3H), 7.25 (m 2H), 7.19-7.07 (m, 4H), 6.91 ( d, 2H), 4.69 (m, 1H), 4.21 (m, 1H), 3.49 (m, 2H), 3.35 (t, 2H), 3.31 (m, 8H), 3.27 (m, 2H), 1.89 (m , 2H).

EXAMPLE 35A Example 34 (786 mg) in dichloromethane (5 ml) at 25 ° C is treated with para-toluenesulfonic anhydride (326 mg), N, N-dimethylaminopyridine (122 mg), and DIEA (350 μl), stirred for 18 hours. hours, treated with ethyl acetate, washed with 1% HCl, saturated NaHCO3, and brine, and dried (Na2SO4), filtered, and concentrated.

EXAMPLE 35B Example 35A (100 mg) in DMF (2 ml) at 25 ° C is treated with DIEA (100 μl) and isopropylamine (60 μl), stirred at 50 ° C for 18 hours, treated with ethyl acetate, Wash with saturated NaHC03, water, and brine, and dry (Na S04), filter, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with dichloromethane, dichloromethane / ethyl acetate 1: 1, and 10% (NH37M in methanol) in dichloromethane. 1 H NMR (500 MHz, DMSO-d 6) d 8.45 (d, 1 H), 8.09 (d, 1H), 7.84 (dd, 1H), 7.72 (d, 2H), 7.47 (m, 4H), 7.40-7.31 (m, 4H), 7. 25 (m 3 H), 7.17 (m, 2 H), 6.94 (d, 1 H), 6.78 (d, 2 H), 4.11 (m, 1 H), 3. 37 (m, 2H), 3.30 (m, 8H), 3.12 (m, 2H), 2.99 (m, 2H), 2.40 (m, 2H), 2.05 (m, 2H), 1.16 (m, 6H).

EXAMPLE 36A This example is prepared by substituting 2-naphthaleboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 36B This example is prepared by substituting example 36A for example 2B in example 2C.

EXAMPLE 36C This example is prepared by substituting example 36B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.12 (br s, 1 H), 9.98 (br s, 1H), 9.60 (br s, 1H), 8.55 (d, 1H), 8.29 (d, 1H), 7.87 (dd, 1H), 7.81 (d, 2H), 7.49 (tt, 2H), 7.41 (m, 3H), 7.35 (m, 3H), 7.23 (m, 3H), 7.18 (d, 2H), 7.12 (m, 2H), 7.02 (d, 2H), 4.19 (m, 1H), 3.99 (br s, 2H), 3.39 (d, 4H), 3.29 (m, 4H), 3.14 (m, 2H), 2.98 (m, 2H), 2.75 (s, 6H), 2.14 (dd, 2H).

EXAMPLE 37A This example is prepared by substituting 1-naphthaleboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 37B This example is prepared by substituting example 37A for example 2B in example 2C.

EXAMPLE 37C This example is prepared by substituting example 37B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.07 (br s, 1H), 9.59 (br s, 2H), 8.54 (d, 1H), 8.29 (d, 1H), 8.01 (dd, 2H), 7.85 ( dd, 2H), 7.74 (d, 2H), 7.59 (m, 4H), 7.47 (m, 2H), 7.35 (d, 1H), 7.24 (m, 3H), 7.18 (d, 2H), 7.12 (m , 2H), 6.88 (d, 2H), 4.19 (m, 1H), 3.75 (br s, 2H), 3.39 (d, 4H), 3.29 (m, 4H), 3.14 (m, 2H), 2.98 (m , 2H), 2.75 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 38A This example is prepared by substituting 3-cyanophenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 38B This example is prepared by substituting example 38A for example 2B in example 2C.

EXAMPLE 38C This example is prepared by substituting example 38B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.09 (br s, 1 H), 9.47 (br s, 2 H), 8.54 (d, 1 H), 8.29 (d, 1 H), 7.89 (d, 1 H), 7.86 ( dd, 2H), 7.77 (d, 2H), 7.69 (m, 3H), 7.56 (m, 2H), 7.37 (m, 1H), 7.24 (m, 2H), 7.14 (d, 5H), 6.93 (d , 2H), 4.18 (m, 1H), 4.04 (m, 2H), 3.75 (m, 2H), 3.39 (d, 4H), 3.15 (m, 4H), 3.06 (m, 2H), 2.75 (s, 3H), 2.74 (s, 3H), 2.14 (dd, 2H).

EXAMPLE 39A This example is prepared by substituting 3-methoxyphenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 39B This example is prepared by substituting example 39A for example 2B in example 2C.

EXAMPLE 39C This example is prepared by substituting example 39B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (br s, 1 H), 9.58 (br s, 1 H), 8.55 (d, 1 H), 8.29 (d, 1 H), 7.86 (dd, 1 H), 7.77 ( d, 2H), 7.72 (m, 1H), 7.50 (m, 2H), 7.37 (m, 2H), 7.24 (m, 2H), 7.14 (d, 4H), 6.98 (m, 1H), 6.92 (m , 4H), 4.31 (br s, 2H), 4.18 (m, 1H), 3.79 (s, 3H), 3.39 (d, 3H), 3.15 (m, 5H), 2.75 (s, 6H), 2.14 (dd) , 2H).

EXAMPLE 40A This example is prepared by substituting 3-chlorophenyl boronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 40B This example is prepared by substituting example 40A for example 2B in example 2C.

EXAMPLE 40C This example is prepared by substituting example 40B for example 2C in example 2D. H NMR (400 MHz, DMSO-d6) d 12.09 (br s, 1 H), 9.86 (br s, 1 H), 9.59 (br s, 1 H), 8.55 (d, 1 H), 8.29 (d, 1 H), 7.86. (dd, 1H), 7.77 (d, 2H), 7.70 (m, 1H), 7.49 (m, 5H), 7.34 (m, 2H), 7.24 (m, 2H), 7.14 (d, 4H), 6.94 ( d, 2H), 4.19 (m, 1H), 3.39 (d, 3H), 3.13 (m, 5H), 2.88 (m, 2H), 2.75 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 41A This example is prepared by substituting 2-chlorophenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 41B This example is prepared by substituting example 41A for example 2B in example 2C.

EXAMPLE 41C This example is prepared by substituting example 41 B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.12 (br s, 1H), 10.00 (br s, 1H), 9.59 (br s, 1H), 8.55 (d, 1H), 8.29 (d, 1H), 7.86 (dd, 1H), 7.77 (d, 2H), 7.76 (m, 1H), 7.58 (m, 3H), 7.45 (m, 3H), 7.28 (dd, 1H), 7.23 (m, 2H), 7.14 (d, 4H), 6.94 (d, 2H), 4.18 (m, 1H), 3.39 (d, 3H), 3.13 (m, 5H), 3.02 (m, 2H), 2.75 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 42A This example is prepared by substituting 3,4-methylene-dioxybenzeneboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 42B This example is prepared by substituting example 42A for example 2B in example 2C.

EXAMPLE 42C This example is prepared by substituting example 42B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.08 (br s, 1 H), 9.85 (br s, 1H), 9.55 (br s, 1H), 8.54 (d, 1H), 8.29 (d, 1H), 7.86 (dd, 1H), 7.77 (d, 2H), 7.69 (m, 1H), 7.48 (br s, 2H), 7.31 (m, 1H), 7.23 (m, 2H), 7.14 (d, 4H), 6.96 (m, 4H), 6.79 (dd, 1H), 6.06 (s, 2H), 4.18 (m, 1H), 3.39 (d, 3H), 3.12 (m, 5H), 2.86 (m, 2H), 2.75 (s, 6H), 2.14 (dd, 2H).

EXAMPLE 43A This example is prepared by substituting thiophene-3-boronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 43B This example is prepared by substituting example 43A for example 2B in example 2C.

EXAMPLE 43C This example is prepared by substituting example 43B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.11 (br s, 1 H), 9.99 (br s, 1H), 9.62 (br s, 1H), 8.55 (d, 1H), 8.29 (d, 1H), 7.86 (dd, 1H), 7. 78 (d, 2H), 7.69 (m, 2H), 7.63 (s, 1H), 7.48 (br s, 2H), 7.41 (m, 1H), 7.24 (m, 2H), 7.14 (d, 5H), 6.95 (d, 2H), 4.18 (m, 1H), 3.39 (d, 3H), 3.14 (m, 5H), 2.89 (m, 2H) ), 2.75 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 44A This example is prepared by substituting pyridine-3-boronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 44B This example is prepared by substituting example 44A for example 2B in example 2C.

EXAMPLE 44C This example is prepared by substituting example 44B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.08 (br s, 1H), 9.99 (br s, 1H), 9.66 (br s, 1H), 8.69 (dd, 1H), 8.54 (d, 1H), 8.29 (d, 1H), 7. 95 (d, 1H), 7.86 (dd, 1H), 7.77 (d, 2H), 7.59 (m, 3H), 7.40 (m, 1H), 7.24 (m, 2H), 7.14 (d, 4H), 6.93 (d, 2H), 4.19 (m, 1H), 3.39 (d, 3H), 3.14 (m, 5H), 2.92 (m, 2H) ), 2.75 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 45A This example is prepared by substituting 8-quinoline boronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 45B This example is prepared by substituting example 45A for example 2B in example 2C.

EXAMPLE 45C This example is prepared by substituting example 45B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (br s, 1 H), 9.84 (br s, 1H), 9.61 (br s, 1H), 8.84 (dd, 1H), 8.54 (d, 1H), 8.48 (dd, 1H), 8.29 (d, 1H), 8.10 (td, 1H), 7.85 (dd, 1H), 7.80 (d, 1H), 7.73 (m, 4H), 7.56 (m, 3H), 7.35 (d, 1H), 7.23 (m, 3H), 7.14 (m, 3H), 6.89 (d, 2H), 4.29 (m, 1H), 4.20 (m, 1H), 3.90 (d, 1H), 3.39 (d, 4H), 3.14 (m, 3H), 2.97 (m, 3H), 2.75 ( s, 6H), 2.15 (dd, 2H).

EXAMPLE 46A This example is prepared by substituting benzofuran-2-boronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 46B This example is prepared by substituting example 46A for example 2B in example 2C.

EXAMPLE 46C This example is prepared by substituting example 46B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.14 (br s, 1 H), 9.81 (br s, 1H), 9.63 (br s, 1H), 8.55 (d, 1H), 8.29 (d, 1H), 7.97 (d, 1H), 7.86 (dd, 1H), 7.81 (d, 2H), 7.69 (m, 3H), 7.60 (m, 2H), 7.46 (s, 1H), 7.38 (td, 1H), 7.32 (t, 1H), 7.22 (m, 2H), 7.15 (d, 4H), 7.01 (d, 2H), 4.19 (m, 1H), 3.39 (d, 3H), 3.27 (m, 2H), 3.15 (m, 5H), 2.75 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 44A This example is prepared by substituting 2-methylphenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 44C This example is prepared by substituting example 44B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.08 (br s, 1 H), 9.94 (br s, 1 H), 9.73 (br s, 1 H), 8.55 (d, 1 H), 8.29 (d, 1 H), 7.86. (dd, 1H), 7.77 (d, 2H), 7.74 (m, 1H), 7.50 (m, 2H), 7.31 (d, 2H), 7.22 (m, 9H), 6.94 (d, 2H), 4.19 ( m, 1H), 3.39 (d, 4H), 3.16 (m, 4H), 2.92 (m, 2H), 2.75 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 48A This example is prepared by substituting 3-quinoline boronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 48B This example is prepared by substituting example 48A for example 2B in example 2C.

EXAMPLE 48C This example is prepared by substituting example 48B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.07 (br s, 1 H), 9.93 (br s, 1 H), 9.56 (br s, 1 H), 8.53 (d, 1 H), 8.42 (s, 1 H), 8.28 (d, 1H), 8.09 (d, 1H), 8.04 (dd, 1H), 7.85 (dd, 1H), 7.82 (m, 2H), 7.74 (d, 2H), 7.68 (td, 1H), 7.50 (d, m, 2H), 7.23 (m, 2H), 7.14 (d, 4H), 6.90 (d, 2H), 4.19 (m, 1H), 3.39 (d, 3H), 3.14 (m, 5H), 2.90 (m , 2H), 2.74 (s, 6H), 2.13 (dd, 2H).

EXAMPLE 49A A mixture of example 1A (272 mg), 1-bromo-naphthalene-2-carbaldehyde (0.409 g), MP-BH3CN (2.47 mmole / g, 1.41 g) and acetic acid (0.14 g) in methanol / dichloromethane 1: 1 (8 ml) is stirred for 1 day at 25 ° C, filtered, and concentrated. The concentrated material is treated with saturated aqueous K2C03 and dichloromethane, and the organic layer is dried (MgSO4), filtered and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% -50% ethyl acetate / hexanes.

EXAMPLE 49B This example is prepared by substituting example 49A for example 2A in example 2B.

EXAMPLE 49C This example is prepared by substituting example 49B for example 2B in example 2C.

EXAMPLE 49D This example is prepared by replacing Example 49C and 3-Nitro-4 - ((2- (phenylsufanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (((1R) -3 - (dimethylamino) -1 - ((phenylsulfanyl) -methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.05 (br s, 1 H), 9.87 (br s, 1 H), 8.76 (t, 1 H), 8.60 (d, 1 H), 8.29 (d, 1 H), 8.13 ( d, 1H), 8. 04 (d, 1H), 7.90 (dd, 1H), 7.86 (d, 1H), 7.77 (d, 2H), 7.62 (d, 2H), 7.60 (m, 1H), 7.50 (t, 1H), 7.37 (m, 3H), 7.28 (d, 2H), 7.19 (m, 2H), 6.94 (d, 2H), 4.23 (br s, 2H), 3.82 (br s, 4H), 3.67 (dd, 2H), 3.28 (m, 2H), 3.16 (br s, 2H), 2.97 (br s, 2H).

EXAMPLE 50 This example is prepared by substituting example 49C for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.12 (br s, 1 H), 9.97 (br s, 1 H), 9.56 (br s, 1 H), 8.55 (d, 1 H), 8.29 (d, 1 H), 8.12 (d, 1H), 8. 05 (d, 1H), 7.87 (d, 1H), 7.86 (d, 1H), 7.79 (d, 2H), 7.61 (m, 3H), 7.50 (m, 1H), 7.38 (d, 2H), 7.28 (d, 1H), 7.22 (m, 2H), 7.14 (m, 4H), 6.95 (d, 2H), 4.25 (br, 2H), 4.19 (m, 1H), 3.39 (d, 3H), 3.14 (m, 5H), 2.94 (m, 2H), 2.75 (s, 3H), 2.74 (s, 3H), 2.15 (dd, 2H).

EXAMPLE 51 This example is prepared by replacing Example 49C and 4 - (((1R) -3- (4-morpholin) -1 - ((f-enylsulfonyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively , in the 2D example. 1 H NMR (400 MHz, DMSO-d 6) d 12.11 (br s, 1 H), 9.89 (br s, 2 H), 8.55 (d, 1 H), 8.29 (d, 1 H), 8.12 (d, 1 H), 8.04 ( d, 1H), 7.86 (m, 2H), 7.78 (d, 2H), 7.62 (d, 2H), 7.60 (m, 1H), 7.50 (t, 1H), 7.38 (d, 2H), 7.28 (d , 1H), 7.15 (d, 4H), 6.95 (d, 2H), 4.19 (m, 1H), 3.95 (m, 4H), 3.62 (m 3H), 3.41 (d, 5H), 3.18 (m, 5H) ), 3.01 (br s, 4H), 2.19 (dd, 2H).

EXAMPLE 52A A mixture of 6-oxa-bicyclo [3.1.0] -hexane (1.68 g) and NaN3 (2.6 g) in water (5 ml) at 60 ° C is stirred for 3 days. The aqueous layer is extracted with dichloromethane, and the extract is dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel 0-40% ethyl acetate / hexanes.

EXAMPLE 52B A mixture of example 52A (1.017 g), di-tert-butyl dicarbonate (2.619 g), Pd (OH) 2 (100 mg) and triethylsilane (1395 g) in ethanol (15 ml) at 50 ° C. it is stirred for 16 hours, partially concentrated, and separated between ethyl acetate and water. The extract is dried (MgSO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10-60% ethyl acetate / hexanes.

EXAMPLE 52C A mixture of example 52B (0.201 g) and diphenyl disulfide (262 mg) in toluene (2 ml) at 25 ° C is treated with tri-n-butylphosphine (243 mg), stirred for 16 hours at 80 ° C, and concentrates. The concentrated material is subjected to flash chromatography on silica gel 0-30% ethyl acetate / hexanes.

EXAMPLE 52D A mixture of example 52C (0.325 g) and 4M HCl in dioxane (2.5 ml) in dichloromethane (3 ml) at 25 ° C is stirred for 3 hours and partially concentrated. The concentrated material is treated with diethyl ether and filtered.

EXAMPLE 52E This example is prepared by substituting example 52D for example 21C in example 21D.

EXAMPLE 52F This example is prepared by replacing Example 52E with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide, in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.08 (br s, 1H), 9.77 (br s, 1H), 8.55 (d, 1H), 8.36 (d, 1H), 7.85 (dd, 1H), 7.77 ( d, 2H), 7.73 (m, 1H), 7.54 (m, 4H), 7.39 (td, 2H), 7.33 (m, 3H), 7.17 (m, 4H), 6.93 (d, 2H), 4.32 (br s, 2H), 4.10 (br s, 2H), 4.09 (quintet, 1H), 3.85 (q, 1H), 3.39 (br, 2H), 3.39 (d, 3H), 3.25 (br s, 2H), 2.89 (br s, 2H), 2.25 (sextet, 2H), 1.79 (m, 2H), 1.64 (m, 2H).

EXAMPLE 53 This example is prepared by substituting Example 52E for 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enyl-sulfonyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide, in Example 32E. 1 H NMR (400 MHz, DMSO-d 6) d 11.94 (br s, 1 H), 8.55 (d, 1 H), 8.35 (d, 1 H), 7.85 (dd, 1 H), 7.68 (d, 2 H), 7.42 (t , 2H), 7.35 (m, 3H), 7.28 (m, 3H), 7.16 (m, 4H), 6.82 (d, 2H), 4.09 (quintet, 1H), 3.84 (q, 1H), 3.39 (d, 2H), 3.03 (s, 3H), 2.89 (s, 2H), 2.83 (t, 1H), 2.25 (sextet, 2H), 1.79 (m, 2H), 1.64 (m, 2H), 1.47 (d, 2H) ), 1.17 (m, 2H).

EXAMPLE 54 This example is prepared by substituting 3-nitro-4 - ((2- (phenylisulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1R) -3- (d-N-methylamino) -1 - ((f-enylsulfanyl) methyl) prop yl) amino) -3-nitrobenzenesulfonamide in Example 4C. 1 H NMR (400 MHz, DMSO-d 6) d 12.06 (br s, 1 H), 9.72. (br s, 1H), 8.76 (t, 1H), 8.60 (d, 1H), 7.90 (dd, 1H), 7.75 (d, 2H), 7.71 (m, 1H), 7.52 (br s, 2H), 7.41 (dd, 2H), 7.35 (m, 2H), 7.28 (m, 2H), 7.19 (m, 2H), 6.92 (d, 2H), 4.24 (br s, 2H), 3.80 (br s, 2H) , 3.66 (q, 2H), 3.28 (t, 2H), 3.14 (br s, 2H), 2.86 (br s, 2H).

EXAMPLE 55A This example is prepared by substituting 3,4-dichlorophenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 55B This example is prepared by substituting example 55A for example 2B in example 2C.

EXAMPLE 55C This example is prepared by substituting example 55B and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.05 (br s, 1H), 9.71 (br s, 1H), 8.76 (t, 1H), 8.60 (d, 1H), 7.90 (dd, 1H), 7.76 ( d, 2H), 7.73 (m, 1H), 7.71 (d, 2H), 7.54 (m, 2H), 7.36 (m, 4H), 7.26 (tt, 2H), 7.18 (m, 2H), 6.94 (d , 2H), 4.28 (br s, 2H), 3.85 (br s, 2H), 3.67 (q, 2H), 3.28 (t, 2H), 3.12 (br s, 2H), 2.93 (br s, 2H).

EXAMPLE 56 This example is prepared by substituting example 55B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (br s, 1 H), 9.94 (br s, 1 H), 9.64 (br s, 1 H), 8.54 (d, 1 H), 8.29 (d, 1 H), 7.86. (dd, 1H), 7.78 (d, 2H), 7.74 (m, 1H), 7.71 (d, 1H), 7.69 (br, 1H), 7.54 (m, 2H), 7.37 (m, 2H), 7.23 (m, 2H), 7.14 (m, 4H), 6.95 (d, 2H), 4.31 (br s, 2H), 4.20 (m, 1H), 3.93 (br s, 2H), 3.39 (d, 3H), 3.14 (m, 5H), 2.90 (m, 2H), 2.75 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 57 This example is prepared by substituting example 55B and 4 - (((1R) -3- (4-morpholinyl) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in the example 2D . 1 H NMR (400 MHz, DMSO-d 6) d 12.12 (br s, 1 H), 10.32 (br s, 1 H), 9.98 (br, 1 H), 8.55 (d, 1 H), 8.30 (d, 1 H), 7.87. (dd, 1H), 7.77 (d, 2H), 7.71 (br s, 1H), 7.70 (d, 2H), 7.53 (m, 2H), 7.36 (m, 2H), 7.24 (m, 2H), 7.15 (m, 4H), 6.94 (d, 2H), 4.25 (br s, 2H), 4.19 (m, 1H), 3.95 (m, 4H), 3.63 (m, 3H), 3.40 (d, 5H), 3.19 (m, 4H), 3.02 (br s, 4H), 2.18 (dd, 2H).

EXAMPLE 58A This example is prepared by substituting 4-trifluoromethylphenylboronic acid for 4-cyclophenylboronic acid in Example 2B.

EXAMPLE 58B This example is prepared by substituting example 58A for example 2B in example 2C.

EXAMPLE 58C This example is prepared by substituting example 58B and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-de) d 12.07 (br s, 1H), 9.85 (br s, 1H), 8.76 (t, 1H), 8.60 (d, 1H), 7.90 (dd, 1H), 7.83 (d, 2H), 7.78 (br s, 1H), 7.76 (d, 2H), 7.61 (d, 2H), 7.54 (m, 2H), 7.37 (m, 3H), 7.26 (t, 2H), 7.19 (t, 2H), 6.93 (d, 2H), 4.30 (br s, 2H), 4.00 (br s, 4H), 3.67 (q, 2H), 3.28 (t, 2H), 3.10 (br s, 2H), 2.94 (br s, 2H) ).

EXAMPLE 59 This example is prepared by substituting example 58B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.08 (br s, 1H), 10.01 (br s, 1H), 9.60 (br, 1H), 8.54 (d, 1H), 8.29 (d, 1H), 7.86. (dd, 1H), 7.82 (d, 2H), 7.78 (br s, 1H), 7.77 (d, 2H), 7.61 (d, 2H), 7.56 (m, 2H), 7.37 (m, 1H), 7.23 (m, 2H), 7.14 (m, 4H), 6.93 (d, 2H), 4.25 (br s, 2H), 4.19 (m, 1H), 3.98 (br s, 2H), 3.39 (d, 3H), 3.13 (m, 5H), 2.90 (m, 2H), 2.74 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 60 This example is prepared by substituting example 58B and 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.08 (br s, 1 H), 9.99 (br s, 2 H), 8.55 (d, 1 H), 8.29 (d, 1 H), 7.86 (dd, 1 H), 7.83 ( d, 2H), 7.79 (br s, 1H), 7.77 (d, 2H), 7.60 (d, 2H), 7.57 (m, 2H), 7.38 (m, 1H), 7.23 (m, 2H), 7.14 ( m, 4H), 6.93 (d, 2H) -, 4.32 (br s, 2H), 4.19 (m, 1H), 3.95 (m, 2H), 3.62 (m, 3H), 3.40 (m, 5H), 3.20 (m, 4H), 3.02 (br s, 4H), 2.18 (dd, 2H).

EXAMPLE 61A This example is prepared by substituting 4-trifluoromethoxyboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 61B This example is prepared by substituting example 61A for example 2B in example 2C.

EXAMPLE 61C This example is prepared by substituting example 61B and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.05 (br s, 1 H), 9.78 (br s, 1 H), 8.76 (t, 1 H), 8.60 (d, 1 H), 7.90 (dd, 1 H), 7.76 ( d, 2H), 7.75 (br s, 1H), 7.54 (m, 2H), 7.50 (d, 2H), 7.45 (d, 2H), 7.37 (m, 3H), 7.26 (t, 2H), 7.18 ( m, 2H), 6.93 (d, 2H), 4.30 (br s, 2H), 3.98 (br s, 4H), 3.67 (q, 2H), 3.28 (t, 2H), 3.11 (br s, 2H), 2.89 (br s, 2H).

EXAMPLE 62 This example is prepared by substituting example 61 B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (br s, 1 H), 10.05 (br s, 1 H), 9.62 (br s, 1 H), 8.54 (d, 1 H), 8.29 (d, 1 H), 7.86. (dd, 1H), 7.77 (d, 2H), 7.76 (br s, 1H), 7.54 (m, 2H), 7.50 (d, 2H), 7.45 (d, 2H), 7.37 (m, 1H), 7.23 (m, 2H), 7.14 (m, 4H), 6.93 (d, 2H), 4.31 (br s, 2H), 4.19 (m, 1H), 3.82 (br s, 2H), 3.39 (d, 3H), 3.13 (m, 5H), 2.92 (m, 2H), 2.74 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 63 This example is prepared by replacing Example 61 B and 4 - (((1 R) -3- (4-morpholin I I) - 1 - ((phenylsulfonyl) methy) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (d imeti lamino) -1 - ((f-enyl-sulfanyl) -methyl) -propyl) -amino) -3 -nitrobencenesulfonamide, respectively, in the 2D example. 1 H NMR (400 MHz, DMSO-d 6) d 12.13 (br s, 1 H), 9.99 (br s, 2H), 8.55 (d, 1H), 8.29 (d, 1H), 7.86 (dd, 1H), 7.77 (d, 2H), 7.76 (br s, 1H), 7.54 (m, 2H), 7.51 (d, 2H), 7.45 (d, 2H), 7.37 (m, 1H), 7.23 (m, 2H), 7.14 (m, 4H), 6.93 (d, 2H), 4.30 (br s, 2H), 4.20 (m, 1H), 3.95 (m, 2H), 3.63 (m, 3H), 3.40 (m, 5H), 3.20 (m, 4H), 3.02 (br s, 4H), 2.18 (dd, 2H).

EXAMPLE 64A This example is prepared by substituting 4-phenoxyphenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 64B This example is prepared by substituting example 64A for example 2B in example 2C.

EXAMPLE 64C This example is prepared by substituting example 64B and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-d6) d 12.05 (br s, 1 H), 9.76 (br s, 1 H), 8.76 (t, 1 H), 8.60 (d, 1 H), 7.91 (dd, 1 H), 7.77 (d, 2H), 7.73 (br s, 1 H), 7.52 (m, 2H), 7.38 (m, 7H), 7.26 (t, 2H), 7.18 (m, 3H), 7.07 ( m, 4H), 6.94 (d, 2H), 4.36 (br s, 2H), 3.80 (br s, 4H), 3.67 (q, 2H), 3.28 (t, 2H), 3.1 5 (br s, 2H) , 2.87 (br s, 2H).

EXAMPLE 65 This example is prepared by substituting example 64B and 4 - (((1 R) -3- (4-moirpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1 R) -3- (dimethylamido) -1 - ((f -nylsulf- nyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide, respectively , in the 2D example. 1 H NMR (400 MHz, DMSO-d 6) d 12.07 (br s, 1H), 9.98 (br s, 2H), 8.56 (d, 1H), 8.30 (d, 1H), 7.87 (dd, 1H), 7.78 ( d, 2H), 7.73 (br s, 1H), 7.51 (m, 2H), 7.38 (m, 5H), 7.23 (m, 2H), 7.15 (m, 5H), 7.07 (d, 4H), 6.95 ( d, 2H), 4.31 (br s, 2H), 4.20 (m, 1H), 3.94 (m, 2H), 3.63 (m, 3H), 3.40 (m, 5H), 3.19 (m, 4H), 3.02 ( br s, 4H), 2.18 (dd, 2H).

EXAMPLE 66A ADDP (11.43 g) in THF (100 ml) at 25 ° C is treated with tributylphosphine (9.16 g), stirred for 10 minutes, treated with (S) -3-tert-butoxycarbonylamino-4-hydroxybutyric acid cyclohexyl ester. (9.1 g), which is prepared as described in Tet. Lett. (1995), 36 (8), 1223, in THF (20 ml) and thiophenol (6.61 g), stirred for 2 days, treated with diethyl ether, and filtered. The filtrate is concentrated, and the concentrated material is subjected to flash chromatography on silica gel with 0-15% ethyl acetate / hexane.

EXAMPLE 66B A mixture of Example 66A (7.1 g) and 4M HCl in dioxane (30 mL) is stirred for 5 hours and concentrated.

EXAMPLE 66C This example is prepared by substituting example 66B for example 21 C in example 21 D.

EXAMPLE 66D A mixture of Example 66C (8.341 g) and lithium hydroxide (1.426 g) in THF / water 1: 1 (100 ml) is stirred for 18 hours at 25 ° C, partially concentrated, treated with water (250 ml). mi), washed with dichloromethane / ethyl acetate, acidified with 12M HCl to pH 2, and extracted with ethyl acetate. The extract is washed with water and brine and dried (MgSO 4), filtered, and concentrated.

EXAMPLE 66E A mixture of example 66D (6.42 g) and NMM (1.67 g) in DME (70 ml) at 0-5 ° C is treated with isobutyl chloroformate (2.14 ml), stirred for 5 minutes, treated with dimethylamine 2M in THF (40 mL), stir at 25 ° C, concentrate, and filter.

EXAMPLE 66F This example is prepared by substituting example 66E for example 18E in example 18F.

EXAMPLE 66G This example is prepared by replacing Example 66F with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-de) d 9.69 (br s, 1 H), 8.47 (d, 1H), 8.19 (d, 1H), 7.82 (dd, 1H), 7.72 (d, 2H), 7.51 (m, 1H), 7.47 (s, 4H), 7.37 (m, 2H), 7.30 (m, 2H), 7.24 (t, 3H), 7.16 (m, 1H), 6.93 (d, 1H), 6.80 (d, 2H), 4.07 (br s, 2H), 3.39 (m, 2H), 3.33 (m, 2H), 3.14 (m, 4H), 3.00 (m, 2H), 2.63 (s, 6H), 2.40 (m, 4H), 2.08 (m, 2H).

EXAMPLE 67A ADDP (16.94 g) in THF (90 ml) at 25 ° C is treated with tributylphosphine (13.55 g), stirred for 10 minutes, treated with tert-butyl ester of (2-hydroxy-1,1-dimethylethyl) acid. Carboxy (8.47 g), which is prepared as described in Synlett. (1997), (8), 893-894, in THF (30 ml) and thiophenol (7.38 g), stirred for 1 day, treated with diethyl ether, and filtered. The filtrate is concentrated, and the concentrated material is subjected to flash chromatography on silica gel 0-15% ethyl acetate / hexanes.

EXAMPLE 67B A mixture of Example 67A (0.562 g) and 80% monoperoxy phthalic acid and magnesium (1.36 g) in THF (10 mL) is stirred for 18 hours, treated with dichloromethane, and filtered. The filtrate is washed with brine and dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel 10-50% ethyl acetate / hexanes.

EXAMPLE 67C This example is prepared by substituting example 67B for example 66A in example 66B.

EXAMPLE 67D This example is prepared by substituting example 67C for example 21 C in example 21 D.

EXAMPLE 67E This example is prepared by substituting Example 67D for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d6) d 12.1 1 (br s, 1 H), 9.69 (br s, 1 H), 8.44 (d, 1 H), 8.33 (s, 1 H), 7.82 (d , 2H), 7.71 (dd, 2H), 7.64 (td, 2H), 7.52 (d, 3H), 7.40 (d, 2H), 7.32 (m, 1 H), 7.25 (d, 1 H), 7.23 (d, tut, 1H), 7.16 (tt, 2H), 6.95 (d, 2H), 4.30 (br s, 2H), 4.13 (s, 2H), 3.84 (br s, 2H), 3.13 (br s, 4H), 2.86 (br s, 2H), 1.62 (s, 6H).

EXAMPLE 68A This example is prepared by substituting 2,4-dichlorophenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 68B This example is prepared by substituting example 68A for example 2B in example 2C.

EXAMPLE 68C This example is prepared by substituting example 68B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (br s, 1 H), 9.89 (br s, 1 H), 9.56 (br s, 1 H), 8.54 (d, 1 H), 8, .28 (d, 1 H ), 7.85 (dd, 1H), 7.77 (d, 2H), 7.74 (m, 1H), 7.52 (m, 3H), 7.43 (d, 1H), 7.26 (d, 1H), 7.22 (d, 2H), 7.13 (m, 4H), 6.94 (d, 2H), 4.26 (br s, 2H), 4.17 (m, 1H), 3.38 (d, 3H), 3.13 (m, 7H), 2.74 (s, 6H), 2.14 (dd, 2H).

EXAMPLE 69A This example is prepared by substituting thiophene-2-boronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 69B This example is prepared by substituting example 69A for example 2B in example 2C.

EXAMPLE 69C This example is prepared by substituting example 69B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.11 (br s, 1 H), 9.95 (br s, 1H), 9.55 (br s, 1H), 8.54 (d, 1H), 8.29 (d, 1H), 7.85 (dd, 1H), 7.78 (d, 2H), 7.73 (m, 1H), 7.68 (d, 1H), 7.51 (m, 3H), 7.24 (m, 2H), 7.17 (m, 2H), 7.14 (m, 4H), 6.96 (d, 2H), 4.41 (br s, 2H), 4.18 (m, 1H), 3.38 (d, 3H), 3.13 (m, 7H), 2.75 (s, 6H), 2.15 (dd, 2H).

EXAMPLE 70A This example is prepared by substituting 4-chloro-2-methylphenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 70B This example is prepared by replacing example 70A with example 2B in example 2C.

EXAMPLE 70C This example is prepared by substituting example 70B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (m, 1H), 9.60 (s, 1H), 8.53 (d, 1H), 8.28 (d, 1H), 7.85 (dd, 1H), 7.77 (d, 3H), 7.52 (m, 2H), 7.41 (d, 1H), 7.31 (dd, 1H) ), 7.20 (m, 4H), 7.12 (m, 4H), 6.94 (d, 1H), 4.18 (m, 1H), 3.85 (m, 7H), 3.38 (d, 2H), 3.11 (m, 6H) , 2.74 (s, 6H), 2.14 (dd, 2H), 1.96 (s, 3H).

EXAMPLE 71A This example is prepared by substituting 2,4-difluorophenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 71B This example is prepared by substituting example 71A for example 2B in example 2C.

EXAMPLE 71C This example is prepared by substituting example 71 B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.07 (br s, 1 H), 9.53 (br s, 1 H), 8.53 (d, 1 H), 8.27 (d, 1 H), 7.85 (dd, 1 H), 7.76 ( d, 2H), 7.54 (quintet, 2H), 7.44 (m, 1H), 7.35 (m, 2H), 7.15 (m, 6H), 6.93 (d, 2H), 4.17 (m, 1H), 3.38 (d , 2H), 3.12 (m, 4H), 2.74 (s, 3H), 2.73 (s, 3H), 2.13 (dd, 2H).

EXAMPLE 72A This example is prepared by substituting (2-benzenesulfonylethyl) carbamic acid tert-butyl ester, which is prepared as described in WO2001-US11395, by example 66A in example 66B.

EXAMPLE 72B This example is prepared by substituting example 72A for example 21C in example 21D.

EXAMPLE 72C This example is prepared by substituting Example 72B for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400 MHz, DMSO-d 6) d 12.09 (br s, 1H), 9.60 (br s, 1H), 8.56 (d, 1H), 8.55 (m, 1H), 7.91 (dd, 1H), 7.84 ( m, 2H), 7.75 (d, 3H), 7.67 (tt, 1H), 7.54 (m, 2H), 7.48 (m, 4H), 7.37 (m, 3H), 7.13 (d, 2H), 6.92 (d , 2H), 4.40 (br s, 2H), 3.82 (br s, 2H), 3.79 (s, 2H), 3.29 (br s, 2H), 3.13 (br s, 2H), 2.81 (br s, 2H) .

EXAMPLE 73 This example is prepared by replacing Example 72B with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (br s, 1 H), 9.52 (br s, 1 H), 8.56 (d, 1 H), 8.55 (m, 1 H), 7.91 (dd, 1 H), 7.84 ( m, 2H), 7. 76 (d, 2H), 7.67 (tt, 1H), 7.54 (m, 6H), 7.39 (m, 2H), 7.34 (m, 1H), 7. 14 (d, 1H), 6.92 (d, 2H), 4.38 (br s, 2H), 3.92 (br s, 2H), 3.78 (s, 4H), 3.26 (br s, 2H), 3.09 (br s, 2H), 2.86 (br s, 2H).

EXAMPLE 74 This example is prepared by substituting Example 31 E for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) -amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400 MHz, DMSO-d 6) d 12.06 (br s, 1 H), 9.88 (br s, 1 H), 8.68 (d, 1 H), 8.54 (d, 1 H), 7.86 (dd, 1 H), 7.76 ( d, 2H), 7.72 (m, 1H), 7.50 (m, 4H), 7.46 (m, 2H), 7.41 (d, 1H), 7.37 (m, 2H), 7.26 (m, 2H), 7.07 (t , 2H), 6.97 (t, 1H), 6.92 (d, 2H), 4.73 (quintet, 1H), 4.44 (dd, 1H), 4.31 (dd, 1H), 4.24 (brs, 2H), 4.17 (dd) , 1H), 3.75 (m, 2H), 3.24 (br s, 4H), 2.88 (br s, 4H).

EXAMPLE 75A This example is prepared by substituting 5-methylthiophen-2-boronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 75B This example is prepared by replacing example 75A with example 2B in example 2C.

EXAMPLE 75C This example is prepared by replacing example 75B with example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.07 (br s, 1H), 10.00 (br s, 1H), 9.58 (br, 1H), 8.55 (d, 1H), 8.29 (d, 1H), 7.85. (dd, 1H), 7.79 (d, 2H), 7.70 (br s, 1H), 7.47 (m, 3H), 7.23 (d, 2H), 7.18 (m, 2H), 7.14 (m, 2H), 7.03 (d, 1H), 6.97 (d, 2H), 6.86 (m, 1H), 4.40 (br s, 2H), 4.19 (m, 1H), 3.39 (d, 3H), 3.13 (m, 3H), 2.99 (br s, 2H), 2.75 (s, 6H), 2.48 (s, 3H), 2.15 (dd, 2H).

EXAMPLE 76A This example is prepared by substituting example 31 C for example 67A in example 67B.

EXAMPLE 76B This example is prepared by substituting example 76A for example 66A in example 66B.

EXAMPLE 76C This example is prepared by replacing example 76B with example 21C in example 21D.

EXAMPLE 76D This example is prepared by substituting Example 76C for 4 - (((1R) -3- (dimethylamine) -1 - ((f-enyl-sulfonyl) -methyl) propyl-I) -amino) -3-nitrobenzenesulfonamide in Example 2D . H NMR (500 MHz, DMSO-d6) d 12.09 (br s, 1H), 9.87 (br s, 1H), 8.50 (d, 1H), 8.48 (d, 1H), 7.82 (d, 2H), 7.77 ( dd, 1H), 7.75 (m, 1H), 7.71 (dd, 2H), 7.53 (m, 4H), 7.39 (m, 2H), 7.34 (m, 1H), 7.25 (m, 3H), 7.12 (d , 1H), 6.96 (d, 2H), 4.88 (sextet, 1H), 4.80 (quintet, 1H), 4.46 (dd, 1H), 4.28 (br s, 2H), 4.23 (dd, 1H), 4.09 (dd) , 1H), 3.86 (dd, 1H), 3.14 (br s, 2H), 2.96 (br s, 4H).

EXAMPLE 77 This example is prepared by replacing Example 76c with 4 - (((1R) -3- (d-methylamino) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (500 MHz, DMSO-d 6) d 12.11 (br s, 1 H), 9.90 (br s, 1 H), 8.50 (d, 1 H), 8.48 (d, 1 H), 7.82 (d, 2 H), 7.77 ( dd, 1H), 7.75 (m, 1H), 7.71 (dd, 2H), 7.52 (m, 2H), 7.48 (t, 2H), 7.42 (t, 1H), 7.36 (m, 2H), 7.23 (m , 3H), 7.12 (d, 1H), 6.96 (d, 2H), 4.88 (sextet, 1H), 4.80 (quintet, 1H), 4.46 (dd, 1H), 4.30 (br s, 2H), 4.22 (dd) , 1H), 4.09 (dd, 1H), 3.86 (dd, 1H), 3.17 (br s, 2H), 2.89 (br s, 4H).

EXAMPLE 78 This example is prepared by replacing the example 832175D by example 49A in example 49B. 1 H NMR (500 MHz, DMSO-d 6) d 11.96 (br s, 1 H), 10.46 (br s, 1 H), 8.60 (d, 1 H), 8.49 (d, 1 H), 7.95 (dd, 1 H), 7.76 ( d, 2H), 7.69 (m, 1H), 7.51 (m, 4H), 7.40 (t, 4H), 7.32 (m, 1H), 7.24 (m, 4H), 6.92 (d, 2H), 4.69 (br s, 1H), 4.25 (br s, 2H), 3.97 (br s, 2H), 3.68 (m, 2H), 3.29 (br s, 4H), 2.91 (s, 3H), 2.75 (br s, 2H) .

EXAMPLE 79 This example is prepared by replacing the example 837538C and 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsufinyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.50 (d, 1H), 8.36 (d, 1H), 7.79 (dd, 1H), 7.72 (d, 2H), 7.36 (d, 2H), 7.28 (d, 2H), 7.21 (t, 2H), 7.15 (d, 1H), 7.12 (d, 2H), 7.03 (d, 1H), 6.84 (d, 2H), 4.13 (m, 1H), 3.52 (m, 4H) ), 3.38 (m, 4H), 3.21 (br s, 4H), 2.82 (br s, 2H), 2.45 (m, 4H), 2.32 (br s, 4H), 2.20 (br s, 2H), 2.17 ( br s, 2H), 2.00 (m, 1H), 1.86 (m, 1H), 1.67 (m, 4H).

EXAMPLE 81A This example is prepared by substituting 4-bromophenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 81B This example is prepared by substituting example 81A for example 2B in example 2C.

EXAMPLE 81 C This example is prepared by substituting example 81 B for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d6) d 12.06 (br s, 1 H), 9.79 (br s, 1 H), 9.47 (br s, 1 H), 8.54 (d, 1 H), 8.28 (d, 1 H), 7.86 (dd, 1 H), 7. 77 (d, 2H), 7.69 (br s, 1 H), 7.64 (d, 2H), 7.50 (m, 2H), 7.35 (m, 3H), 7.23 (m, 2H), 7.14 (m, 4H) , 6.93 (d, 2H), 4.29 (br s, 2H), 4.19 (m, 1 H), 3.77 (br s, 2H), 3.14 (m, 3H), 2.74 (s, 6H), 2.14 (dd, 2H).

EXAMPLE 82A The 4'-chloro-biphenyl-2-carbonitrile compound, which is prepared as described in J. Org. Chem. (1984), 49 (9), 1594-1603), (0.35 g) in diethyl ether (25 ml) at -75 ° C is treated with titanium isopropoxide (0.53 ml) and 3M ethylmagnesium bromide in diethyl ether (1 0.2 ml), stirred for 10 minutes, stirred at 25 ° C for 1 hour, treated with BF3-diethyl etherate (0.41 ml), stirred for 1 hour, treated with 1 M HCl (5 ml) then 10% NaOH (15 mL), and extracted with diethyl ether. The extract is dried (MgSO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel 10% -50% ethyl acetate / hexanes).

EXAMPLE 82B A mixture of 4- (bis- (2-methanesulfonyloxyethyl) -amino) -benzoic acid ethyl ester, which is prepared as described in J. Med. Chem. (1977), 21 (1), 16-26, (80.6 mg), example 82A (58.5 mg), and potassium carbonate (69.1 mg) in acetonitrile (5 ml) in a microwave reactor at 160 ° C. , stirred for 30 minutes, treated with ethyl acetate (10 mL), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10-30% ethyl acetate / hexanes.

EXAMPLE 82C This example is prepared by substituting example 82B for example 2B in example 2C.

EXAMPLE 82D This example is prepared by substituting example 82C for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d6) d 12.02 (br s, 1 H), 9.49 (br s, 1 H), 8.54 (d, 1 H), 8.28 (d, 1 H), 7.86 (dd, 1 H), 7.73 (d, 2H), 7.47 (m, 5H), 7.38 (m, 2H), 7.23 (d, 2H), 7.14 (m, 5H), 6.89 (d, 2H), 4.18 (m, 2H), 3.39 (d, 2H), 3.20 (m, 6H), 2.75 (s, 3H), 2.74 (s, 3H), 2.44 (br s, 4H), 2.1 3 (dd, 2H), 1 .01 (br s, 2H), 0.82 (br s, 2H).

EXAMPLE 83A A mixture of 2M dimethylamine in THF (27 ml), acid (R) -2-benzyloxycarbonylamino-3-phenylthiopropionic acid (5.8 g), HoBT (2.67 g), and EDAC HCl (5.2 g) in THF (50 ml) is stirred for 18 hours at 25 ° C, treated with water and it is extracted with dichloromethane. The extract is dried (MgSO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 15-50% ethyl acetate / hexanes.

EXAMPLE 83B This example is prepared by substituting example 83A for example 18B in example 18C.

EXAMPLE 83C This example is prepared by substituting example 83B for example 18E in example 18F.

EXAMPLE 83D This example is prepared by substituting example 83C for example 21C in example 21D.

EXAMPLE 83E This example is prepared by replacing the example 837538C and example 83D by example 2C and 4 - (((1R) -3- (d imeti lamino) -1 - ((f-enylsulfanyl) methyl) propyl) am i no) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 12.11 (br s, 1 H), 9.46 (br s, 1 H), 9.36 (br s, 1 H), 8.52 (d, 1 H), 8.28 (d, 1 H), 7.88 (dd, 1H), 7.79 (d, 2H), 7.41 (d, 2H), 7.35 (d, 2H), 7.17 (m, 4H), 7.09 (m, 2H), 6.96 (d, 2H), 4.67 ( m, 1H), 3.89 (br s, 2H), 3.75 (m, 4H), 3.43 (m, 2H), 3.36 (m, 4H), 3.16 (br s, 2H), 2.82 (s, 3H), 2.75 (s, 3H), 2.26 (br s, 2H), 2.21 (br s, 2H), 1.71 (br s, 4H).

EXAMPLE 84 This example is prepared by substituting Example 83D for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.12 (br s, 1 H), 9.94 (br s, 1H), 9.42 (br s, 1H), 8.51 (d, 1H), 8.28 (d, 1H), 7.87 (dd, 1H), 7. 78 (d, 2H), 7.73 (br s, 1H), 7.52 (d, 4H), 7.39 (d, 2H), 7.34 (m, 2H), 7.17 (m, 2H), 7.09 (m, 3H), 6.93 (d, 2H), 4.66 (m, 1H), 4.29 (br s, 2H), 3.85 (br s, 2H), 3.75 (t , 2H), 3.43 (d, 2H), 3.36 (m, 2H), 3.12 (br s, 4H), 2.87 (br s, 3H), 2.82 (s, 3H).

EXAMPLE 85A This example is prepared by substituting diethylamine for dimethylamine in Example 83A.

EXAMPLE 85B This example is prepared by replacing example 85A with example 18B in example 18C.

EXAMPLE 85C This example is prepared by substituting example 85B for example 18E in example 18F.

EXAMPLE 85D This example is prepared by substituting example 85C for example 21 C in example 21 D.

EXAMPLE 85E This example is prepared by replacing Example 85D with 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.15 (br s, 1 H), 9.99 (br s, 1 H), 9.02 (br s, 1 H), 8.51 (d, 1 H), 8.33 (d, 1 H), 7.87 (dd, 1H), 7.77 (d, 2H), 7.74 (br s, 1H), 7.52 (d, 4H), 7.39 (d, 2H), 7.33 (m, 2H), 7.18 (m, 2H), 7.10 (m, 3H), 6.93 (d, 2H), 4.60 (m, 1H), 4.26 (br s, 2H), 3.85 (br s, 2H), 3.43 (m, 2H), 3.36 (dd, 2H), 3.15 (m, 6H), 2.92 (br s, 4H), 1.19 (m, 6H).

EXAMPLE 86A This example is prepared by substituting morpholine for dimethylamine in Example 83A.

EXAMPLE 86B This example is prepared by replacing example 86A with example 18B in example 18C.

EXAMPLE 86C This example is prepared by replacing example 86B with example 18E in example 18F.

EXAMPLE 86D This example is prepared by substituting example 86C for example 21C in example 21D.

EXAMPLE 86E This example is prepared by replacing Example 86D with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.13 (br s, 1 H), 9.95 (br s, 1H), 8.51 (d, 1H), 8.33 (d, 1H), 7.86 (dd, 1H), 7.78 (d, 2H), 7. 74 (br s, 1H), 7.52 (d, 4H), 7.39 (d, 2H), 7.34 (m, 1H), 7.25 (d, 1H), 7.19 (m, 2H), 7.09 (m, 3H), 6.93 (d, 2H), 4.59 (br s, 1H), 4.29 (br s, 2H), 3.39 (m, 4H), 3.12 (br s, 6H), 2.90 (br s, 3H).

EXAMPLE 87 This example is prepared by substituting example 837538C and example 85D for example 2C and 4 - (((1R) -3- (dimethylamino) -l - ((f-enylsulfanyl) methyl) p-ro-pyl) amino) -3-nitrobenzenesulfonamide , respectively, in the example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.16 (br s, 1 H), 9.67 (br s, 1H), 9.06 (br s, 1H), 8.52 (d, 1H), 8.33 (d, 1H), 7.87 (dd, 1H), 7.79 (d, 2H), 7.41 (d, 2H), 7.33 (d, 1H), 7.17 (m, 4H), 7.10 (m, 3H), 6.96 (d, 2H), 4.61 (m, 1H), 3.88 (br s, 2H), 3.76 (m, 4H), 3.59 (br s, 2H), 3.42 (m, 2H), 3.15 (m, 4H), 2.80 (br s, 2H), 2.27 (br s, 2H), 2.22 (br s, 2H), 1.71 (br s , 4H), 1.19 (dd, 6H).

EXAMPLE 88 This example is prepared by substituting example 837538C and example 86D for example 2C and 4 - (((1R) -3- (d imeti lamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3 -nitrobencenesulfonamide, respectively, in the 2D example. 1 H NMR (400 MHz, DMSO-d 6) d 12.11 (br s, 1 H), 9.97 (br s, 1 H), 9.55 (br s, 1 H), 8.51 (d, 1 H), 8.38 (d, 1 H), 7.86 (dd, 1H), 7.79 (d, 2H), 7.41 (d, 2H), 7.25 (d, 1H), 7.17 (m, 5H), 7.09 (m, 2H), 6.96 (d, 2H), 4.58 ( m, 1H), 3.90 (br s, 2H), 3.39 (m, 4H), 3.17 (br s, 4H), 2.80 (br s, 2H), 2.26 (br s, 2H), 2.22 (br s, 2H) ), 1.71 (br s, 4H).

EXAMPLE 89 A mixture of example 833566 (44.9 mg) and 2.47 mmol / g of MP-BH3CN (0.81 g) in dichloromethane / methanol 1: 1 at 25 ° C (4 ml) is treated with DIEA and acetic acid at pH 5-6, stir for 18 hours, filter, and concentrate. The concentrated material is subjected to chromatography on C-18 with 30-100% acetonitrile / water / 0.1% TFA. 1 H NMR (500 MHz, DMSO-d 6) d 12.1 3 (br s, 1 H), 9.76 (br s, 1 H), 9.18 (br s, 1 H), 8.54 (d, 1 H), 8.32 ( d, 1 H), 7.87 (dd, 1 H), 7.78 (d, 2H), 7.71 (br s, 1 H), 7.53 (m, 4H), 7.41 (d, 2H), 7.34 (m, 1 H) ), 7.23 (m, 3H), 7.14 (m, 3H), 6.93 (d, 2H), 4.33 (br s, 2H), 4.22 (m, 1 H), 3.85 (br s, 2H), 3.12 (m , 4H), 2.82 (s, 3H), 2.19 (m, 2H), 0.81 (m, 4H).

EXAMPLE 90A A mixture of magnesium chips (0.144 g) and a crystal of iodine at 25 ° C is treated with 2-phenylbenzyl bromide (1.48 g) in diethyl ether (10 ml), stirred for 3 hours, cooled to 0 ° C, treated with 4- (4-oxo-piperidin-1-yl) -benzoic acid ethyl ester, which is prepared as described in J. Het. Chem. 1969, 6, 941, (1.48 g) in diethyl ether (5 ml) and THF (5 ml), is stirred at 25 ° C for 18 hours, and treated with ethyl acetate and aqueous NH 4 Cl. The extract is extracted with ethyl acetate, and the combined extracts are dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 25% ethyl acetate / hexane.

EXAMPLE 90B Example 90A (0.27 g) in THF (10 ml) at 25 ° C is treated with 60% oily NaH (0.24 g), stirred for 2 hours at 50 ° C, treated with HMPA (2 ml) and iodide of methyl (2 ml), refluxed for 1 8 hours, cooled to 0 ° C, and treated with ethyl acetate and aqueous NaHS0. The extract is extracted with ethyl acetate, and the combined extracts are dried (Na2SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10% ethyl acetate / hexanes.

EXAMPLE 90C A mixture of Example 90B (0.09 g) and 1 M LiOH (1 mL) in dioxane (5 mL) at 60 ° C is stirred for 18 hours, and concentrated. The material concentrated in water is treated with 2M HCl and filtered.

EXAMPLE 90D This example is prepared by substituting example 90C for example 2C in example 2D. 1 H NMR (400MHz, DMSO-d6) d 1.95 (br s, 1 H), 9.38 (s, 1 H), 8.54 (d, 1 H), 8.28 (d, 1 H), 7.86 (dd, 1 H), 7.70 (d, 2H), 7.30 (m, 10H), 7.15 (m, 4H), 6.82 (d, 2H), 4.19 (m, 1 H), 3.45 (m, 4H), 3.13 (m, 2H), 3.04 (s, 3H), 2.88 (m, 4H), 2.74 (d, 6H), 2.14 (q, 2H), 1 .47 (m, 2H), 1.18 (m, 2H).

EXAMPLE 91 A A mixture of magnesium shavings (0.432 g) and an iodide crystal at 25 ° C is treated with 2-bromobenzyl bromide (4.5 g) in diethyl ether (30 ml), stirred for 3 hours, cooled to 0 °. C, treated with ethyl ester of 4- (4-oxo-piperidin-1-l) -benzoic acid, which is prepared as described in J. Het. Chem. 1969, 6, 941, (3.7 g) in diethyl ether (20 ml) and THF (10 ml), is stirred at 25 ° C for 1 8 hours, and treated with ethyl acetate and aqueous NH 4 Cl. The extract is extracted with ethyl acetate, and the combined extracts are dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexane.

EXAMPLE 91 B Example 91 A (1.6 g) in THF (20 ml) at 25 ° C is treated with 60% oily NaH (0.288 g), stirred for 2 hours at 50 ° C, treated with HMPA (3 ml). ) and methyl iodide (3 mL), stirred at reflux for 18 hours, cooled to 0 ° C, and treated with ethyl acetate and aqueous NaHS04. The extract is extracted with ethyl acetate, and the combined extracts are dried (Na2SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10-15% ethyl acetate / hexanes.

EXAMPLE 91 C A mixture of Example 91 B (0.6 g) and 1 M LiOH (5 mL) in dioxane (5 mL) at 60 ° C is stirred for 18 hours and concentrated. The material concentrated in water is treated with 2M HCl and filtered.

EXAMPLE 91 D This example is prepared by replacing example 91 C with example 2C in example 2D.

EXAMPLE 91 E A mixture of Example 91 D (0.08 g), 3-pyridine-boronic acid (0.04 g), Pd (dppf) 2 C2 (0.01 g), and Cs2CO3 (0.1 g) in DMF (1 ml) at 80 ° C is stirred for 2 days and treated with ethyl acetate and brine. The extract is extracted with ethyl acetate, and the extracts are combined and dried (Na2SO), filtered, and concentrated. The concentrated material is purified by high pressure liquid chromatography on a C8 Symmetry Waters column (25 mm x 100 mm, particle size 7 μm) with 10-100% acetonitrile / 0.1% aqueous TFA in a lapse of 8 minutes at a flow rate of 40 ml / minute. 1 H NMR (400MHz, DMSO-d 6) d 9.44 (s, 1H), 8.64 (d, 2H), 8.54 (d, 1H), 8.28 (d, 1H), 7.97 (dd, 1H), 7.86 (dd, 1H) ), 7.70 (d, 2H), 7.62 (m, 1H), 7.37 (m, 3H), 7.23 (m, 3H), 7.13 (m, 4H), 6.83 (d, 2H), 4.19 (m, 1H) , 3.45 (m, 2H), 3.39 (d, 2H), 3.13 (m, 2H), 2.99 (s, 3H), 2.88 (m, 4H), 2.74 (d, 6H), 2.14 (q, 2H), 1.49 (d, 2H), 1.20 (dt, 2H).

EXAMPLE 92 This example is prepared by substituting 4-pyridine-boronic acid for 4-pyridine boronic acid in Example 91. 1 H NMR (400MHz, DMSO-d 6) d 9.47 (br s, 1H), 8.75 (d, 2H), 8.53 ( d, 1H), 8.28 (d, 1H), 7.86 (dd, 1H), 7.70 (d, 2H), 7.66 (d, 2H), 7.39 (m, 3H), 7.23 (d, 2H), 7.13 (m , 4H), 6.83 (d, 2H), 4.18 (m, 1H), 3.46 (m, 2H), 3.39 (d, 2H), 3.13 (m, 2H), 2.99 (s, 3H), 2.86 (m, 4H), 2.74 (d, 6H), 2.14 (q, 2H), 1.49 (d, 2H), 1.20 (dt, 2H).

EXAMPLE 93 This example is prepared by substituting thiophene-2-boronic acid for 4-pyridineboronic acid in Example 91. 1 H NMR (400MHz, DMSO-d 6) d 8.44 (d, 1H), 8.26 (d, 1H), 7.79 (dd) , 1H), 7.67 (d, 2H), 7.57 (dd, 1H), 7.3 (m, 8 H), 7.17 (d, 1H), 7.10 (m, 2H), 6.87 (d, 1H), 6.71 (d , 2H), 4.05 (m, 1H), 3.30 (m, 4H), 3.12 (s, 3H), 3.03 (s, 2H), 2.74 (m, 4H), 2.43 (s, 6H), 2.00 (m, 2H), 1.55 (d, 2H), 1.30 (dt, 2H).

EXAMPLE 94 This example is prepared by substituting thiophene-3-boronic acid for 4-pyridineboronic acid in Example 91. 1 H NMR (400MHz, DMSO-d 6) d 8.44 (d, 1H), 8.26 (d, 1H), 7.79 (dd, 1H), 7.67 (d, 2H), 7.59 (m, 1H), 7.44 (m, 1H), 7.28 (m, 7H), 7.16 (m, 2H), 6.87 (d, 1H), 6.71 (d, 2H), 4.05 (m, 1H), 3.30 (m, 4H), 3.07 (s, 3H), 2.94 ( s, 2H), 2.74 (m, 4H), 2.45 (s, 6H), 2.00 (m, 2H), 1.49 (d, 2H), 1.25 (dt, 2H).

EXAMPLE 95A The compound N-methyl-2,2,2-trifluoroacetamide (6.35 g) in diethyl ether (25 ml) at -15 ° C is treated with lithium aluminum hydride (3.8 g) in diethyl ether (25 ml) through 1 hour, stirred for 2 hours, stirred at 25 ° C for 16 hours, cooled to 0 ° C, treated with water, and distilled at 34-36 ° C. The distillate is treated with HCl and filtered.

EXAMPLE 95B This example is prepared by replacing Example 95A with isopropylamine in Example 28. 1 H NMR (400MHz, DMSO-d 6) d 8.67 (d, 1H), 8.52 (d, 1H), 7.83 (dd, 1H), 7.74 (d, 2H), 7.52 (d, 1H), 7.47 (m, 4H) ), 7.38 (m, 2H), 7.24 (m, 2H), 7.14 (m, 4H), 6.82 (d, 2H), 4.46 (m, 1H), 4.12 (q, 2H), 3.35 (m, 10H) , 3.04 (s, 3H), 2.42 (m, 4H).

EXAMPLE 96A This example is prepared by substituting 2,2,2-trifluoroethylamine for isopropylamine in Example 28.

EXAMPLE 96 Treat with borane-dimethyl sulfide (0.37 ml) with example 96A (110 mg) in THF (2 ml) at 25 ° C, for 5 hours, treat with methanol, and concentrate. The concentrated material is purified by HPLC with 0-70% acetonitrile / water / 0.1% TFA 1 H NMR (400MHz, DMSO-d 6) d 8.53 (d, 1H), 8.30 (d, 1H), 7.84 (dd, 1H), 7.76 (d, 2H), 7.52 (m, 3H), 7.35 (m, 4H) ), 7.15 (m, 6H), 6.92 (d, 2H), 4.46 (m, 1H), 3.75 (m, 2H), 3.5 (m, 12H), 2.42 (m, 4H).

EXAMPLE 97A This example is prepared by substituting methyl trifluoroacetamide for example 100A in Example 100B.

EXAMPLE 97B This example is prepared by substituting example 97A and example 30A for isopropylamine and example 27E in example 28.

EXAMPLE 97C This example is prepared by substituting example 97C for example 96A in example 96.

EXAMPLE 97D This example is prepared by substituting example 97C for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400MHz, DMSO-d6) d 8.72 (d, 1 H), 8.59 (d, 1 H), 7.99 (d, 1 H), 7.95 (d, 2H), 7.71 (m, 3H), 7.55 (m, 3H), 7.41 (d, 2H), 7.29 (m, 5H), 7.1 1 (d, 2H), 4.46 (br s, 1 H), 4.33 (m, 1 H), 3. 75 (m, 12H), 3.31 (q, 2H), 2.78 (m, 2H), 2.68 (s, 3H), 2.09 (m, 2H).

EXAMPLE 98 This example is prepared by substituting example 32D and 4 - (((1R) -3- (4-morpholinyl) -l - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (d-methylamino) -1 - ((f-enylsulfanyl) methyl) propyl) am i -no) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (400MHz, DMSO-d 6) d 9.71 (s, 1H), 8.54 (d, 1H), 8.29 (d, 1H), 7.87 (dd, 1H), 7.69 (d, 2H), 7.46 (d, 2H) ), 7.30 (m, 7H), 7.14 (m, 4H), 6.82 (d, 2H), 4.18 (m, 1H), 3.95 (m, 2H), 3.67 (m, 4H), 3.39 (m, 4H), 3.19 (m, 2H), 3.03 (s, 3H), 3.00 (m, 2H), 2. 85 (m, 4H), 2.17 (m, 2H), 1.47 (d, 2H), 1.17 (t, 2H).

EXAMPLE 99 This example is prepared by substituting example 32D and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyI) propyl) -amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400MHz, DMSO-d 6) d 8.74 (t, 1H), 8.53 (d, 1H), 7.90 (dd, 1H), 7.68 (d, 2H), 7.46 (d, 2H), 7.46 (m, 3H), 7.28 (m, 6H), 7.16 (m, 3H), 6.81 (d, 2H) ), 3.66 (q, 2H) 3.41 (m, 2H), 3.03 (s, 3H), 2.48 (m, 4H), 1.47 (m, 2H), 1.18 (dt, 2H).

EXAMPLE 100A Trifluoroacetic anhydride (15 g) is treated in diethyl ether (80 ml) at -10 ° C is treated with ethylamine for 40 minutes and distilled under vacuum at 68 ° C.

EXAMPLE 100B Example 100A (7.8 g) in diethyl ether (25 ml) at -15 ° C is treated with lithium aluminum hydride (4.17 g) in diethyl ether (25 ml) over a period of 1 hour, stirred for 2 hours then at 25 ° C for 16 hours, it is cooled to 0 ° C, treated with water (10 ml), 15% NaOH (10 ml), and water (30 ml), stirred for 30 minutes, and filtered . The filtrate is washed with water and brine, dried (Na S04), and filtered. The filtrate is treated with HCl, and filtered.

EXAMPLE 100C This example is prepared by replacing Example 100B and Example 30A with isopropylamine and Example 27E in Example 28.

EXAMPLE 100D This example is prepared by substituting example 100C for example 96A in example 96.

EXAMPLE 100E This example is prepared by substituting Example 100D for 4 - (((1 R) -3- (d-imethylamino) -1- ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 11.90 (br s, 1 H), 8.51 (d, 1H), 8.32 (d, 1H), 7.80 (dd, 1H), 7.74 (d, 2H), 7.46 (m, 5H), 7.37 (m, 2H), 7.24 (d, 2H), 7.12 (m, 3H), 7.02 (d, 1H), 6.89 (d, 2H), 4.12 (m, 1H), 3.42 (s, 2H), 3.35 (m, 6H), 3.13 (q, 2H), 2.63 (t, 2H), 2.56 (q, 2H), 2.40 (s, 4H), 1.90 ( m, 2H), 0.88 (t, 3H).

EXAMPLE 101 This example is prepared by substituting 2-fluoroethylamine for isopropylamine in Example 35B. 1 H NMR (400MHz, DMSO-d 6) d 8.80 (s, 2H), 8.53 (d, 1H), 8.26 (d, 1H), 7.86 (dd, 1H), 7.75 (m, 3H), 7.52 (m, 4H), 7.38 (d, 2H), 7.33 (m, 1H), 7.15 (m, 5H), 6.92 (d, 2H), 4.71 (t, 1H), 4.61 (t, 1H), 4.30 (, 2H), 4.21 (m, 1H), 3.38 (d, 2H), 3.25 (m, 12H), 2.11 (m, 2H).

EXAMPLE 102 This example is prepared by substituting 2,2-difluoroethylamine for isopropylamine in Example 35B. 1 H NMR (400MHz, DMSO-d6) d 9.1 5 (s, 2H), 8.53 (d, 1 H), 8.26 (d, 1 H), 7.86 (dd, 1 H), 7.77 (d, 2H), 7.74 (m, 1 H), 7.52 (m, 4H), 7.38 (d, 2H), 7.33 (m, 1 H), 7.1 5 (m, 5H), 6.92 (d, 2H), 6.36 (tt, 1 H), 4.23 (m, 1 H), 4.00 (m, 4H), 3.49 (t, 2H), 4.39 (d, 2H), 3.10 (m, 4H), 2.90 (m, 2H), 2.54 (s, 2H), 2.1 3 (m, 2H).

EXAMPLE 103A A mixture of Example 2 (250 mg) and Pd on 10% carbon (100 mg) in methanol (5 ml) and ethyl acetate (5 ml) at 25 ° C under H2 (balloon) was stirred for 18 hours, filter through diatomaceous earth (Celite®), and concentrate.

EXAMPLE 103B A mixture of Example 103A (0.06 g) in 80% formic acid (3 mL) at 100 ° C is stirred for 3 hours and concentrated. The concentrated material is purified by high pressure liquid chromatography on a C8 Symmetry Waters column (25 mm x 100 mm, particle size 7 μm) with 10-100% acetonitrile / 0.1% aqueous TFA in a lapse of 8 minutes at a flow rate of 40 ml / minute. 1 H NMR (400MHz, DMSO-d 6) d 12.01 (s, 1H), 9.64 (s, 1H), 8.56 (s, 1H), 8.22 (s, 1H), 7.83 (d, 1H), 7.75 (m, 4H), 7.52 (m, 4H), 7.40 (d, 2H), 7.33 (m, 1H), 7.14 (m, 3H), 7.07 (m, 1H), 6.92 (d, 2H), 4.76 (m, 1H), 3.85 (m, 6H) ), 3.66 (d, 2H), 3.15 (m, 4H), 2.71 (s, 6H), 2.45 (m, 2H).

EXAMPLE 104 A mixture of Example 103A (0.06 g) and 12M HCl (0.56 mL) in acetic acid (2 mL) at 0 ° C is treated with NaN02 (7.2 mg) in water (0.38 mL), stirred for 2 hours, and concentrate The concentrated material is purified by high pressure liquid chromatography on a C8 Symmetry Waters column (25 mm x 100 mm, particle size 7 μm) with 10-100% acetonitrile / 0.1% aqueous TFA in a lapse of 8 minutes at a flow rate of 40 ml / minute. 1 H NMR (400MHz, DMSO-d 6) d 9.50 (s, 1H), 8.57 (s, 1H), 8.06 (d, 1H), 7.99 (d, 1H), 7.77 (d, 2H), 7.74 (m, 1H) ), 7.52 (m, 4H), 7.42 (d, 2H), 7.33 (m, 1H), 7.04 (m, 5H), 6.92 (d, 2H), 5.24 (m, 1H), 3.74 (m, 2H) , 3.45 (m, 6H), 3.15 (m, 4H), 2.71 (s, 6H).

EXAMPLE 105A Treat 3-cyano-4-fluorobenzenesulfonyl chloride (5 g) in dichloromethane (110 ml) at -78 ° C, treat with 7M NH3 in methanol (8.1 ml), stir at -20 ° C, and acidify with 1M HCl. The aqueous layer is separated and extracted with dichloromethane. The extract is dried (MgSO4), filtered, and concentrated. The concentrated material is recrystallized from hexane / ethyl acetate.

EXAMPLE 105B This example is prepared by substituting example 18C with example 18E in example 18F.

EXAMPLE 105B A mixture of example 105A (0.5 g), example 105B (0.5 g), and DIEA (0.8 ml) in TH F (6 ml) at 80 ° C is stirred for 16 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% methanol / dichloromethane.

EXAMPLE 105C A mixture of example 105B (0.05 g) and KOH (0.031 g) in tert-butanol (2 ml) at reflux is stirred for 6 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5-10% methanol / dichloromethane.

EXAMPLE 105D This example is prepared by substituting Example 105C for 4 - (((1R) -3- (d-methylamino) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 11.82 (s, 1 H), 9.63 (s, 1H), 8.82 (d, 1H), 8.15 (s, 1H), 7.76 (d, 2H), 7.70 (d, 1H), 7.52 (d, 4H), 7.39 (d, 2H), 7.33 (m, 2H) ), 7.27 (m, 2H), 7.19 (m, 1H), 6.92 (d, 2H), 6.69 (s, 1H), 4.14 (m, 1H), 3.86 (m, 2H), 3.45 (m, 6H), 3.15 (m, 4H), 2.74 (s, 6H), 2.10 (m, 1H), 1.96 (m, 1H).

EXAMPLE 106B A mixture of Example 1A (1.5 g), 2-bromobenzoyl chloride (1.5 g), and DIEA (2 mL) in THF (20 mL) at 25 ° C is stirred for 16 hours, filtered, and concentrated.

EXAMPLE 106C Example 106B (0.3g), 4- (N, N-dimethylamino) -phenylboronic acid (0.146 g), PdCI2 (PPh3) 4 (0.03 g), and 2M Na2C03 (0.4 ml) in DME / water / ethanol 7: 3: 2 (3 ml) at 150 ° C in a 10 ml microwave reaction tube is stirred in a microwave reactor for 20 minutes, filtered through diatomaceous earth (Celite®) and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5-50% ethyl acetate / hexanes.

EXAMPLE 106D This example is prepared by substituting example 106C for example 2B in example 2C.

EXAMPLE 106E This example is prepared by substituting example 106D for example 2C in example 2D. 1 H NMR (400MHz, DMSO-d6) d 12.01 (s, 1 H), 9.29 (s, 1 H), 8.53 (d, 1 H), 8.29 (d, 1 H), 7.86 (dd, 1 H), 7.30 (m, 1 1 H), 6.80 (d, 2 H), 6.73 (d, 2 H) , 4.18 (m, 1 H), 3.50 (m, 4H), 3.39 (m, 4H), 3.04 (m, 6H), 2.78 (s, 6H), 2.74 (d, 6H), 2.14 (m, 2H) .

EXAMPLE 107A This example is prepared by replacing 4- (methylsulfanyl) -phenylboronic acid with 4- (N, N-dimethylamino) -phenylboronic acid in Example 106C.

EXAMPLE 107B This example is prepared by substituting example 107A for example 2B in example 2C.

EXAMPLE 107C This example is prepared by substituting example 107B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 12.01 (s, 1 H), 9.38 (s, 1H), 8.53 (d, 1H), 8.29 (d, 1H), 7.86 (dd, 1H), 7.49 (m, 3H), 7.33 (m, 5H), 7.17 (m, 5H), 6.83 (d, 2H) ), 4.18 (m, 1H), 3.65 (m, 2H), 3.39 (m, 4H), 3.11 (m, 4H), 2.97 (m, 1H), 2.85 (m, 1H), 2.73 (d, 6H) , 2.39 (s, 3H), 2.14 (m, 2H).

EXAMPLE 108A This example is prepared by substituting 4-chlorophenylboronic acid for 4- (N, N-dimethylamino) -phenylboronic acid in Example 106C.

EXAMPLE 108B This example is prepared by substituting example 108A for example 2B in example 2C.

EXAMPLE 108C This example is prepared by substituting example 108B for example 2C in example 2D. 1 H NMR (400MHz, DMSO-d 6) d 12.01 (s, 1H), 9.38 (s, 1H), 8.53 (d, 1H), 8.29 (d, 1H), 7.86 (dd, 1H), 7.74 (d, 2H) ), 7.49 (m, 8H), 7.17 (m, 5H), 6.83 (d, 2H), 4.18 (m, 1H), 3.65 (m, 2H), 3.39 (m, 4H), 3.11 (m, 4H) , 2.99 (m, 1H), 2.89 (m, 1H), 2.74 (d, 6H), 2.14 (m, 2H).

EXAMPLE 109 This example is prepared by substituting example 105B for 4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) prop i) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400MHz, DMSO-d 6) d 11.70 (s, 1H), 9.60 (s, 1H), 7.68 (d, 1H), 7.52 (d, 2H), 7.27 (m, 43H), 7.14 (d, 2H) ), 7.08 (m, 1H), 7.00 (m, 5H), 6.91 (m, 1H), 6.67 (d, 2H), 6.37 (m, 2H), 3.96 (m, 1H), 3.70 (m, 2H) , 3.80 (m, 4H), 3.02 (m, 4H), 2.89 (m, 4H), 2.58 (s, 6H), 1.84 (m, 2H).

EXAMPLE 110A The methyl ester of 3,4-dihydroxy-butyric acid, which is prepared as described in Chem. Lett., 1984, 1389, (510 mg) in dimethylamine in THF (19 ml) in a sealed tube at 80 °, is stirred. C for 12 hours and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 0-20% methanol / dichloromethane.

EXAMPLE 110B A mixture of Example 1 10A (200 mg), benzenethiol (153 μL), and tributylphosphine (372 μL) in THF (10 mL) at 0 ° C is treated with 1.1 '- (azodicarbonyl) -dipiperidine (377 mg) , it is stirred at 25 ° C for 12 hours, and treated with ethyl acetate and 1 M NaOH. The extract is extracted with ethyl acetate, and the extract is dried (MgSO), filtered and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0% to 80% ethyl acetate / dichloromethane.

EXAMPLE 110C Example 1 10B (160 mg) in THF (2.3 ml) at 25 ° C is treated with borane-THF (1 ml), stirred for 5 hours, treated with saturated methanolic HCl (3 ml), heated to reflux for 2 hours, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 0-10% methanol saturated with NH3 (saturated N H3) / dichloromethane.

EXAMPLE 110D Example 1 10C (224 mg) in DMF (1 mL) at 0 ° C is treated with NaH (40 mg), stirred at 25 ° C for 1 hour, cooled to 0 ° C, treated with 15-crown -5 (146 μl), stirred for 15 minutes, treated with 4-fluoro-3-nitrobenzenesulfonamide, which is prepared as described in WO02 / 24636, (10 mg), stirred at 25 ° C. C for 2 hours, treated with NH CI saturated (200 μl), and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 50-100% ethyl acetate / hexane then changed to 0-10% methanol saturated with NH3 / dichloromethane.

EXAMPLE 110E This example is prepared by substituting Example 1 10D for 4 - (((1 R) -3- (dimethylamido) -1 - ((f-enylsulfonyl) methyl) propyl) am i no) -3-nitrobenzenesulfonamide in Example 2D . 1 H NMR (400MHz, DMSO-d6) d 9.70 (s, 1 H), 8.38 (d, 1 H), 8.09 (dd, 1 H), 7.78 (m, 3H), 7.51 (m, 5H), 7.27 (m, 8H), 6.92 (d, 2H), 5.01 (m, 1 H), 3.47 (m, 2H), 3.33 (m, 2H), 3.21 (m, 4H), 3.14 (m, 2H), 3.05 (s, 2H), 2.76 (s, 6H), 2.23 (m, 2H).

EXAMPLE 111 This example is prepared by substituting 4,4-dimethyl-4,5-dihydro-1H-imidazole for isopropylamine in Example 35B. 1 H NMR (400MHz, DMSO-d 6) d 10.29 (s, 1H), 8.54 (d, 1H), 8.29 (s, 1H), 7.86 (dd, 1H), 7.76 (d, 2H), 7.65 (m, 2H) ), 7.46 (m, 5H), 7.30 (m, 1H), 7.22 (d, 2H), 7.12 (m, 4H), 6.92 (d, 2H), 4.14 (m, 1H), 3.54 (m, 4H) , 3.40 (m, 10H), 2.18 (m, 2H), 1.32 (s, 6H), 0.87 (m, 2H).

EXAMPLE 112 This example is prepared by replacing 1, 4,5,6-tetrahydro-pyrimidine with isopropylamine in Example 35B. 1 H NMR (400MHz, DMSO-d 6) d 12.09 (s, 1H), 9.62 (d, 1H), 8.53 (d, 1H), 8.27 (d, 1H), 8.02 (d, 1H), 7.85 (dd, 1H), 7.76 (d, 2H), 7.51 (m, 3H), 7.40 (m, 1H) ), 7.14 (m, 7H), 6.93 (d, 2H), 4.14 (m, 1H), 3.40 (m, 14H), 3.19 (m, 2H), 2.12 (m, 2H), 1.88 (m, 2H) .

EXAMPLE 113 This example is prepared by substituting 2-methyl-4,5-dihydro-1H-imidazole for isopropylamine in Example 35B. H NMR (400MHz, DMSO-d6) d 10.06 (s, 1H), 8.56 (d, 1H), 8.32 (d, 1H), 7.90 (dd, 1H), 7.81 (d, 2H), 7.55 (m, 4H) ), 7.43 (d, 2H), 7.37 (m, 1H), 7.26 (m, 3H), 7.14 (m, 3H), 6.97 (d, 2H), 4.28 (m, 2H), 3.85 (m, 14H) ), 3.42 (m, 2H), 2.14 (m, 2H), 2.08 (s, 3H), 1.27 (m, 2H).

EXAMPLE 114 This example is prepared by replacing Example 842657F and 1, 4,5,6-tetrahydro-pyrimidine with isopropylamine and 35A in Example 35B. 1 H NMR (400MHz, DMSO-d 6) d 11.92 (s, 1H), 9.60 (s, 1H), 8.01 (d, 1H), 7.95 (d, 1H), 7.80 (dd, 1H), 7.73 (d, 2H), 7.68 (m, 1H), 7.49 (m, 3H), 7.41 (d, 2H) ), 7.27 (m, 5H), 7.17 (m, 1H), 6.90 (d, 2H), 6.82 (d, 1H), 6.00 (d, 1H), 3.83 (m, 2H), 3.40 (m, 16H) , 2.08 (m, 2H), 1285 (t, 2H).

EXAMPLE 115 This example is prepared by substituting 2,4,6-dimethyl-4,5-dihydro-1H-imidazole for 1, 4,5,6-tetrahydro-pyrimidine in Example 114. 1 H NMR (400MHz, DMSO-d 6) d 11.92 ( s, 1H), 10.02 (s, 1H), 7.95 (d, 1H), 7.82 (dd, 1H), 7.73 (d, 2H), 7.70 (m, 1H), 7.50 (m, 3H), 7.40 (d, 2H), 7.27 (m, 5H), 6.92 (m, 3H), 6.04 (d, 1H), 4.08 (m, 2H), 3.90 (m, 4H), 3.40 (m, 10H), 2.04 (m, 2H), 2.02 (s, 3H), 1.10 (m, 3H).

EXAMPLE 116 This example is prepared by substituting 2, methyl-4,5-dihydro-1H-imidazole for 1, 4,5,6-tetrahydro-pyrimidine in Example 114. 1 H NMR (400MHz, DMSO-de) d 11.92 (s, 1H ), 9.82 (s, 1H), 7.88 (d, 1H), 7.75 (dd, 1H), 7.68 (d, 2H), 7.62 (m, 1H), 7.43 (m, 3H), 7.35 (d, 2H) , 7.28 (m, 5H), 6.82 (m, 3H), 5.98 (d, 1H), 3.90 (m, 2H), 3.70 (m, 4H), 3.40 (m, 12H), 2.00 (m, 2H), 1.95 (s, 3H).

EXAMPLE 117 This example is prepared by substituting 4,4-dimethyl-4,5-dihydro-1H-imidazole for 1, 4,5,6-tetrahydro-pyrimidine in Example 114. 1 H NMR (400MHz, DMSO-d6) d 11.92 (s) , 1H), 10.22 (s, 1H), 8.25 (d, 1H), 7.95 (d, 1H), 7.80 (dd, 1H), 7.75 (d, 2H), 7.65 (m, 1H), 7.52 (m, 3H), 7.50 (d, 2H), 7.25 (m, 5H), 7.18 (m, IH), 6.90 (d, 2H), 6.82 (d, 1H), 6.00 (d, 1H), 3.88 (m, 2H), 3.50 (m, 4H), 3.40 (m, 10H), 2.08 (m, 2H), 1.25 (m, 6H) )., EXAMPLE 118A Example 18D (200 mg), cesium carbonate (671 mg) and tetrabutylammonium iodide (61 mg) in DMF (4 ml) at 25 ° C is treated with 4-methoxybenzyl chloride (246 μl), stirred for 12 hours. hours, and treated with ethyl acetate and saturated NH CI. The extract is extracted with ethyl acetate, and the combined extracts are dried (MgSO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0-50% ethyl acetate / hexane.

EXAMPLE 118B Example 1 10C (38 mg) in N-methyl-2-pyrrolidinone (845 μl) at 25 ° C is treated with NaH (8 mg), stirred for 20 minutes, treated with example 1 18A (122 mg) , it is stirred for 3 hours, treated with NaH (6.6 mg) and example 1 18A (76 mg), stirred for 3 hours, treated with saturated NaHCO3, (1 ml), and separated between ethyl acetate and Saturated NaHCO3. The extract is extracted with ethyl acetate, and the combined extracts are dried (MgSO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0- to 50% acetonitrile (1% methanol saturated with NH3) / 1% ethyl acetate saturated with NH3.

EXAMPLE 118C Example 1 18C (90 mg) in triethylsilane / TFA / dichloromethane (0.05 ml / 0.45 ml / 0.5 ml) at 25 ° C is stirred for 12 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% methanol saturated with NH3 / dichloromethane.

EXAMPLE 118D This example is prepared by substituting example 1 18C and example 837538C for example 2C and 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide ( which is prepared in accordance with the procedure described in the combined document WO02 / 24636, filed September 20, 2001) in example 2D. 1 H NMR (400MHz, DMSO-d6) d 12.02 (s, 1 H), 9.40 (s, 1 H), 8.12 (d, 2H), 7.72 (d, 2H), 7.41 (m, 3H), 7.31 ( d, 2H), 7.26 (m, 2H), 7.17 (m, 3H), 6.95 (d, 2H), 4.97 (m, 1 H), 3.50 (m, 12H), 3.16 (m, 4H), 2.76 ( s, 6H), 2.23 (m, 4H), 1.70 (s, 4H).

EXAMPLE 119A A mixture of 4-bromo-3- (trifluoromethyl) -benzenesulfonamide (0.121 g), example 847124C (0.17 g) EDAC (0.153 g), and DMAP (0.098 g) in dichloromethane (2 ml) at 25 ° C is stirred for 16 hours, treated with ethyl acetate, washed with saturated NH 4 Cl solution and brine, and dried (Na S04), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% methanol / dichloromethane.

EXAMPLE 119B A mixture of example 119A (0.1 g), example 105B (0.038 g), Pd2 (dba) 3 (0.011 g), BINAP (0.009 g), Cs2C03 (0.07 g) in toluene (1.5 ml) at 100 ° C is stirred for 16 hours, it is filtered, and concentrated. The concentrated material is purified by high pressure liquid chromatography on a C8 Symmetry Waters column (25 mm x 100 mm, particle size 7 μm) with 10-100% acetonitrile / 0.1% aqueous TFA in a lapse of 8 minutes at a flow rate of 40 ml / minute. 1 H NMR (400MHz, DMSO-d 6) d 9.60 (s, 1H), 7.95 (d, IH) j 7.81 (dd, 1H), 7.76 (d, 2H), 7.41 (d, 2H), 7.28 (m, 4H) ), 7.12 (d, 2H), 6.94 (d, 2H), 6.87 (d, 1H), 6.02 (d, 1H), 3.91 (m, 3H), 3.63 (m, 2H), 3.40 (m, 2H), 3.28 (m, 2H), 3.15 (m, 4H), 3.00 (m, 2H), 2.73 (d, 6H), 2.46 (m, 4H), 2.10 (m, 2H), 1.82 (m, 2H), 1.57 (m, 4H).

EXAMPLE 120 This example is prepared by substituting bis- (2-methoxyethyl) amine for isopropylamine in Example 35B. 1 H NMR (500MHz, DMSO-d 6) d 12.02 (s, 1H), 9.50 (s, 1H), 8.54 (d, 1H), 8.27 (d, 1H), 7.87 (dd, 1H), 7.77 (m, 3H) ), 7.52 (m, 4H), 7.39 (d, 2H), 7.34 (m, 1H), 7.16 (m, 5H), 6.94 (d, 2H), 4.32 (m, 1H), 4.20 (m, 2H) , 3.61 (m, 4H), 3.39 (m, 2H), 3.30 (m, 12), 3.23 (s, 6H), 2.17 (m, 2H).

EXAMPLE 121 This example is prepared by substituting bis- (2-methoxyethyl) amine for 1,4,5,6-tetrahydropyrimidine in Example 114. 1 H NMR (500MHz, DMSO-d 6) d 12.02 (s, 1H), 9.50 (s, 1H ), 7.95 (d, 1H), 7.83 (dd, 1H), 7.75 (m, 3H), 7.53 (m, 4H), 7.39 (d, 2H), 7.34 (m, 5H), 7.16 (m, 1H) , 6.94 (m, 2H), 6.02 (d, 1H), 4.32 (m, 1H), 3.96 (m, 2H), 3.61 (m, 4H), 3.39 (m, 16H), 3.23 (s, 6H), 2.17 (m, 2H).

EXAMPLE 122A A mixture of Example 29C (0.5g) and diethylamine (4 mL) in THF (4 mL) at 25 ° C is stirred for 2 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% to 10% methanol / dichloromethane.

EXAMPLE 122B This example is prepared by replacing example 122A with example 105B example 119B. 1 H NMR (400MHz, DMSO-d 6) d 12.02 (s, 1H), 9.60 (s, 1H), 8.50 (s, 1H), 7.95 (d, 1H), 7.81 (dd, 1H), 7.76 (d, 2H) ), 7.41 (d, 2H), 7.28 (m, 4H), 7.12 (d, 2H), 6.94 (m, 3H), 6.12 (d, 1H), 4.02 (m, 1H), 3.89 (m, 2H) , 3.63 (m, 4H), 3.42 (m, 4H), 3.17 (m, 2H), 2.93 (m, 2H), 2.79 (m, 2H), 2.46 (m, 4H), 2.10 (m, 2H), 1.82 (m, 2H), 1.57 (m, 4H), 1.23 (m, 12H).

EXAMPLE 859948 This example is prepared by substituting 4,4-difluoropiperidine for isopropylamine in Example 35B. 1 H NMR (400 MHz, DMSO-d 6) d 10.06 (s, 1 H), 8.55 (d, 1H), 8.30 (d, 1H), 7.87 (dd, 1H), 7.77 (d, 2H), 7.55 (m, 4H), 7.40 (d, 2H) "7.39 (m, 1H), 7.24 (m, 3H ), 7.13 (m, 3H), 6.93 (d, 2H), 4.20 (m, 2H), 3.86 (m, 4H), 3.42 (m, 4H), 3.17 (m, 8H), 2.28 (m, 4H), 2. 18 (m, 4H).

EXAMPLE 855996 This example is prepared by substituting 2-methylpyrrolidine for isopropylamine in Example 35B. 1 NMR (400MHz, DMSO-d6) d 9.42 (s, 1H), 8.54 (d, 1H), 8. 32 (d, 1H), 7.87 (dd, 1H), 7.77 (d, 2H), 53 (m, 4H), 7.39 (d, 2H), 7.36 (m, 1H), 7.23 (m, 3H), 7.14 (m, 3H), 6.94 (d, 2H), 4.05 (m, 6H), 3.57 (m, 2H), 3.40 (m, 4H), 3.06 (m, 4H), 2.14 (m, 2H), 1. 93 (m, 2H), 1.57 (m, 2H), 1.27 (m, 3H).

EXAMPLE 123A 2.5 g / 100 ml of magnesium Rieke in diethyl ether (12.75 ml) is treated at 25 ° C with 1-bromo-3-methyl-2-butene (1.81 g), stirred for 1 hour, added to (2- benzyloxyethylidene) -amide of 2-methylpropan-2-sulfonic acid, which is prepared as described in J. Org. Chem. 2001, 26, 8772-8778, (1.85 g) in toluene (30 ml) at -78 ° C, and treated, at 25 ° C, with saturated NH CI, ethyl acetate, and water. The extract is washed with water and brine and dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10-20% acetone / hexanes.

EXAMPLE 123B Example 123A (1.01 g) in methanol (20 ml) at 25 ° C is treated with 4M HCl in dioxane (8 ml), stirred for 10 minutes, treated with 10% Pd / C, shaken under H2 (balloon ) for 18 hours, filtered through diatomaceous earth (Celite®), and concentrated. The concentrated material is mixed with 2M Na 2 CO 3 / chloroform 1: 1 (60 ml), treated with benzyl chloroformate (0.58 ml) and benz triethylammonium chloride (catalytic), and stirred for 3 hours. The extract is washed with water, dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 3: 1 -2: 1 hexanes / ethyl acetate.

EXAMPLE 123C A mixture of Example 123B (0.52 g), diphenyl disulfide (0.40 g), and tributylphosphine (0.81 g) in toluene (15 ml) at 85 ° C is stirred for 18 hours, cooled to 25 ° C, and concentrated . The concentrated material is subjected to flash chromatography on silica gel with 20: 1 then 10: 1 and 5: 1 hexanes / ethyl acetate.

EXAMPLE 123D Example 123C (0.52 g) in 30% HBr in acetic acid (15 ml) at 25 ° C is stirred for 2 hours, poured into HCl at % (75 ml), washed with ethyl acetate, brought to pH 12 with % NaOH, and extracted with chloroform. The extract is dried (MgSO4) and concentrated.

EXAMPLE 123E This example is prepared by substituting example 123D for example 21 C in example 21 D.

EXAMPLE 123F This example is prepared by substituting example 123E for 4 - (((1R) -3- (d-imeti-lamino) -1- ((f-enyl-sulfonyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide in the example 2D 1 H NMR (300 MHz, DMSO-d 6) d 12.07 (s, 1H), 9.61 (s, 1H), 8.49 (d, 1H), 8.35 (d, 1H), 7.64-7.96 (m, 4H), 7.41- 7.60 (m, 5H), 7.24-7.40 (m, 4H), 7.01-7.20 (m, 4H), 6.92 (d, 2H), 4.38 (m, 2H), 4.05 (m, 1H), 3.68-3.95 ( m, 2H), 3.21-3.65 (m, 1H), 2.96-3.25 (m, 2H), 2.61-2.95 (m, 2H), 1.17-1.50 (m, 1H), 0.93 (d, 6H), 0.80 ( t, 4H).

EXAMPLE 124 This example is prepared by substituting (5R) -5 - ((4- (aminosulfonyl) -2-nitrophenyl) amino) -6- (phenylsuifanyl) -hexylcarbamate ter-butyl, which is prepared as described in WO 02 / 24636, by 4 - (((1 R) -3- (dimethylamino) -1- ((f-enyl-sulfonyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide or namide in Example 2D. 1 H NMR (300 MHz, DMSO-d 6) d 11.96 (s, 1 H), 8.51 (d, 1 H), 8.28 (d, 1 H), 7.83 (dd, 1 H), 7.74 (d, 2 H), 7.49-7.56 ( m, 3H), 7.44_7.49 (m, 2H), 7.34-7.41 (m, 2H), 7.20-7.28 (m, 3H), 7.03-7.19 (m, 4H), 6.89 (d, 2H), 6.66 -6.77 (m, 1H), 3.95-4.12 (m, 1H), 3.41 (m, 1H), 3.17-3.27 (m, 4H), 2.79-2.96 (m, 4H), 2.33-2.45 (m, 5H) , 1.73 (m, 4H), 1.18-1.43 (m, 9H).

EXAMPLE 125 Example 124 (0.40 g) in dichloromethane (10 ml) is treated with 4M HCl in dioxane (2 ml), stirred for 20 hours at 25 ° C, and concentrated to obtain the desired product as the hydrochloride salt. 1 H NMR (300 MHz, DMSO-d 6) d 12.09 (s, 1 H), 9.76 (s, 10 1 H), 8.53 (d, 1 H), 8.30 (d, 1 H), 7.85 (dd, 1 H), 7.77 (d , 3H), 7.62 (m, 4H), 7.52 (d, 2H), 7.40 (d, 1H), 7.34 (d, 2H), 7.18-7.26 (m, 3H), 7.03-7.18 (m, 2H), 6.93 (d, 2H), 4.33 (m, 2H), 4.08 (m, 3H), 3.28- 3.42 (m, 4H), 3.11 (m, 4H), 2.81-2.96 (m, 1H), 2.64-2.81 ( m, 4H), 1.66-1.85 (m, 2H), 1.43-1.58 (m, 2H), 1.24-1.43 (m, 2H). '15 EXAMPLE 126 Example 125 (0.075 g) in dichloromethane (7 ml) is treated with DIEA (0.055 g), cooled to 0 ° C, treated with chloride of methanesulfonyl (0.013 g), stirred for 1 hour, and treated with water. The extract is washed with water and brine, and dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0-2.5% methanol in dichloromethane. 25 H NMR (300 MHz, DMSO-d 6) d 12.00 (s, 1H), 8.52 (d, 1H), 8.30 (d, 1H), 7.84 (dd, 1H), 7.74 (d, 2H), 7.43-7.57 (m, 1H), 7.47 (s, 2H), 7.32-7.42 (m, 2H), 7.20-7.29 (m, 3H), 7.04-7.19 (m, 4H), 6.84-6.94 (m, 3H), 3.98 -4.16 (m, 1H), 3.16-3.48 (m, 7H), 2.85-2.95 (m, 2H), 2.83 (s, 3H), 2.41 (m, 3H), 1.67-1.83 (m, 2H), 1.28 -1.50 (m, 4H).

EXAMPLE 127 Example 125 (0.065 g) in dichloromethane (7 ml) at 25 ° C is treated with DIEA (0.048 g), cooled to 0 ° C, treated with trimethylsilyl isocyanate (0.011 g), stirred at 25 ° C. for 24 hours, treated with methanol (0.5 ml), and concentrated. The concentrated material is purified by reverse phase HPLC (C-18) with -100% acetonitrile / water containing 0.1% TFA. 1 H NMR (300 MHz, DMSO-d 6) d 12.07 (s, 1 H), 9.56 (s, 1H), 8.52 (s, 1H), 8.31 (d, 1H), 7.84 (dd, 1H), 7.77 (d, 3H), 7.52 (m, 3H), 7.28-7.44 (m, 3H), 7.03-7.27 (m, 6H), 6.93 (d, 2H), 5.80-5.93 (m, 1H), 5.18-5.42 (m, 2H), 4.26-4.51 (m, 2H), 4.08 (m, 2H), 3.75-3.98 (m, 2H), 2.99-3.20 (m, 3H), 2.79 -2.98 (m, 4H), 1.63-1.89 (m, 2H), 1.24-1.44 (m, 4H).

EXAMPLE 128A A mixture of ethyl 4-fluorobenzoate (7.71 g), 1- (tert-butoxycarbonyl) piperazine (9.31 g), potassium carbonate (13.8 g), and 1-methyl-2-pyrrolidinone (20 ml) at 130 ° C. it is stirred for 16 hours, poured into water, and filtered. The filtrate is washed with water and dried in a vacuum oven at 50 ° C and 18 mm Hg.

EXAMPLE 128B This example is prepared by substituting example 128A for example 1 B in example 1 C.

EXAMPLE 128C This example is prepared by substituting example 128B for example 1 C in example 1 D.

EXAMPLE 128D Example 128C (3.7 g) in dichloromethane (10 ml) and HCl 4M in dioxane (10 ml) at 25 ° C is stirred for 5 hours, concentrated, treated with diethyl ether (20 ml), and filtered. The filtrate is washed with diethyl ether and dried in a vacuum oven at 50 ° C and 1 8 mm Hg.

EXAMPLE 128E Example 128D (10 mg) in dichloromethane (2 ml) at 25 ° C is treated with 2- (methylsulfanyl) -benzaldehyde (27 mg), N, N-DIEA (52 mg), and sodium triacetoxyborohydride (38 mg). ), stirred for 16 hours, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10% methanol / dichloromethane. 1 H NMR (300MHz, DMSO-d6) d 8.45 (d, 1 H), 8.36 (d, 1 H), 7.78 (dd, 1 H), 7.73 (d, 2H), 7.38-7.21 (m, 6H), 7.18 (d, 1 H), 7. 18-7.10 (m, 2H), 6.87 (d, 1 H), 6.80 (d, 2H), 4.10-4.01 (m, 1 H), 3. 52 (s, 2H), 3.33 (d, 2H), 3.18 (t, 4H), 2.65-2.40 (m, 6H), 2.44 (s, 3H), 2.27 (s, 6H), 2.07-1.82 ( m, 2H).

EXAMPLE 129A 2- (Methylsulfanyl) -benzaldehyde (1 g) in dichloromethane (35 ml) is treated with 70% 3-chloroperoxybenzoic acid (3.32 g), stirred for 75 minutes, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with ethyl acetate / hexanes 1: 1.

EXAMPLE 129B Example 128D (10 mg) in dichloromethane (2 ml) is treated with example 129A (33 mg), 3.45 mmol / g resin N, N-DI EA (16 mg), and sodium triacetoxyborohydride (38 mg). ), stirred at 25 ° C for 16 hours, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10% methanol / dichloromethane. 1 H NMR (300MHz, DMSO-d 6) d 8.45 (d, 1H), 8.21 (d, 1H), 7.08 (d, 1H), 7.81 (dd, 1H), 7.73 (d, 2H), 7.70 (td, 1H ), 7.61 (d, 2H), 7.32 (dd, 2H), 7.24 (tt, 2H), 7.17 (tt, 1H), 6.90 (d, 1H), 6.82 (d, 2H), 4.11-4.01 (m, 1H), 3.93 (s, 2H), 3.42 (s, 3H), 3.33 (d, 2H), 3.18 (t, 4H), 3.00-2.80 (m, 2H), 2.62-2.48 (m, 4H), 2.56 (s, 6H), 2.13-1.98 (m, 2H).

EXAMPLE 130A The N- (tert-butoxycarbonyl) glycine methyl ester (5 g) in THF (60 ml) is treated at 0 ° C with 1.4 M methylmagnesium bromide in toluene / THF 3: 1 (75.5 ml), stirred at 25 ° C. C for 16 hours, cooled to 0 ° C, treated with saturated NH CI, and extracted with ethyl acetate. The extract is washed with brine and dried (Na 2 SO), filtered, and concentrated.

EXAMPLE 130B Example 130A (1 g) in THF (27 ml) at 0 ° C is treated with potassium tert-butoxide (663 mg), stirred for 30 minutes, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% methanol / ethyl acetate.

EXAMPLE 130C A mixture of example 1 30B (120 mg), 2-bromobenzaldehyde (289 mg), and sodium tert-butoxide (150 mg) in toluene (5 ml) in a sealable container is de-gasified / purged with nitrogen three times and it is treated with dichloro- (1,1 '-bis- (diphenylphosphino) -ferrocene) palladium (II) -dichloromethane (82 mg). The container is sealed, and the mixture is heated at 120 ° C for 16 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 130D Example 128C (4.02 g) in dioxane (7 ml) at 25 ° C is treated with 4M HCl (7 ml), stirred for 16 hours, neutralized and extracted with dichloromethane. The extract is concentrated. The concentrated material is subjected to chromatography on C18 with acetonitrile / 0.1% aqueous TFA 1: 1.

EXAMPLE 130E Example 130C (50 mg) in dichloromethane (2 ml) and methanol (0.4 ml) at 25 ° C is treated with example 130D (130 mg) and 2.38 mmol / g MP-BH3CN (18 mg), stirred for 16 hours, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 20% methanol / dichloromethane. 1 H NMR (300MHz, DMSO-d6) d 8.42 (d, 1 H), 8.26 (d, 1 H), 7.79 (dd, 1 H), 7.74 (dd, 2H), 7.62-7.44 (m, 2H) , 7.40-7.35 (m, 2H), 7.32 (d, 2H), 7.25 (td, 2H), 7.17 (tt, 1 H), 6.88 (d, 1 H), 6.82 (t, 2H), 4.10-4.01 (m, 1 H), 3.78 (s, 2H), 3.49 (s, 2H), 3.34 (d, 2H), 3.23-3.14 (m, 6H), 2.90-2.62 (m, 4H), 2.43 (s, 6H), 2.10-1.90 (m, 2H), 1.50 (s, 6H).

EXAMPLE 131 A A mixture of 2-bromobenzaldehyde (4 g), butylamine (1.58 g), and sieves 4Á (3 g) in dichloromethane (75 ml) at 25 ° C is stirred for 72 hours, filtered and concentrated.

EXAMPLE 131 B Example 131 A (400 mg) in THF (5 ml) at 0 ° C is treated with MnCl 2 (21 mg) and 2M cyclohexylmagnesium chloride in THF (1.67 ml), stirred for 25 minutes, treated with N H4CI saturated, and extracted with diethyl ether. The extract is washed with brine, dried (Na S04), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% ethyl acetate / hexanes.

The relevant fractions are combined and concentrated. The material concentrated in 1,4-dioxane / water 1: 1 is stirred at 25 ° C for 16 hours and extracted with diethyl ether. The extract is washed with brine and dried (Na 2 SO), filtered, and concentrated.

EXAMPLE 131C This example is prepared by substituting example 131B for example 130C in example 130D. 1 H NMR (300 MHz, DMSO-d 6) d 8.43 (d, 1 H), 8.18 (d, 1H), 7.82 (dd, 1H), 7.73 (d, 2H), 7.45-7.37 (m, 1H), 7.30 (d, 2H), 7. 28-7.07 (m, 6H), 6.92 (d, 1H), 6.82 (d, 2H), 4.12-4.01 (m, 1H), 3. 51 (s, 2H), 3.33 (d, 2H), 3.17 (s, 4H), 3.05-2.88 (m, 3H), 2.70- 2.52 (m, 2H), 2.61 (s, 6H), 2.16-1.98 ( m, 2H), 1.84-1.65 (m, 6H), 1.50-1.22 (m, 6H).

EXAMPLE 132 This example is prepared by substituting 2-morpholinobenzaldehyde for example 130C in Example 130D. 1 H NMR (300MHz, DMSO-d 6) d 8.46 (d, 1H), 8.22 (d, 1H), 7.81 (dd, 1H), 7.72 (d, 2H), 7.39 (dd, 1H), 7.32 (d, 2H), 7.28- 7.22 (m, 3H), 7.20-7.04 (m, 3H), 6.90 (d, 1H), 6.81 (d, 2H), 4.14- 4.00 (m, 1H), 3.75 (t, 4H), 3.57 (s, 2H), 3.33 (d, 2H), 3.18 (s, 4H), 2.94 (t, 4H), 2.88-2.50 (m, 6H), 2.56 (s, 6H), 2.15-1.90 (m, 2H).

EXAMPLE 133A Treat 2-propanethiol (797 mg) in 1-methyl-2-pyrrolidinone (20 ml) at 25 ° C with 60% sodium hydride (419 mg) and 2-fluorobenzaldehyde (1 g), stir for 10 minutes , treated with 1M NaOH (20 ml), and extracted with diethyl ether. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, and concentrated.

EXAMPLE 133B This example is prepared by substituting example 133A for example 130C in example 130D. 1 H NMR (300MHz, DMSO-d 6) d 8.45 (d, 1H), 8.30 (d, 1H), 7.78 (dd, 1H), 7.74 (d, 2H), 7.44 (dt, 2H), 7.33 (d, 2H) ), 7.28- 7.22 (m, 4H), 7.17 (tt, 1H), 6.87 (d, 1H), 6.81 (d, 2H), 4.11-4.00 (m, 1H), 3.61 (s, 2H), 3.33 (d, 2H), 3.17 (t, 4H), 2.80-2.50 (m, 6H), 2. 44-2.36 (m, 1H), 2.39 (s, 6H), 2.10-1.86 (m, 2H), 1.23 (d, 6H).

EXAMPLE 134A A mixture of 3- (R) - ((carbobenzyloxy) amino) -? - butyrolactone, which is prepared according to the procedure described in J. Am. Chem. Soc. 1986, 4943-4952, (15 g) and N-methylisopropylamine (25 ml) in diglyme (200 ml) at 120 ° C is stirred for 48 hours, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% methanol / ethyl acetate.

EXAMPLE 134B This example is prepared by substituting example 134A for example 18A in example 18B.

EXAMPLE 134C This example is prepared by substituting example 1 34B for example 18B in example 18C.

EXAMPLE 134D This example is prepared by substituting example 134C for example 1 9C in example 19D.

EXAMPLE 134E This example is prepared by substituting example 134D for example 21 C in example 21 D.

EXAMPLE 134F This example is prepared by replacing the example 8550516E and example 837538C by 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO02 / 24636 , and example 1 C, respectively, in example 1 D. 1 H NMR (300MHz, DMSO-d6) d 8.43 (d, 1 H), 8.16 (s, 1 H), 7.79 (d, 1 H), 7.70 (d, 2H), 7.39-7.28 (m, 4H), 7.25 (td, 2H), 7.18 (dt, 1 H), 7.12 (dt, 2H), 6.90 (d, 1 H), 6.76 (d, 2H), 4.13-4.01 (m, 1 H), 3.34 (d, 2H), 3.12 (s, 4H), 2.76 (s, 2H), 2.67-2.49 (m, 2H), 2. 27 (s, 4H), 2.23-2.00 (m, 8H), 1 .66 (s, 4H), 1 .22-0.96 (m, 8H).

EXAMPLE 135A This example is prepared by substituting di-n-propylamine for N-methylisopropylamine in Example 134A.

EXAMPLE 135B This example is prepared by substituting example 135A for example 18A in example 18B.

EXAMPLE 135C This example is prepared by substituting example 135B for example 18B in example 18C.

EXAMPLE 135D This example is prepared by substituting example 135C for example 19C in example 19D.

EXAMPLE 135E This example is prepared by substituting example 135D for example 21C in example 21D.

EXAMPLE 135F This example is prepared by substituting example 135E and example 837538C for 4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO02 / 24636, and example 1C, respectively, in example 1D. 1 H NMR (300 MHz, DMSO-d 6) d 8.44 (d, 1 H), 8.18 (s, 1H), 7.78 (d, 1H), 7.71 (d, 2H), 7.38-7.29 (m, 4H), 7.24 (t, 2H), 7.18 (dt, 1H), 7.12 (d, 2H), 6.93-6.84 (m, 1H), 6.77 (d, 2H), 4.12-3.98 (m, 1H), 3.32 (d, 2H), 3.12 (s, 4H), 2.76 (s, 2H), 2.50-2.30 (m, 2H) ), 2.27 (s, 4H), 2.23-2.14 (m, 6H), 2.10-1.94 (m, 2H), 1.66 (s, 4H), 1.60-1.20 (m, 6H), 0.80 (s, 6H).

EXAMPLE 136 This example is prepared by substituting Example 135E for 4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) am'mo) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-d 6) d 8.45 (d, 1H), 8.18 (s, 1H), 7.89 (d, 1H), 7.72 (d, 2H), 7.51 (dd, 1H), 7.48 (s, 4H) ), 7.40-7.34 (m, 2H), 7.32 (dd, 2H), 7.27-7.21, (m, 3H), 7.16 (tt, 1H), 6.94-6.85 (m, 1H), 6.79 (d, 2H) , 4.12-4.00 (m, 1H), 3.38 (s, 2H), 3.33 (d, 2H), 3.13 (t, 4H), 3.00-2.85 (m, 2H), 2.40 (t, 4H), 2.08-1.93 (m, 2H), 1.60-1.20 (m, 8H), 0.81 (s, 6H).

EXAMPLE 137A This example is prepared by substituting diethylamine for N-methylisopropylamine in Example 134A.

EXAMPLE 137B This example is prepared by substituting example 137A for example 18A in example 18B.

EXAMPLE 137C This example is prepared by substituting example 137B for example 18B in example 18C.

EXAMPLE 137D This example is prepared by substituting example 137C for example 19C in example 19D.

EXAMPLE 137E This example is prepared by substituting example 137D for example 21C in example 21D.

EXAMPLE 137F This example is prepared by replacing Example 137E and Example 837538C with 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO02 / 24636, and example 1C, respectively, in example 1D. 1 H NMR (300 MHz, DMSO-d 6) d 8.44 (d, 1 H), 8.18 (d, 1H), 7.81 (dd, 1H), 7.71 (d, 2H), 7.37 (d, 2H), 7.31 (dd, 2H), 7.24 (tt, 2H), 7.18 (dt, 1H), 7.12 (d, 2H) ), 6.92 (d, 1H), 6.77 (d, 2H), 4.17-4.04 (m, 1H), 3.34 (d, 2H), 3.12 (s, 4H), 2.95 (m, 6H), 2.76 (s, 2H), 2.27 (s, 4H), 2.19 (m, 4H), 2.06 (m, 2H), 1.66 (s, 4H), 1.08 (t, 6H).

EXAMPLE 138 This example is prepared by substituting Example 137E for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-d 6) d 8.46 (d, 1H), 8.18 (s, 1H), 7.82 (dd, 1H), 7.72 (d, 2H), 7.52 (dd, 1H), 7.48 (s, 4H ), 7.40-7.35 (m, 2H), 7.31 (dd, 2H), 7.27-7.22, (m, 3H), 7.17 (tt, 1H), 6.94 (d, 1H), 6.79 (d, 2H), 4.15 -4.04 (m, 1H), 3.38 (s, 2H), 3.35 (d, 2H), 3.14 (t, 4H), 3.13-2.95 (m, 6H), 2.40 (t, 4H), 2.15-2.00 (m , 2H), 1.10 (s, 6H).

EXAMPLE 139A This example is prepared by substituting 3-bromobenzyl bromide for 2-bromobenzylbromide in Example 2A.

EXAMPLE 139B This example is prepared by substituting example 139A and phenylboronic acid for example 2A and 4-chlorophenylboronic acid, respectively, in example 2B.

EXAMPLE 139C This example is prepared by substituting example 139B for example 2B in example 2C.

EXAMPLE 139D This example is prepared by substituting example 139C and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (300MHz, DMSO-d 6) d 12.12 (br, 1H), 9.92 (br, 1H), 8.78 (t, 1H), 8.60 (d, 1H), 7.91 (dd, 1H), 7.81 (m, 4H ), 7.70 (m, 2H), 7.59 (t, 1H), 7.51 (m, 3H), 7.3g (m, 3H), 7.21 (m, 4H), 7.00 (d, 2H), 4.44 (m, 2H) ), 4.07 (m, 2H), 3.67 (t, 2H), 3.39 (m, 4H), 3.28 (t, 2H), 3.18 (m, 2H).

EXAMPLE 140 This example is prepared by substituting example 139C for example 2C in example 2D. 1 H NMR (300MHz, DMSO-d 6) d 12.15 (br, 1H), 10.11 (br, 1H), 9.46 (br, 1H), 8.55 (d, 1H), 8.30 (d, 1H), 7.89 (d, 1H) ), 7.82 (m, 4H), 7.70 (m, 2H), 7.59 (t, 1H), 7.51 (m, 3H), 7.42 (m, 1H), 7.17 (m, 6H), 7.02 (d, 2H) , 4.46 (m, 2H), 3.50 (m, 13H), 2.74 (d, 6H), 2.14 (q, 2H).

EXAMPLE 141 This example is prepared by substituting example 139C and 4 - (((1R) -3- (4-morpholin I) -1 - ((f-enyl-sulfonyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (d-methylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3- Nitrobencenesulfonamide, respectively, in Example 2D. 1 H NMR (300MHz, DMSO-d 6) d 12.17 (br, 1H), 10.10 (br, 1H), 9.77 (br, 1H), 8.55 (d, 1H), 8.31 (d, 1H), 7.89 (dd, 1H) ), 7.80 (m, 4H), 7.70 (m, 2H), 7.59 (t, 1H), 7.51 (m, 3H), 7.41 (m, 1H), 7.18 (m, 6H), 7.01 (d, 2H) , 4.46 (m, 2H), 3.60 (m, 21H), 2.17 (q, 2H).

EXAMPLE 142A 3,4-Difluorobenzoic acid (1 g) in THF (6 mL) and methanol (3 mL) are treated at 25 ° C with 2M (trimethylsilyl) -diazomethane in hexane (4 mL), stirred for 2 hours, and dried. concentrate The concentrated material is subjected to flash chromatography on silica gel with 5% ethyl acetate / hexane.

EXAMPLE 142B Example 142A in acetonitrile (6 ml) at 25 ° C is treated with K2CO3 (0.46 g) and piperazine (250 mg), refluxed for 24 hours, cooled to 25 ° C, treated with K2C03 (0.40 g) ) and 2-phenylbenzyl bromide (0.53 ml), stirred for 18 hours, and concentrated. The concentrate is separated between ethyl acetate and brine. The extract is dried (Na2SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% acetone / hexane.

EXAMPLE 142C This example is prepared by substituting example 142B for example 2B in example 2C.

EXAMPLE 142D This example is prepared by substituting example 142C for example 2C in example 2D. 1 H NMR (300MHz, DMSO-d6) d 9.79 (br, 1 H), 9.47 (br, 1 H), 8.53 (d, 1 H), 8.30 (d, 1 H), 7.86 (dd, 1 H) , 7.69 (m, 3H), 7.43 (m, 8H), 7.14 (m, 8H), 3.65 (m, 15H), 2.74 (d, 6H), 2.14 (q, 2H).

EXAMPLE 143 This example is prepared by substituting example 142C and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1 R) -3- (dimethylamino) -1- ((f-enyl-sulfonyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonam id a, respectively, in Example 2D. 1 H NMR (300MHz, DMSO-d 6) d 12.28 (br, 1H), 9.66 (m, 1H), 8.78 (t, 1H), 8.58 (d, 1H), 7.89 (dd, 1H), 7.74 (br, 1H) ), 7.68 (s, 1H), 7.64 (m, 1H), 7.48 (m, 4H), 7.37 (m, 5H), 7.23 (m, 4H), 7.05 (t, 2H), 4.38 (m, 2H) 3.24 (m, 12H).

EXAMPLE 144 This example is prepared by substituting example 142C and 4 - (((1R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) p-ropil) amino) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (300MHz, DMSO-d 6) d 9.74 (br, 1H), 8.54 (d, 1H), 8.30 (d, 1H), 7.86 (dd, 1H), 7.68 (m, 3H), 7.48 (m, 9H) ), 7.13 (m, 6H), 3.63 (m, 23H), 2.18 (m, 2H).

EXAMPLE 145A This example is prepared by substituting 3,4,5-trifluorobenzoic acid for 3,4-difluorobenzoic acid in Example 142A.

EXAMPLE 145B This example is prepared by substituting example 145A for example 142A in example 142B.

EXAMPLE 145C This example is prepared by replacing example 145B with example 2B in example 2C.

EXAMPLE 145D This example is prepared by substituting example 145C for example 2C in example 2D. 1 H NMR (300MHz, DMSO-d 6) d 9.72 (br, 1H), 9.44 (br, 1H), 8.51 (d, 1H), 8.27 (d, 1H), 7.84 (dd, 1H), 7.75 (m, 1H ), 7.49 (m, 8H), 7.36 (m, 3H), 7.18 (m, 6H), 3.50 (m, 15H), 2.74 (d, 6H), 2.13 (q, 2H).

EXAMPLE 146 This example is prepared by substituting example 145C and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 ~ (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (300MHz, DMSO-d6) d 9.55 (br, 1 H), 8.72 (t, 1 H), 8.55 (d, 1 H), 7.87 (dd, 1 H), 7.73 (br, 1 H) , 7.34 (m, 16H), 4.36 (m, 2H), 3.25 (m, 12H).

EXAMPLE 147 This example is prepared by replacing example 145C and 4 - (((1 R) -3- (4-morpholin il) -1 - ((f-enylsulfanyl) methyl) prop il) am i no) -3-nitrobenzenesulfonamide, which is prepared as described in the document WO 02/24636, for example 2C and 4 - (((1 R) -3- (dimethylamino) -1 - ((phen i sulphanyl) methyl) p ropil) amino) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (300MHz, DMSO-d6) d 9.70 (br, 1 H), 8.51 (d, 1 H), 8.27 (d, 1 H), 7.86 (dd, 1 H), 7.75 (m, 1 H) , 7.49 (m, 7H), 7.35 (m, 3H), 7.25 (m, 2H), 7.16 (m, 4H), 4.40 (m, 2H), 4.16 (m, 2H), 3.38 (m, 19H), 2.1 5 (m, 2H).

EXAMPLE 148A 1-phenylimidazole (0.44 ml) is treated in THF at 0 ° C with 2.5 M butyl lithium in hexane (1.7 ml), stirred for 20 minutes, treated with DMF (0.8 ml), stirred for 1 hour. 5 hours, and treated with saturated aqueous NH4CI and ethyl acetate. The extract is washed with brine and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 15% acetone / hexane.

EXAMPLE 148B A mixture of Example 1 A and Example 148A in 1,2-dichloroethane (2 mL) at 25 ° C is treated with sodium triacetoxyborohydride (368 mg), stirred for 1 hour, and treated with dichloromethane and 1 M NaOH. The extract is washed with brine and dried (Na 2 SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 3-5% methanol / dichloromethane.

EXAMPLE 148C This example is prepared by substituting example 148B for example 2B in example 2C.

EXAMPLE 148D This example is prepared by substituting example 148C and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (300MHz, DMSO-d 6) d 12.02 (br, 1H), 8.78 (t, 1H), 8.59 (d, 1H), 7.90 (dd, 1H), 7.80 (d, 1H), 7.77 (d, 2H) ), 7.60 (m, 6H), 7.35 (m, 2H), 7.21 (m, 4H), 6.95 (d, 2H), 4.10 (m, 2H), 3.50 (m, 6H), 3.28 (t, 2H) , 2.86 (m, 4H).

EXAMPLE 149 This example is prepared by substituting example 148C and 4 - (((1 R) -3- (4-morpholin) -1 - ((phenylsulfanyl) methyl I) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (d-imethylamino) -1- ((f-enylsulfanyl) methyl) propyl) amino) -3- Nitrobencenesulfonamide, respectively, in Example 2D. 1 H NMR (300MHz, DMSO-d 6) d 12.10 (br, 1H), 9.74 (br, 1H), 8.55 (d, 1H), 8.31 (d, 1H), 7.87 (dd, 1H), 7.83 (d, 1H) ), 7.78 (d, 2H), 7.61 (m, 6H), 7.17 (m, 6H), 6.95 (d, 2H), 3.53 (m, 23H), 2.19 (m, 2H).

EXAMPLE 150A This example is prepared by substituting 1-phenylpyrazole for 1-phenylimidazole in Example 148A.

EXAMPLE 150B This example is prepared by substituting example 150A for example 148A in example 148B.

EXAMPLE 150C This example is prepared by substituting example 1 50B for example 2B in example 2C.

EXAMPLE 150D This example is prepared by substituting example 150C and 3-nitro-4 - ((2- (phenylsufanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (300MHz, DMSO-d6) d 12.07 (br, 1 H), 8.78 (t, 1 H), 8.59 (d, 1 H), 7.91 (dd, 1 H), 7.76 (d, 2H), 7.75 (s, 1 H), 7.52 (m, 5H), 7.36 (m, 2H), 7.21 (m, 4H), 6.95 (d, 2H), 6.67 (br, 1 H), 3.28 (t, 2H) , 3.22 (m, 12H).

EXAMPLE 151 This example is prepared by substituting example 150C and 4 - (((1 R) -3- (4-morpholin) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1 R) -3- (d-methylamino) -1 - ((f-enyl-sulfonyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide, respectively, in example 2D. 1 H NMR (300MHz, DMSO-d6) d 12.10 (br, 1 H), 9.76 (br, 1 H), 8.55 (d, 1 H), 8.31 (d, 1 H), 7.87 (dd, 1 H) , 7.77 (d, 2H), 7.74 (s, 1 H), 7.54 (m, 5H), 7.17 (m, 6H), 6.95 (d, 2H), 6.64 (br, 1 H), 3.25 (m, 23H ), 2.17 (m, 2H).

EXAMPLE 152A The ethyl ester of 3-phenyI-3H-imidazole-4-carboxylic acid is treated, which is prepared as described in Tet. Lett. 2000, 41, 5453-5456, (150 mg) in dichloromethane (2.5 ml) at -78 ° C with DI BAL 1 M in dichloromethane (1.4 ml), stirred for 30 minutes, and treated with sodium tartrate. sodium and 25% aqueous potassium, ethyl acetate (50 ml) and 25% aqueous potassium sodium tartrate (50 ml). The extract is washed with 25% aqueous potassium sodium tartrate (50 ml) and brine (50 ml) and dried (Na 2 SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20-30-50% acetone / hexane.

EXAMPLE 152B This example is prepared by substituting example 152A for example 148A in example 148B.

EXAMPLE 152C This example is prepared by substituting example 152B for example 2B in example 2C.

EXAMPLE 152D This example is prepared by substituting example 152C and 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1 R) -3- (d-methylamino) -1 - ((f-enylsulfanyl) methyl) prop il) am i no) -3-nitrobenzenesulfonamide , respectively, in the example 2D. 1 H NMR (300MHz, DMSO-d6) d 8.50 (d, 1 H), 8.36 (d, 1 H), 7.88 (d, 1 H), 7.80 (dd, 1 H), 7.72 (d, 2H), 7.61 (m, 2H), 7.50 (m, 3H), 7.22 (m, 5H), 7.03 (m, 2H), 6.85 (d, 2H), 4.14 (m, 2H), 3.38 (m, 8H), 2.40 (m, 9H), 2.00 (m, 2H), 1.87 (m, 2H), 1.29 (m, 2H).

EXAMPLE 153A A mixture of example 30C (50.5 mg) and 3-azetidine-carboxylic acid (13 mg) in methanol (1 ml) at 25 ° C is treated with sodium cyanoborohydride (8.5 mg), stirred for 4 hours, treated with Silica gel and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 5% methanol / dichloromethane, 20% methanol / 2% water / 0.2% acetic acid / dichloromethane and 40% methanol / 0% water / 1 % acetic acid / dichloromethane.

EXAMPLE 153B A mixture of example 2C (1 g) and N-hydroxysuccinimide (296 mg) in ethyl acetate (9 ml) and THF (4 ml) at 25 ° C is treated with 1,3-dicyclohexycarbodiimide (556 mg), stirred at 40 ° C for 6 hours and at 25 ° C for 16 hours, cooled to 0 ° C, treated with 40% ethyl acetate / hexane, and filtered through silica gel with 40% ethyl acetate / hexane. The filtrate is concentrated and the concentrated material is subjected to flash chromatography on silica gel with 35-40% ethyl acetate / hexane.

EXAMPLE 153C A mixture of example 153A (28 mg) and example 153B (34 mg) in DMF (0.4 ml) at 25 ° C is treated with DBU (0.031 ml), stirred for 20 hours, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% methanol / dichloromethane, 10% methanol / 1% water / 0.1% acetic acid / dichloromethane, and 20% methanol / 20% water / 2% acetic acid / dichloromethane. 1 H NMR (300MHz, DMSO-d 6) d 8.46 (d, 1H), 8.30 (br, 1H), 7.81 (dd, 1H), 7.72 (d, 2H), 7.46 (m, 5H), 7.26 (m, 7H) ), 6.93 (m, 1H), 6.81 (d, 2H), 4.06 (m, 2H), 2.99 (m, 16H), 1.65 (m, 4H).

EXAMPLE 154A This example is prepared by substituting 1,1-dimethylethanolamine for azetidine hydrochloride in Example 30D.

EXAMPLE 154B This example is prepared by substituting example 154A for example 153A in example 153C. 1 H NMR (300MHz, DMSO-d 6) d 8.45 (d, 1H), 8.12 (d, 1H), 7.82 (dd, 1H), 7.72 (d, 2H), 7.51 (m, 5H), 7.26 (m, 7H) ), 6.93 (d, 1H), 6.78 (d, 2H), 4.10 (m, 2H), 3.26 (m, 7H), 2.92 (m, 2H), 2.75 (m, 2H), 2.40 (m, 4H) , 2.08 (m, 2H), 1.14 (s, 6H).

EXAMPLE 155A This example is prepared by substituting sarcosine for 3-azetidinecarboxylic acid in Example 153A.

EXAMPLE 155B This example is prepared by substituting example 155A for example 153A in example 153C. 1 H NMR (300MHz, DMSO-d 6) d 12.08 (br, 1H), 9.76 (br, 1H), 8.52 (d, 1H), 8.28 (d, 1H), 7.85 (dd, 1H), 7.77 (d, 2H) ), 7.69 (br, 1H), 7.43 (m, 7H), 7.15 (m, 6H), 6.93 (d, 2H), 5.56 (br, 1H), 4. 21 (m, 2H), 4.03 (m, 2H), 3.37 (m, 11H), 2.79 (s, 3H), 2.19 (m, 2H), 1.65 (m, 2H).

EXAMPLE 156A This example is prepared by substituting D-proline for 3-azetidinecarboxylic acid in Example 153A.

EXAMPLE 156B This example is prepared by substituting example 156A for example 153A in example 153C. 1 H NMR (300 MHz, DMSO-d 6) d 12.15 (br, 1 H), 9.67 (br, 1H), 8.52 (d, 1H), 8.29 (d, 2H), 7.80 (m, 4H), 7.44 (m, 7H), 7.15 (m, 4H), 6.93 (d, 2H), 5.56 (br, 1H) ), 4.30 (m, 3H), 2.33 (m, 21H).

EXAMPLE 157A This example is prepared by substituting isonipecotic acid for 3-azetidinecarboxylic acid in Example 153A.

EXAMPLE 157B This example is prepared by substituting example 157A for example 153A in example 153C. 1 H NMR (300 MHz, DMSO-d 6) d 12.05 (br, 1 H), 8.47 (d, 1H), 8.21 (m, 1H), 7.81 (dd, 1H), 7.72 (d, 2H), 7.50 (m, 5H), 7.27 (m, 9H), 6.g7 (m, 1H), 6.82 (d , 2H), 4.10 (m, 2H), 3.35 (m, 10H), 3. 17 (m, 3H), 2.50 (m, 4H), 2.40 (m, 3H), 2.07 (m, 2H), 1.63 (m, 2H).

EXAMPLE 158A This example is prepared by substituting 2- (methylamino) ethanol for azetidine hydrochloride in Example 30D.

EXAMPLE 158B This example is prepared by substituting example 158A for example 1 53A in example 153C. 1 H NMR (300MHz, DMSO-d6) d 8.45 (d, 1 H), 8.18 (d, 1 H), 7.81 (dd, 1 H), 7.72 (d, 2H), 7.51 (m, 5H), 7.27 (m, 8H), 6.93 (d, 1 H), 6.79 (d, 2H), 5.10 ( m, 1 H), 4.09 (m, 2H), 3.61 (m, 4H), 3.39 (m, 2H), 3.14 (m, 4H), 2.97 (m, 3H), 2.62 (m, 3H), 2.50 ( m, 3H), 2.40 (m, 4H), 2.09 (m, 2H).

EXAMPLE 159A This example is prepared by substituting L-proline for 3-azetidinecarboxylic acid in Example 153A.

EXAMPLE 159B This example is prepared by substituting example 159A for example 153A in example 153C. 1 H NMR (300MHz, DMSO-d6) d 12.10 (br, 1 H), 9.67 (br, 1 H), 8.52 (d, 1 H), 8.29 (d, 2H), 7.46 (m, 15H), 6.93 (d, 2H), 5.56 (br, 1 H), 4.24 (m, 3H), 2.35 (m, 21 H).

EXAMPLE 160A A mixture of 3-azetidine-carboxylic acid (251 mg) and 1 M NaOH (6 ml) in dioxane (6 ml) at 25 ° C is treated with 95% benzyl chloroformate (0.54 ml), stirred for 18 hours and concentrates. The concentrated material is treated with water, and the mixture is adjusted to pH greater than 10, washed with diethyl ether, adjusted to a pH of less than 3, and extracted with dichloromethane. The extract is dried (Na2SO4), filtered, and concentrated.

EXAMPLE 160B Example 833294A (574 mg) in dichloromethane (5 ml) at 0 ° C is treated with oxalyl chloride (0.75 ml) and DMF (2 drops), stirred for 1 hour, and concentrated twice from dichloromethane. The material concentrated in ethyl acetate (5 ml) is treated with 30% aqueous ammonium hydroxide (1.3 ml) while cooling in an ice water bath, stirred at 25 ° C for 2 hours, and treated with water and dichloromethane. The aqueous layer is extracted with ethyl acetate, and the combined extracts are dried (Na2SO4), filtered, and concentrated.

EXAMPLE 160C Example 833294B (481 mg) in DMF (4 mL) at 25 ° C is treated with cyanuric chloride (189 mg), stirred for 30 minutes, and treated with water and ethyl acetate. The extract is washed with 1 M NaHCO 3 and water and dried (Na 2 SO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20% acetone / hexane.

EXAMPLE 160D A mixture of example 160C (394 mg), azidotrimethylsilane (0.52 ml), and dibutyltin oxide (45 mg) in toluene (3.5 ml) at reflux is stirred for 38 hours, treated with methanol, and concentrated twice from methanol. The concentrated material is treated with ethyl acetate and saturated NaHCO 3. The aqueous layer is adjusted to pH less than 2 with 12M HCl and extracted with ethyl acetate. The extract is dried (MgSO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 2% methanol / dichloromethane and 5% methanol / 0.5% acetic acid / dichloromethane.

EXAMPLE 160E A mixture of Example 160D (224 mg) and palladium black (0.20 g) at 25 ° C is treated with a mixture of 96% formic acid (0.19 ml) in methanol (4 ml), stirred for 30 minutes, filter, concentrate, and concentrate again from methanol.

EXAMPLE 160F This example is prepared by substituting example 160E for 3-azetidinecarboxylic acid in Example 1 53A.

EXAMPLE 160G This example is prepared by substituting example 160F for example 153A in example 153C. 1 H NMR (300MHz, DMSO-d6) d 8.48 (d, 1 H), 8.36 (d, 1 H), 7.82 (d, 1 H), 7.70 (m, 3H), 7.32 (m, 12H), 6.99 (d, 1 H), 6.83 (d, 2H), 2.93 (m, 22H).

EXAMPLE 161 A A mixture of example 832729 (25 mg), Boc-Ala-Ala-OH (9 mg), EDAC HCI (7 mg), and HoBT (6 mg) in dichloromethane (0.5 ml) at 25 ° C is treated with DI EA (0.009 ml), stirred for 16 hours, and treated with water and ethyl acetate. The extract is washed with 20% aqueous NH4CI and brine (25 mL) and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 8% methanol / dichloromethane.

EXAMPLE 161B Example 161A (15 mg) in dichloromethane (1 ml) at 25 ° C is treated with water (0.08 ml) and TFA (0.6 ml), stirred for 1 hour, and concentrated twice from dichloromethane. 1 H NMR (300MHz, DMSO-de) d 12.09 (br, 1H), 9.68 (br, 1H), 8.52 (d, 1H), 8.51 (d, 1H), 8.29 (d, 1H), 8.05 (m, 3H) ), 7.77 (m, 4H), 7.52 (m, 3H), 7.37 (m, 3H), 7.17 (m, 7H), 6.93 (d, 2H), 3.55 (m, 17H), 1.92 (m, 2H) , 1.30 (d, 3H), 1.18 (d, 3H).

EXAMPLE 162A This example is prepared by substituting 5-pyrrolidin-2-yl-tetrazole, which is prepared as described in J. Med. Chem. 1985, 28, 1067-1071, by 3-azetidinecarboxylic acid in example 153A.

EXAMPLE 162B This example is prepared by substituting example 162A for example 153A in example 153C. 1 H NMR (300MHz, DMSO-d 6) d 8.50 (d, 1H), 8.27 (d, 1H), 7.85 (dd, 1H), 7.73 (d, 2H), 7.43 (m, 7H), 7.17 (m, 7H) ), 6.88 (d, 2H), 4.1 1 (m, 3H), 2.88 (m, 17H), 1.93 (m, 4H).

EXAMPLE 163A This example is prepared by substituting isonipecotic acid for 3-azetidinecarboxylic acid in Example 160A.

EXAMPLE 163B This example is prepared by substituting example 163A and methanesulfonamide for example 2C and 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in the 2D example.

EXAMPLE 163C This example is prepared by substituting example 163B for example 160D in example 160E.

EXAMPLE 163D This example is prepared by replacing Example 163C with 3-azetidinecarboxylic acid in Example 1 53A.

EXAMPLE 163E This example is prepared by substituting example 163D for example 153A in example 153C. MS (ESI) m / e 974.1 (M + H).

EXAMPLE 164A This example is prepared by replacing Example 18C by 19C in Example 19D.

EXAMPLE 164B Treat 4-bromobenzenesulfonyl chloride (0.40 g) in dichloromethane (10 ml) at 0 ° C with TEA (0.26 ml), bis- (2,4-dimethoxy-benzyl) -amine, which is prepared as described in US Pat. Synthesis, 1991, 703-708, (0.50 g) and DMAP, (35 mg), is stirred at 25 ° C for 4.5 hours, and treated with water and ethyl acetate. The extract is washed with brine and dried (Na 2 SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20% ethyl acetate / hexane.

EXAMPLE 164C A mixture of example 164A (356 mg), example 164B (151 mg), sodium tert-butoxide (81 mg), tris (dibenzylidene ketone) dipalladium (O) (32 mg) and rac-2,2'-bis- ( diphenylphosphino) -l, 1'-biphenyl (42 mg) in toluene (3 mL) at reflux is stirred for 3.5 hours, and treated with ethyl acetate and brine. The extract is dried (Na2SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 2-4% methanol / dichloromethane.

EXAMPLE 164D A mixture of Example 164C (0.34 g) and triethylsilane (0.25 mL) in dichloromethane (5 mL) at 25 ° C is treated with TFA (0.5 mL), stirred for 1.25 hours, and concentrated twice from dichloromethane. The concentrated material is subjected to flash chromatography on silica gel with 5% methanol / dichloromethane and 5-10% methanol / saturated with NH3 gas / dichloromethane.

EXAMPLE 164E This example is prepared by replacing Example 164D with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-d6) d 7.71 (d, 2H), 7.57 (d, 2H), 7.48 (m, 5H), 7.29 (m, 8H), 6.86 (d, 2H), 6.51 (br, 1 H), 6.47 (d, 2H).

EXAMPLE 165A Example 163A (0.50 g) in dichloromethane (5 ml) at 0 ° C is treated with DMF (2 drops) and oxalyl chloride (0.58 ml), stirred for 10 minutes, stirred at 25 ° C for 30 minutes, and concentrated twice from dichloromethane. The material concentrated in THF (5 ml) at 25 ° C is treated with 50% aqueous hydroxylamine (0.46 ml), stirred for 17 hours and concentrated. The material concentrated in ethyl acetate is washed with 0.5M HCl, water, and brine, dried (Na 2 SO), filtered, and concentrated.

EXAMPLE 165B This example is prepared by substituting example 165A for example 160D in example 160E.

EXAMPLE 165C This example is prepared by replacing Example 165B with 3-azetidinecarboxylic acid in Example 153A.

EXAMPLE 165D This example is prepared by substituting example 165C for example 153A in example 153C.

EXAMPLE 166A This example is prepared by substituting 4-bromo-2-chlorobenzenesulfonyl chloride for 4-bromobenzenesulfonyl chloride in Example 164B.

EXAMPLE 166B This example is prepared by substituting example 166A for example 164B in example 164C.

EXAMPLE 166C This example is prepared by substituting example 166B for example 164C in example 164D.

EXAMPLE 166D This example is prepared by substituting Example 166C for 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-d6) d 7.74 (d, 2H), 7.65 (d, 1 H), 7.50 (m, 5 H), 7.30 (m, 9 H), 6.83 (d, 2 H), 6.47 (m, 1 H), 6.39 (m, 2H), 3.59 (m, 1 H), 3.39 (s, 2H), 3.17 (m, 4H), 3.08 (m, 2H), 2.73 (m, 2H), 2.51 (s, 3H), 2.49 (s, 3H), 2.40 (m, 4H), 2.00 (m, 1 H), 1.75 (m, 1 H).

EXAMPLE 167A This example is prepared by substituting 4-bromo-2,6-dichlorobenzenesulfonyl chloride for 4-bromobenzenesulfonyl chloride in Example 164B.

EXAMPLE 167B This example is prepared by substituting example 167A for example 164B in example 164C.

EXAMPLE 167C This example is prepared by substituting example 167B for example 164C in example 164D.

EXAMPLE 167D This example is prepared by substituting example 167C for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsufinanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-d6) d 7.73 (d, 2H), 7.51 (m, 5H), 7.30 (m, 9H), 6.81 (d, 2H), 6.48 (m, 1 H), 6.43 (s) , 2H), 3.55 (m, 1 H), 3.3g (s, 2H), 3.17 (m, 4H), 3.07 (m, 2H), 2.87 (m, 2H), 2.51 (s, 3H), 2.49 ( s, 3H), 2.41 (m, 4H), 2.02 (m, 1 H), 1.75 (m, 1 H).

EXAMPLE 168A Treat tropane in 1,2-dichloroethane (8 ml) at 0 ° C with 1-chloroethyl chloroformate (0.47 ml), stir for 15 minutes, reflux for 2 hours, and concentrate twice from of dichloromethane. The methanol-concentrated material (8 ml) is refluxed for 2 hours and concentrated twice from dichloromethane.

EXAMPLE 168B This example is prepared by replacing Example 168A with azetidine hydrochloride in Example 30D.

EXAMPLE 168C This example is prepared by substituting example 168B for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-d6) d 8.87 (m, 1 H), 8.44 (d, 1 H), 8.09 (m, 1 H), 7.82 (m, 1 H), 7.71 (d, 2H), 7.50 (m, 5H), 7.27 (m, 8H), 6.92 (m, 1 H), 6.78 (d, 2H), 4.07 (m, 1 H), 3.90 (m, 2H), 3.38 (m, 3H) , 3.12 (m, 4H), 2.97 (m, 2H), 2.41 (m, 4H), 2.09 (m, 4H), 1.83 (m, 4H), 1.61 (m, 4H), 1.48 (m, 1H).

EXAMPLE 169A This example is prepared by substituting 7-aza-bicyclo [2.2.1] -heptane hydrochloride, which is prepared as described in Org. Lett. 2001, 3, 1371-1374, by azetidine hydrochloride in Example 30D.

EXAMPLE 169B This example is prepared by substituting example 169A for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amin o) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, DMSO-d 6) d 9.20 (m, 1 H), 8.44 (d, 1H), 8.13 (m, 1H), 7.82 (d, 1H), 7.71 (d, 2H), 7.51 (m, 5H), 7.27 (m, 8H), 6.92 (d, 1H), 6.78 (d, 2H), 4.12 (m, 3H), 3.38 (m, 3H), 3.13 (m, 4H), 2.97 (m, 2H), 2.40 (m, 4H), 2.09 (m, 3H), 1.85 (m, 4H), 1.58 (m, 4H).

EXAMPLE 170A This example is prepared by substituting 1-bromo-2-nitrobenzene for 1-fluoro-2- (trifluoromethyl) -benzene in Example 18D.

EXAMPLE 170B This example is prepared by replacing Example 170A with 4-bromobenzenesulfonyl chloride in Example 164B.

EXAMPLE 170C Example 170B (150 mg) at 25 ° C is treated with a mixture of 95% sodium hydride (8 mg) and 2- (phenylsulfanyl) ethanol (0.042 ml) in DMF (1.5 ml), stirred for 6 hours and treated with ethyl acetate and brine. The aqueous layer is extracted with ethyl acetate, and the extract is dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 25% acetone / hexane.

EXAMPLE 170D This example is prepared by substituting example 170C for example 164C in example 164D.

EXAMPLE 170E This example is prepared by replacing Example 170D with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-d6) d 8.32 (d, 1 H), 8.08 (dd, 1 H), 7.73 (d, 2H), 7.35 (m, 14H), 6.85 (d, 2H), 4.41 (d. t, 2H), 3.46 (m, 2H), 3.39 (t, 2H), 3.23 (m, 4H), 2.44 (m, 4H).

EXAMPLE 171 A This example is prepared by substituting 4-bromo-3-trifluoromethylbenzenesulfonyl chloride for 4-bromobenzenesulfonyl chloride in Example 164B.

EXAMPLE 171 B This example is prepared by substituting example 171 A for example 170B in example 170C.

EXAMPLE 171 C This example is prepared by substituting example 171 B for example 164C in example 164D.

EXAMPLE 171 D This example is prepared by replacing Example 171 C by 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-d6) d 8.05 (m, 2H), 7.71 (d, 2H), 7.50 (m, 5H), 7.30 (m, 9H), 6.84 (d, 2H), 4.36 (t, 2H), 3.41 (s, 2H), 3.38 (t, 2H), 3.20 (m, 4H), 2.41 (m, 4H).

EXAMPLE 172A The tert-butyl ester of 2 (S) -hydroxymethyl-4 (R) - (toluene-4-sulfonyloxy) pyrrolidin-1-carboxylic acid, which is prepared as described in J, is treated. Med. Chem. 1091, 34, 2787-2797), (467 mg) in methanol (21 ml) at 25 ° C with 95% sodium methoxide (74 mg) in ethanol (3.5 ml), refluxed for 9.5 hours, and concentrate. The material concentrated in water and diethyl ether is washed with brine and dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20% acetone / hexane.

EXAMPLE 172B Example 172A (178 mg) is treated with 1 M HCl in methanol (20 mL), stirred for 21 hours, concentrated, and re-concentrated from diethyl ether.

EXAMPLE 172C This example is prepared by replacing Example 172B with azetidine hydrochloride in Example 30D.

EXAMPLE 172D This example is prepared by substituting example 172C for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-de) d 8.46 (d, 1H), 8.33 (m, 1H), 7.79 (dd, 1H), 7.71 (d, 2H), 7.50 (m, 5H), 7.27 (m, 9H), 6.92 (d, 1H), 6.80 (d, 2H), 4.43 (m, 1H), 4.09 (m, 1H), 3.85 (m, 1H), 3.54 (m, 1H), 3.39 (s, 2H), 3.33 (m, 2H), 3.15 (m, 5H), 2.94 (m, 2H), 2.40 (m, 5H), 1.94 (m, 4H), 1.72 ( m, 1H).

EXAMPLE 173A This example is prepared by substituting 2 (R) -hydroxymethyl-4 (S) - (toluene-4-sulfonyloxy) pyrrolidine-1-carboxylic acid tert-butyl ester, which is prepared as described in J. Med. Chem. 1991, 34, 2787-2797, by 2-S-hydroxyl-4 (R) - (toluene-4-sulfonyloxy) pyrrolidin-1-carboxylic acid tert-butyl ester in Example 172A.

EXAMPLE 173B This example is prepared by substituting example 173A or example 172A in example 172B.

EXAMPLE 173C This example is prepared by substituting Example 173B for azetidine hydrochloride in Example 30D.

EXAMPLE 173D This example is prepared by substituting example 173C for 4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300MHz, DMSO-d 6) d 8.46 (d, 1H), 8.25 (m, 1H), 7.81 (dd, 1H), 7.71 (d, 2H), 7.51 (m, 5H), 7.27 (m, 9H), 6.94 (d, 1H), 6.80 (d, 2H), 4.46 (m, 1H), 4.14 (m, 1H), 3.87 (m, 1H), 3.56 (m, 1H), 3.39 (s, 2H), 3.33 (m, 2H), 3.16 (m, 5H), 2.95 (m, 2H), 2.40 (m, 5H), 1.95 (m, 4H), 1.76 ( m, 1H).

EXAMPLE 174 This example is prepared by substituting example 837538C and example 172C for example 2C and 4 - (((1R) -3- (d-imethylamino) -1- ((f-enyl-sulfonyl) -methyl) -propyl) -amino) - 3-nitrobenzenesulfonamide, respectively, in example 2D. 1 H NMR (300MHz, DMSO-d 6) d 8.46 (d, 1H), 8.32 (m, 1H), 7.81 (dd, 1H), 7.71 (d, 2H), 7.24 (m, 10H), 6.94 (d, 1H) ), 6.79 (d, 2H), 4.45 (m, 1H), 4.11 (m, 1H), 3.87 (m, 1H), 3.56 (m, 1H), 3.32 (m, 4H), 3.15 (m, 5H) , 2.97 (m, 2H), 2.78 (m, 4H), 2.22 (m, 6H), 1.96 (m, 4H), 1.66 (m, 4H).

EXAMPLE 175 This example is prepared by substituting example 837538C and example 173C for example 2C and 4 - (((1R) -3- (dimethylamino) -l - ((phenylsulfonyl) methyl) propyl) am i no) -3-nitrobenzenesulfonamide , respectively, in the example 2D. 1 H NMR (300MHz, DMSO-d 6) d 8.46 (d, 1H), 8.26 (m, 1H), 7.80 (dd, 1H), 7.71 (d, 2H), 7.24 (m, 10H), 6.94 (d, 1H), 6.79 (d, 2H), 4.45 (m, 1H), 4.13 (m, 1H) ), 3.86 (m, 1H), 3.57 (m, 1H), 3.32 (m, 4H), 3.15 (m, 5H), 2.94 (m, 2H), 2.78 (m, 4H), 2.22 (ni, 6H) , 1.95 (m, 4H), 1.66 (m, 4H).

EXAMPLE 176 This example is prepared by substituting example 837538C and example 169A for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (300MHz, DMSO-d 6) d 9.18 (br, 1H), 8.44 (d, 1H), 8.14 (m, 1H), 7.80 (d, 1H), 7.71 (d, 2H), 7.24 (m, 9H) ), 6.93 (d, 1H), 6.78 (d, 2H), 4.09 (m, 2H), 3.35 (m, 4H), 3.14 (m, 6H), 2.76 (br s, 4H), 2.22 (m, 7H) ), 2.04 (m, 2H), 1.84 (m, 4H), 1.66 (m, 6H).

EXAMPLE 177A This example is prepared by substituting 2,5- (cis) -dimethylpyrrolidine toluenesulfonate, which is prepared as described in A. R. Katritzky et al. J. Org. Chem. 1999, 64, 1979-1985) by azetidine hydrochloride in Example 30D.

EXAMPLE 177B This example is prepared by substituting example 837538C and example 177A for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfaniI) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (300MHz, DMSO-d 6) d 8.57 (br, 1H), 8.45 (d, 1H), 8.15 (m, 1H), 7.81 (d, 1H), 7.71 (d, 2H), 7.24 (m, 9H), 6.96 (m, 1H), 6.78 (d, 2H), 4.11 (m, 1H) ), 3.49 (m, 1H), 3.31 (m, 2H), 3.13 (m, 8H), 2.77 (m, 4H), 2.17 (m, 7H), 1.62 (m 6H), 1.29 (m, 6H).

EXAMPLE 178A A mixture of 2 (5H) -furanone (1 ml) and N- (methoxymethyl) -N- (trimethylsilylmethyl) -benzylamine (4.2 ml) in dichloromethane (30 ml) at 0 ° C is treated with TFA (0.10 ml), stir for 2.5 hours, and treat with dichloromethane and saturated aqueous NaHCO3. The extract is washed with brine and dried (Na2SO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 15% acetone / hexane.

EXAMPLE 178B Example 178A (2.76 g) in 1,2-dichloroethane (25 ml) a ° C is treated with 95% benzyl chloroformate (3.8 ml), refluxed for 24 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 25% acetone / hexane.

EXAMPLE 178C Example 178B (2.26 g) in THF (40 mL) at -78 ° C is treated with 1 M DIBAL in dichloromethane (20 mL) then methanol (40 mL), filtered at 25 ° C, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 30% acetone / hexane.

EXAMPLE 178D A mixture of Example 178C (1.282 g) and triethylsilane (1.17 mL) in dichloromethane (25 mL) at 0 ° C is treated with BF3 diethyl etherate (0.68 mL), stirred at 25 ° C for 3 hours. , and treated with ethyl acetate and saturated aqueous NaHCO3. The extract is washed with brine and dried (Na 2 SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 15% acetone / hexane.

EXAMPLE 178E This example is prepared by substituting example 178D for example 160D in example 160E.

EXAMPLE 178F This example is prepared by replacing Example 178E with azetidine hydrochloride in Example 30D.

EXAMPLE 178G This example is prepared by substituting example 837538C and example 178F for example 2C and 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- nitrobenzenesulfonamide, respectively , in the 2D example. 1 H NMR (300MHz, DMSO-d 6) d 8.46 (d, 1H), 8.23 (m, 1H), 7.77 (d, 1H), 7.71 (d, 2H), 7.24 (m, 10H), 6.96 (d, 1H) ), 6.79 (d, 2H), 4.08 (m, 1H), 3.61 (m, 2H), 2.68 (m, 26H), 1.66 (m, 6H).

EXAMPLE 179A Cyclohexanol (880 mg) in DMF (2 ml) is treated at 25 ° C with 60% oily NaH (400 mg) and DMF (3 ml), stirred for 1.5 hours, treated with 15-crown-5 (0.6 mi), 4-fluoro-3-nitrobenzenesulfonamide, which is prepared as described in WO02 / 24636, (440 mg), and DMF (0.5 ml), stirred for 1.5 hours, and treated with water and ethyl acetate. ethyl. The extract is dried (MgSO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with hexanes / ethyl acetate (10-30%).

EXAMPLE 179B This example is prepared by substituting example 179A for 4 - (((1 R) -3- (d imetilamino) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (500MHz, DMSO-d 6) d 8.31 (d, 1H), 8.07 (dd, 1H), 7.72 (d, 2H), 7.55 (t, 2H), 7.40 (m, 7H), 7.23 (dd, 1H) ), 6.85 (d, 2H), 6.73 (m, 1H), 3.51 (s, 2H), 3.23 (s, 4H), 2.44 (s, 4H), 1.85 (m, 2H), 1.66 (m, 2H) , 1.55 (m, 2H), 1.46 (m, 1H), 1.28 (m, 3H).

EXAMPLE 180A This example is prepared by substituting cyclohexyl methanol for cyclohexanol in Example 179A.

EXAMPLE 180B This example is prepared by replacing the example 779855A by 4 - (((1R) -3- (dimethylamine) -1 - ((phenylsulfanyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (300MHz, DMSO-d 6) d 8.41 (d, 1H), 8.17 (dd, 1H), 7.77 (s, 1H), 7.74 (s, 2H), 7.58 (d, 1H), 7.53 (m, 2H) ), 7.46 (m, 3H), 7.37 (m, 3H), 6.93 (d, 2H), 4.31 (br s, 1H), 3.80 (br s, 4H), 3.19 (br s, 3H), 2.83 (br s, 2H), 1.74 (m, 6H), 1.23 (m, 3H), 1.07 (m, 2H).

EXAMPLE 181A This example is prepared by substituting 2-cyclohexyl ethanol for cyclohexanol in Example 179A.

EXAMPLE 181B This example is prepared by replacing Example 181 A with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyI) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (500MHz, DMSO-d6) d 8.41 (d, 1 H), 8.17 (dd, 1 H), 7.77 (s, 1 H), 7.75 (s, 2H), 7.60 (d, 1 H), 7.53 (m , 2H), 7.52 (t, 2H), 7.43 (t, 1 H), 7.37 (m, 3H), 6.92 (d, 2H), 4.30 (t, 4H), 2.95 (br s, 4H), 1. 71 (d, 2H), 1.65 (m, 8H), 1.46 (m, 1 H), 1.1 (m, 4H), 0.04 (m, 2H).

EXAMPLE 182A It is treated with ammonium formate (5.8 g) in water (2.9 mln) a ° C with tetrahydropyran-4-one (1 g) in methanol (26 ml), stir for 5 minutes, treat with 10% Pd / C (1.2 g), stir for 18 hours, filter through diatomaceous earth (Celite®), and concentrate. A mixture of the concentrated material in ethanol (23 ml) is stirred at 0 ° C as 12M HCl (1.7 ml) is added dropwise, stirred for 1 hour, and filtered.

EXAMPLE 182B This example is prepared by substituting example 182A for example 21 C in example 21 D.

EXAMPLE 182C This example is prepared by substituting Example 780431B for 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400MHz, DMSO-d 6) d 8.62 (d, 1H), 8.27 (d, 1H), 7.83 (dd, 1H), 7.4g (d, 2H), 7.46 (d, 2H), 7.42 (d, 1H), 7.36 (m, 4H), 6.g? (d, 2H), 4.22 (br s, 1H), 3.03 (m, 1H), 3.86 (d, 2H), 3.72 (br s, 2H), 3.46 (t, 3H), 2.91 (br s, 4H), 2.49 (s, 2H), 1.91 (d, 2H), 1. 62 (m, 2H).

EXAMPLE 183A This example is prepared by substituting 2-cyclohexylethylamine for Example 21C in Example 21D.

EXAMPLE 183B This example is prepared by substituting Example 183A for 4 - (((1 R) -3- (d-methylamino) -1 - ((f-enylsulfan-1) methyl) propyI) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400 MHz, DMSO-d 6) d 12.20 (br s, 1 H), 8.62 (d, 1H), 8.52 (t, 1H), 7.94 (dd, 1H), 7.75 (d, 3H), 7.52 (m, 2H), 7.47 (d, 1H), 7.42 (m, 1H), 7.37 (m, 3H) ), 7.21 (d, 1H), 6.92 (d, 2H), 4.28 (br s, 2H), 3.75 (br s, 4H), 3.44 (m, 2H), 3.17 (br s, 2H), 2.86 (br s, 2H), 1.73 (d, 2H), 1.65 (m, 2H), 1.52 (m, 2H), 1.36 (m, 1H), 1.18 (m, 4H), 0.95 (m, 2H).

EXAMPLE 184A This example is prepared by substituting N-methylcyclohexylamine for Example 21 C in Example 21 D.

EXAMPLE 184B This example is prepared by substituting Example 184A for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR ( 400MHz, DMSO-d6) d 8.26 (d, 1 H), 7.89 (dd, 1 H), 7.75 (d, 3H), 7.52 (m, 2H), 7.47 (d, 2H), 7.43 (m, 2H), 7.37 (m, 3H), 6.92 (d, 2H), 4.27 (br s, 2H), 3.81 (br s, 3H), 3.56 (t, 1 H), 3.15 (br s, 3H), 2.84 (br s, 2H), 2.65 (s, 3H), 1.76 (t, 4H), 1.59 (m, 3H), 1.35 (m, 2H), 1 .15 (m, 1 H).

EXAMPLE 185A This example is prepared by substituting 3,3-dimethylglutarimide for Example 18E in Example 18F.

EXAMPLE 185B This example is prepared by substituting example 185A for example 21 C in example 21 D.

EXAMPLE 185C This example is prepared by substituting Example 185B for 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enyl-sulfonyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide in Example 1 D. H NMR (500MHz, DMSO-d6) d 8.29 (d, 1 H), 7.g3 (dd, 1 H), 7.74 (d, 3H), 7.51 (m, 2H), 7.47 (t, 2H), 7.42 (m, 2H), 7.35 (m, 3H), 6.91 (d, 2H), 4.29 (s, 2H), 3.79 (br s, 4H), 3.15 (m, 6H), 2.90 (br s, 2H), 1.42 (m, 4H), 0.96 (s, 6H).

EXAMPLE 186A A mixture of tert-butyl 4-oxo-1-piperidine carboxylate (2 g) in methanol (50 ml) at 0 ° C is treated with NaBH 4 (2 g), stirred for 0.5 hours, stirred for 2 hours at 25 ° C, concentrate, treat with water, and extract with dichloromethane. The extract is washed with water and dried (MgSO 4), filtered, and concentrated.

EXAMPLE 186B This example is prepared by replacing Example 186A with cyclohexanol in Example 179A.

EXAMPLE 186C This example is prepared by substituting example 186B for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (300MHz, DMSO-d 6) d 8.26 (d, 1H), 8.03 (dd, 1H), 7.72 (d, 2H), 7.54 (m, 1H), 7.49 (m, 1H), 7.42 (m, 3H), 7.36 (m, 3H), 7.24 (m, 1H), 6.81 (d, 2H), 4.92 (m, 1H), 3.44 (m, 4H), 3. 35 (m, 2H), 3.17 (d, 4H), 2.41 (m, 4H), 1.87 (m, 2H), 1.60 (m, 2H), 1.40 (s, 9H).

EXAMPLE 187 This example is prepared by substituting example 186C for example 21B in example 21C. 1 H NMR (400MHz, DMSO-d 6) d 12.30 (br s, 1H), 11.58 (br s, 1H), 9.31 (s, 1H), 9.08 (s, 1H), 8.46 (d, 1H), 8.19 (dd) , 1H), 8.18 (m, 1H), 7.76 (d, 2H), 7.71 (d, 1H), 7.52 (t, 2H), 7.46 (t, 2H), 7.42 (d, 1H), 7.35 (d, 3H), 6.92 (d, 2H), 5.11 (m, 1H), 4.35 (s, 2H), 3.84 (m, 2H), 3.67 (s, 3H), 3.38 (m, 2H), 3.12 (m, 2H) ), 2.73 (s, 2H), 2.72 (d, 1H), 2.15 (m, 2H), 1.98 (m, 2H).

EXAMPLE 188 A mixture of example 187 (53 mg) and 37% formalin (6.6, μl), in dichloromethane / methanol 1: 1 (1.5 ml) at 25 ° C is treated with 2.47 mmoles / g of MP-NaCNBH3 (55 mg) and DIEA (1 drop), stirred for 18 hours, treated with dichloromethane / methanol 1: 1 (5 ml), and filtered through diatomaceous earth (Celite®). The filtrate is dried (MgSO 4), filtered, concentrated. The concentrated material is subjected to flash chromatography on silica gel with dichloromethane / 2-5% methanol / 0.5-1% NH4OH. 1 H NMR (500MHz, DMSO-d 6) d 8.28 (d, 1H), 8.04 (dd, 1H), 7.72 (d, 2H), 7.54 (d, 1H), 7.45 (d, 2H), 7.46 (t, 2H) ), 7.42 (m, 3H), 7.36 (m, 3H), 7.24 (dd, 1H), 6.79 (d, 2H), 4.91 (s, 1H), 4.42 (s, 2H), 3.14 (m, 8H), 2.74 (s, 3H), 2.39 (m, 4H), 2.10 (s, 2H), 1.96 (s, 2H).

EXAMPLE 189 This example is prepared by substituting 4 - ((cyclohexylmethyl) amino) -3-nitrobenzenesulfonamide for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in the 2D example. 1 H NMR (400MHz, DMSO-d 6) d 8.64 (m, 2H), 7.93 (dd, 1H), 7.78 (d, 2H), 7.72 (s, 1H), 7.52 (d, 4H), 7.40 (d, 2H) ), 7.33 (m, 1H), 7.24 (d, 1H), 6.92 (d, 2H), 4.22 (br s, 1H), 3.82 (br s, 2H), 3.29 (t, 4H), 2.88 (br s , 2H), 1.70 (m, 8H), 1.18 (m, 4H), 0.98 (m, 2H).

EXAMPLE 190A Treat cyclohexane-carboxaldehyde (2 g) in methanol (20 mL) at 0 ° C with n-propylamine (0.77 mL) and NaCNBH 3 (600 mg), stir at 25 ° C for 18 hours, treat with water, and It is extracted with diethyl ether. The extract is dried (MgSO4), filtered, and concentrated.

EXAMPLE 190B This example is prepared by substituting example 190A for example 21 C in example 21 D.

EXAMPLE 190C This example is prepared by substituting Example 190B for 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.24 (d, 1 H), 7.89 (t, 1 H), 7.76 (m, 2 H), 7.70 (br s, 1 H), 7.51 (m, 4 H), 7.45 (d, 1 H), 7.39 (m, 2 H), 7.32 (m, 1 H), 6.91 (d, 2H), 3.15 (dd, 2H), 3.07 (d, 2H), 2. 05 (s, 2H), 1.61 (m, 6H), 1.48 (m, 3H), 1.11 (m, 4H), 0.78 (m, 5H).

EXAMPLE 191 A This example is prepared by substituting 1-N-Boc-4-cyanopiperidine for Example 21 B in Example 21 C.

EXAMPLE 191 B A mixture of Example 191 A (520 mg), K2C03 (1.7g), benzyl bromide (0.62ml), and acetone (7ml) at reflux is stirred for 2.5 hours and concentrated. The concentrated material is treated with water and 1 M HCl, washed with hexanes, basified with 2.5 M NaOH, and extracted with dichloromethane. The extract is dried (MgSO4), filtered, and concentrated.

EXAMPLE 191 C A mixture of example 191 B (420 mg) and Raney nickel (4.5 g) in 20% NH3 / methane (100 ml) at 25 ° C is stirred under H2 at 4.22 kg / cm2 for 16 hours, filtered, and concentrate EXAMPLE 191 D This example is prepared by substituting example 191 C for example 21 C in example 21 D.

EXAMPLE 191 E This example is prepared by substituting Example 191 D for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsufinyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (400 MHz, DMSO-d6) d 12.08 (br s, 1 H), 1 1 .50 (br s, 1 H), 10.68 (br s, 1 H), 8.69 (m, 1 H), 8.62 (s) , 1 H), 8.10 (br s, 1 H), 7.91 (m, 1 H), 7.74 (d, 3 H), 7.57 (br s, 2 H), 7.46 (m, 7 H), 7.33 (m, 4 H) , 7.27 (d, 1 H), 6.g? (d, 2H), 4.34 (br s, 2H), 4.20 (m, 2H), 3.81 (m, 2H), 3.26 (m, 7H), 3.15 (s, 2H), 2.79 (m, 5H), 2.49 (s, 1 H), 1.87 (m, 4H), 1.60 (m, 2H), 1.24 (m, 1 H), 0.85 (, 1 H).

EXAMPLE 192A Cyclohexane-methylamine (2 mL) in THF (8 mL) is treated at 25 ° C with formic acetic anhydride, which is prepared as described in Tet. Lett. 1982, 33, 3315, (5.7 g), stir for 3.5 hours, concentrate, cool to 0 ° C, treat with 1 M borane-THF (5.1 ml), stir at reflux for 2.5 hours, concentrate , it is cooled to 0 ° C, treated with methanol (10 ml) and methanolic HCl (50 ml), stirred at reflux for 1 hour, concentrated, treated with water, and washed with diethyl ether. The aqueous layer is basified with 1 M KOH and extracted with dichloromethane. The extract is dried (MgSO4), filtered, and concentrated.

EXAMPLE 192B This example is prepared by substituting example 192A for example 21C in example 21D.

EXAMPLE 192C This example is prepared by replacing Example 192B with 4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (500 MHz, DMSO-d 6) d 8.27 (d, 1H), 7.86 (dd, 1H), 7.74 (m, 3H), 7.52 (m, 2H), 7.47 (m, 2H), 7.42 (m, 2H), 7.35 (m, 3H), 6.91 (d, 2H), 4.29 (br s, 2H), 3.27 (d, 4H), 2.81 (m, 3H), 1.63 (m, 8H), 1.13 (m, 4H), 0.86 (m, 2H).

EXAMPLE 193A This example is prepared by substituting 4-amino-1-benzylpiperidine for Example 21C in Example 21D.

EXAMPLE 193B This example is prepared by substituting Example 193A for 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (500 MHz, DMSO-d 6) d 9.g5 (br s, 1H), 8.62 (br s, 1H), 8.15 (br s, 1H), 7.95 (d, 1H), 7.73 (d, 4H) , 7.50 (m, 10H), 7.41 (m, 1H), 7.34 (m, 5H), 6.90 (d, 2H), 4.46 (br s, 1H), 4.34 (br s, 2H), 4.23 (br s, 1 H), 3.92 (br s, 1 H), 3.18 (m, 2 H), 3.06 (m, 3 H), 2.20 (m, 2 H), 1.83 (br s, 1 H).

EXAMPLE 194A A mixture of tetrahydrothiopyran-4-one (1 g), hydroxylamine hydrochloride (1.5 g), and TEA (3 ml) in absolute ethanol (5 ml) is stirred under reflux for 3 hours, cooled to 25 ° C. , it is treated with water, and extracted with dichloromethane. The extract is dried (MgSO), filtered, and concentrated.

EXAMPLE 194B Example 193A (300 mg) is treated with LiAIH4 (400 mg) in THF (4 ml) / diethyl ether (11 ml), stirred at reflux for 5 hours, and processed as described in Fieser and Fieser, Reagents for Organic Synthesis, Vol 1, p.584.

EXAMPLE 194C This example is prepared by substituting example 194B for example 21 C in example 21 D.

EXAMPLE 194D This example is prepared by replacing Example 194C with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyI) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400 MHz, DMSO-d 6) d 12.01 (br s, 1 H), 8.64 (d, 1 H), 8.31 (d, 2 H), 7.94 (dd, 1 H), 7.74 (d, 3 H), 7.47 (m , 4H), 7.34 (m, 3H), 6.91 (d, 4H), 4.29 (br s, 1H), 3.79 (m, 3H), 2.79 (m, 3H), 2.67 (m, 2H), 2.21 (m , 2H), 1.75 (m, 2H).

EXAMPLE 195A This example is prepared by substituting ethyl 4-amino-1-piperidine carboxylate for Example 21C in Example 21D.

EXAMPLE 195B This example is prepared by substituting example 195A for 4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (500 MHz, DMSO-d 6) d 12.10 (br s, 1 H), 8.64 (d, 1H), 8.29 (d, 1H), 7.95 (dd, 1H), 7.75 (d, 3H), 7.54 (m, 2H), 7.48 (m, 1H), 7.43 (m, 1H), 7.37 (m, 2H), 6.92 (d, 2H), 4.36 (br s, 2H), 4. 05 (m, 2H), 3.94 (m, 3H), 3.77 (br s, 3H), 3.01 (br s, 4H), 2.83 (br s, 2H), 1.94 (d, 2H), 1.55 (m, 2H) ), 1.19 (t, 5H).

EXAMPLE 196A This example is prepared by substituting 1-bromopropane for benzyl bromide in Example 191B.

EXAMPLE 196B This example is prepared by substituting example 196A for example 191B in example 797197C.

EXAMPLE 196C This example is prepared by substituting example 196B for example 21C in example 21D.

EXAMPLE 196D This example is prepared by substituting the example 196C for 4 - (((1R) -3- (dimethylamido) -1 - ((f-enylsulfanyl) methyl I) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400 MHz, DMSO-d 6) d 8.51 (d, 1 H), 8.43 (t, 2H), 7.90 (dd, 1H), 7.72 (d, 2H), 7.53 (m, 1H), 7.42 (m, 4H), 7.35 (m, 3H), 7.24 (m, 1H), 7.10 (d, 1H), 6.78 (d, 2H), 3.41 (s, 2H), 3.36 (m, 5H), 3.13 (m, 4H), 2.77 (m, 3H), 2.39 (m, 4H), 1.87 (d, 3H), 1.59 (m, 2H), 1.42 (m, 2H), 0.87 ( t, 3H).

EXAMPLE 197A This example is prepared by substituting isopropylamine for Example 21 C in Example 21 D.

EXAMPLE 197B This example is prepared by replacing Example 197A with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyI) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR ( 500 MHz, DMSO-d6) d 8.64 (d, 1 H), 8.24 (d, 1 H), 7.95 (dd, 1 H), 7.74 (m, 3 H), 7.50 (m, 4 H), 7.42 (m, 1 H), 7.35 (m, 3 H), 7.27 (d, 1 H), 6.91 (d, 2 H), 4.25 (br s, 2 H), 4.00 (m, 1 H), 1.28 (d, 6 H).

EXAMPLE 198A A mixture of tributylphosphine (0.8 ml), (1, 1 '-azodicarbonyl) dipiperidine (0.8 g), and THF (5.1 ml) at 25 ° C is stirred for 10 minutes, treated with N- (2-hydroxyethyl) carbamate. of tert-butyl (0.32 ml), 2-mercaptothiazole (500 mg), and THF (5 ml), stirred for 20 hours, treated with ethyl acetate (50 ml), washed with water, dried (MgSO). ), filter, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 5-30% ethyl acetate / hexanes.

EXAMPLE 198B This example is prepared by substituting example 198A for example 21 B in example 21 C.

EXAMPLE 198C This example is prepared by substituting example 198B for example 21 C in example 21 D.

EXAMPLE 198D This example is prepared by substituting the example 198C for 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) p-ropil) amino) -3-nitrobenzenesulfonamide in Example 1 D. H NMR (400 MHz, DMSO-d6) d 8.80 (t, 1 H), 8.61 (d, 1 H), 7.96 (dd, 1 H), 7.73 (m, 4H), 7.62 (d, 1 H), 7.51 (m, 2H), 7.46 (d, 2H), 7.40 (m, 2H), 7.34 (m, 4H), 6.91 (d, 2H), 4.28 (br s, 2H), 3.81 (m, 4H), 3.50 (t, 4H), 2.06 (s, 2H).

EXAMPLE 199A This example is prepared by substituting 4-phenyl-2-mercaptothiazole for 2-mercaptothiazole in Example 198A.

EXAMPLE 199B This example is prepared by substituting example 199A for example 21B in example 21C.

EXAMPLE 199C This example is prepared by substituting example 199B for example 21C in example 21D.

EXAMPLE 199D This example is prepared by substituting example 199C for 4 - (((1R) -3- (dimethylamino) -1 - ((phenyl isulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400 MHz, DMSO-d 6) d 8.77 (m, 1 H), 8.57 (d, 1 H), 8.00 (s, 1 H), 7.91 (m, 3 H), 7.73 (d, 2 H), 7.54 (m, 1H), 7.39 (m, 11H), 7.24 (m, 1H), 6.86 (d, 2H), 3.87 (m, 2H), 3.57 (dd, 2H), 3.43 (s, 2H), 3.22 (m, 4H ), 2.39 (m, 4H).

EXAMPLE 200A This example is prepared by replacing 2-mercaptobenzothiazole with 2-mercaptothiazole in Example 198A.

EXAMPLE 200B This example is prepared by substituting example 200A for example 21 B in example 21 C.

EXAMPLE 200C This example is prepared by substituting example 200B for example 21 C in example 21 D.

EXAMPLE 200D This example is prepared by substituting the example 200C for 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (500 MHz, DMSO-d6) d 8.86 (t, 1 H), 8.50 (d, 1 H), 7.76 (m, 4 H), 7.54 (m, 2 H), 7.48 (m, 2 H), 7.43 (m , 2H), 7.36 (m, 4H), 6. 2 (d, 2H), 4.31 (br s, 2H), 3.91 (m, 2H), 3.66 (t, 4H), 2.97 (br s, 4H).

EXAMPLE 201 This example is prepared by substituting Example 198C for 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.80 (m, 1 H), 8.61 (d, 1H), 7.95 (dd, 1H), 7.74 (m, 4H), 7.71 (d, 1H), 7.62 (d, 1H), 7.52 (m, 4H), 7.40 (m, 1H), 7.39 (m, 2H), 7.37 (m, 1H), 7.33 (m, 1H), 6. 91 (d, 2H), 3.81 (m, 4H), 3.50 (m, 4H), 3.32 (m, 1H), 3.27 (m, 1H), 2.49 (m, 1H), 2.06 (s, 1H).

EXAMPLE 202A This example is prepared by substituting 2-mercapto-benzoxazole for 2-mercaptothiazole in Example 198A.

EXAMPLE 202B This example is prepared by substituting example 202A for example 21B in example 21C.

EXAMPLE 202C This example is prepared by substituting example 202B for example 21C in example 21D.

EXAMPLE 202D This example is prepared by replacing Example 202C with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) -propyl) amino) -3- nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.84 (m, 1 H), 8.58 (d, 1 H), 8.00 (dd, 1 H), 7.76 (d, 2 H), 7.71 (br s, 1 H), 7.57 (m , 2H), 7.50 (m, 4H), 7.30 (m, 2H), 7.29 (m, 3H), 6.91 (d, 2H), 4.22 (br s, 2H), 3.92 (m, 2H), 3.60 (t , 4H), 2.97 (m, 4H).

EXAMPLE 203 This example is prepared by replacing Example 200C with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.06 (br s, 1 H), 8.85 (t, 1 H), 8.58 (d, 1 H), 8.01 (dd, 1 H), 7.97 (d, 1 H), 7.75 (m , 3H), 7.71 (br s, 1H), 7.51 (m, 4H), 7.37 (m, 4H), 6.91 (d, 2H), 4.26 (br s, 2H), 3.90 (m, 2H), 3.64 ( t, 4H), 2.96 (m, 6H).

EXAMPLE 204A This example is prepared by substituting 2-mercaptopyrimidine for 2-mercaptothiazole in Example 198A.

EXAMPLE 204B This example is prepared by substituting example 204A for example 21B in example 21C.

EXAMPLE 204C This example is prepared by substituting example 204B for example 21 C in example 21 D.

EXAMPLE 204D This example is prepared by substituting Example 204C for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methy1) -propy) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.07 (br s, 1 H), 8.83 (t, 1 H), 8.66 (d, 2 H), 8.63 (d, 1 H), 8.04 (dd, 1 H ), 7.76 (d, 2H), 7.72 (br s, 1 H), 7.52 (m, 5H), 7.40 (d, 2H), 7.33 (m, 1 H), 7.24 (t, 1 H), 6.92 ( d, 2H), 4.29 (br s, 2H), 3.78 (m, 4H), 3.39 (t, 4H), 2.85 (br s, 2H).

EXAMPLE 205A This example is prepared by substituting 2-bromoethylamine hydrochloride for example 21 C in Example 21 D.

EXAMPLE 205B Example 205A and 2-mercaptoimidazole are subjected to the procedure described in J. Med. Chem. 1995, 38, 1067.

EXAMPLE 205C This example is prepared by replacing Example 205B with 4 - (((1 R) -3- (dimethylamido) -1 - ((f-enylsulf- nyl) methyl) propyI) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.73 (t, 1 H), 8.63 (d, 1 H), 7.94 (dd, 1 H), 7.76 (d, 3 H), 7.53 (m, 4 H), 7.40 (d, 2H), 7.34 (m, 1H), 7.30 (m, 1H), 6.93 (d, 2H), 4.26 (br s, 2H), 3.72 (m, 4H), 3.42 (t, 4H), 2.98 (br s , 4H).

EXAMPLE 206 This example is prepared by replacing Example 191D with 4 - (((1R) -3- (d-methylamido) -1 - ((f-enylsulfanyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.11 (br s, 1 H), 11.43 (br s, 1 H), 10.67 (br s, 1 H), 8.73 (t, 1 H), 8.63 (d, 1 H), 8.15 (m, 1H), 7.92 (dd, 1H), 7.76 (d, 2H), 7.59 (m, 2H), 7.53 (m, 4H), 7.44 (m, 4H), 7.38 (d, 2H), 7.33 (d, m, 1H), 7.28 (d, 1H), 6.93 (d, 2H), 4.34 (br s, 2H), 4.22 (d, 2H), 3.89 (d, 2H), 3.37 (m, 4H), 3.31 ( d, 2H), 3.25 (d, 2H), 2.84 (m, 4H), 1.88 (d, 3H), 1.61 (m, 2H).

EXAMPLE 207 This example is prepared by substituting example 205A for 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (500 MHz, DMSO-de) d 12.12 (br s, 1 H), 8.75 (m, 1 H), 8.65 (d, 1 H), 7.86 (dd, 1 H), 7.75 (d, 3 H ), 7.53 (m, 2H), 7.48 (m, 2H), 7.43 (m, 1 H), 7.36 (m, 4H), 6.92 (d, 2H), 4.29 (br s, 2H), 3.88 (m, 4H), 3.82 (m, 2H), 3.72 (t, 2H), 3.03 (m, 4H).

EXAMPLE 208A This example is prepared by substituting 4-methylthiazole-2-thiol for 2-mercaptoimidazole in Example 205B.

EXAMPLE 208B This example is prepared by substituting Example 208A for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d6) d 12.07 (br s, 1 H), 8.81 (t, 1 H), 8.63 (d, 1 H), 7.95 (dd, 1 H), 7.76 (d, 2H), 7.73 (br, 1 H), 7.52 (m, 3H), 7.39 (d, 2H), 7.34 (m, 1 H), 6.93 (d, 2H), 4.25 (br s, 2H), 3. 82 (m, 2H), 3.48 (m, 4H), 3.02 (m, 4H), 2.29 (s, 3H), 2.07 (s, 2H).

EXAMPLE 209A This example is prepared by substituting benzylamine for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsufinanM) methyl) propyl) amino) -3-nitrobenzenesulfonamide and 4-methoxycyclohexanecarboxylic acid for example 2C in the 2D example.

EXAMPLE 209B This example is prepared by substituting example 209A for example 18E in example 18F.

EXAMPLE 209C Example 209B (710 mg) and Pd (OH) 2 (0.28 g) in methanol (70 ml) at 50 ° C are stirred under H2 (4.22 kg / cm2) for 22 hours, cooled to 25 °, filtered, and concentrates.

EXAMPLE 209D This example is prepared by substituting example 209C for example 21 C in example 21 D.

EXAMPLE 209E This example is prepared by substituting Example 209D for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylisulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-de) d 8.55 (d, 1H), 8.48 (t, 1H), 7.90 (dd, 1H), 7.72 (d, 2H), 7.51 (m, 1H), 7.47 (s, 3H), 7.37 (m, 2H), 7.25 (m, 1H), 7.14 (d, 1H), 6.84 (d, 2H), 3.39 (s, 2H), 3.36 (m, 1H), 3.27 (m, 4H), 3.19 (m, 5H), 2.40 (t, 4H), 1.80 (m, 2H), 1.69 (m, 1H), 1.48 (m, 2H), 1.33 (m, m, 4H).

EXAMPLE 210A This example is prepared by substituting 2-mercaptothiophene for 2-mercaptothiazole in Example 198A.

EXAMPLE 210B This example is prepared by substituting example 210A for example 21B in example 21C.

EXAMPLE 210C This example is prepared by substituting example 210B for example 21C in example 21D.

EXAMPLE 210D This example is prepared by replacing Example 210C with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- nitrobenzenesulfonamide in Example 1D. 1 H NMR (500 MHz, DMSO-d 6) d 8.74 (t, 1 H), 8.62 (d, 1H), 7.90 (dd, 1H), 7.75 (m, 2H), 7.61 (dd, 1H), 7.54 (m, 2H), 7.49 (m, 2H), 7.43 (m, 1H), 7.36 (m, 2H), 7.21 (dd, 1H), 7.13 (d, 1H), 7.02 (dd, 1H), 6.92 (d, 2H), 4.36 ( br s, 2H), 3.63 (m, 4H), 3.11 (t, 4H), 2.54 (s, 4H).

EXAMPLE 211A A mixture of Boc-2-amino-2-methylpropanol (633 mg) and 2-thienyl disulfide (1 g) in THF (12 ml) at 25 ° C is treated with tributylphosphine (1.1 ml), heated to 85 ° C. C for 2.5 hours, treated with ethyl acetate, washed with water, dried (MgSO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 30-70% ethyl acetate / hexanes.

EXAMPLE 211B This example is prepared by substituting example 211A for example 21B in example 21C.

EXAMPLE 211C This example is prepared by substituting example 8030757B for example 21C in example 21D.

EXAMPLE 211D This example is prepared by substituting Example 211C for 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.58 (d, 1 H), 8.54 (s, 1 H), 7.82 (dd, 1 H), 7.79 (d, 2 H), 7.72 (br s, 1 H), 7.52 (m , 4H), 7.33 (d, 2H), 7.21 (dd, 1H), 6.96 (dd, 1H), 6.94 (d, 2H), 6.66 (dd, 1H), 4.19 (br s, 4H), 2.90 (br s, 6H), 1.54 (s, 6H).EXAMPLE 212A This example is prepared by replacing Example 19A with Boc-2-amino-2-methylpropanol and Example 22A by 2-thienyl disulfide in Example 211 A.

EXAMPLE 212B This example is prepared by substituting example 212A for example 18B in example 18C.

EXAMPLE 212C This example is prepared by substituting example 212B for example 18E in example 18F.

EXAMPLE 212D This example is prepared by substituting example 212C for example 21C in example 21D.

EXAMPLE 212E This example is prepared by substituting Example 212D for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 9.97 (br s, 1 H), 8.61 (d, 1H), 8.34 (d, 1H), 7.95 (dd, 1H), 7.75 (d, 2H), 7.72 (br s, 1H), 7.66 (d, 1H), 7.5 (d, 1H), 7.51 (d, 4H), 7.32 (m, 1H), 6.g2 (d, 2H), 4.35 (m, 2H), 4.22 (br s, 2H), 3. 5 (br s, 4H), 3.21 (m, 4H), 2.94 (m, 6H), 2.20 (m, 2H).

EXAMPLE 213A This example is prepared by replacing 2-mercaptopyrimidine with 2-mercaptothiazole in Example 22A.

EXAMPLE 213B This example is prepared by replacing Example 18A with Boc-2-amino-2-methylpropanol and Example 213A with 2-thienyl disulfide in Example 211A.

EXAMPLE 213C This example is prepared by substituting example 213B for example 18B in example 18C.

EXAMPLE 213D This example is prepared by substituting example 213C for example 21C in example 21D.

EXAMPLE 213E This example is prepared by substituting example 212D for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.08 (br s, 1 H), 9.86 (br s, 1H), 8.97 (d, 1H) 8.62 (d, 2H,) 8.60 (d, 1H), 7.9g (dd, 1H), 7. 77 (d, 2H), 7.74 (br s, 1H), 7.53 (m, 5H), 7.39 (d, 2H), 7.34 (m, 1H), 7.22 (t, 1H), 6.93 (d, 2H), 4.59 (m, 1H), 4.29 (br s, 2H), 3.42 (dd, 3H), 3.04 (dd, 2H), 2.95 (s, 4H), 2.81 (m, 5H).

EXAMPLE 214A This example is prepared by replacing Example 19A with Boc-2-amine-2-methylpropanol in Example 21 1 A.

EXAMPLE 214B This example is prepared by substituting example 214A for example 18B in example 18C.

EXAMPLE 214C This example is prepared by substituting example 214B for example 21 C in example 21 D.

EXAMPLE 214D This example is prepared by replacing Example 214C with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-de) d 12.06 (br s, 1 H), 8.77 (d, 1 H), 7.86 (dd, 1 H), 7.74 (d, 2 H), 7.71 (br s, 1 H), 7.55 (dd, 1 H), 7.51 (m, 4H), 7.38 (d, 2H), 7.32 (m, 1 H), 7.08 (d, 1 H), 7.04 (dd, 1H), 6.94 ( dd, 1H), 6.91 (d, 2H), 4.39 (m, 2H), 3.51 (m, 5H), 3.25 (m, 4H), 2.99 (dd, 2H), 2.75 (dd, 2H).

EXAMPLE 215A This example is prepared by substituting Example 213A for 2-thienyl disulfide in Example 211 A.

EXAMPLE 215B This example is prepared by substituting example 215A for example 21B in example 21C.

EXAMPLE 215C This example is prepared by substituting example 215B for example 21C in example 21D.

EXAMPLE 215D This example is prepared by substituting example 215C for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulphanyl) methy1) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.55 (d, 1 H), 8.53 (d, 2 H), 8.49 (br s, 1 H), 7.97 (dd, 1 H), 7.74 (d, 2 H), 7.53 (m , 2H), 7.47 (brs, 4H), 7.37 (m, 2H), 7.25 (m, 1H), 7.11 (t, 1H), 6.87 (d, 2H), 3.80 (brs, 2H), 3.41 ( br s, 3H), 3.22 (m, 5H), 2.40 (m, 4H), 1.58 (br s, 6H).

EXAMPLE 216C This example is prepared by substituting example 22C for example 21C in example 21D.

EXAMPLE 216D This example is prepared by replacing Example 216C with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.05 (br s, 1H), 8.91 (d, 1H), 8.59 (d, 1H), 7.92 (dd, 1H), 7.77 (d, 2H), 7.74 (br, 1H), 7.71 (d, 1H), 7.60 (d, 1H), 7.52 (m, 4H), 7.42 (d, 1H), 7.39 (d, 2H), 7.34 (m, 1H), 6.93 (d, 2H), 4.63 (m, 1H), 4.30 (br s, 1H), 3.69 (m, 2H), 3.02 (m, 2H), 2.93 (br s, 4H), 2.82 (d, 1H), 2.79 (br s, 4H).

EXAMPLE 217A This example is prepared by substituting example 214C for example 18E in example 18F.

EXAMPLE 217B This example is prepared by substituting Example 217A for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulf a nl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.55 (d, 8.38 (m, 1H), 7. 82 (dd, 1H), 7.72 (d, 2H), 7.58 (dd, 1H), 7.51 (dd, 1H), 7.47 (m, 4H), 7.37 (m, 2H), 7.24 (m, 1H), 7.10 (dd, 1H), 6.98 (m, 2H), 6.85 (d, 2H), 4.08 (m, 1H), 3.54 (br s, 4H), 3.40 (s, 2H), 3.19 (m, 6H), 2.39 (m, 10H), 2.00 (m, 1H), 1.83 (m, 1H).

EXAMPLE 218A A mixture of Example 18A (1.6 g) and 10% Pd / C (0.16 g) in methanol (70 ml) at 25 ° C is stirred under H 2 (4.22 kg / cm 2) for 3 hours, filtered and concentrated.

EXAMPLE 218B This example is prepared by substituting example 218A for example 21C in example 21D.

EXAMPLE 218C Methanesulfonyl chloride (68 μl) is treated with example 218B (270 mg) and pyridine (1 ml) at 0 ° C, stirred for 1 hour, treated with 1 M HCl (10 ml) and water, stirred for 0.5 hours, and filtered. The filtrate is washed with water and concentrated.

EXAMPLE 218D A mixture of example 218C (120 mg), 4- (trifluoromethoxy) -thiophenol (140 mg), K2C03 (158 mg), and acetone (14 ml) at reflux is stirred for 30 minutes, cooled to 25 ° C, and It is concentrated. The material concentrated in dichloromethane is washed with water and dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 1-2% dichloromethane / methanol.

EXAMPLE 218E This example is prepared by substituting example 218D for example 18E in example 18F.

EXAMPLE 218F This example is prepared by substituting Example 218D for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.09 (br s, 1 H), 9.58 (br s, 1 H), 8.54 (d, 1 H), 8.26 (d, 1 H), 7.89 (dd, 1 H), 7.77 (d, 2H), 7.72 (br s, 1H), 7.52 (d, 4H), 7.40 (d, 2H), 7.33 (m, 3H), 7.24 (d, 1H), 7.12 (d, 2H), 6.92 (d, 2H), 4.23 (m, 2H), 3.43 (m, 4H), 3.13 (m, 4H), 2.74 (br s, 6H), 2.14 (m, 2H).

EXAMPLE 219A This example is prepared by substituting 2-phenoxyethylamine for Example 21C in Example 21D.

EXAMPLE 219B This example is prepared by substituting Example 219A for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.89 (br s, 1 H), 8.71 (t, 1H), 8.62 (d, 1H), 7.97 (dd, 1H), 7.73 (d, 2H), 7.52 (m, 1H), 7.47 (m, 4H), 7.37 (m, 3H), 7.26 (m, 3H), 6.94 (m, 3H), 6.88 (d, 2H), 4. 24 (t, 2H), 3.84 (m, 2H), 3.42 (br s, 2H), 3.24 (m, 4H), 2.41 (m, 4H).

EXAMPLE 220A This example is prepared by substituting example 19A for example 18A in example 218A.

EXAMPLE 220B This example is prepared by replacing example 220A or example 21 C in example 21 D.

EXAMPLE 220C This example is prepared by substituting example 220B or example 218B in example 218C.

EXAMPLE 220D This example is prepared by substituting example 220C for example 218C in example 218D.

EXAMPLE 220E This example is prepared by substituting example 83977F for example 18E in example 18F.

EXAMPLE 220F This example is prepared by replacing Example 220E with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-de) d 9.70 (br s, 1 H), 8.55 (d, 1H), 8.26 (d, 1H), 7.90 (dd, 1H), 7.76 (d, 2H), 7.51 (d, 3H), 7.41 (d, 2H), 7.33 (m, 3H), 7.24 (d, 1H), 7.13 (d, 2H), 6.92 (d, 2H), 4.23 (m, 1H), 3.96 (br s, 2H), 3.61 (br s, 4H), 3.19 (br s, 4H), 3.01 (br s, 2H), 2.16 (m, 2H).

EXAMPLE 221A This example is prepared by replacing 4-methoxythiophenol with 4- (trifluoromethoxy) -thiophenol and Example 220C by Example 218C in Example 218D.

EXAMPLE 221B This example is prepared by substituting example 221A for example 18E in example 18F.

EXAMPLE 221C This example is prepared by replacing Example 221 B with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyI) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.11 (br s, 1 H), 9.86 (br s, 1 H), 8.56 (d, 1 H), 8.25 (d, 1 H), 7.87 (dd, 1 H), 7.76 ( d, 3H), 7.72 (br s, 1H), 7.51 (d, 4H), 7.40 (d, 2H), 7.33 (m, 1H), 7.18 (d, 2H), 7.12 (d, 1 H), 6.02 (d, 2H), 6.74 (d, 2H), 4.10 (m, 3H), 3.95 (br s, 4H), 3.68 (s, 3H), 3.27 (br s, 4H), 3.17 (br s, 4H) , 3.01 (br s, 3H), 2.15 (m, 2H).

EXAMPLE 222A This example is prepared by substituting 4-methylthiophenol for 4- (trifluoromethoxy) -thiophenol and Example 220C for example 218C in Example 218D.

EXAMPLE 222B This example is prepared by substituting example 222A for example 18E in example 18F.

EXAMPLE 222C This example is prepared by substituting Example 222B for 4 - (((1 R) -3- (dimethylamine) -1 - ((phenylsulfonyl) methyl) propy!) Amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d6) d 9.92 (br s, 1 H), 8.53 (d, 1 H), 8.26 (d, 1 H), 7.87 (dd, 1 H), 7.78 (d, 2H), 7.74 (m, 1 H), 7.53 (m, 4H), 7.40, (d, 2H), 7.34 (m, 1 H), 7.16 (d, 1 H), 7.10 (d, 2H), 6.93 (m, 4H), 4.28 (br s, 2H), 4.16 (m, 1 H), 3.96 (br s, 2H), 3.62 (br s, 4H), 3.34 (d, 2H), 3.18 (m, 4H) ), 3.01 (br s, 4H), 2.17 (m, 4H).

EXAMPLE 223A This example is prepared by substituting example 23C for example 18C in example 18E.

EXAMPLE 223B This example is prepared by substituting Example 223A for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d6) d 9.60 (br s, 1 H), 7.98 (d, 1 H), 7.83 (dd, 1 H), 7.73 (m, 3H), 7.63 (dd, 1 H), 7.52 (d, 4H), 7.40 (d, 2H), 7.33 (m, 1 H), 7.13 (m, 1 H), 7.03 (m, 1 H), 6.92 (d, 2H), 6.80 (d, 1 H), 6.08 (d, 1 H), 4.27 (br s, 4 H), 3.85 (m, 2 H), 3.17 (m, 4 H), 3.06 (dd, 2 H), 2.99 (m, 2 H) , 2.10 (m, 2H).

EXAMPLE 224A This example is prepared by substituting 4-chlorothiophenol for 4- (trifluoromethoxy) -thiophenol and Example 220C for example 218C in Example 218D.

EXAMPLE 224B This example is prepared by substituting example 224A for example 18E in example 18F.

EXAMPLE 224C This example is prepared by substituting Example 224B for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d6) d 8.52 (d, 1 H), 8.34 (d, 1 H), 7.85 (dd, 1 H), 7.73 (d, 2H), 7.51 (m, 1 H), 7.47 (m, 4H), 7.37 (m, 2H), 7.26 (m, 5H), 7.12 ( d, 1 H), 6.86 (d, 2 H), 4.16 (br s, 1 H), 3. 53 (m, 4H), 3.39 (m, 4H), 2.45 (br s, 2H), 2.40 (m, 4H), 1.99 (m, 1 H), 1.86 (m, 1 H).

EXAMPLE 225A This example is prepared by substituting 4-fluorothiophenol for 4- (trifluoromethoxy) -thiophenol in Example 218D.

EXAMPLE 225B This example is prepared by substituting example 225A for example 18E in example 18F.

EXAMPLE 225C This example is prepared by substituting Example 225B for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.35 (d, 1H), 8.04 (d, 1H), 7.73 (dd, 1H), 7.61 (d, 2H), 7.39 (m, 1H), 7.36 (br s , 4H), 7.24 (m, 4H), 7.13 (dd, 1H), 6.96 (t, 2H), 6.83 (d, 1H), 6.68 (d, 2H), 3.95 (m, 1H), 3.27 (br s , 2H), 3.02 (m, 4H), 2.87 (br s, 1H), 2.80 (br s, 1H), 2.49 (br s, 6H), 2.28 (m, 4H), 1.94 (m, 2H).

EXAMPLE 226A This example is prepared by replacing 4-fluorothiophenol with 4- (tpfluoromethoxy) -thiophenol and Example 220C by Example 218C in Example 218D.

EXAMPLE 226B This example is prepared by substituting example 226A for example 18E in example 18F.

EXAMPLE 226C This example is prepared by substituting Example 226B for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.61 (d, 1 H), 8.42 (d, 1 H), 7.94 (d, 1 H), 7.82 (d, 2 H), 7.60 (m, 1 H), 7.55 (m, 4H), 7.47 (m, 2H), 7.40 (m, 2H), 7.33 (m, 1 H), 7.18 (d, 1 H), 7.13 (t, 2H), 6.96 (d, 2H), 4.22 (br s, 1 H), 3.65 (br s, 6 H), 3.31 (m, 6 H), 2.64 (br s, 4 H), 2.54 (br s, 2 H), 2.49 (m, 4 H), 2.09 (m , 1 H), 1.97 (m, 1 H).

EXAMPLE 227A This example is prepared by substituting tert-butyl-1-piperazine for Example 1A in Example 2A.

EXAMPLE 227B This example is prepared by substituting example 227A for example 2A in example 2B.

EXAMPLE 227C This example is prepared by substituting example 227B for example 21 B in example 21 C.

EXAMPLE 227D A mixture of ethyl 2,4-difiuorobenzoate (194 mg), example 227C (250 mg), and K2CO3 (420 mg) in DMSO (1.7 ml) at 125 ° C is stirred for 3 hours, cooled to 25 ° C, treated with dichloromethane, washed with water, and dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 2-10% ethyl acetate / hexanes.

EXAMPLE 227E This example is prepared by substituting example 227E for example 1 B in example 1 C.

EXAMPLE 227F This example is prepared by substituting example 227E for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 1 1 .92 (br s, 1 H), 8.62 (br s, 1 H), 8.54 (d, 1 H), 8.29 (d, 1 H), 7.86 (dd, 1 H), 7.71 (br s, 1 H), 7.50 (m, 5H), 7.40 ( d, 2H), 7.33 (m, 1 H), 7.24 (m, 2H), 7.15 (m, 4H), 6.76 (m, 2H), 4.21 (m, 2H), 3.40 (d, 3H), 3.15 ( m, 4H), 2.75 (br s, 6H), 2.15 (m, 2H).

EXAMPLE 228A A mixture of 1 .5M LDA in cyclohexane (5.5 ml) and THF (7.5 ml) at -78 ° C is treated with tert-butyl 4-oxo-1-piperidine-carboxylate (1.5 g) in THF (7.5 ml), stirred for 25 minutes, treated with N-phenyl -bis- (trifluoromethanesulfonamide) (2.8 g) in THF (7.5 ml), stirred for 10 minutes, stirred for 3 hours at 0 ° C, and concentrated. The concentrated material is subjected to neutral alumina chromatography with 10% ethyl acetate / hexanes.

EXAMPLE 228B A mixture of example 228A (480 mg), 4-ethoxycarbonylphenylboronic acid (308 mg), LiCl (182 mg), tetrakis- (triphenylphosphine palladium (82 mg), and 2M Na 2 CO 2 (2 ml) in toluene (4.8 ml) 90 ° C is stirred for 3 hours, cooled to 25 ° C, and treated with water and ethyl acetate.The extract is washed with water and brine and dried (MgSO), filtered, and concentrated. concentrate is subjected to flash chromatography on silica gel with 2-5% ethyl acetate / hexanes.

EXAMPLE 228C This example is prepared by substituting example 228B for example 21 B in example 21 C.

EXAMPLE 228D This example is prepared by substituting example 228C for example 1A in example 2A.

EXAMPLE 228E This example is prepared by substituting example 228D for example 2A in example 2B.

EXAMPLE 228F This example is prepared by substituting example 228E for example 1B in example 1C.

EXAMPLE 228G This example is prepared by substituting example 228F for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 0.35 (br s, 1H), 8.30 (d, 1H), 8.04 (d, 1H), 7.63 (m, 3H), 7.53 (m, 1H), 7.30 (m, 2H), 7.24 (d, 2H), 7.20 (d, 2H), 7.14 (d, 2H) ), 7.11 (m, 1H), 6.98 (m, 2H), 6.93 (d, 1H), 6.87 (m, 3H), 5.84 (br s, 1H), 4.13 (br s, 2H), 3.94 (m, 1H), 2.89 (m, 4H), 2.49 (br s, 6H), 2.24 (m, 2H), 1.89 (m, 2H).

EXAMPLE 229 This example is prepared by substituting example 228F for example 2C and 4 - (((1R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in the example 2D 1 H NMR (500 MHz, DMSO-d 6) d 10.07 (br s, 2 H), 8.56 (d, 1 H), 8.30 (d, 1 H), 7.89 (d, 3 H), 7.79 (m, 1 H), 7.55 (m, 2H), 7.50 (m, 2H), 7.45 (d, 2H), 7.40 (m, 2H), 7.36 (m, 1 H), 7.24 (m, 2H), 7.19 (d, 1 H) , 7.13 (m, 3H), 6.10 (br s, 1 H), 4.39 (br s, 2H), 4.20 (m, 1 H), 3.95 (br s, 3H), 3.40 (m, 4H), 3.18 ( m, 4H), 3.02 (br s, 2H), 2.65 (br s, 1 H), 2.54 (s, 3H), 2.18 (m, 2H).

EXAMPLE 230 This example is prepared by substituting example 227E for example 2C and example 18F for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in the 2D example. 1 H NMR (400 MHz, DMSO-d6) d 7.87 (d, 1 H), 7.71 (dd, 1 H), 7.57 (t, 1 H), 7.51 (m, 1 H), 7.47 (br s, 4 H), 7.38 (m, 4 H), 7.32 (m, 2H), 7.23 (m, 2H), 6.62 (d, 2H), 6.53 (dd, 1 H), 3.83 (m, 1 H), 3.38 (br s, 2H), 3.23 (m, 2H) , 3.16 (m, 4H), 2.91 (br s, 1 H), 2.74 (br s, 1 H), 2.52 (br s, 6 H), 2.37 (m, 4 H), 2.01 (m, 2 H).

EXAMPLE 231 A A mixture of methyl 6-chloronicotinate (250 mg), example 227C (458 mg), TEA (0.24 ml), and acetonitrile (1.5 ml) at 95 ° C is stirred for 10 hours, cooled to 25 ° C, treat with dichloromethane, wash with water, and dry (MgSO 4), filter, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 0-2% methanol dichloromethane.

EXAMPLE 231B This example is prepared by substituting example 231A for example 1B in example 1C.

EXAMPLE 231C This example is prepared by substituting example 231 B for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 9.31 (br s, 1 H), 8.36 (d, 1H), 8.28 (d, 1H), 8.03 (d, 1H), 7.72 (dd, 1H), 7.61 (dd, 1H), 7.47 (br s, 1H), 7.25 (d, 4H), 7.13 (d, 2H), 7.06 (m, 1H), 6.98 (m, 2H), 6.89 (m, 4H), 6.60 (d, 1H), 3.94 (m, 4H), 2.88 (m, 4H), 2.49 (br, 6H), 2.24 (m, 2H), 1.89 (m, 2H).

EXAMPLE 232A This example is prepared by substituting 1-benzyl-4-piperidone for tert-butyl 4-oxo-l-piperidine-carboxylate in Example 228A.

EXAMPLE 232B This example is prepared by substituting example 232A for example 228A in example 228B.

EXAMPLE 232C A mixture of example 232B (0.98 g) and 10% Pd / C (0.1 g) in ethanol (50 ml) at 50 ° C is stirred under hydrogen for 2 hours, cooled to 25 °, filtered, and concentrated .

EXAMPLE 232D This example is prepared by substituting example 232C for example 1A in example 2A.

EXAMPLE 232E This example is prepared by substituting example 232D for example 2A in example 2B.

EXAMPLE 232F This example is prepared by substituting example 232E for example 1 B in example 1 C.

EXAMPLE 232G This example is prepared by substituting example 232F for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-de) d 9.57 (br s, 1 H), 9.46 (br s, 1 H), 8.55 (d, 1 H), 8.28 (d, 1 H), 7.86 (dd, 1 H), 7.83 (d, 2H), 7.79 (m, 1 H), 7.55 (m, 4H), 7.40 (d, 2H), 7.35 (m, 1 H), 7.28 (d, 2H), 7.23 ( d, 2H), 7.14 (m, 4H), 4.32 (br s, 2H), 4.19 (m, 2H), 3.39 (d, 2H), 3.29 (d, 2H), 3.13 (m, 2H), 2.81 ( br s, 2H), 2.74 (br s, 6H), 2.14 (m, 2H), 1.84 (m, 3H).

EXAMPLE 233 This example is prepared by substituting example 232F for example 2C and 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 9.98 (m, 1 H), 9.51 (br s, 1 H), 8.55 (d, 1 H), 8.30 (d, 1 H), 7.87 (dd, 1 H), 7.83. (d, 2H), 7.70 (m, 1H), 7.56 (m, 4H), 7.40 (d, 2H), 7.35 (m, 1H), 7.28 (d, 2H), 7.24 (d, 2H), 7.14 ( m, 4H), 4.32 (br s, 2H), 4.18 (m, 1H), 3.93 (br s, 2H), 3.39 (d, 4H), 3.29 (d, 3H), 3.18 (br s, 3H), 3.02 (br s, 2H), 2.80 (m, 3H), 2.17 (m, 2H), 1.84 (m, 3H).

EXAMPLE 234 This example is prepared by substituting example 228F for example 2C and example 18F for 4 - (((1R) -3- (dimethylamino) -1- ((phenylsufinanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in the example 2D 1 H NMR (500 MHz, DMSO-de) d 9.32 (br s, 1 H), 7.72 (d, 1H), 7.62 (d, 2H), 7.59 (dd, 1H), 7.53 (br s, 1H), 7.29 (m, 2H), 7.25 (d, 2H), 7.20 (d, 2H), 7.16 (d, 2H), 7.11 (m, 1H), 7.04 (m, 4H), 6.94 (t, 1H), 6.63 (d, 1H), 5.86 (br s, 1H), 5.78 (d, 1H), 4.11 (br s, 1H), 3. 69 (m, 1H), 2.90 (m, 2H), 2.75 (m, 2H), 2.49 (s, 6H), 2.25 (m, 2H), 1.86 (m, 2H).

EXAMPLE 235 This example is prepared by substituting example 231 B for example 2C and 4 - (((1 R) -3- (4-morpholinyl) -1- ((f-enylsulfonyl) methyl) propyl) amino) -3-nitrobencenesulfonam id a, which is prepared as described in WO 02/24636, by 4- (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) p rop I) amino) -3 -nitrobenzenesulfonamide in the example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 9.91 (br s, 1 H), 8.61 (d, 1 H), 8.55 (d, 1 H), 8.30 (d, 1 H), 7.98 (dd, 1 H), 7.87 (dd) , 1H), 7.74 (br s, 1H), 7.51 (d, 4H), 7.39 (d, 2H), 7.33 (m, 1H), 7.24 (m, 2H), 7.19 (d, 1H), 7.13 (m , 3H), 6.86 (d, 1H), 4.33 (br s, 2H), 4.20 (m, 2H), 3.96 (br, 4H), 3.62 (br s, 4H), 3.40 (m, 4H), 3.19 (m, 3H), 3.01 (br s, 2H), 2.80 (br s, 2H), 2.17 (m, 2H).

EXAMPLE 848866 This example is prepared by substituting example 231 B for example 2C and example 18F for 4 - (((1 R) -3 ~ (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3- Nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 9.60 (br s, 1 H), 8.60 (d, 1H), 7.95 (m, 1H), 7.82 (dd, 1H), 7.73 (br s, 1H), 7.51 (d, 3H), 7.39 (d, 2H), 7.30 (m, 4H), 7.19 (m, 1H), 6.88 (d, 1H), 6.85 (d, 1H), 6.04 (d, 1H), 3.94 (m, 1H), 3.29 (m, 4H), 3.15 (m, 2H), 3.01 (m, 2H), 2.74 (s, 6H), 2.11 (m, 2H).

EXAMPLE 237A Treat 2.5M n-butyllithium in hexanes (3 mL) at 25 ° C, treat with methyltriphenylphosphonium bromide (2.6 g) in diethyl ether (37 mL), stir for 1.5 hours, treat with 4- Ethyl (4-oxopiperidin-1-yl) -benzoate, which is prepared as described in Synthesis 1981, 8, 606, (1.47 g), in diethyl ether (15 ml), is stirred for 18 hours, and it is filtered. The filtrate is washed with water and dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10% ethyl acetate / hexanes.

EXAMPLE 237B A mixture of example 237A (400 mg) and 9-BBN 0.5M (3.3 ml) in THF (2 ml) at 60 ° C is stirred for 1.5 hours, cooled to 25 ° C, treated by dripping with 2 g. -bromo-4'-chlorobiphenyl (434 mg), K2C03 (296 mg), and dichloro- (1,1 '-bis- (diphenylphosphino) -ferrocene) palladium (II) dichloromethane (24.5 mg) in water (0.36 ml) and DMF (3.6 ml), stirred for 3 hours at 60 ° C, cooled to 25 ° C, and treated with water and ethyl acetate. The extract is washed with brine and dried (MgSO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 2-5% ethyl acetate / hexanes.

EXAMPLE 237C This example is prepared by substituting example 237B for example 1 B in example 1 C.

EXAMPLE 237D This example is prepared by substituting example 237C for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.84 (br s, 1 H), 8.43 (br s, 1H), 8.54 (d, 1H), 7.87 (dd, 1H), 7.70 (d, 2H), 7.47 (d, 2H), 7.32 (m, 3H), 7.27 (dd, 1H), 7.25 (d, 2H), 7.17 (m, 3H), 7.11 (m, 2H), 6.84 (d, 2H), 4.20 (m, 1H), 3.78 (d, 2H), 3.38 (d, 2H), 3.14 ( m, 2H), 2.74 (s, 6H), 2.65 (t, 2H), 2.53 (m, 2H), 2.14 (m, 2H), 1.55 (m, 1H), 1.44 (d, 2H), 0.96 (m , 2H).

EXAMPLE 238 This example is prepared by substituting example 237C for example 2C and 4 - (((1R) -3- (4-morpholinyl) -1- ((phenylsulfanyl) methyl) propiI) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4- (((1R) -3- (d-methylamino) -1 - ((phenylsulfanyl) methyl) p ropyl) amino) -3-nitrobenzenesulfonamide in the 2D example . 1 H NMR (500 MHz, DMSO-d 6) d 11.95 (br s, 1 H), 9.75 (br s, 1H), 8.55 (d, 1H), 8.29 (d, 1H), 7.87 (dd, 1H), 7.70 (d, 2H), 7. 48 (m, 2H), 7.32 (m, 4H), 7.28 (m, 1H), 7.25 (m, 2H), 7.17 (m, 4H), 7.11 (m, 1H), 6.84 (d, 2H), 4.19 (m, 1H), 3.96 (br s, 2H), 3.78 (d, 4H), 3.40 (d, 4H), 3.20 (m, 2H), 3.02 (br s, 2H), 2.66 (t, 2H), 2.53 (m, 2H), 2.17 (m, 2H), 1.56 (m, 1H), 1.45 (d, 2H), 0.98 (m, 2H).

EXAMPLE 239A A mixture of 2,5-dibromopyridine (2.4 g), dichloro- (1,1 '-bis- (diphenylphosphino) -ferrocene) palladium (II) dichloromethane (430 mg), and TEA (2.9 ml) in methanol (10 mg). mi), and DMF (10 ml) in a Parr shaker at 50 ° C is shaken under CO (14.06 kg / cm2) in a lapse of 5.5 hours, cooled to 25 ° C, filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10-20% ethyl acetate / hexanes.

EXAMPLE 239B A mixture of example 239A (g00 mg), example 227C (1.6 g), and DI EA (2.1 ml) in DMSO (5.9 ml) is stirred at 130 ° C for 24 hours, cooled to 25 ° C, and concentrated . The concentrated material is subjected to flash chromatography on silica gel with 30-50% ethyl acetate / hexanes.

EXAMPLE 239C This example is prepared by substituting example 239B for example 1B in example 1C.

EXAMPLE 239D This example is prepared by substituting example 239C for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 9.60 (br s, 1 H), 8.59 (d, 1H), 8.30 (m, 2H), 7.90 (dd, 1H), 7.82 (d, 1H), 7.70 (br s, 1H), 7.51 (m, 4H), 7.41 (d, 2H), 7.38 (dd, 1H), 7.32 (m, 1H), 7.22 (d, 2H), 7.17 (d, 1H), 7.12 (m, 3H), 4.19 ( m, 2H), 3.39 (d, 2H), 3.13 (m, 4H), 2. 74 (s, 6H), 2.14 (m, 2H).

EXAMPLE 240 This example is prepared by substituting example 239C for example 2C and 4 - (((1 R) -3- (4-morpholinyl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) prop yl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 9.89 (br s, 1 H), 8.59 (d, 1 H), 8.30 (m, 2 H), 7.91 (dd, 1 H), 7.83 (d, 1 H), 7.73 (br s, 1H), 7.52 (d, 4H), 7.40 (m, 3H), 7.34 (m, 1H), 7.23 (d, 2H), 7.18 (d, 1H), 7.12 (m, 3H), 4.20 (m , 2H), 3.96 (br s, 4H), 3.40 (d, 2H), 3.19 (m, 2H), 3.01 (br s, 4H), 2.17 (m, 2H).

EXAMPLE 241 A Example 855947A (12.3 g) in propan-2-ol (57 ml) at 0 ° C is treated with NaBH 4 (2.2 g) in ethanol / propan-2-ol 1: 1 (100 ml), stirred at 25 ° C. C for 18 hours, treated with NH 4 Cl and brine, and extracted with diethyl ether. The extract is dried (MgSO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10-30% ethyl acetate / hexanes.

EXAMPLE 241 B This example is prepared by substituting example 241 A for example 2A in example 2B.

EXAMPLE 241 C A mixture of example 241 B (420 mg) and TEA (0.95 ml) in dichloromethane (8.7 ml) at 0 ° C is treated with methanesulfonyl chloride (0.16 ml), stirred for 0.5 hours, treated with example 228C ( 0.57 g), stirred for 1 hour at 0 ° C and for 5 hours at 25 ° C, treated with dichloromethane, washed with water and brine, and dried (MgSO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0-2% methanol / dichloromethane.

EXAMPLE 241D This example is prepared by substituting example 241 C for example 1B in example 1C.

EXAMPLE 241E This example is prepared by substituting example 241 D for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.47 (d, 1 H), 8.17 (d, 1H), 7.82 (m, 3H), 7.38 (d, 2H), 7.31 (d, 4H), 7.24 (m, 2H), 7.18 (m, 1H), 7.14 (m, 2H), 6.90 (d, 1H) ), 6.13 (br s, 1H), 4.07 (m, 1H), 2.93 (m, 6H), 2.61 (m, 6H), 2.39 (br s, 2H), 2.24 (m, 2H), 2.08 (m, 2H), 1.99 (m, 2H), 1.44 (t, 2H), 0.97 (br s, 2H).

EXAMPLE 242A This example is prepared by substituting 2-bromo-cyclohex-1-encarboxaldehyde, which is prepared as described in Collect. Czech Chem. Commun. 1961, 26, 3059-3073, for example 855947A in example 241A.

EXAMPLE 242B This example is prepared by substituting example 242A for example 2A in example 2B.

EXAMPLE 242C This example is prepared by substituting example 242B for example 241B in example 241C.

EXAMPLE 242D This example is prepared by substituting example 242C for example 1B in example 1C.

EXAMPLE 242E This example is prepared by substituting example 242D for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.68 (br s, 1 H), 8.60 (br s, 1 H), 8.56 (d, 1 H), 8.30 (d, 1 H), 7.89 (m, 3 H), 7.45 ( d, 2H), 7.37 (m, 2H), 7.17 (m, 8H), 6.14 (br s, 1H), 4.20 (m, 1H), 3.89 (m, 1H), 3.66 (d, 4H), 3.40 (d, 3H), 3.12 (m, 4H), 2.75 (br s, 6H), 2.69 (br s, 1H), 2.29 (br s, 2H), 2.22 (br s, 2H), 2.15 (m, 2H), 1.71 (br s, 4H).

EXAMPLE 243 This example is prepared by substituting example 242D for example 2C and 4 - (((1 R) -3- (4-morpholinyl) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 9.84 (br s, 1 H), 9.60 (br s, 1 H), 8.56 (d, 1 H), 8.30 (d, 1 H), 7.89 (m, 3 H), 7.45 ( d, 2H), 7.37 (m, 2H), 7.24 (m, 2H), 7.15 (m, 6H), 6.13 (br s, 1H), 4.20 (m, 1H), 3. 92 (m, 2H), 3.64 (m, 4H), 3.19 (m, 4H), 3.02 (br s, 4H), 2.70 (m, 2H), 2.29 (br s, 2H), 2.18 (m, 4H) ), 1.71 (br s, 4H).

EXAMPLE 244 This example is prepared by substituting example 241 D for example 2C and 4 - (((1R) -3- (4-morpholiniI) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.47 (d, 1 H), 8.27 (d, 1H), 7.84 (d, 2H), 7.79 (dd, 1H), 7.3g (d, 2H), 7.32 (m, 4H), 7.24 (t, 2H), 7.16 (m, 3H), 6.93 (d, 1H), 6.10 (br s, 1H), 4.09 (m, 1H), 3.55 (br s, 4H), 3.34 (m, 4H), 3.02 (m, 2H), 2.76 (s, 1H), 2.27 (m , 2H), 2.01 (br s, 3H), 1.86 (m, 1H), 1.46 (t, 2H), 0.98 (s, 6H).

EXAMPLE 245A This example is prepared by replacing 1,4-cyclohexanedione monoethylene ketal with ethyl 4- (4-oxopiperidin-1-yl) benzoate in Example 237A.

EXAMPLE 245B This example is prepared by substituting example 245A for example 237A in example 237B.

EXAMPLE 245C A mixture of Example 245B (1.9 g) and 35% aqueous TFA (42 mL) in chloroform (61 mL) is stirred at 25 ° C for 7 hours and treated with water and dichloromethane. The extract is washed with NaHCO3 saturated and brine and dried (MgSO4), filtered, and concentrated.

EXAMPLE 245D This example is prepared by replacing Example 245C with tert-butyl 4-oxo-1-piperidine-carboxylate and substituting 2- (N, N-bis- (trifluoromethylsulfonyl) amino) -5-chloropyridine for N-phenylbis- (trifluoromethanesulfonamide) in example 228A.

EXAMPLE 245E This example is prepared by substituting example 245D for example 228A in example 228B.

EXAMPLE 245F This example is prepared by substituting example 245E for example 1B in example 1C.

EXAMPLE 245G This example is prepared by substituting example 245F for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 9.45 (br s, 1 H), 8.56 (d, 1H), 8.30 (d, 1H), 7.88 (dd, 1H), 7.81 (d, 2H), 7.47 (d, 2H), 7.42 (d, 2H), 7.34 (m, 3H), 7.32 (s, 1H) ), 7.28 (m, 1H), 7.24 (m, 2H), 7.16 (m, 4H), 7.11 (m, 1H), 6.16 (br s, 1H), 4.19 (m, 1H), 3.14 (m, 3H) ), 2.74 (s, 6H), 2.61 (m, 2H), 2.24 (m, 2.14 (m, 2H), 2.03 (m, 1H), 1.68 (m, 3H), 1.17 (m, 1H).

EXAMPLE 246 This example is prepared by substituting example 245F for example 2C and 4 - (((1 R) -3- (4-morpholinyl) -1- ((phenylisulfanyl) methyl) propyl) amine) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by 4 - (((1R) -3- (dithylamine) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.55 (d, 1H), 8.29 (d, 1H), 7.87 (dd, 1H), 7.79 (d, 2H), 7.46 (d, 2H), 7.40 (d, 2H), 7.32 (m, 4H), 7.27 (m, 1H), 7.23 (m, 2H), 7.15 (m, 4H), 7.10 (m, 1H), 6.14 (br s, 1H), 4.18 (m, 1H), 3.77 (br s, 4H), 3.15 (m, 4H), 2.59 (m, 2H), 2.20 (m, 4H), 2.02 (d, 1H), 1.67 (m, 3H), 1.15 (m, 1 HOUR).

EXAMPLE 247A This example is prepared by substituting methyl 4-fIuorobenzoate for ethyl 2,4-difluorobenzoate and cis-octahydropyrrolo [3,4-c] -pyrrole for example 227C in Example 227D.

EXAMPLE 247B This example is prepared by replacing Example 247A with Example 1A in Example 2A.

EXAMPLE 247C This example is prepared by substituting example 247B for example 2A in example 2B.

EXAMPLE 247D This example is prepared by substituting example 247C for example 1 B in example 1 C.

EXAMPLE 247E This example is prepared by substituting example 247D for example 2C in example 2D. 1 H NMR (500 MHz, CDC1 3) d 8.77 (br s, 1 H), 8.34 (d, 1 H), 7.96 (d, 1 H), 7.92 (br s, 1 H), 7.65 (brs, 2H), 7.49 (m, 4H), 7.38 (br s, 2H), 7.30 (m, 2H), 7.19 (m, 6H), 6.83 (m, 1 H), 6.46 (m, 2H), 4.34 (br s, 2H), 3.84 (m, 1 H) ), 3.28 (m, 4H), 3.15 (m, 4H), 2.80 (m, 6H), 2.41 (br s, 2H).

EXAMPLE 248A A mixture of 4-chloro-3-nitrobenzenesulfonyl chloride (10 g), TEA (10.87 ml), and bis- (2,4-dimethoxybenzyl) amine (12.38 g) in dichloromethane (200 ml) at 25 ° C is stirred for 12 hours, treated with dichloromethane (200 ml) , wash with saturated sodium bicarbonate (100 ml) and brine, and concentrate.

EXAMPLE 248B A mixture of example 248A (20.98 g) and 2M methylamine in THF (400 ml) at 80 ° C is stirred for 4 hours and concentrated. The concentrated material is treated with ethyl acetate and saturated sodium bicarbonate. The extract is dried (Mg S0), filtered and concentrated.

EXAMPLE 248C A mixture of example 248B (1 g) and 3.56 mmol / g N, N-DIEA with polymer support (2.65 g) in dichloromethane (10 ml) is treated with 20% phosgene in toluene (10.1 ml), heated to 40 g. ° C for 24 hours, filter and concentrate.

EXAMPLE 248D A mixture of example 248C (200 mg), TEA (141 μl) and N-methyl-4-trifluoromethoxyphenyl aniline (129 mg) in dichloromethane (2 ml) at 50 ° C is heated for 12 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 70% ethyl acetate / hexane.

EXAMPLE 248E Example 248D (57 mg) in triethylsilane / TFA / dichloromethane (0.05 ml / 0.45 ml / 0.5 ml) is stirred at 25 ° C for 30 minutes and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 80% ethyl acetate / hexane.

EXAMPLE 248F This example is prepared by substituting Example 248E for 4 - (((1 R) -3- (dimethylamine) -1 - ((phenylsulfanyl) methyl) p ropil) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (400MHz, DMSO-d6) d 8.26 (d, 1 H), 7.80 (d, 2H), 7.72 (br, 1 H), 7.41 (m, 8H), 7.28 (d, 1 H), 6.92 (m , 6H), 4.26 (br, 2H), 3.74 (br, 2H), 3.13 (br, 2H), 2.96 (s, 6H), 2.82 (br, 2H).

EXAMPLE 249A This example is prepared by substituting N-methyl-2-methylanaline for N-methyl-4-trifluoromethoxyaniline in Example 248D.

EXAMPLE 249B This example is prepared by substituting example 249A for example 248D in example 248E.

EXAMPLE 249C This example is prepared by substituting Example 249B for 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methy) propyl) am i no) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400MHz, DMSO-d 6) 8.30 (d, 1H), 7.86 (d, 1H), 7. 83 (d, 2H), 7.75 (br, 1H), 7.53 (m, 2H), 7.47 (d, 2H), 7.43 (q, 1H), 7.37 (m, 3H), 7.21 (d, 1H), 6.97 (d, 2H), 6.83 (d, 1H), 6.74 (t, 1H), 6. 64 (t, 1H), 6.56 (d, 1H), 4.31 (br, 2H), 3.80 (br, 2H), 3.18 (s, 3H), 3. 14 (br, 2H), 2.90 (s, 3H), 2.84 (br, 4H), 1.95 (s, 3H).

EXAMPLE 250A This example is prepared by substituting N-methyl-4-methoxyanaline for N-methyl-4-trifluoromethoxyaniline in Example 248D.

EXAMPLE 250B This example is prepared by replacing example 250A with example 248D in example 248E.

EXAMPLE 250C This example is prepared by replacing Example 250B with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (400MHz, DMSO-d6) d 8.28 (d, 1 H), 7.86 (dd, 1 H), 7.81 (d, 2H), 7.73 (br, 1 H), 7.52 (br, 2H), 7.47 (d, 2H), 7.43 (d, 1 H), 7.36 (m, 3 H), 7.20 (d, 1 H), 6.94 (d, 2 H), 6.70 (d, 2 H), 6.49 (d, 2H), 4.28 (br, 2H), 3.81 (br, 2H), 3.43 (s, 3H), 3.19 (s, 3H), 3.14 (br, 2H), 2.90 (s, 3H), 2.82 (br, 4H) ).

EXAMPLE 251 A This example is prepared by substituting N-methyl-4-methylanaline for N-methyl-4-trifluoromethoxyaniline in Example 248D.

EXAMPLE 251 B This example is prepared by substituting example 251 A for example 248D in example 248E.

EXAMPLE 251 C This example is prepared by replacing Example 251 B with 4 - (((1R) -3- (dimethylamido) -1 - ((phenylsulfanyl) methyl) propy) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400MHz, DMSO-d 6) d 8.25 (d, 1H), 7.83 (m, 3H), 7.73 (br, 1H), 7.52 (m, 2H), 7.47 (d, 2H), 7.42 (d, 1H) ), 7.36 (m, 3H), 7.20 (d, 1H), 6.86 (d, 2H), 6.71 (d, 2H), 6.66 (d, 2H), 4.28 (br, 2H), 3.80 (br, 2H) , 3.22 (s, 3H), 3.14 (br, 2H), 2.81 (s, 3H), 2.82 (br, 4H), 1.90 (s, 3H) EXAMPLE 252A This example is prepared by substituting N-diphenylmethyl methylamine for N-methyl-4-trifluoromethoxyaniline in Example 248D.

EXAMPLE 252B This example is prepared by substituting example 252A for example 248D in example 248E.

EXAMPLE 252C This example is prepared by replacing Example 252B with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) am i no) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (400MHz, DMSO-d 6) d 8.35 (d, 1H), 8.15 (dd, 1H), 7.74 (dd, 4H), 7.50 (m, 4H), 7.43 (d, 1H), 7.36 (m, 6H) ), 7.29 (m, 2H), 7.16 (d, 4H), 6.82 (d, 2H), 6.30 (s, 1 H), 4.33 (br, 2H), 3.84 (br, 4H), 3.25 (s, 3H) ), 3.13 (br, 3H), 2.82 (br, 2H), 2.69 (s, 3H).

EXAMPLE 253A This example is prepared by substituting (S) - (-) - N-methyl-1-phenethylamine for N-methyl-4-trifluoromethoxyaniline in Example 248D.

EXAMPLE 253B This example is prepared by substituting example 253A for example 248D in example 248E.

EXAMPLE 253C This example is prepared by replacing Example 253B with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyI) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (400MHz, DMSO-d6) d 8.38 (d, 1 H), 8.19 (dd, 1 H), 7.76 (d, 2H), 7.70 (d, 1 H), 7.50 (br, 6H), 7.33 (br, 8H), 6.93 (d, 2H), 5.17 '(q, 1 H), 4.37 (br, 2H) 3.84 (br, 2H), 3.26 (s, 3H), 3.1 1 (br, 4H), 2.84 (br, 2H), 2.61 (s, 3H), 1 .46 (d, 3H) EXAMPLE 254A This example is prepared by substituting 2- (4-methylpiperazinyl) -1-phenethyl-methylamine for N-methyl-4-trifluoromethoxyaniline in Example 248D.

EXAMPLE 254B This example is prepared by substituting example 254A for example 248D in example 248E.

EXAMPLE 254C This example is prepared by substituting Example 254B for 4 - (((1 R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (400MHz, DMSO-d6) d 8.37 (d, 1 H), 8.20 (dd, 1 H), 7.76 (d, 3 H), 7.65 (d, 1 H), 7.48 (m, 5 H), 7.34 (m, 8 H), 6.93 (d, 2H), 5.31 (dd, 1 H), 4.36 (br, 2H), 3.84 (br, 2H), 3.42 (br, 4H), 3.30 (s, 3H), 3.07 (br, 8H), 2.86 (m, 2H), 2.80 (s, 3H), 2.75 (s, 3H), 2.33 (m, 2H).

EXAMPLE 255A This example is prepared by substituting 2-morpholin-4-yl-1-phenethyl-methylamine for N-methyl-4-trifluoromethoxyaniline in Example 248D.

EXAMPLE 255B This example is prepared by substituting example 255A for example 248D in example 248E.

EXAMPLE 255C This example is prepared by substituting example 255B for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (400MHz, DMSO-d6) d 8.40 (d, 1 H), 8.15 (dd, 1 H), 7.76 (m, 3H), 7.66 (d, 1 H), 7.47 (m, 13H), 6.93 (d, 2H), 5.57 (br, 1 H), 4.37 (br, 2H), 3.83 (br, 8H), 3.25 (s, 3H), 3.13 (br, 6H), 2.84 (br, 4H), 2.64 (s, 3H) EXAMPLE 256A This example is prepared by substituting (1, 2-diphenyl-ethyl) methylamine for N-methyl-4-trifluoromethoxyaniline in Example 248D.

EXAMPLE 256B This example is prepared by substituting example 256A for example 248D in example 248E.

EXAMPLE 256C This example is prepared by substituting Example 256B for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfan) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (400MHz, DMSO-d6) d 8.33 (d, 1 H), 8.05 (dd, 1 H), 7.75 (d, 3 H), 7.38 (m, 18 H), 7.22 (m, 1 H), 6.92 (d, 2H), 5.58 (dd, 1 H), 4.32 (br, 2H), 3.65 (br, 6H), 3.40 (dd, 1 H), 3.22 (dd, 1 H), 3.10 (br, 2H) , 2.69 (s, 3H), 2.66 (s, 3H).

EXAMPLE 257A This example is prepared by substituting (2- (methylamino) -2-phenylethyl) -dimethylamine for N-methyl-4-trifluoromethoxyaniline in Example 248D.

EXAMPLE 257B This example is prepared by substituting example 257A for example 248D in example 248E.

EXAMPLE 257C This example is prepared by replacing Example 257B with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulf to nyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (500MHz, DMSO-d6) d 8.39 (d, 1 H), 8.12 (dd, 1 H), 7.74 (d, 3H), 7.64 (d, 1 H), 7.40 (m, 13H), 6.91 (d, 2H), 5.54 (dd, 1 H), 4.00 (br, 8H), 3.25 (s, 3H), 3.14 (br, 2H), 2.69 (s, 6H), 2.61 (s, 3H).

EXAMPLE 258 A mixture of Example 10 (400 mg) and 30% Pd / C (120 mg) in methanol / ethyl acetate 1: 1 (10 ml) at 25 ° C is stirred under H2 (balloon) for 2 hours and filtered . The filtrate is concentrated and subjected to flash chromatography on silica gel with 40% acetonitrile / dichloromethane. H NMR (500MHz, CDI3) d 7.87 (br, 1 H), 7.64 (m, 2H), 7.40 (m, 6H), 7.17 (m, 8H), 6.38 (br, 1 H), 5.17 (br, 4H) ), 4.29 (s, 2H), 3.30 (m, 4H), 2.95 (s, 2H), 2.49 (br, 2H).

EXAMPLE 259 A mixture of example 258 (50 mg) and sodium nitrite (7.2 mg) in water / hydrochloric acid / acetic acid (0.38 ml / 0.562 ml / 2 ml) at 0 ° C is stirred for 2 hours and concentrated. The material was concentrated in DMSO / methanol 1: 1 (10.5 ml) and purified by HPLC with 0-70% acetonitrile / water with 0.1% TFA. 1 H NMR (500MHz, CDCl 3) d 8.75 (s, 1H), 8.23 (dd, 1H), 7.78 (dd, 1H), 7.60 (d, 2H), 7.49 (m, 3H), 7.42 (d, 2H), 7.30 (m, 1H), 7.26 (m, 2H), 7.19 (m, 5H), 5.66 (d, 2H), 4.82 (t, 2H), 4.39 (s, 2H), 3.50 (t, 2H), 3.42 (br, 8H).

EXAMPLE 260 Example 258 (60 mg) in formic acid (2 mL) is heated at 100 ° C for 3 hours, and concentrated. The concentrated material is purified by HPLC with 0-70% acetonitrile / water with 0.1% TFA. 1 H NMR (400MHz, CDCl 3) d 8.53 (s, 1H), 8.46 (s, 1H), 8. 13 (d, 1H), 7.75 (dd, 1H), 7.62 (d, 2H), 7.46 (m, 4H), 7.30 (d, 1H), 7.16 (m, 8H), 6.63 (d, 2H), 4.48 (t, 2H), 4.35 (s, 2H), 3.42 (br, 4H), 3.35 (t, 2H), 3.00 (br, 4H).

EXAMPLE 261 This example is prepared by replacing example 90C and 4- (cyclohexylmethylamino) -3-nitrobenzenesulphonamide, which is prepared as described in WO02 / 24636, for example 1C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsufinanyl) methyl) propi) amino) -3- nitrobenzenesulfonamide, respectively, in Example 1D. 1 H NMR (300 MHz, DMSO-d 6) d 11.95 (m, 1 H), 8.61 (m, 1 H), 7.91 (dd, 1 H), 7.67 (d, 2 H), 7.44 (m, 1 H), 7.39 (m, 1H), 7.34 (m, 2H), 7.30 (m, 2H), 7.27 (m, 2H), 7.22 (m, 1H), 7.16 (m, 1H), 6.80 (m, 2H), 3.38 (m, 2H) ), 3.27 (m, 3H), 3.03 (s, 3H), 2.89 (s, 2H), 2.84 (m, 1H), 2.76 (m, 1H), 1.77 (m, 1H), 1.66 (m, 5H) , 1.47 (m, 2H), 1.08 (m, 7H).

EXAMPLE 262 This example is prepared by substituting example 90C and 4- (cyclohexylamino) -3-nitrobenzenesulfonamide, which is prepared as described in WO02 / 24636, by example 1C and 4 - (((1R) -3- (d! methylamino) -1- ((phenylsulfonyl) methyl) propyl) am i no) -3-nitrobenzenesulfonamide, respectively, in Example 1D. 1 H NMR (300 MHz, DMSO-d 6) d 8.62 (d, 1H), 8.31 (d, 1H), 7.92 (dd, 1H), 7.66 (d, 2H), 7.34 (m, 9H), 7.15 (m, 1H), 6.79 (d, 2H), 3.71 (m, 1H), 3.39 (d, 2H), 3.02 (m, 3H), 2.84 (m, 4H), 1.94 (m, 2H), 1.65 (m, 3H) ), 1.30 (m, 9H).

EXAMPLE 263 This example is prepared by replacing example 90C and 4 - ((1,1-dimethyl-2- (phenylisulfanyl) ethyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO0224636, by example 1 C and 4 - (((1 R) - 3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) -amino) -3-nitrobenzenesulfonamide, respectively, in Example 1 D. 1 H NMR (300 MHz, DMSO-d 6) d 1 1 .96 (m , 1 H), 8.51 (m, 2H), 7.82 (dd, 1 H), 7.71 (d, 2H), 7.33 (m, 1 1 H), 7.15 (m, 1 H), 7.00 (m, 2H) , 6.92 (m, 1 H), 6.82 (d, 2H), 3.54 (s, 2H), 3.40 (m, 2H), 3.03 (s, 3H), 2.85 (m, 4H), 1.57 (s, 6H), 1.46 (m, 2H), 1.17 (m, 2H).

EXAMPLE 264A A mixture of thiophenol (0.2 ml), (1-amino-cyclopentyl) methanol (0.2 g), tributylphosphine (0.5 ml), and THF (30 ml) at 0 ° C is treated with ADDP (0.482 g), stirred for 1 hour, stir at 25 ° C for 18 hours, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes and 5% methanol / dichloromethane.

EXAMPLE 264B This example is prepared by substituting example 264A for example 21 C in example 21 D.

EXAMPLE 264C This example is prepared by replacing Example 264B with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulf to nyl) methyl) propyl) amine) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (300 MHz, DMSO-d 6) d 8.50 (s, 1 H), 8.42 (s, 1 H), 8.35 (d, 1 H), 7.74 (m, 4 H), 7.39 (m, 8 H), 7.11 (m, 3H), 6.79 (m, 5H), 4.33 (s, 1H), 3.81 (s, 1H), 3.50 (s, 2H), 3.07 (m, 4H), 2.35 (m, 4H), 1.98 (m, 4H) ), 1.64 (m, 4H).

EXAMPLE 265 This example is prepared by substituting example 90C and example 264B for example 1C and 4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulf- nyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide , respectively, in example 1D. 1 H NMR (300 MHz, DMSO-d 6) d 11.96 (s, 1 H), 8.49 (s, 1 H), 8.41 (d, 1 H), 7.82 (dd, 1 H), 7.73 (d, 1 H), 7.34 (m, 8H), 7.16 (m, 4H), 6.83 (m, 5H), 3.57 (s, 2H), 3.31 (s, 2H), 3.02 (s, 3H), 2.85 (m, 4H), 2.11 (m, 2H) ), 1.99 (m, 2H), 1.71 (m, 4H), 1.47 (m, 2H), 1.18 (m, 2H).

EXAMPLE 266 This example is prepared by replacing Example 264B with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, CD 3 OD) d 8.52 (d, 1 H), 7.85 (m, 3 H), 7.72 (m, 1 H), 7.58 (m, 2 H), 7.51 (d, 2 H), 7.42 (m, 1 H), 7.35 (d, 2H), 7.12 (m, 2H), 6.99 (m, 3H), 6.72 (m, 3H), 4.46 (s, 2H), 3.50 (s, 2H), 3.31 (m, 4H) ), 3.17 (m, 4H), 2.13 (m, 4H), 1.80 (m, 4H).

EXAMPLE 267A A mixture of (S) -2-aminobutan-1 -ol (1 g), tributylphosphine (3 ml) and phenyl disulfide (2.64 g) in toluene (20 ml) at 85 ° C is stirred for 16 hours, and concentrate The concentrated material is subjected to flash chromatography on silica gel with 1% methanol / dichloromethane.

EXAMPLE 267B This example is prepared by substituting example 267A for example 21 C in example 21 D.

EXAMPLE 267C This example is prepared by replacing Example 267B with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, CD3OD) d 8.30 (d, 1 H), 7.90 (dd, 1 H), 7.75 (d, 2H), 7.52 (m, 1 H), 7.38 (m, 6H), 7.24 ( m, 3H), 7.05 (m, 2H), 6.96 (d, 1 H), 6.90 (d, 2H), 3.95 (m, 1 H), 3.54 (s, 2H), 3.27 47 (m, 4H), 2.51 (m, 4H), 1.81 (m, 2H), 1.00 (t, 3H).

EXAMPLE 268 This example is prepared by substituting example 00C and example 267B for example 1C and 4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulf- nyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonam gone, respectively, in example 1D. 1 H NMR (300 MHz, CDCl 3) d 8.78 (s, 1 H), 8.37 (m, 1 H), 8.01 (d, 1 H), 7.57 (m, 2 H), 7.35 (m, 10 H), 7.19 (m, 4 H) , 6.72 (d, 2H), 6.64 (d, 1H), 3.72 (m, 1H), 3.36 (m, 2H), 3.13 (m, 5H), 2.99 (m, 1H), 2.92 (s, 3H), 1.92 (m, 1H), 1.58 (m, 3H), 1.31 (m, 2H), 0. 98 (t, 3H).

EXAMPLE 269 This example is prepared by replacing Example 267B with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (300 MHz, CDCl 3) d 8.80 (s, 1 H), 8.42 (m, 1 H), 8. 03 (dd, 1H), 7.67 (m, 3H), 7.36 (m, 10H), 7.19 (m, 3H), 6.74 (d, 2H), 6.65 (d, 1H), 3.64 (m, 3H), 3.31 (m, 4H), 3.11 (s, 2H), 2.53 (m, 4H), 1.69 (m, 2H), 0.98 (t, 3H).

EXAMPLE 270A This example is prepared by substituting (S) -2-amino-4-methyl-pentan-1-ol for (S) -2-amino-butan-1-ol in Example 267A.

EXAMPLE 270B This example is prepared by substituting example 270A for example 21C in example 21D.

EXAMPLE 270C This example is prepared by substituting example 270B for 4 - (((1R) -3- (d-methylamine) -1 - ((phenylsulfanyl) methyl) propyl) am i no) -3-nitrobenzenesulfonamide in the 2D example. 1 H NMR (300 MHz, CDCl 3) d 8.80 (d, 1 H), 8.38 (d, 1 H), 8. 00 (dd, 1H), 7.63 (d, 2H), 7.48 (m, 1H), 7.35 (m, 8H), 7.22 (m, 4H), 6.78 (d, 2H), 6.60 (d, 1H), 3.85 (m, 1H), 3.42 (s, 2H), 3.28 (m, 4H), 3.08 (d, 2H), 2.47 (m, 4H), 1.73 (m, 3H), 0.86 (d, 3H), 0.86 (d, 3H).

EXAMPLE 271 This example is prepared by substituting the example SOC and example 270B for example 1C and 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively , in Example 1 D. 1 H NMR (300 MHz, CDCl 3) d 8.77 (d, 1 H), 8.36 (d, 2 H), 7.98 (dd, 1 H), 7.60 (d, 2 H), 7.35 (m , 9H), 7.20 (m, 4H), 6.64 (m, 3H), 3.80 (m, 1 H), 3.34 (s, 2H), 3.12 (s, 3H), 3.07 (m, 2H), 2.92 (m , 4H), 1.57 (m, 5H), 1.30 (m, 2H), 0.95 (d, 3H), 0.85 (d, 3H).

EXAMPLE 272A Treat 1-tert-butoxycarbonylaminocyclopropane-carboxylic acid (1.018 g) in THF (6 mL) at 0 ° C with 1 M borane-THF (15 mL), stir at 25 ° C, treat with 3M NaOH, (5 mL). mi), and extracted with diethyl ether. The extract is dried (MgSO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10% ethyl acetate / hexanes.

EXAMPLE 272B This example is prepared by replacing Example 272A with (S) -2-amino-butan-1-ol in Example 267A.

EXAMPLE 272C Example 272B (0.090 g) in dichloromethane / TFA at 25 ° C is stirred for 16 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% methanol / dichloromethane.

EXAMPLE 272 D This example is prepared by substituting example 272C for example 21 C in example 21 D.

EXAMPLE 272E This example is prepared by replacing Example 272D with 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfanyl) methyl) p ropil) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.74 (d, 1 H), 8.60 (s, 1 H), 8.14 (d, 1 H), 7.63 (d, 2 H), 7.49 (m, 1 H), 7.35. (m, 6H), 7.25 (m, 3H), 7.06 (m, 3H), 6.80 (d, 2H), 3.41 (s, 2H), 3.28 (m, 4H), 3.22 (s, 2H), 2.47 ( m, 4H), 1.01 (m, 4H).

EXAMPLE 273A This example is prepared by substituting the (l-hydroxymethyl-cyclohexyl) carbamic acid tert-butyl ester, which is prepared as described in Bioorg. Med. Chem. Lett. , 2003; 13; 1883, by (S) -2-amino-butan-1 -ol in Example 267A.

EXAMPLE 273B This example is prepared by substituting example 273A for example 272B in example 272C.

EXAMPLE 273C This example is prepared by substituting example 273B for example 21 C in example 21 D.

EXAMPLE 273D This example is prepared by replacing Example 273C with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.71 (s, 1 H), 8.63 (s, 1 H), 7.92 (d, 1 H), 7.68 (m, 2 H), 7.47 (m, 5 H), 7.32 ( m, 1 H), 7.20 (m, 4H), 6.94 (m, 6H), 6.78 (m, 1 H), 4.38 (s, 2H), 3.56 (m, 4H), 3.38 (s, 2H), 2.31 (m, 4H), 1.47 (m, 10H).

EXAMPLE 274A This example is prepared by substituting (R) -2-amino-propan-1 -ol for (S) -2-amino-butan-1-ol in Example 267A.

EXAMPLE 274B This example is prepared by substituting example 274A for example 21C in example 21D.

EXAMPLE 274C This example is prepared by replacing Example 274B with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.80 (br s, 1 H), 8.42 (br s, 1 H), 8.03 (d, 1 H), 7.65 (d, 2 H), 7.50 (m, 1 H), 7.34 (m, 9H), 7.22 (m, 3H), 6.77 (d, 2H), 6.63 (m, 1H), 3.88 (m, 1H), 3.42 (s, 2H), 3.26 (m, 4H), 3.10 (d, 2H) ), 2.48 (m, 4H), 1.43 (d, 3H).

EXAMPLE 275A This example is prepared by substituting (S) -2-amino-propan-1-ol for (S) -2-amino-butan-1-ol in Example 267A.

EXAMPLE 275B This example is prepared by replacing example 275A with example 21C in example 21D.

EXAMPLE 275C This example is prepared by substituting example 275B for 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfanyl) methyl) p rop I) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR (300 MHz, CDCl 3) d 8.82 (d, 1 H), 8.45 (d, 1 H), 8.04 (dd, 1 H), 7.64 (d, 2 H), 7.56 (m, 1 H) , 7.35 (m, 10H), 7.20 (m, 3H), 6.77 (d, 2H), 6.65 (d, 1 H), 3.91 (m, 1 H), 3.51 (s, 2H), 3.27 (t, 4H ), 3.12 (m, 2H), 2.48 (t, 4H), 1.45 (d, 3H).

EXAMPLE 276A This example is prepared by substituting (1 R, 2R) - (2-hydroxycyclohexyl) carbamic acid tert-butyl ester, which is prepared as described in Synth. Commun. 1992, 22, 3003, by (S) -2-amino-butanol in Example 267A.

This example is prepared by substituting example 276A for example 272B in example 272C.

EXAMPLE 276C This example is prepared by substituting example 276B for example 21 C in example 21 D.

EXAMPLE 276D This example is prepared by replacing Example 276C with 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. H NMR (300 MHz, CDCl 3) d 8.82 (s, 1 H), 8.78 (s, 1 H), 8.07 (d, 1 H), 7.61 (m, 3 H), 7.35 (m, 10 H), 7.09 (m, 3 H) , 6.76 (m, 3H), 3.84 (s, 1H), 3.65 (s, 1H), 3.48 (m, 2H), 3.25 (m, 4H), 2.47 (m, 4H), 1.73 (, 8H).

EXAMPLE 277 This example is prepared by replacing Example 276C with 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfonyl) methyl) prop i) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.92 (d, 1 H), 8.80 (d, 1 H), 8.08 (dd, 1 H), 7.66 (d, 2 H), 7.53 (m, 1 H), 7.35 (m, 8 H) , 7.23 (m, 1H), 7.11 (m, 3H), 6.78 (m, 3H), 3.87 (m, 1H), 3.65 (m, 1H), 3.46 (s, 2H), 3.28 (m, 4H), 2.49 (m, 4H), 1.75 (m, 8H).EXAMPLE 278A This example is prepared by substituting the (1S, 2R) - (2-hydroxycyclohexyl) carbamic acid tert-butyl ester, which is prepared as described in Eur. J. Org. Chem., 1988, 8, 1771, by (S) -2-amino-butan-1-ol in Example 267A.

EXAMPLE 278B This example is prepared by substituting example 278A for example 272B in example 272C.

EXAMPLE 278C This example is prepared by substituting example 278B for example 21 C in example 21 D.

EXAMPLE 278D This example is prepared by substituting Example 278C for 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfanyl) methyl) p-ropil) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.93 (d, 1 H), 8.80 (d, 1 H), 8. 09 (dd, 1 H), 7.64 (d, 2H), 7.53 (m, 1 H), 7.35 (m, 8H), 7.12 (m, 3H), 6.80 (m, 3H), 3.87 (m, 1 H) ), 3.66 (m, 1 H), 3.50 (s, 2H), 3.32 (m, 4H), 2.50 (m, 4H), 1.85 (m, 8H).

EXAMPLE 279A This example is prepared by substituting the S- (1-hydroxymethyl-2-pyrridin-3-yl-ethyl) -carbamic acid tert-butyl ester for (S) -2-amino-butan-1-ol in the example 267A.

EXAMPLE 279B This example is prepared by substituting example 279A for example 272B in example 272C.

EXAMPLE 279C This example is prepared by substituting example 279B for example 21 C in example 21 D.

EXAMPLE 279D This example is prepared by substituting Example 795333C for 4 - (((1 R) -3- (dimethylamine) -1 - ((phenylisulfanyl) methyI) propyl) amino) -3-nitrobenzenesulfonamide in Example 1 D. 1 H NMR ( 300 MHz, CDCl 3) d 8.74 (d, 1 H), 8.48 (m, 3H), 7. 97 (dd, 1 H), 7.64 (d, 2H), 7.53 (m, 2H), 7.37 (m, 9H), 7.23 (m, 5H), 6.75 (d, 2H), 6.53 (d, 1 H) , 4.00 (m, 1 H), 3.50 (s, 2H), 3.26 (m, 5H), 3.13 (d, 2H), 2.98 (m, 1 H), 2.48 (m, 4H).

EXAMPLE 280 This example is prepared by substituting example 90C and example 279C for example 1C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in the example 1D. 1 H NMR (300 MHz, CDCl 3) d 8.90 (s, 1 H), 8.62 (s, 1 H), 8. 53 (s, 1H), 8.45 (d, 1H), 8.15 (d, 1H), 7.81 (d, 1H), 7.69 (m, 3H), 7. 34 (m, 9H), 7.19 (m, 4H), 6.90 (d, 2H), 6.54 (d, 1H), 4.18 (m, 1H), 3.34 (m, 6H), 3.12 (s, 3H), 3.04 (m, 2H), 2.94 (s, 2H), 1.61 (m, 2H), 1. 45 (m, 2H).

EXAMPLE 281 This example is prepared by replacing Example 278C with 4 - (((1R) -3- (d-methylamino) -1 - ((phenylsulfa or I) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (300 MHz, CDCl 3) d 8.95 (d, 1 H), 8.79 (d, 1 H), 8. 06 (dd, 1H), 7.69 (m, 3H), 7.41 (m, 8H), 7.24 (m, 1H), 7.11 (m, 3H), 6.80 (d, 1H), 6.74 (d, 2H), 3.86 (m, 1H), 3.66 (m, 1H), 3.29 (m, 8H), 2.52 (s, 2H), 2.07 (m, 1H), 1.81 (m, 5H), 1.51 (m, 2H).

EXAMPLE 282A This example is prepared by substituting (1-amino-480 cyclopentyl) -methanol and bis- (2-methyl-3-furyl) -disulfide by (S) -2-amino-butan-1-ol and phenyl disulfide, respectively, in Example 267A.

EXAMPLE 282B This example is prepared by substituting example 282A for example 21 C in example 21 D.

EXAMPLE 282C This example is prepared by replacing Example 282B with 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfanyl) methyl) propyI) amino) -3-nitrobenzenesulfonamide in Example 1 D. H NMR (500 MHz, CDCl 3) d 8.82 (d, 1 H), 8.68 (s, 1 H), 8. 06 (dd, 1 H), 7.65 (d, 2H), 7.53 (m, 1 H), 7.33 (m, 7H), 6.91 (m, 1 H), 6.88 (s, 1 H), 6.78 (d, 2H), 5.99 (d, 1 H), 3.47 (s, 2H), 3.26 (m, 4H), 3.18 (s, 2H), 2.46 (m, 4H), 2.14 (br s, 3H), 2.08 (m , 4H), 1.78 (m, 4H).

EXAMPLE 283 This example is prepared by substituting Example 282B for 4 - (((1 R) -3- (d-methylamino) -1 - ((phenyl-Isulfan I) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D . 481 1 H NMR (500 MHz, CDCl 3) d 8.82 (d, 1 H), 8.68 (s, 1 H), 8.07 (dd, 1 H), 7.65 (d, 2 H), 7.49 (m, 1 H), 7.34. (m, 6H), 7.23 (m, 1 H), 6.90 (m, 2H), 6.79 (d, 2H), 6.00 (d, 1 H), 3.41 (s, 2H), 3.26 (m, 4H), 3.18 (s, 2H), 2.46 (m, 4H), 2.14 (s, 3H), 2.08 (m, 4H), 1.78 (m, 4H).

EXAMPLE 284 This example is prepared by replacing Example 279C with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.76 (d, 1 H), 8.50 (m, 3 H), 7.98 (dd, 1 H), 7.62 (d, 2 H), 7.50 (m, 2 H), 7.35 (m , 8H), 7.21 (m, 4H), 6.78 (d, 2H), 6.53 (d, 1 H), 4.01 (m, 1 H), 3.42 (s, 2H), 3.27 (m, 5H), 3.13 ( d, 2H), 2.99 (m, 1 H), 2.48 (m, 4H).

EXAMPLE 285A This example is prepared by substituting 2-bromo-3-bromomethylpyridine, which is prepared as described in J. Am. Chem. Soc, 1985, 107, 7487, by 2-bromobenzyl bromide in Example 2A.

EXAMPLE 285B This example is prepared by substituting example 285A for example 2A in example 2B.

EXAMPLE 285C This example is prepared by substituting example 285B for example 2B in example 2C.

EXAMPLE 285D This example is prepared by substituting example 285C for example 1C in example 1D. 1 H NMR (300 MHz, DMSO-d 6) d 12.10 (s, 1 H), 8.70 (m, 1H), 8.54 (d, 1H), 8.29 (d, 1H), 8.11 (m, 1H), 7.86 (dd, 1H), 7.76 (d, 2H), 7.58 (m, 5H), 7.16 (m, 6H), 6.94 (d, 2H), 4.19 (m, 1H), 3.54 (m, 4H), 3.3g (d, 2H), 3.13 (m, 4H), 2.75 (s, 3H), 2.74 (s, 3H), 2.49 (m, 4H), 2.14 (m, 2H).

EXAMPLE 286 This example is prepared by replacing Example 285C and 3-Nitro-4- (2-phenylsulfanylethylamine) -benzenesulfonamide, which is prepared as described in WO02 / 24636, by example 1C and 4 - (((1 R) -3- (dimethylamine) -1- ( (phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in example 1D. 483 1 H NMR (300 MHz, CDCl 3) d 8.83 (d, 1 H), 8.78 (d, 1 H), 8.67 (t, 1 H), 8.34 (d, 1 H), 8.10 (dd, 1 H), 7.67 (d, 1 H) , 7.52 (m, 3H), 7.41 (m, 4H), 7.30 (m, 2H), 7.23 (m, 1H), 6.82 (d, 1H), 6.73 (d, 2H), 4.35 (s, 2H), 3.57 (q, 2H), 3.47 (m, 4H), 3.20 (t, 2H), 2.97 (m, 4H).

EXAMPLE 287 This example is prepared by substituting example 285C and 4 - (((1R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (300 MHz, DMSO-d 6) d 8.70 (d, 1 H), 8.55 (d, 1 H), 8.30 (d, 1 H), 8.12 (m, 1 H), 7.87 (dd, 1 H), 7.76 (d, 2H), 7.57 (m, 5H), 7.16 (m, 6H), 6.94 (d, 2H), 4.19 (m, 1H), 3.97 (d, 2H), 3.58 (m, 7H), 3.38 (m, 5H) ), 3.19 (m, 4H), 3.01 (m, 4H), 2.17 (m, 2H).

EXAMPLE 288A This example is prepared by substituting phenylboronic acid and Example 285A for 4-chlorophenylboronic acid and Example 2A, respectively, in Example 2B. 484 EXAMPLE 288B This example is prepared by example 288A by example 2B in example 2C.

EXAMPLE 288C This example is prepared by substituting example 288B and 3-nitro-4- (2-phenylsulphanyl) ethylamino) -benzenesulfonamide, which is prepared as described in WO02 / 24636, by example 1 C and 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsufinyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 1 D. 1 H NMR (300 MHz, CDCl 3) d 8.86 (d, 1 H ), 8.65 (m, 2H), 8.14 (dd, 1 H), 7.81 (m, 1 H), 7.60 (m, 4H), 7.43 (m, 5H), 7.28 (m, 4H), 6.80 (m, 3H), 3.56 (m, 4H), 3.31 (m, 4H), 3.21 (t, 2H), 2.51 (m, 4H).

EXAMPLE 289 This example is prepared by substituting example 288B and 4 - (((1 R) -3- (4-morpholin il) -1 - ((phenylsulfanyl) methyl I) propyl) am i no) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (((1 R) -3- (d-imethylamino) -1- ((f in l-sulphanyl) methyl) propyl) amino ) -3- nitrobenzenesulfonamide, respectively, in example 2D. 1 H NMR (300 MHz, CD 3 OD) d 8.67 (d, 1 H), 8.49 (dd, 1H), 8.07 (dd, 1H), 7.88 (dd, 1H), 7.78 (d, 2H), 7.48 (m, 6H), 7.26 (m, 2H), 7.12 (m, 3H), 6.95 (d, 1H), 6.88 (d, 2H), 4.14 (m, 1H), 3.66 (m, 4H), 3.53 (m, 2H), 3.25 ( m, 6H), 2.51 (m, 10H), 2.13 (m, 1H), 1. 02 (m, 1H).

EXAMPLE 290 This example is prepared by substituting example 288B for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.56 (dd, 1 H), 8.44 (d, 1H), 8.31 (d, 1H), 7.94 (dd, 1H), 7.79 (dd, 1H), 7.72 (d, 2H), 7.62 (m, 2H), 7.43 (m, 5H), 7.32 (m, 2H), 7.25 (m, 2H), 7.17 (m, 1H), 6.87 (d, 1H), 6.79 (d, 2H), 4.05 ( m, 1H), 3.50 (s, 2H), 3.30 (m, 2H), 3. 16 (s, 4H), 2.43 (m, 4H), 2.35 (m, 6H), 2.01 (m, 1H), 1.91 (m, 1 HOUR).

EXAMPLE 291A This example is prepared by substituting 4- (methylsulfanyl) -phenylboronic acid and Example 285A for 4-chlorophenylboronic acid and Example 2A, respectively, in Example 2B.

EXAMPLE 291 B This example is prepared by substituting example 291A for example 2B in example 2C.

EXAMPLE 291 C This example is prepared by substituting example 291 B for example 2C in example 2D. 1 H NMR (300 MHz, CD3OD) d 8.74 (dd, 1 H), 8.67 (d, 1 H), 8.42 (dd, 1 H), 7.93 (dd, 1 H), 7.74 (m, 3H), 7.50 (d, 2H), 7.44 (d, 2H), 7.22 (m, 2H), 7.04 ( m, 4H), 6.94 (d, 2H), 4.36 (s, 2H), 4.17 (m, 1 H), 3.43 (m, 5H), 3.24 (m, 3H), 3.04 (t, 4H), 2.87 ( s, 6H), 2.51 (s, 3H), 2.24 (m, 2H).

EXAMPLE 292A This example is prepared by substituting 4-methoxyphenylboronic acid and Example 285A for 4-chlorophenylboronic acid and Example 2A, respectively, in Example 2B.

EXAMPLE 292B This example is prepared by substituting example 292A for example 2B in example 2C.

EXAMPLE 292C This example is prepared by substituting example 292B for example 2C in example 2D. 1 H NMR (300 MHz, DMSO-d6) d 8.55 (dd, 1 H), 8.45 (d, 1 H), 8.33 (d, 1 H), 7.91 (dd, 1 H), 7.78 (dd, 1 H), 7.73 (d, 2H), 7.63 (d, 2H), 7.33 (m, 3H), 7.21 (m, 3H), 7.01 (d, 2H), 6.86 (d, 1 H), 6.80 (d, 2H), 4.04 (m, 1 H), 3.79 (s, 3H), 3.50 (s, 2H), 3.18 (s, 4H), 3.00 (d, 2H), 2.68 (m, 2H), 2.45 (m, 4H), 2.33 (s, 6H), 1.95 (m, 2H).

EXAMPLE 293A This example is prepared by substituting 4-dimethylaminophenylboronic acid and Example 285A for 4-chlorophenylboronic acid and Example 2A, respectively, in Example 2B.

EXAMPLE 293B This example is prepared by substituting example 293A for example 2B in example 2C. 488 EXAMPLE 293 This example is prepared by substituting example 283B for example 2C in example 2D. 1 H NMR (300 MHz, CD3OD) d 8.66 (d, 1 H), 8.46 (dd, 1 H), 8.08 (dd, 1 H), 7.84 (dd, 1 H), 7.75 (d, 2H), 7.42 (m, 3H), 7.24 (m, 2H), 7.08 (m, 3H), 6.96 (d, 1 H), 6.91 (d, 2H), 6.84 (d, 2H), 4.14 (m, 1 H), 3.64 (s, 2H), 3.38 (m, 4H), 3.23 (m, 4H), 3.00 (s, 6H), 2.86 (s, 7H), 2.54 (m, 4H), 2.22 (m, 2H).

EXAMPLE 294A This example is prepared by substituting 4-fluorophenylboronic acid and Example 285A for 4-chlorophenylboronic acid and Example 2A, respectively, in Example 2B.

EXAMPLE 294B This example is prepared by substituting example 294A for example 2B in example 2C.

EXAMPLE 294 This example is prepared by substituting example 294B for example 2C in example 2D. 488 1 H NMR (300 MHz, CD3OD) d 8.74 (dd, 1 H), 8.67 (d, 1 H), 8.37 (dd, 1 H), 7.83 (dd, 1 H), 7.73 (m, 3H), 7.60 (m, 2H), 7.31 (m, 2H), 7.22 (m, 2H), 7.03 (m, 4H), 6.95 (d, 2H), 4.39 (s, 2H), 4.17 (m, 1 H), 3.47 (m, 4H), 3.38 (m, 1 H), 3.23 (m, 3H), 3.08 (m, 4H), 2.86 (s, 6H), 2.24 (m, 2H).

EXAMPLE 295A This example is prepared by substituting 4- (methanesulfonyl) -phenyl boronic acid and Example 285A for 4-chlorophenylboronic acid and Example 2A, respectively, in Example 2B.

EXAMPLE 295B This example is prepared by substituting example 295A for example 2B in example 2C.

EXAMPLE 295C This example is prepared by substituting example 295B for example 2C in example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.62 (m, 3H), 8.02 (d, 2H), 7. 89 (m, 3H), 7.80 (m, 3H), 7.32 (m, 3H), 7.19 (m, 3H), 6.73 (m, 3H), 4.06 (m, 1 H), 3.46 (s, 2H), 3.24 (m, 4H), 3.12 (d, 2H), 2.85 (m, 3H), 2.59 (s, 6H), 2.51 (m, 5H), 2.19 (m, 1 H), 2.08 (m, 1 H) .

EXAMPLE 205A This example is prepared by substituting 2-bromoethylamine hydrobromide for Example 21 C in Example 21 D.

EXAMPLE 296A This example is prepared by substituting pyridin-4-yl-methanethiol for 2-mercaptoimidazole in Example 205B.

EXAMPLE 296B This example is prepared by substituting 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide for 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylisulfanyl) methyl) propyl) am i no) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.87 (d, 1 H), 8.62 (m, 1 H), 8.42 (d, 2 H), 8.19 (dd, 1 H), 7.62 (d, 3 H), 7.35 (d. m, 7H), 7.15 (d, 2H), 6.92 (d, 1 H), 6.77 (d, 2H), 3.70 (q, 2H), 3.54 (s, 2H), 3.32 (m, 6H), 2.53 ( m, 4H).

EXAMPLE 297A This example is prepared by substituting 4- (methanesulfonyl) -phenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 297B This example is prepared by substituting example 297A for example 2B in example 2C.

EXAMPLE 297C This example is prepared by substituting example 297B for example 2C in example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.66 (d, 1 H), 8.57 (d, 1 H), 7. 96 (d, 2H), 7.80 (m, 3H), 7.66 (d, 2H), 7.49 (m, 1 H), 7.38 (m, 2H), 7. 29 (m, 2H), 7.19 (m, 4H), 6.71 (m, 3H), 4.04 (m, 1 H), 3.38 (s, 2H), 3.18 (m, 4H), 3.10 (m, 6H), 2.85 (m, 2H), 2.58 (s, 6H), 2.45 (m, 4H), 2.20 (m, 1 H), 2.07 (m, 1 HOUR).

EXAMPLE 298 This example is prepared by substituting example 297B and 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3- nitrobenzenesulfonamide for 2C and 4 - ((( 1R) -3- (dimethylamino) -1 - ((phenylsufinyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.55 (d, 1 H), 8.29 (d, 1 H), 8.01 (d, 2 H), 7.87 (dd, 1 H), 7.76 (d, 2 H), 7.67 (d, 2H), 7.55 (m, 2H), 7.37 (d, 1 H), 7.23 (m, 2H), 7.15 (m, 4H), 6.93 (s, 2H), 4.19 (m, 1 H), 3.95 (s, 2H), 3.54 (m, 12H), 3.40 (d, 2H), 3.26 (s, 3H), 3.19 (m, 4H), 3.02 (m, 2H), 2.17 (m, 2H).

EXAMPLE 299A Example 19C (0.938 g) in dichloromethane (10 ml) a ° C is treated with di- (tert-butyl) dicarbonate (0.873 g), stirred for 24 hours, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20-60% ethyl acetate / hexanes.

EXAMPLE 299B This example is prepared by substituting example 299A for example 67A in example 67B.

EXAMPLE 299C This example is prepared by substituting example 299B for example 272B in example 272C.

EXAMPLE 299D This example is prepared by substituting example 299C for example 21 C in example 21 D.

EXAMPLE 299E Example 299D (0.485 g) at 25 ° C is treated with 1 M borane-THF (8 mL), stirred for 16 hours, treated with methanol (5 mL), and concentrated. The concentrated material is refluxed in methanol / 12M HCl (30 ml / 6 ml) for 8 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 1-20% methanol / dichloromethane saturated with NH3.

EXAMPLE 299F This example is prepared by substituting example 299E for example 2C in example 2D. 1 H NMR (300 MHz, CDCl 3) d 8.80 (d, 1 H), 8.41 (d, 1 H), 8.07 (dd, 1 H), 7.77 (d, 2 H), 7.63 (dd, 3 H), 7.46 (d. m, 3H), 7.34 (m, 6H), 7.24 (m, 1 H), 7.00 (d, 1 H), 6.78 (d, 2H), 4.54 (m, 1 H), 3.69 (m, 4H), 3.45 (d, 2H), 3.41 (s, 2H), 3.26 (m, 4H), 2.47 (m, 6H), 2.34 (m, 3H), 2.20 (m, 2H), 1.86 (m, 2H) .

EXAMPLE 300A This example is prepared by substituting 4-dimethylaminophenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 300B This example is prepared by substituting example 300A for example 2B in example 2C.

EXAMPLE 300C This example is prepared by substituting example 300B for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d6) d 8.46 (d, 1 H), 8.20 (d, 1 H), 7.81 (d, 1 H), 7.72 (m, 2 H), 7.50 (m, 1 H) , 7.30 (m, 6H), 7.24 (m, 4H), 6.90 (d, 1 H), 6.79 (m, 4H), 4.07 (m, 1 H), 3.43 (s, 2H), 3.21 (m, 8H) ), 2.92 (s, 6H), 2.56 (s, 6H), 2.43 (m, 4H), 2.05 (m, 2H).

EXAMPLE 301 A This example is prepared by substituting example 18C or example 19C in example 299A.

EXAMPLE 301B This example is prepared by substituting example 301A for example 67A in example 67B.

EXAMPLE 301C This example is prepared by substituting example 301 B for example 272B in example 272C.

EXAMPLE 301D This example is prepared by substituting example 301 C for example 21C in example 21D.

EXAMPLE 301E This example is prepared by replacing Example 301 D with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyI) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, DMSO-d 6) d 8.51 (m, 2H), 7.90 (dd, 1H), 7.76 (d, 2H), 7.58 (dd, 2H), 7.50 (m, 6H), 7.38 (m, 4H), 7.23 (m, 2H), 6.90 (d, 2H), 4.70 (m, 1H), 4.17 (m, 1H), 3.76 (m, 1H), 3.43 (s, 2H), 3.25 (m, 4H) ), 84 (m, 1 H), 2.88 (s, 3H), 2.77 (m, 4H), 2.42 (m, 4H).

EXAMPLE 302A This example is prepared by substituting 3-amino-4-hydroxy-pyrrolidin-1-carboxylic acid tert-butyl ester, which is prepared as described in J. Org. Chem., 1887, 62, 4197, by (S) -2-amino-butan-1-ol in Example 267A.

EXAMPLE 302B This example is prepared by substituting example 302A for example 21 C in example 21 D.

EXAMPLE 302C This example is prepared by substituting example 302B for 4 - (((1 R) -3- (d-methylamino) -1- ((phenylsulphyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 302D This example is prepared by substituting example 302C for example 272B in example 272C. 1 H NMR (300 MHz, CD 3 OD) d 8.78 (d, 1 H), 7.94 (dd, 1 H), 7.74 (m, 3 H), 7.55 (m, 7 H), 7.36 (m, 7 H), 6.96 (d , 2H), 6.75 (d, 1 H), 4.51 (m, 1 H), 4.44 (s, 2H), 4.02 (m, 2H), 3.86 (q, 1 H), 3.49 (m, 2H), 3.43 (m, 2H), 3.35 (m, 2H), 3.14 (m, 4H).

EXAMPLE 303 This example is prepared by substituting pyridine-4-thiol for isopropylamine in Example 35B. 1 H NMR (400 MHz, CD3OD) d 8.64 (m, 1 H), 8.23 (m, 2H), 7. 83 (m, 3H), 7.50 (m, 1 H), 7.36 (m, 7H), 7.23 (m, 5H), 7.11 (m, 3H), 6.85 (d, 2H), 6.78 (d, 1 H) , 4.14 (m, 1 H), 3.60 (m, 1 H), 3.47 (s, 2H), 3.21 (m, 6H), 3.10 (m, 1 H), 2.46 (m, 4H), 2.26 (m, 1 H), 2.12 (m, 1 H).

EXAMPLE 304A A mixture of 3-bromo-4-methylpyridine (1.34 g) and NCS (1.43 g) in CCI4 (10 mL) at reflux is stirred for 21 hours and filtered. The filtrate is dried (MgSO4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 0-30% ethyl acetate / hexanes.

EXAMPLE 304B This example is prepared by replacing Example 304A with 2-bromobenzyl bromide in Example 2A.

EXAMPLE 304C This example is prepared by substituting example 304B for example 2A in example 2B.

EXAMPLE 304D This example is prepared by replacing example 304C with example 2B in example 2C.

EXAMPLE 304E This example is prepared by substituting example 304D for example 2C in example 2D. 1 H NMR (300 MHz, DMSO-d 6) d 12.09 (d, 1 H), 9.33 (d, 1 H), 8.69 (d, 1 H), 8.54 (d, 1 H), 8.29 (d, 1 H), 7.87 (dd, 1 H), 7.75 (m, 3H), 7.57 (d, 2H), 7.48 (d, 2H), 7.17 (m, 6H), 6.94 (d, 2H), 4.18 (m, 1 H), 3.39 (d, 2H), 3.13 (m, 4H), 2.75 (m, 3H), 2.73 (m, 3H), 2.14 (m, 2H).

EXAMPLE 305 This example is prepared by substituting example 304D and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amine) -benzenesulfonamide for example 2C and 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, CDCl 3) d 8.83 (d, 1 H), 8.75 (d, 1 H), 8. 66 (m, 2H), 8.1 1 (dd, 1 H), 8.08 (d, 1 H), 7.66 (d, 2H), 7.51 (d, 2H), 7.40 (d, 2H), 7.27 (m, 5H) ), 6.81 (d, 1 H), 6.78 (d, 2H), 3.90 (s, 2H), 3.57 (m, 2H), 3.42 (m, 4H), 3.20 (t, 2H), 2.75 (m, 4H) ).

EXAMPLE 306A It is 2-bromo-cyclopent-1-in-carbaldehyde, which is prepared as described in Collect. Czech Chem. Commun. , 1961, 26, 3059-3073, (1.5 g), 4-piperazin-1-yl-benzoic acid ethyl ester (2 g) in ethanol (10 ml) at 25 ° C with sodium cyanoborohydride (0.36 g) ), the pH is adjusted to 5-6 with acetic acid, stirred for 18 hours, filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5-10% ethyl acetate / hexanes.

EXAMPLE 306B This example is prepared by replacing example 306A with example 2A in example 2B.

EXAMPLE 306C This example is prepared by substituting example 306B for example 2B in example 2C.

EXAMPLE 306D This example is prepared by substituting example 306C for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d6) d 12.10 (m, 1 H), 8.54 (d, 1 H), 8.28 (d, 1 H), 7.86 (dd, 1 H), 7.78 (d, 2H), 7.32 (d, 2H), 7.28 (d, 2H), 7.22 (d, 2H), 7.14 ( m, 4H), 6.97 (d, 2H), 4.18 (m, 1 H), 3.90 (m, 4H), 3.54 (m, 4H), 3.39 (d, 2H), 3.14 (m, 4H), 2.92 ( m, 2H), 2.76 (s, 6H), 2.64 (m, 2H), 2.15 (m, 2H), 1.96 (m, 2H).

EXAMPLE 307A This example is prepared by substituting 2-bromo-cyclohex-1-in-carbaldehyde, which is prepared as described in Collect. Czech Chem. Commun. , 1961, 26, 3059, by 2-bromo-cyclopent-1-in-carbaldehyde in Example 306A.

EXAMPLE 307B This example is prepared by replacing Example 307A with Example 2A in Example 2B.

EXAMPLE 307C This example is prepared by substituting example 307B for example 2B in example 2C.

EXAMPLE 307D This example is prepared by substituting example 307C for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d6) d 8.29 (d, 1 H), 8.03 (d, 1 H), 7.61 (dd, 1 H), 7.53 (d, 2H), 7.15 (d, 2H), 6.97 (m, 2H), 6.89 (m, 6H), 6.70 (d, 2H), 3.93 (m, 1 H), 3.37 (m, 4H), 3.13 (m, 4H), 2.89 (m, 4H), 2.49 (s, 6H), 2.24 (s, 2H), 1 .98 (d, 4H), 1 .89 (q, 2H), 1.43 (m, 4H).

EXAMPLE 308A This example is prepared by replacing example 306A with example 2B in example 2C.

EXAMPLE 308B This example is prepared by substituting example 308A for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 9.48 (s, 1 H), 8.50 (d, 1H), 8.25 (d, 1H), 7.83 (dd, 1H), 7.77 (d, 2H), 7.17 (m, 3H), 7.09 (m, 4H), 6.98 (d, 2H), 4.14 (m, 1H), 3.80 (s, 2H), 3.35 (d, 2H), 3.28 (m, 4H), 3.11 (m, 4H), 2.70 ( s, 6H), 2.64 (m, 2H), 2.41 (m, 2H), 2. 10 (q, 2H), 1.93 (m, 2H).

EXAMPLE 79 This example is prepared by replacing Example 307C and 4 - (((1R) -3- (4-morpholin il) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide by example 2C and 4 - (((1R) -3 - (d imethylami no) - 1 - ((phenylsulfanyl) methyl) p ropil) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (300 MHz, DMSO-d 6) d 8.50 (d, 1 H), 8.37 (d, 1H), 7.80 (dd, 1H), 7.72 (d, 2H), 7.37 (d, 2H), 7.28 (m, 2H), 7.17 (m, 5H), 7.04 (d, 1H), 6.85 (d, 2H) ), 4.14 (s, 1H), 3.53 (m, 4H), 3.36 (m, 4H), 3.21 (m, 4H), 2.80 (s, 2H), 2.45 (m, 2H), 2.34 (m, 5H) , 2.19 (m, 5H), 2.01 (m, 1H), 1.87 (m, 1H), 1.67 (m, 4H).

EXAMPLE 310 This example is prepared by substituting example 307C and example 18F for example 2C and 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively , in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 7.80 (d, 1 H), 7.63 (m, 3H), 7.24 (m, 6H), 7.12 (m, 1H), 7.02 (d, 2H), 6.70 (d, 2H), 6.58 (d, 1H), 5.74 (s, 1H), 3.76 (m, 1H), 3.16 (m, 6H), 3.07 (m, 4H), 2.80 (m, 2H), 2.68 (s, 2H), 2.41 (m, 2H) ), 2.18 (m, 4H), 2.10 (m, 4H), 1. 85 (m, 2H), 1.57 (m, 4H).

EXAMPLE 311A This example is prepared by replacing example 307A with example 2B in example 2C.

EXAMPLE 311B This example is prepared by substituting example 311 A for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.55 (d, 1H), 8.29 (d, 1H), 7.87 (dd, 1H), 7.81 (d, 2H), 7.21 (m, 3H), 7.12 (m, 3H), 7.03 (d, 2H), 4.19 (m, 1H), 3.89 (s, 2H), 3.30 (m, 8H), 3.15 (m, 4H), 2.74 (s, 6H), 2.56 (m, 2H) ), 2.25 (m, 2H), 2.15 (q, 2H), 1.68 (, 4H).

EXAMPLE 312A A mixture of DMF (10 mL) and chloroform (200 mL) at 5 ° C is treated with PBr3 (10 mL), stirred at 25 ° C for 40 minutes, treated with tetrahydropyran-4-one (5 g) in chloroform (50 ml) at 0 ° C, stirred at 25 ° C for 18 hours, poured into ice, treated with sodium bicarbonate, and extracted with diethyl ether. The extract is washed with saturated sodium bicarbonate and brine and dried (MgSO), filtered and concentrated. The concentrated material is subjected to flash chromatography with silica gel with 10% ethyl acetate / hexanes.

EXAMPLE 312B This example is prepared by substituting 312A for 2-bromo-cyclopent-1-in-carbaldehyde in Example 306A.

EXAMPLE 312C This example is prepared by substituting example 312B for example 2A in example 2B.

EXAMPLE 312D This example is prepared by substituting example 312C for example 2B in example 2C.

EXAMPLE 312E This example is prepared by substituting example 312D for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.20 (d, 1 H), 8.03 (d, 1 H), 7.61 (d, 1 H), 7.52 (d, 2 H), 7.19 (d, 2 H), 6.98 (m, 4H), 6.89 (m, 4H), 6.70 (d, 2H), 3.99 (s, 2H), 3.93 (m, 1 H), 3.69 (s, 2H), 3.58 (t, 2H), 3.13 (s, 8H), 2.88 (m, 4H), 2.49 (s, 6H), 2.12 (m, 2H), 1.89 (q, 2H).

EXAMPLE 313A This example is prepared by substituting example 312B and 4-methoxyphenylboronic acid for example 2A and 4-chlorophenylboronic acid, respectively, in example 2B.

EXAMPLE 313B This example is prepared by substituting example 313A for example 2B in example 2C.

EXAMPLE 313 This example is prepared by substituting example 313B for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-de) d 8.54 (d, 1 H), 8.28 (d, 1 H), 7.87 (dd, 1 H), 7.78 (d, 2H), 7.23 (m, 2H), 7.14 (m, 4H), 7.05 (d, 2H), 6.85 (d, 2H), 6.91 (d, 2H), 4.19 (m, 1 H), 3.86 (m, 2H), 3.73 (s, 3H), 3.60 (m, 4H), 3.39 (d, 2H), 3.15 (m, 4H), 2.74 (m, 8H), 2.26 (s, 2H), 2.20 (s, 2H), 2.15 ( q, 2H), 1.70 (s, 4H).

EXAMPLE 314A This example is prepared by substituting example 312B and 4-fluorophenylboronic acid for example 2A and 4-chlorophenylboronic acid, respectively, in example 2B.

EXAMPLE 313B This example is prepared by replacing Example 314A with Example 2B in Example 2C.

EXAMPLE 314C This example is prepared by substituting example 313B for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 8.55 (d, 1 H), 8.29 (d, 1 H), 7.87 (dd, 1 H), 7.79 (d, 2 H), 7.23 (m, 2 H), 7.15 (m, 8H), 6.96 (d, 2H), 4.19 (m, 1 H), 3.86 (m, 4H), 3.60 (s, 2H), 3.39 (d, 2H), 3.15 (m, 4H), 2.77 (m, 8H), 2.27 (s, 2H), 2.22 (s, 2H), 2.15 (q, 2H), 1.72 (s, 4H).

EXAMPLE 315A This example is prepared by substituting example 307A and phenylboronic acid for example 2A and 4-chlorophenylboronic acid, respectively, in example 2B.

EXAMPLE 315B This example is prepared by substituting example 315A for example 2B in example 2C.

EXAMPLE 315C This example is prepared by substituting example 315B for example 2C in 2D. 1 H NMR (400 MHz, DMSO-d6) d 8.54 (d, 1 H), 8.29 (d, 1 H), 7.87 (dd, 1 H), 7.78 (d, 2H), 7.36 (m, 2H), 7.28 (m, 1 H), 7.21 (m, 2H), 7.13 (m, 6H), 6.95 (d, 2H), 4.19 (s, 1 H), 3.87 (s, 2H), 3.62 (m, 4H), 3.39 (d, 2H), 3.15 (m, 4H), 2.74 (m, 8H), 2.29 (s, 2H), 2.22 (s, 2H), 2.14 (q, 2H), 1.72 ( m, 4H).

EXAMPLE 316A This example is prepared by replacing 2-bromo-cyclo-oct-1-in-carbaldehyde with 2-bromo-cyclopent-1-ene-carbaldehyde in Example 306A.

EXAMPLE 316B This example is prepared by substituting example 316A for example 2A in example 2B.

EXAMPLE 316C This example is prepared by substituting example 316B for example 2B in example 2C.

EXAMPLE 316D This example is prepared by substituting example 316C for example 2C in example 2D. 1 H NMR (300 MHz, DMSO-d6) d 8.54 (d, 1 H), 8.30 (d, 1 H), 7.86 (dd, 1 H), 7.78 (d, 2H), 7.43 (d, 2H), 7.17 (m, 8H), 6.95 (d, 2H), 4.19 (m, 5H), 3.89 (m, 2H), 3.64 (s, 2H), 3.39 (m, 4H), 3.13 (m, 4H), 2.75 (s, 3H), 2.74 (s, 3H) ), 2.46 (m, 2H), 2.14 (q, 2H), 1.66 (m, 2H), 1.54 (m, 4H), 1.41 (m, 2H).

EXAMPLE 317A This example is prepared by substituting example 312B and 4-methylthiophenylboronic acid for example 2A and 4-chlorophenylboronic acid, respectively, in example 2B.

EXAMPLE 317B This example is prepared by substituting example 317A for example 2B in example 2C.

EXAMPLE 317C This example is prepared by substituting example 317B for example 2C in example 2D. 1 H NMR (300 MHz, DMSO-d6) d 8.54 (d, 1 H), 8.28 (d, 1 H), 7.86 (dd, 1 H), 7.78 (d, 2 H), 7.22 (m, 4 H), 7.1 1 (m, 6 H), 6.95 (d, 2 H), 4.17 (m, 1 H), 3.90 (m, 4H), 3.65 (m, 4H), 3.39 (d, 2H), 3.12 (m, 4H), 2.75 (s, 3H), 2.74 (s, 3H), 2.45 (s, 3H), 2.24 (m, 4H), 2.14 (q, 2H), 1.71 (m, 4H).

EXAMPLE 318A This example is prepared by substituting 2-bromo-cyclohept-1-in-carbaldehyde for 2-bromo-cyclopent-1-in-carbaldehyde in Example 306A.

EXAMPLE 318B This example is prepared by replacing Example 318A or Example 2A in Example 2B.

EXAMPLE 318C This example is prepared by substituting example 318B for example 2B in example 2C.

EXAMPLE 318D This example is prepared by substituting example 318C for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d6) d 8.54 (d, 1 H), 8.29 (d, 1 H), 7.86 (dd, 1 H), 7.78 (d, 2H), 7.40 (d, 2H), 7.22 (m, 2H), 7.14 (m, 6H), 6.95 (d, 2H), 4.19 (m , 1 H), 3.87 (s, 2H), 3.61 (m, 2H), 3.39 (m, 4H), 3.1 5 (m, 4H), 2.75 (m, 8H), 2.46 (m, 4H), 2.14 ( m, 2H), 1.80 (m, 2H), 1.56 (m, 4H).

EXAMPLE 319 This example is prepared by replacing Example 318C and 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) p ropil) amino) -3-nitrobenzenesulfonamide by Example 2C and 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.55 (d, 1 H), 8.29 (d, 1 H), 7.87 (dd, 1 H), 7.78 (d, 2 H), 7.40 (d, 2 H), 7.22 (m, 3H), 7.14 (m, 6H), 6.93 (d, 2H), 4.20 (m, 1 H), 3.91 (m, 4H), 3.39 (m, 6H), 3.18 (m, 6H), 3.03 (m, 2H), 2.79 (m, 2H), 2.45 (m, 4H), 2.16 (q, 2H), 1.81 (m, 2H), 1.56 (m, 4H).

EXAMPLE 320A This example is prepared by substituting 4,4-dimethyl-cyclohexanone for tetrahydro-pyran-4-one in Example 312A.

EXAMPLE 320B This example is prepared by substituting 320A for 2-bromo-cyclopent-1-in-carbaldehyde in Example 306A.

EXAMPLE 320C This example is prepared by substituting example 320B for example 2A in example 2B.

EXAMPLE 320D This example is prepared by substituting example 320C for example 2B in example 2C.

EXAMPLE 320E This example is prepared by substituting example 320D for example 2C in example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.54 (d, 1 H), 8.28 (d, 1H), 7.86 (dd, 1H), 7.79 (d, 2H), 7.41 (m, 2H), 7.23 (m, 2H), 7.14 (m, 6H), 6.95 (d, 2H), 4.19 (m, 1H) ), 3.90 (m, 1H), 3.39 (d, 2H), 3.15 (s, 6H), 2.74 (m, 8H), 2.54 (m, 3H), 2.28 (m, 2H), 2.14 (q, 2H) , 2.03 (s, 2H), 1.47 (t, 2H), 0.98 (s, 6H).

EXAMPLE 321 This example is prepared by substituting example 320D and 4 - (((1R) -3- (4-morpholin) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide for example 2C and 4 - (((1R) -3- (di metilami no) - 1 - ((phenylsulfonyl) methyl) propiI) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.54 (d, 1 H), 8.29 (d, 1H), 7.87 (dd, 1H), 7.78 (d, 2H), 7.41 (m, 2H), 7.22 (m, 2H), 7.14 (m, 6H), 6.95 (d, 2H), 4.20 (m, 1H) ), 3.93 (m, 2H), 3.57 (m, 4H), 3.39 (m, 6H), 3.19 (m, 4H), 3.02 (m, 2H), 2.81 (m, 2H), 2.53 (s, 2H) , 2.27 (m, 2H), 2.17 (q, 2H), 2.01 (s, 2H), 1.47 (t, 2H), 0.98 (s, 6H).

EXAMPLE 322A A mixture of example 32A (1 g) and 60% oily sodium hydride (0.30 g) in toluene (15 ml) is refluxed for 1 hour, treated with 4- (2-chloroethyl) morpholine (2 g). it is refluxed for 18 hours, treated with aqueous NH Cl and extracted with ethyl acetate. The extract is washed with water and brine and dried (Na 2 SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5-15% 7M NH3 in methanol / dichloromethane.

EXAMPLE 322B This example is prepared by substituting example 322A and phenylboronic acid for Example 32B and 4-chlorophenylboronic acid, respectively, in Example 32C.

EXAMPLE 322C This example is prepared by substituting example 322B for example 1B in example 1C.

EXAMPLE 322D This example is prepared by substituting example 322C and 4- (1,1-dimethyl-2-phenylsulfanylethylamino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (((1 R) -3- (dimethylamine ) -1 ~ ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 11.76 (s, 1 H), 11.08 (m, 1 H), 10.02 (m, 1 H), 8.30 (s, 1 H), 8.28 (d, 1 H), 7.88 (t, 2H), 7.61 (dd, 1H), 7.50 (d, 2H), 7.11 (m, 8H), 6.75 (m, 5H), 6.63 (d, 1H), 3.67 (m, 6H), 3.12 (m, 4H) ), 2.78 (m, 10H), 1.52 (m, 4H), 1.34 (s, 6H).

EXAMPLE 323 This example is prepared by replacing example 322C and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1 R) -3- (dimethylamino) -1- ((phenylsuifanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400 MHz, DMSO-de) d 11.76 (s, 1 H), 11.16 (m, 1 H), 10.08 (m, 1 H), 8.53 (t, 1 H), 8.36 (d, 1 H), 7.68 (dd, 1 H), 7.47 (d, 2H), 7.07 (m, 16H), 6.62 (d, 1 H), 3.55 (m, 4H), 3.45 (m, 4H), 2.95 (m, 12H) , 1.52 (m, 2H), 1.26 (m, 2H), 1.00 (m, 2H).

EXAMPLE 324A This example is prepared by substituting 1- (2-chloroethyl) pyrrolidine for 4- (2-chloroethyl) morpholine in Example 322A.

EXAMPLE 324B This example is prepared by substituting example 324A and phenylboronic acid for Example 32B and 4-chlorophenylboronic acid, respectively, in Example 32C.

EXAMPLE 324C This example is prepared by substituting example 324B for example 1 B in example 1 C.

EXAMPLE 324D This example is prepared by substituting example 324C and 4- (1,1-dimethyl-2-phenylsulfanylethylamino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (( (1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.06 (s, 1H), 10.39 (m, 1H), 8.50 (d, 2H), 7.82 (dd, 1H), 7.71 (d, 2H), 7.33 (m, 10H), 7.16 (dd, 1H), 6.99 (t, 2H), 6.91 (t, 1H), 6.82 (d, 2H), 3.62 (m, 2H), 3.38 (m, 6H), 3.28 (m, 2H), 2.96 (m, 6H), 1.93 (m, 2H), 1.82 (m, 2H), 1. 55 (s, 6H), 1.48 (m, 2H), 1.20 (m, 2H).

EXAMPLE 325 This example is prepared by substituting example 324C and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-de) d 11.95 (s, 1 H), 10.46 (m, 1 H), 8.74 (t, 1 H), 8.58 (d, 1 H), 7.90 (m, 1 H), 7.67 (d, 2H), 7.28 (m, 14H), 6.81 (d, 2H), 3.66 (m, 2H), 3.38 (m, 6H), 3.27 (m, 4H), 2.98 (m, 6H), 1.93 (m, 2H) ), 1.82 (m, 2H), 1.48 (m, 2H), 1.19 (m, 2H).

EXAMPLE 326 This example is prepared by substituting example 324C and example 264B for example 2C and 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively , in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 1 1 .97 (s, 1 H), 10.65 (m, 1 H), 8.47 (s, 1 H), 8.41 (d, 1 H), 7.82 (dd) , 1 H), 7.73 (d, 2H), 7.27 (m, 10H), 6.81 (m, 6H), 3.63 (m, 2H), 3.35- (m, 6H), 2.96 (m, 6H), 1.90 ( m, 12H), 1.48 (m, 2H), 1.20 (m, 2H).

EXAMPLE 327A This example is prepared by substituting 2- (dimethylamino) ethyl chloride for 4- (2-chloroethyl) morpholine in Example 322A.

EXAMPLE 327B This example is prepared by substituting example 327A and phenylboronic acid for Example 32B and 4-chlorophenylboronic acid, respectively, in Example 32C.

EXAMPLE 327C This example is prepared by substituting example 327B for example 1 B in example 1 C.

EXAMPLE 327D This example is prepared by substituting example 327C and 4- (1,1-dimethyl-2-phenylsulfanylethylamino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (( (1R) -3- (dimethylamine) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzene sulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.75 (s, 1 H), 10.00 (m, 1 H), 8.28 (s, 1 H), 8.27 (d, 1 H), 7.60 (dd, 1 H), 7.48 (d, 2H), 7.10 (m, 10H), 6.83 (d, 1H), 6.77 (t, 2H), 6.68 (t, 1H), 6.60 (d, 2H), 3.63 (m, 2H), 3.29 (m, 6H), 2.85 (m, 6H), 1.51 (m, 1H), 1.33 (s, 6H), 1.25 (m, 2H), 1.08 (m, 1H), 1.0 (m, 2H).

EXAMPLE 328 This example is prepared by substituting example 327C and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- (((1R) -3- (dimethylamino) -1- ((f-enyl-sulfonyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.71 (s, 1 H), 9.86 (m, 1H), 8.51 (t, 1H), 8.35 (s, 1H), 7.65 (dd, 1H), 7.44 (d, 2H), 7.15 (m, 14H), 6.58 (d, 2H), 3.43 (m, 2H ), 3.13 (m, 2H), 3.13 (t, 2H), 3.03 (m, 6H), 2.76 (m, 6H), 1.51 (m, 1H), 1.24 (m, 2H), 0.97 (m, 2H) .

EXAMPLE 329 This example is prepared by substituting example 327C and example 264B for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylisulfaniI) methyl) propiI) amino) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 11.72 (s, 1 H), 9.75 (m, 1 H), 8.23 (s, 1 H), 8.17 (d, 1 H), 7.58 (dd, 1 H), 7.11 (m, 10H), 6.94 (d, 1H), 6.90 (d, 2H), 6.58 (d, 2H), 6.57 (d, 1H), 3.38 (m, 2H), 3.15 (m, 2H), 2.98 (m, 2H), 2.74 (m, 4H), 2.50 (s, 3H), 2.49 (s, 3H), 1.85 (m, 4H), 1.76 (m, 4H), 1.47 (m, 2H), 1.24 (m, 2H), 0.97 (m, 2H).

EXAMPLE 330A This example is prepared by substituting 1- (2-chloroethyl) piperidine for 4- (2-chloroethyl) morpholine in Example 322A.

EXAMPLE 330B This example is prepared by substituting Example 330A and phenylboronic acid for example 32B and 4-chlorophenylboronic acid, respectively, in Example 32C.

EXAMPLE 330C This example is prepared by substituting example 330B for example 1B in example 1C.

EXAMPLE 330D This example is prepared by replacing Example 330C and 4- (1,1-dimethyl-2-phenylsulfanylethylamino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (( (1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.87 (s, 1 H), 10.27 (m, 1 H), 8.51 (s, 1 H), 8.48 (d, 1 H), 7.82 (dd, 1 H), 7.72 (d, 2H), 7.33 (m, 10H), 7.16 (d, 1H), 6.99 (t, 2H), 6.91 (t, 1H), 6.82 (d, 2H), 3.37 (m, 2H), 3.17 (m, 2H) ), 3.03 (s, 2H), 2.95 (m, 8H), 1.73 (m, 6H), 1.55 (s, 6H), 1.50 (m, 2H), 1.30 (m, 2H), 1.19 (m, 2H) .

EXAMPLE 331 This example is prepared by replacing Example 330C and 3-Nitro-4 - ((2- (phenylisulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.85 (s, 1 H), 10.16 (m, 1 H), 8.74 (t, 1 H), 8.58 (s, 1 H), 7.88 (dd, 1 H), 7.67 (d, 2H), 7.28 (m, 14H), 6.81 (d, 2H), 3.66 (m, 2H), 3.37 (m, 2H), 3.27 (t, 2H), 3.17 (m, 2H), 2.85 (m, 8H ), 1.73 (m, 4H), 1.63 (m, 2H), 1.49 (m, 2H), 1.30 (m, 2H), 1.19 (m, 2H).

EXAMPLE 332 This example is prepared by substituting example 330C and example 264B for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 11.97 (s 1 H), 10.27 (m, 1H), 8.47 (s, 1H), 8.40 (d, 1H), 7.82 (dd, 1H), 7.74 (d, 2H), 7.27 (m, 13H), 6.80 (m, 3H), 3.67 (m, 2H) ), 3.37 (m, 2H), 3.17 (m, 2H), 3.03 (s, 2H), 2.92 (m, 6H), 2.09 (m, 2H), 1.98 (m, 2H), 1.70 (m, 10H) , 1.49 (m, 2H), 1.30 (m, 2H), 1.19 (m, 2H).

EXAMPLE 333A This example is prepared by substituting (S) -3- (benzyloxycarbonyl) aminobutyrolactone, which is prepared as described in J. Am. Chem. Soc. 1986, 108, 4943-4952, by (R) -3- (benzyloxycarbonyl) aminobutyrolactone in example 19A.

EXAMPLE 333B This example is prepared by substituting example 333A for example 18A in example 18B.

EXAMPLE 333C This example is prepared by substituting example 333B for example 18B in example 18C.

EXAMPLE 333D This example is prepared by substituting example 333C for example 19C in example i D.

EXAMPLE 333E This example is prepared by substituting example 333D for example 18C in example 18E.

EXAMPLE 333F This example is prepared by substituting example 1 C and example 333E for example 2C and 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in the example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 1 1 .86 (s, 1 H), 1 1 .20 (m, 1 H), 1 1 .07 (m, 1 H), 9.87 (m, 1 H), 8.30 (d, 1 H), 8.05 (2, 1 H), 7.87 (dd, 1 H), 7.60 (t, 1 H), 7.53 (d, 2H), 7.06 (m, 13H), 6.69 (d, 2H), 4. 12 (s, 2H), 3.62 (m, 4H), 3.1 1 (m, 5H), 2.95 (m, 4H), 2.78 (m, 8H), 1.51 (m, 2H).

EXAMPLE 334A This example is prepared by substituting 4-hydroxyphenylboronic acid for 4-chlorophenylboronic acid in Example 2B.

EXAMPLE 334B A mixture of Example 334A (0.24 g), 2- (dimethylamino) ethyl chloride (0.22 g), and K2CO3 (0.5 g) in acetone (20 ml) at reflux is stirred for 18 hours, concentrated, and treated with ethyl acetate and water. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% 7M NH3 in methanol / dichloromethane.

EXAMPLE 334C This example is prepared by substituting example 334B for example 1B in example 1C.

EXAMPLE 334D This example is prepared by substituting example 334C for example 2C in example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.12 (s, 1 H), 11.55 (m, 1H), 10.88 (m, 1H), 10.70 (m, 1H), 8.54 (d, 1H), 8.29 (d, 1H), 8.11 (dd, 1H), 7.78 (d, 2H), 7.49 (t, 2H) ), 7.20 (m, 10H), 6.93 (d, 2H), 4.42 (t, 2H), 4.36 (s, 2H), 4.29 (m, 1H), 3.86 (m, 2H), 3.52 (m, 2H) , 3.39 (m, 2H), 3.13 (m, 6H), 2.82 (s, 3H), 2.83 (s, 3H), 2.70 (m, 8H), 2.20 (m, 2H).

EXAMPLE 335 This example is prepared by substituting example 334C and 4 - (((1R) -3- (4-morpholinyl) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (((1R) -3- (dimethylamino) -l - ((phenylsulfanyl) methyl) p ropil) amino) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 12.11 (s, 1 H), 11.37 (m, 1 H), 11.19 (m, 1 H), 10.71 (m, 1 H), 8.53 (d, 1 H), 8.29 (d, 1H), 8.06 (dd, 1H), 7.85 (dd, 2H), 7.78 (d, 2H), 7.50 (t, 2H), 7.20 (m, 10H), 6.93 (d, 2H), 4.41 (t, 2H) ), 4.36 (s, 2H), 4.28 (m, 1H), 3.92 (m, 2H), 3.80 (t, 2H), 3.52 (m, 2H), 3.39 (m, 2H), 3.23 (m, 8H) , 2.98 (m, 2H), 2.84 (s, 6H), 2.25 (m, 2H).

EXAMPLE 336 This example is prepared by substituting example 334C and 4- (1,1-dimethyl-2-phenylsulfanyletylamine) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (( (1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.11 (s, 1 H), 11.47 (m, 1H), 10.83 (m, 1H), 10.23 (m, 1H), 8.53 (s, 1H), 8.51 (d, 1H), 8.10 (m, 1H), 7.83 (dd, 1H), 7.80 (d, 2H) ), 7.50 (t, 2H), 7.39 (d, 1H), 7.31 (m, 3H), 7.25 (d, 2H), 7.10 (d, 2H), 7.01 (t, 2H), 6.93 (m, 3H) , 4.41 (t, 2H), 4.36 (s, 2H), 3.86 (m, 2H), 3.38 (m, 2H), 3.20 (s, 2H), 3.23 (m, 2H), 2.98 (m, 2H), 3.01 (m, 4H), 2.84 (d, 3H), 2.73 (d, 3H), 1.56 (s, 6H).

EXAMPLE 337 This example is prepared by substituting example 334C and 3-nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4- ( ((1 R) -3- (dimethylamino) -1 - ((phenylisulfanyl) methyl) propyl) -amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d6) d 12.00 (s, 1 H), 1 1 .39 (m, 1 H), 10.73 (m, 1 H), 10.13 (m, 1 H), 8.76 (t, 1 H), 8.60 (d, 1 H), 8.07 (m, 1 H), 7.91 (dd, 1 H ), 7.76 (d, 2H), 7.50 (t, 2H), 7.25 (m, 10H), 7.00 (d, 2H), 6. 2 (d, 2H), 4.41 (t, 2H), 4.36 (s, 2H), 3.86 (m, 2H), 3.67 (m, 2H), 3.28 (m, 2H), 3.20 (s, 2H), 3.01 (m, 4H), 2.84 (d, 3H), 2.73 (d, 3H) ).

EXAMPLE 338A This example is prepared by substituting 4- (2-chloroethyl) morpholine for 2- (dimethylamino) ethyl chloride in Example 334B.

EXAMPLE 338B This example is prepared by substituting example 338A for example 1 B in example 1 C.

EXAMPLE 338C This example is prepared by substituting example 338B for example 2C in example 2D. H NMR (500 MHz, DMSO-d6) d 11.89 (s, 1H), 11.50 (m, 1H), 11.30 (m, 1H), 10.46 (m, 1H), 8.31 (d, 1H), 8.06 (d, 1H), 7.88 (m, 1H), 7.55 (d, 2H), 7.27 (t, 2H), 6.98 (m, 11H), 6.70 (d, 2H), 4.28 (t, 2H), 4.13 (s, 2H), 3.68 ( m, 4H), 3.33 (m, 2H), 3.28 (m, 2H), 3.06 (m, 6H), 2.78 (m, 6H), 2.48 (m, 6H), 1.97 (m, 2H).

EXAMPLE 339 This example is prepared by substituting example 338B and 4 - (((1 R) -3- (4-morpholinyl) -1 - ((phenylsulfani) methyI) propy) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by Example 2C and 4 - (((1R) -3- (di methyl amino) -1 - ((phenylsulfonyl) methyl) pro pil) am i no) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 11.88 (s, 1 H), 11.47 (m, 1 H), 11.28 (m, 1 H), 11.13 (m 1 H), 10.01 (m, 1 H), 8.30 (d, 1 H) ), 8.05 (d, 1H), 7.87 (m, 1H), 7.61 (dd, 1H), 7.54 (d, 2H), 7.26 (t, 2H), 6.96 (m, 11H), 6.70 (d, 2H) , 4.26 (t, 2H), 4.12 (s, 2H), 4.07 (m, 1H), 3.63 (m, 6H), 3.33 (m, 2H), 3.27 (m, 2H), 3.05 (m, 6H), 2.79 (m, 8H), 1.52 (m, 2H).

EXAMPLE 340 This example is prepared by substituting example 338B and 4- (1,1-dimethyl-2-phenylsulfanylethylamino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (( (1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.12 (s, 1 H), 11.83 (m, 1 H), 11.62 (m, 1 H), 10.43 (m, 1 H), 8.53 (s, 1 H), 8.51 (d, 1H), 8.12 (m, 1H), 7.83 (dd, 1H), 7.80 (d, 2H), 7.40 (t, 2H), 7.38 (d, 1H), 7.31 (m, 3H), 7.25 (d, 2H) ), 7.10 (d, 2H), 6.88 (t, 2H), 6.83 (m, 3H), 4.51 (t, 2H), 4.36 (s, 2H), 3.81 (m, 2H), 3.35 (m, 8H) , 3.02 (m, 8H), 1.56 (s, 6H).

EXAMPLE 341 This example is prepared by substituting example 338B and 3-Nitro-4 - ((2- (phenylsulfanyl) etiI) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (((1R) -3- ( dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (500 MHz, DMSO-d 6) d 12.08 (s, 1H), 11.67 (m, 1H), 11.46 (m, 1H), 10.24 (m, 1H), 8.76 (t, 1H), 8.60 (d, 1H), 8.10 (m, 1H), 7.81 (dd, 1H), 7.76 (d, 2H), 7.50 (t, 2H), 7.26 (m, 10H), 7.10 (d, 2H), 6.82 (d, 2H) ), 4.50 (t, 2H), 4.36 (s, 2H), 3.81 (m, 4H), 3.35 (m, 10H), 3.01 (m, 8H).

EXAMPLE 342A A mixture of Example 30B (1.2 g) and pyridine (3 mL) in dichloromethane (10 mL) at 25 ° C is treated with p-toluenesulfonyl chloride (0.572 g), stirred for 18 hours, treated with dichloromethane (150 ml), washed with 5% HCl, water, and brine, and dried (Na 2 SO), filtered, and concentrated.

EXAMPLE 342B A mixture of Example 342A (1.7g) and imidazole (0.42g) in DMF (25ml) at 60 ° C is stirred for 4 hours, treated with ethyl acetate (200ml), washed with NH CI aqueous , water, and brine, and dried (Na2SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexane and 5% methanol / dichloromethane.

EXAMPLE 342C This example is prepared by substituting Example 342B for 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d6) d 8.47 (d, 1 H), 8.17 (d, 1 H), 7.73 (m, 3 H), 7.65 (s, 1 H), 7.51 (dd, 1 H) , 7.37 (m, 2H), 7.19 (m, 10H), 6.83 (s, 1H), 6.82 (d, 2H), 6.63 (d, 1H), 4.08 (t, 2H), 3.87 (m, 1H), 3.31 (m, 8H), 3.15 (m, 4H), 2.23 (m, 2H).

EXAMPLE 343 This example is prepared by substituting Example 342B for 4 - (((1R) -3- (d-methylamino) -1 - ((phenylsulf to nyl) methyl) amino) -3-nitrobenzenesulfonamide in Example 1D.H NMR (500 MHz, DMSO-d6) d 8.11 (m, 1H), 8.06 (m, 1H), 8.53 (d, 1H), 8.23 (m, 2H), 8.08 (m, 1H), 7.82 (dd, 1H), 7.78 (d, 2H), 7.71 (t, 1H), 7.70 (d, 2H), 7.64 (t, 2H), 7.43 (m, 8H), 7.06 (m, 4H), 4.35 (s, 2H), 4.31 (t, 2H), 4.08 (m, 1H), 3.83 (m, 2H), 3.28 (m, 6H), 2.76 (m, 2H), 2.38 (m, 2H).

EXAMPLE 344 This example is prepared by substituting the example SOC and example 342B for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzene sulfonamide, respectively, in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 8.11 (m, 1 H), 8.06 (m, 2H), 8.53 (d, 2H), 8.22 (m, 2H), 7.82 (dd, 1H), 7.71 (m, 4H), 7.64 (t, 1H), 7.26 (m, 10H), 6.88 (t, 2H), 6.83 (d, 1H), 4.31 (t, 2H), 4.04 (m, 1H), 3.37 (m, 5H), 3.18 (s, 3H), 2.88 (m, 3H), 2.38 (m, 2H), 1.46 (m, 2H), 1.17 (m, 2H).

EXAMPLE 345 This example is prepared by substituting (R) -4- (4- (4-methyl-piperazin-1-yl) -1-phenylsulfanylmethyl-butylamino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02 / 24636, by 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonam in Example 2D. 1 H NMR (300 MHz, DMSO-d 6) d 12.12 (m, 1 H), 10.88 (m, 1 H), 8.53 (d, 1 H), 8.30 (d, 1 H), 8.05 (m, 1 H ), 7.86 (dd, 1 H), 7.78 (d, 2H), 7.54 (m, 3H), 7.24 (m, 10H), 6.S3 (d, 2H), 4.35 (s, 2H), 4.16 (m , 1 H), 3. SO (m, 2H), 3.28 (m, 8H), 2.80 (m, 8H).

EXAMPLE 346 This example is prepared by substituting 4 - (((1 R) -2 - ((2- (dimethylamino) ethyl) (methyI) amino) -1 - ((phenylsulfanyl) methyl) ethyl) amino) -3-nitrobenzenesulfonamide (which is prepared as described in WO 02/24636), by 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in the example 2D 1 H NMR (300 MHz, DMSO-d 6) d 12.14 (m, 1 H), 1 1 .08 (m, 1 H), 8.49 (d, 1 H), 8.34 (d, 1 H), 8.08 (m , 1 H), 7.86 (dd, 1 H), 7.78 (d, 2H), 7.54 (m, 3H), 7.24 (m, 10H), 6.93 (d, 2H), 4.34 (s, 2H), 3.87 ( m, 2H), 3.29 (m, 8H), 2.78 (m, 9H), 2.83 (m, 6H).

EXAMPLE 347 This example is prepared by substituting (4R) -4 - ((4- (aminosulfonyl) -2-n-troten iI) amino) -N, Nd-imethyl-5- (phenylsulfanyl) -pentanamide, which is prepared as described in WO 02/24636, by 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzene sulfonamide in Example 2D. 1 H NMR (300 MHz, DMSO-d 6) d 8.53 (d, 1 H), 8.31 (d, 1 H), 7.83 (d, 1 H), 7.73 (d, 2 H), 7.51 (m, 2 H), 7.24 (m, 12H), 6.90 (d, 2H), 4.12 (m, 1 H), 3.40 (m, 8H), 3.26 (m, 4H), 2.83 (s, 3H), 2.74 (s, 3H), 2.39 (m, 4H), 1.97 (m, 2H).

EXAMPLE 348A A mixture of (2E, 4R) -4 - ((tert-butoxycarbonyl) amino) -5- (phenylsulfanyl) pent-2-enoate of tert-butyl, which is prepared as described in WO02 / 24636, (14 g) and tris (triphenylphosphine) rhodium chloride (Wilkinson's catalyst) (2 g) in toluene (250 ml) at 45 ° C is stirred under hydrogen (balloon) for 48 hours, filtered through silica gel and concentrate EXAMPLE 348B Example 348A (6.3 g) in dichloromethane at 25 ° C is treated with mefa-chloroperbenzoic acid (8.8 g), stirred for 6 hours, poured into ethyl acetate, washed with aqueous sodium carbonate and brine, and concentrate The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 348C This example is prepared by substituting example 348B for example 1 B in example 1 C.

EXAMPLE 348D Example 348C (5.1 g), dimethylamine hydrochloride (2.33 g), EDAC HCI (8.21 g), DMAP (1.74 g), and TEA (3.97 ml) in dichloromethane (75 ml) at 25 ° C are stirred for 24 hours. hours, poured into water, and extracted with ethyl acetate. The extract is washed with water and brine and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10% methanol / ethyl acetate.

EXAMPLE 348E This example is prepared by substituting example 348D for example 18E in example 18F.

EXAMPLE 348F This example is prepared by substituting example 348E for example 21C in example 21D.

EXAMPLE 348G This example is prepared by replacing Example 348F with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amin or) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (300 MHz, DMSO-d 6) d 12.14 (m, 1H), 10.90 (m, 1H), 9.82 (m, 1H), 8.50 (d, 1H), 8.12 (d, 1H), 8.05 (m, 1H), 7.90 (dd, 1H), 7.80 (d, 2H), 7.45 (m, 12H), 6.93 (d, 2H), 4.35 (s, 2H), 4. 22 (m, 1H), 3.89 (m, 2H), 3.28 (m, 4H), 2.96 (m, 4H), 2.80 (m, 4H), 2.68 (m, 6H), 1.71 (m, 4H).

EXAMPLE 349 A mixture of example 26H (45 mg), 2-chloro-N, N-dimethylacetamide (50 mg), and DIEA (0.2 ml) in dioxane (1 ml) at 80 ° C is stirred for 18 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5% NH37M in methanol / dichloromethane. 1 H NMR (500 MHz, DMSO-d 6) d 12.13 (m, 1 H), 11.31 (m, 1 H), 9.58 (m, 1 H), 8.53 (d, 1 H), 8.28 (d, 1 H), 8.11 (m, 1H), 7.87 (m, 1H), 7.78 (d, 2H), 7.53 (m, 4H), 7.24 (m, 10H), 6.93 (d, 2H), 4.35 (s, 2H), 4.23 (m, 1H) ), 4.21 (s, 2H), 3.89 (m, 2H), 3.27 (m, 8H), 2.88 (m, 6H), 2.78 (s, 3H), 2.22 (m, 2H).

EXAMPLE 350 This example is prepared by substituting tert-butylamine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-de) d 12.03 (m, 1 H), 9.58 (m, 1 H), 8.70 (d, 1 H), 8.52 (d , 1H), 7.83 (dd, 1H), 7.77 (d, 2H), 7.67 (s, 1H), 7.53 (m, 4H), 7.25 (m, 10H), 6.93 (d, 2H), 4.37 (m, 2H), 3.89 (m, 2H), 2.98 (m, 8H), 2.62 (dd, 2H), 1.15 (s, 9H).EXAMPLE 351 This example is prepared by substituting di-isopropylamine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 12.08 (m, 1 H), 9.61 (m, 1 H), 8.79 (d, 1 H), 8.52 (d , 1H), 7.83 (dd, 1H), 7.77 (d, 2H), 7.54 (m, 3H), 7.25 (m, 10H), 6.93 (d, 2H), 4.41 (m, 2H), 3.96 (m, 3H), 2.g8 (m, 8H), 2.84 (m, 2H), 1.14 (m, 12H).

EXAMPLE 352 This example is prepared by substituting N-methyl-tert-butylamine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 12.05 (m, 1 H), S 5 S (m, 1 H), 8.80 (d , 1H), 8.53 (d, 1H), 7.83 (dd, 1H), 7.77 (d, 2H), 7.52 (m, 3H), 7.25 (m, 10H), 6.83 (d, 2H), 4.42 (m, 2H), 3.82 (m, 1H), 2.88 (m, 8H), 2.80 (s, 3H), 2.84 (m, 2H), 1.27 (s, SH).

EXAMPLE 353 This example is prepared by substituting N-methyl-isopropylamine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 12.07 (m, 1 H), 8.62 (m, 1 H), 8.82 (d, 1 H), 8.53 (d, 1H), 7.83 (dd, 1H), 7.77 (d, 2H), 7.25 (m, 10H), 6.83 (d, 2H), 4.61 (m, 1H), 4.43 (m, 2H), 4.05 ( m, 1H), 3.S2 (m, 1H), 2.88 (m, 8H), 2.72 (s, 3H), 2.84 (m, 2H), 0.88 (m, 6H).

EXAMPLE 354 This example is prepared by substituting piperidine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 12.06 (m, 1 H), 8.62 (m, 1H), 8.78 (d, 1H), 8.53 (d, 1H), 7.83 (dd, 1H), 7.77 (d, 2H), 7.52 (m, 3H), 7.25 (m, 10H), 6.83 (d, 2H) ), 4.44 (m, 2H), 3.88 (m, 1H), 3.35 (m, 4H), 2.99 (m, 8H), 3.00 (dd, 2H), 2.75 (dd, 2H), 1.42 (m, 6H) .

EXAMPLE 355A This example is prepared by substituting (5R) -5 - ((4- (aminosulfonyl) -2-nitrophenyl) amino) -6- (phenylsulfanyl) -hexylcarbamate tert -butyl (which is prepared as described in WO 02 / 24636), by 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylisulfanyl) methy1) propyI) amino) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 355B A mixture of Example 355A (100 mg) and TFA (1 mL) in dichloromethane (1 mL) at 25 ° C is stirred for 2 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 5-10% (7M NH3 in methanol) / dichloromethane.

EXAMPLE 355C A mixture of example 355B (50 mg), N, N-dimethylglycine (23 mg), EDAC HCI (42 mg) and DMAP (27.2 mg) in dichloromethane (2 ml) at 25 ° C is stirred for 18 hours, With ethyl acetate, wash with aqueous NaHCO3, water and brine, and dry (Na2SO4), filter, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 5-10% NH37M in methanol / dichloromethane. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1H), 11.53 (m, 1H), 8.S2 (m, 1H), 8.63 (t, 1H), 8.53 (d, 1H), 8.30 (d, 1H), 8.16 (m, 1H), 7.86 (dd, 1H), 7.77 (d, 2H), 7.52 (m, 3H), 7.22 (m, 8H), 6.83 (d, 2H), 4.33 (s, 2H), 4.10 (m, 1H) ), 3.85 (m, 2H), 3.37 (m, 4H), 3.12 (m, 8H), 2.84 (m, 6H), 1.76 (m, 2H), 1.34 (m, 4H).

EXAMPLE 356 This example is prepared by substituting dimethylamine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 8.83 (d, 1 H), 8.52 (d, 1 H), 7.83 (dd, 1 H), 7.74 (d, 2 H) ), 7.45 (m, 7H), 7.18 (m 6H), 6. SO (d, 2H), 4.40 (m, 1H), 3.40 (m, 4H), 3.25 (m, 4H), 2.86 (dd, 2H) ), 2.88 (s, 3H), 2.78 (s, 3H), 2.70 (dd, 2H), 2.45 (m 2H).

EXAMPLE 357 This example is prepared by substituting tiomorpholine 1,1-dioxide, which is prepared as described in J. Med. Chem 1994, 37, 913-933, by isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 8.52 (d, 1H), 8.47 (d, 1H), 7.80 (dd, 1H), 7.73 (d, 2H), 7.32 (m, 13H), 6.83 (d, 2H), 3.82 (m, 4H), 3.39 (m, 4H), 3.18 (m, 8H), 3.04 (m, 3H), 2.89 (dd, 2H), 2.40 (m, 2H).

EXAMPLE 357 This example is prepared by replacing 0.5M NH3 in dioxane with isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d6) d 8.57 (d, 1H), 8.46 (d, 1H), 7.79 (dd, 1H), 7.73 (d, 2H), 7.32 (m, 13H), 6.83 (d, 2H), 4.33 (m, 2H), 3.39 (m, 2H), 3.33 (m, 2H) ), 3.18 (m, 5H), 2.60 (m, 4H), 2.40 (m, 2H).

EXAMPLE 359 This example is prepared by substituting cyclopropylamine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 8.60 (d, 1H), 8.48 (d, 1H), 8.11 (d, 1H), 7.80 (dd, 1H ), 7.73 (d, 2H), 7.32 (m, 12H), 6.83 (d, 2H), 4.32 (m, 2H), 3.39 (m, 2H), 3.34 (m, 2H), 3.20 (m, 5H) , 2.56 (m, 4H), 2.40 (m 2H), 0.54 (m, 2H), 0.29 (m, 2H).

EXAMPLE 360 This example is prepared by substituting cyclobutylamine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 8.63 (d, 1 H), 8.48 (d, 1H), 8.27 (d, 1H), 7.80 (dd, 1H), 7.73 (d, 2H), 7.32 (m, 12H), 6.85 (d, 2H), 4.33 (m, 2H), 4.10 (m, 1H) ), 3.40 (m, 2H), 3.38 (m, 2H), 3.20 (m, 5H), 2.57 (m, 4H), 2.40 (m 2H), 2.08 (m, 2H), 1.77 (m, 2H) ), 1.58 (m, 2H).

EXAMPLE 361 This example is prepared by substituting 1-methylpiperazine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 12.08 (m, 1 H), 10.52 (m, 1 H), 8.73 (m, 1 H) , 8.53 (d, 1 H), 7.84 (dd, 1 H), 7.76 (d, 2H), 7.53 (m 4H), 7.24 (m, 10H), 6.83 (d, 2H), 4.37 (m, 3H), 3.86 (m, 4H), 3.28 (m, 6H), 3.20 (m, 5H), 2.88 (m, 4H), 2.75 (m 3H), 2.54 (m, 2H).

EXAMPLE 362 This example is prepared by substituting morpholine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d6) d 8.68 (d, 1 H), 8.50 (d, 1 H), 7.81 (dd, 1 H), 7.73 (d, 2H), 7.32 (m, 12H), 6.86 (d, 2H), 4.38 (m, 2H), 3.44 (m, 13H), 3.32 (m, 2H), 2.98 (dd, 2H), 2.77 ( dd, 2H), 2.40 (m, 2H).

EXAMPLE 363 This example is prepared by substituting azetidine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 8.71 (d, 1H), 8.50 (d, 1H), 7.81 (dd, 1H), 7.73 (d, 2H), 7.31 (m, 12H), 6.86 (d, 2H), 4.31 (m, 1H), 4.04 (t, 2H), 3.78 (m, 2H), 3.40 (m, 4H), 3.23 (m, 4H), 2.64 (dd, 2H), 2.52 (dd, 2H) ), 2.40 (m, 2H), 2.12 (m, 2H).

EXAMPLE 364 This example is prepared by substituting 4- (2-aminoethyl) morpholine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 12.10 (m, 1 H), 10.52 (m, 1H), 8.74 (d, 1H), 8.51 (d, 1H), 8.45 (t, 1H), 7.83 (dd, 1H), 7.77 (d, 2H), 7.54 (m, 3H), 7.24 (m, 10H) ), 6.S2 (d, 2H), 4.40 (m, 1H), 4.35 (m, 2H), 3.88 (m, 4H), 3.72 (m, 4H), 3.38 (m, 6H), 3.20 (m, 4H), 3.10 (m, 2H), 2.88 (m, 2H), 2.73 (m, 2H).

EXAMPLE 365 This example is prepared by substituting methylamine for isopropylamine in Example 28. 1 H NMR (300 MHz, DMSO-d 6) d 8.59 (d, 1 H), 8.45 (d, 1H), 7.98 (m, 1H), 7.78 (dd, 1H), 7.73 (d, 2H), 7.32 (m, 12H), 6.83 (d, 2H), 4.30 (m, 1H), 3.39 (s, 2H) ), 3.29 (m, 2H), 3.18 (m, 4H), 2.61 (m, 4H), 2.53 (d, 3H), 2.40 (m, 2H).

EXAMPLE 366 This example is prepared by substituting 7M NH3 in methanol for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 8.43 (d, 1 H), 8.08 (d, 1H), 7.83 (dd, 1H), 7.72 (d, 2H), 7.31 (m, 12H), 6.83 (m, 1H), 6.78 (d, 2H), 4.10 (m, 2H), 3.38 (s, 2H) ), 3.33 (m, 2H), 3.12 (m, 5H), 2.87 (t, 2H), 2.40 (m, 2H), 2.00 (m, 2H).

EXAMPLE 367 This example is prepared by substituting sodium cyanide for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 8.51 (d, 1H), 8.22 (d, 1H), 7.83 (dd, 1H), 7.74 (d, 2H), 7.31 (m, 12H), 7.04 (d, 1H), 6.87 (d, 2H), 4.11 (m, 2H), 3.35 (m, 4H), 3.22 (m, 5H), 2.60 (t, 2H), 2.38 (m, 2H), 2.08 (m, 2H) ).

EXAMPLE 368 This example is prepared by substituting tert-butylamine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.94 (m, 1H), 8.75 (m, 1H), 8.53 (d, 1H), 8.30 (d, 1H), 8.05 (m, 1H), 7.87 (dd, 1H), 7.78 (d, 2H), 7.53 (m, 4H) ), 7.23 (m, 10H), 6.93 (d, 2H), 4.34 (m, 2H), 3.88 (m, 2H), 3.42 (d, 2H), 3.27 (m, 5. H), 2.88 (m, 4H), 2.14 (m, 2H), 1.24 (s, 9H).

EXAMPLE 369 This example is prepared by substituting cyclopropylamine for isopropylamine in Example 35B. H NMR (300 MHz, DMSO-d6) d 12.11 (m, 1H), 10.84 (m, 1H), 8.04 (m, 1H), 8.53 (d, 1H), 8.30 (d, 1H), 8.02 (m, 1H), 7.86 (dd, 1H), 7.78 (d, 2H), 7.53 (m, 4H) ), 7.24 (m, 8H), 6.83 (d, 2H), 4. 35 (m, 3H), 3.88 (m, 2H), 3.27 (m, 5H), 3.08 (m, 2H), 2.87 (m, 2H), 2.66 (m, 2H), 2.14 (m, 2H), 0.82. (m, 2H), 0.70 (m, 2H).

EXAMPLE 370 This example is prepared by substituting cyclobutylamine for iopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.88 (m, 1H), 8.04 (m, 1H), 8.53 (d, 1H), 8.27 (d, 1H), 8.04 (m, 1H), 7.86 (dd, 1H), 7.78 (d, 2H), 7.53 (m, 4H) ), 7.24 (m, 8H), 6.83 (d, 2H), 4. 35 (m, 3H), 3.88 (m, 2H), 3.61 (m, 2H), 3.27 (m, 6H), 2.86 (m, 4H), 2.71 (m, 1H), 2.11 (m, 4H), 1.76 (m, 2H).

EXAMPLE 138 This example is prepared by substituting diethylamine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.88 (m, 1 H), 10.08 (m, 1 H), 8.53 (d, 1 H), 8.28 (d, 1 H), 8.06 (m, 1H), 7.86 (dd, 1H), 7.78 (d, 2H), 7.53 (m, 4H), 7.24 (m, 8H), 6.83 (d, 2H), 4.34 (m, 3H), 3.88 (m, 2H) ), 3.38 (m, 2H), 3.27 (m, 6H), 3.08 (m, 4H), 2.81 (m, 2H), 2.15 (m, 2H), 1.17 (m, 6H).

EXAMPLE 372 This example is prepared by substituting N-methylisopropylamine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.88 (m, 1H), 8.86 (m, 1H), 8.53 (d, 1H), 8.2S (m, 1H), 8.04 (m, 1H), 7.85 (dd, 1H), 7.78 (d, 2H), 7.53 (m, 4H), 7.24 (m, 8H), 6.83 (d, 2H), 4.34 (m, 3H), 3.88 (m, 2H), 3.42 (m, 2H), 3.27 (m, 6H), 2.86 (m, 2H) ), 2.60 (m, 3H), 2.15 (m, 2H), 1.19 (m, 6H).

EXAMPLE 373 This example is prepared by substituting N-methyl-tert-butylamine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.10 (m, 1 H), 10.84 (m, 1 H), S.70 (m, 1 H), 8.53 (d, 1 H), 8.30 (t, 1 H), 8.03 ( m, 1H), 7.85 (dd, 1H), 7.78 (d, 2H), 7.52 (m, 4H), 7.23 (m, 8H), 6.S3 (d, 2H), 4.35 (m, 3H), 3.88 (m, 2H), 3.43 (m, 2H), 3.27 (m, 6H), 2.86 (m, 2H), 2.64 (m, 3H), 2.22 (m, 2H), 1.28 (d, 9H).

EXAMPLE 374 This example is prepared by substituting piperidine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.10 (m, 1 H), 10.85 (m, 1H), S.S7 (m, 1H), 8.53 (d, 1H), 8.28 (d, 1H), 8.04 (m, 1H), 7.85. (dd, 1H), 7.78 (d, 2H), 7.54 (m, 4H), 7.23 (m, 8H), 6.83 (d, 2H), 4. 35 (m, 2H), 4.22 (m, 1H), 3.88 (m, 2H), 3.40 (m, 2H), 3.27 (m, 6H), 3.10 (m, 2H), 2.81 (m, 6H), 2.22 (m, 2H), 1.75 (m, 4H), 1.35 (m, 2H).

EXAMPLE 375 This example is prepared by substituting 4-hydroxypiperidine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.10 (m, 1 H), 10.85 (m, 1 H), 8.38 (m, 1 H), 8.53 (d, 1 H), 8.28 (d, 1 H), 8.04 (m, 1H), 7.85 (dd, 1H), 7.78 (d, 2H), 7.54 (m, 4H), 7.24 (m, 8H), 6.83 (d, 2H), 4. 36 (m, 2H), 4.22 (m, 1H), 3.83 (m, 3H), 3.27 (m, 6H), 3.10 (m, 2H), 2.87 (m, 4H), 2.22 (m, 2H), 1.91 (m, 4H), 1.70 (m, 2H).

EXAMPLE 376 This example is prepared by substituting 1-acetylpiperazine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.10 (m, 1 H), 10.69 (m, 1 H), 8.53 (d, 1 H), 8.28 (d, 1 H), 7.99 (m, 1 H), 7.85 (dd, 1H), 7.78 (d, 2H), 7.54 (m, 4H), 7.23 (m, 8H), 6.93 (d, 2H), 4.36 (m, 2H), 4.22 (m, 1H), 3.92 (m, 2H) ), 3.41 (m, 4H), 3.27 (m, 6H), 3.00 (m, 2H), 2.85 (m, 6H), 2.22 (m, 2H), 2.02 (s, 3H).

EXAMPLE 377 This example is prepared by substituting thiomorpholine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.10 (m, 1 H), 10.69 (m, 1H), 10.55 (m, 1H), 8.53 (d, 1H), 8.28 (d, 1H), 7.99 (m, 1H), 7.85 (dd, 1H), 7.78 (d, 2H), 7.53 (m, 4H) ), 7.25 (m, 8H), 6.93 (d, 2H), 4.36 (m, 2H), 4.25 (m, 1H), 3.90 (m, 2H), 3.64 (m, 4H), 3.41 (m, 4H) , 3.17 (m, 9H), 2.82 (m, 4H), 2.22 (m, 2H).

EXAMPLE 378 This example is prepared by substituting 4- (2-aminoethyl) morphoin for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.63 (m, 1 H), 8.26 (m, 1 H), 8.53 (d, 1 H), 8.29 (d, 1 H), 7.99 (m, 1H), 7.86 (dd, 1H), 7.78 (d, 2H), 7.53 (m, 4H), 7.25 (m, 8H), 6.93 (d, 2H), 4.36 (m, 2H), 4.25 (m, 1H) ), 3.90 (m, 2H), 3.77 (m, 2H), 3.41 (m, 4H), 3.27 (m, 6H), 3.05 (m, 6H), 2.82 (m, 4H), 2.17 (m, 2H) .

EXAMPLE 379A This example is prepared by substituting tert-butyl 1-piperazine-carboxylate for isopropylamine in Example 35B.

EXAMPLE 379B This example is prepared by substituting example 379A for example 27B in example 29A. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.90 (m, 1H), 9.50 (m, 1H), 8.53 (d, 1H), 8.30 (d, 1H), 8.04 (m, 1H), 7.84 (dd, 1H), 7.78 (d, 2H), 7.53 (m, 4H) ), 7.22 (m, 8H), 6.93 (d, 2H), 4.36 (m, 2H), 4.27 (m, 1H), 3.90 (m, 2H), 3.40 (m, 6H), 3.17 (m, 10H) , 2.86 (m, 2H), 2.23 (m, 2H).

EXAMPLE 380 This example is prepared by substituting (S) -3-hydroxypyrrolidine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.73 (m, 1 H), 10.26 (m, 1 H), 8.53 (d, 1 H), 8.20 (d, 1 H), 8.04 (m, 1H), 7.85 (m, 1H), 7.78 (d, 2H), 7.53 (m, 4H), 7.24 (m, 8H), 6.83 (d, 2H), 4.35 (m, 3H), 3.88 (m, 2H) ), 3.38 (m, 4H), 3.17 (m, 6H), 3.03 (m, 1H), 2.87 (m, 4H), 2.17 (m, 2H), 1.91 (m, 2H).

EXAMPLE 381A This example is prepared by substituting 3 (R) - (tert-butoxycarbonylamino) pyrroidine for isopropylamine in Example 35B.

EXAMPLE 381B This example is prepared by substituting example 381A for example 27B in example 29A. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1H), 11.09 (m, 1H), 10.92 (m, 1H), 8.53 (d, 1H), 8.47 (m, 1H), 8.30 (d, 1H), 8.04 (m, 1H), 7.85 (m, 1H), 7.78 (d, 2H), 7.53 (m, 4H), 7.23 (m, 8H), 6. 93 (d, 2H), 4.35 (m, 3H), 3.88 (m, 2H), 3.40 (m, 4H), 3.27 (m, 6H), 3.08 (m, 1H), 2.86 (m, 4H), 2.22 (m, 2H), 2.05 (m, 2H).

EXAMPLE 382 This example is prepared by substituting 3-hydroxyazetidine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.10 (m, 1 H), 10.73 (m, 1H), 10.23 (m, 1H), 8.53 (d, 1H), 8.27 (d, 1H), 8.00 (m, 1H), 7.85 (dd, 1H), 7.78 (d, 2H), 7.52 (m, 4H), 7.24 (m, 8H), 6.93 (d, 2H), 4. 35 (m, 2H), 4.26 (m, 3H), 4.04 (m, 1H), 3.88 (m, 2H), 3.71 (m, 2H), 3.24 (m, 8H), 2.86 (m, 2H), 1.98 (m, 2H).

EXAMPLE 383 This example is prepared by substituting 1-methylpiperazine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.91 (m, 1H), 8.53 (d, 1H), 8.31 (d, 1H), 8.04 (m, 1H), 7.85 (dd, 1H), 7.78 (d, 2H), 7.54 (m, 4H), 7.24 (m, 8H), 6.93 (d, 2H), 4.34 (m, 2H), 4.26 (m, 1H), 3.88 (m, 2H), 3.40 (m, 6H), 3.27 (m, 8H), 2.86 (m, 4H), 2.80 (s, 3H), 2.21 (m, 2H).

EXAMPLE 384 This example is prepared by substituting tiomorpholine 1,1-dioxide, which is prepared as described in J. Med. Chem 1994, 37, 913-933, by isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.08 (m, 1H), 10.97 (m, 1H), 8.53 (d, 1H), 8.31 (d, 1H), 8.04 (m, 1H), 7.86 (dd, 1H), 7.77 (d, 2H), 7.53 (m, 4H), 7.23 (m, 8H), 6.93 (d, 2H), 4.35 (m, 2H), 4.26 (m, 2H), 3.88 (m, 2H), 3.55 (m, 5H) ), 3.24 (m, 8H), 2.8g (m, 4H), 1.98 (m, 2H).

EXAMPLE 385 This example is prepared by substituting 3,4-methylenedioxianiline for isopropylamine in Example 35B. 1 H NMR (400 MHz, DMSO-d 6) d 12.09 (m, 1H), 11.29 (m, 1H), 8.53 (d, 1H), 8.28 (d, 1H), 8.12 (m, 1H), 7.82 (dd, 1H), 7.77 (d, 2H), 7.53 (m, 4H), 7.24 (m, 9H), 6.93 (m, 4H), 6.07 (s, 2H), 4.35 (m, 2H), 4.26 (m, 2H) ), 3.28 (m, 9H), 2.85 (m, 4H), 2.15 (m, 2H).

EXAMPLE 386 This example is prepared by substituting 3,4-methylenedioxybenzylamine for isopropylamine in Example 35B. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (m, 1 H), 11.29 (m, 1H), 9.26 (m, 1H), 8.53 (d, 1H), 8.26 (d, 1H), 8.11 (m, 1H), 7.86 (dd, 1H), 7.77 (d, 2H), 7.53 (m, 4H), 7.24 (m, 9H), 6.g? (m, 4H), 6. 02 (s, 2H), 4.34 (m, 3H), 3.98 (m, 2H), 3.87 (m, 2H), 3.61 (m, 2H), 3.28 (m, 4H), 2.91 (m, 4H), 2.16 (m, 2H).

EXAMPLE 387 This example is prepared by substituting 2-aminomethylpyridine for isopropylamine in Example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 12.11 (m, 1 H), 11.57 (m, 1H), 9.46 (m, 3H), 8.53 (d, 1H), 8.26 (d, 1H), 8.11 (m, 1H), 7.86 (m, 1H), 7.78 (d, 2H), 7.51 (m, 4H), 7.24 (m, 9H), 6.g3 (d, 2H), 4.33 (m, 2H), 4.26 (m, 1H), 3.87 (m, 2H), 3.39 (m, 4H), 3.25 (m, 4H), 2.84 (m, 4H), 2.22 (m, 2H).

EXAMPLE 388 This example is prepared by substituting 2-aminoethylpyridine for isopropylamine in Example 35B. 1 H NMR (400 MHz, DMSO-d 6) d 12.10 (m, 1 H), 11.36 (m, 1H), 9.29 (m, 3H), 8.62 (d, 1H), 8.53 (d, 1H), 8.28 (d, 1H), 8.13 (m, 1H), 7.86 (d, 1H), 7.78 (d, 2H), 7.53 (m, 4H), 7.18 (m, 9H), 6.g3 (d, 2H), 4.33 (m, 2H), 3.87 (m, 2H), 3.31 (m, 7H), 3.05 (m, 4H), 2.84 (m, 4H), 2.18 (m, 2H).

EXAMPLE 389 This example is prepared by substituting 4-aminomethylpyridine for isopropylamine in Example 35B. 1 H NMR (400 MHz, DMSO-d 6) d 12.08 (m, 1H), 11.30 (m, 1H), 9.85 (m, 2H), 9.17 (m, 1H), 8.76 (d, 1H), 8.53 (d, 1H), 8.27 (d, 1H), 8.11 (m, 1H), 7.85 (d, 1H), 7.78 (d, 2H), 7.53 (m, 4H), 7.19 (m, 9H), 6.93 (d, 2H), 4.33 (m, 2H), 4.23 (m, 1H), 3.87 (m, 2H), 3.29 (m, 6H), 3.05 (m, 2H), 2.84 (m, 4H) ), 2.23 (m, 2H).

EXAMPLE 390 This example is prepared by substituting 4-aminomorpholine for isopropylamine in Example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 12.09 (m, 1H), 11.55 (m, 1H), 9.39 (m, 3H), 8.54 (d, 1H), 8.32 (d, 1H), 8.11 (m, 1H), 7.87 (d, 1H), 7.77 (d, 2H), 7.51 (m, 4H), 7.24 (m, 8H), 6.92 (d, 2H), 4.33 (m, 2H), 4.23 (m, 1H) ), 4.00 (m, 1H), 3.87 (m, 2H), 3.31 (m, 9H), 3.05 (m, 4H), 2.84 (m, 4H), 2.33 (m, 2H).

EXAMPLE 391 This example is prepared by substituting N-methyl-4-aminopyridine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.83 (m, 1H), 8.68 (m, 3H), 8.52 (d, 1H), 8.19 (t, 2H), 8.01 (m, 1H), 7.83 (d, 1H), 7.77 (d, 2H), 7.52 (m, 4H) ), 7.25 (m, 8H), 7.01 (d, 1H), 6.93 (d, 2H), 6.74 (m, 2H), 4.33 (m, 2H), 4.24 (m, 2H), 3.87 (m, 3H) , 3.36 (m 4H), 3.26 (m, 4H), 2.83 (d, 3H), 2.33 (m, 2H).

EXAMPLE 392 This example is prepared by substituting 3-aminopyridine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1 H), 10.80 (m, 1 H), 8.72 (m, 3 H), 8.52 (d, 1 H), 8.22 (d, 2 H), 7.99 (m, 1H), 7.83 (d, 1H), 7.77 (d, 2H), 7.52 (m, 4H), 7.19 (m, 8H), 7.02 (d, 1H), 6.93 (d, 2H), 6.59 (m, 1H) ), 4.52 (m, 2H), 4.33 (m, 2H), 4.12 (m, 1H), 3.87 (m, 2H), 3.36 (m 4H), 3.26 (m, 2H), 2.85 (d, 2H), 2.40 (m, 2H).

EXAMPLE 393 This example is prepared by substituting 2,6-dimethylpiperidine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.09 (m, 1H), 10.62 (m, 1H), 9.74 (m, 1H), 8.64 (m, 1H), 8.50 (d, 1H), 8.30 (d, 1H), 7.99 (m, 1H), 7.86 (d, 1H), 7.77 (d, 2H) ), 7.52 (m, 4H), 7.24 (m, 8H), 6.93 (d, 2H), 4.36 (m, 2H), 3.88 (m, 2H), 3.31 (m 9H), 2.85 (d, 4H), 2.15 (m, 2H), 1.79 (m, 2H), 1.64 (m, 4H), 1.26 (m, 6H).

EXAMPLE 394 This example is prepared by substituting cis-2,6-dimethylpiperidine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.10 (m, 1 H), 10.78 (m, 1 H), 9.80 (m, 1 H), 8.74 (m, 1 H), 8.50 (d, 1 H), 8.30 (d, 1H), 8.01 (m, 1H), 7.86 (d, 1H), 7.77 (d, 2H), 7.52 (m, 4H), 7.24 (m, 8H), 6.93 (d, 2H), 4.35 (m, 2H), 3.88 (m, 2H), 3.31 (m 9H), 2.85 (d, 4H), 2.15 (m, 2H), 1.79 (m, 2H), 1.64 (m, 4H), 1.26 (m, 6H).

EXAMPLE 395 This example is prepared by substituting 1 -aminopyrrolidine for isopropylamine in Example 35B. 1 H NMR (300 MHz, DMSO-d 6) d 12.12 (m, 1 H), 10.86 (m, 1 H), 8.73 (m, 1 H), 8.54 (d, 1 H), 8.32 (d, 1 H ), 8.02 (m, 1 H), 7.86 (d, 1 H), 7.77 (d, 2H), 7.52 (m, 4H), 7.25 (m, 8H), 6.93 (d, 2H), 4.36 (m, 2H), 4.22 (m, 1 H), 3.88 (m, 2H), 3.31 (m 10H), 2.85 (d, 4H), 2.32 (m, 2H), 2.1 1 (m, 4H).

EXAMPLE 396A A mixture of tert-butyl 4-oxo-1-piperidine carboxylate (2 g), methoxylamine hydrochloride (0.85 g), and potassium acetate (0.S8 g) in ethanol (40 ml) is stirred at reflux for 18 hours and concentrates. The concentrated material is treated with ethyl acetate (200 ml), washed with water and brine, and dried (Na 2 SO 4), filtered, and concentrated. The concentrated material is used without further purification.

EXAMPLE 396B A mixture of example 396A (2.1 g) and TFA (10 ml) in dichloromethane (10 ml) at 25 ° C is stirred for 4 hours and concentrated.

EXAMPLE 396C This example is prepared by replacing Example 396B with isopropylamine in Example 35B. H NMR (300 MHz, DMSO-d6) d 8.51 (d, 1H), 7.82 (dd, 1H), 7.72 (d, 2H), 7.52 (m, 4H), 7.32 (m, 10H), 6.87 (d, 2H), 4.17 (m, 1H), 3.71 (s, 3H), 3.32 (m, 10H) ), 2.73 (m, 2H), 2.40 (m, 6H), 2.25 (m, 4H), 1.91 (m, 2H).

EXAMPLE 397 A mixture of example 367 (80 mg), sodium azide (33 mg), and ammonium chloride (27 mg) in DMF (2 ml) at 110 ° C is stirred for 18 hours, treated with ethyl acetate (100 g). mi), washed with water and brine, dried (Na2SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 3% methanol / dichloromethane. 1 H NMR (300 MHz, DMSO-d 6) d 12.09 (m, 1H), 10.15 (m, 1H), 8.52 (d, 1H), 8.32 (d, 1H), 7.82 (dd, 1H), 7.78 (d, 2H), 7.52 (m, 4H), 7.24 (m, 8H), 6.93 (d, 2H), 4.37 (m, 2H), 4.20 (m, 1H), 3.71 (s, 3H), 3.28 (m, 5H) ), 2.08 (t, 2H), 2.83 (m, 2H), 2.23 (m, 2H).

EXAMPLE 398A This example is prepared by replacing 4-bromo-3-trifluoromethylbenzenesulfonamide with 4 - (((1R) -3- (dimethylamine) -1 - ((phenylsufinanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 398B A mixture of example 27B (2 g) and diethylamine (5 ml) in THF (20 ml) at 25 ° C is stirred for 18 hours and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 3% (7M NH3 in methanol) / dichloromethane.

EXAMPLE 398C This example is prepared by substituting example 398A and example 398B for example 164B and 164A, respectively, in example 164C.

EXAMPLE 398D This example is prepared by substituting example 398C for example 27D in example 27E.

EXAMPLE 398E This example is prepared by substituting example 388D for example 27E in example 34.

EXAMPLE 398F This example is prepared by substituting example 3S8E for example 34 in example 35A.

EXAMPLE 398G This example is prepared by substituting example 398F and di-isopropylamine for Example 35A and isopropylamine, respectively, in Example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 11.94 (m, 1H), 11.07 (m, 1H), 9.25 (m, 1H), 8.06 (m, 1H), 7.93 (d, 1H), 7.82 (dd, 1H), 7.74 (d, 2H), 7.51 (m, 4H), 7.27 (m, 8H), 6.93 (t, 2H), 6.08 (d, 1H), 4.33 (m, 2H), 4.00 (m, 1H), 3.87 (m, 2H), 3.55 (m, 4H), 3.28 (m, 4H), 2.90 (m, 4H), 2.17 (m, 2H), 1.22 ( m, 12H).

EXAMPLE 399 This example is prepared by substituting example 398F for example 35A in example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 11.95 (m, 1 H), 11.11 (m, 1H), 8.74 (m, 1H), 8.06 (m, 1H), 7.04 (d, 1H), 7.91 (s, 1H), 7.81 (dd, 1H), 7.74 (d, 2H), 7.51 (m, 4H), 7.26 (m, 6H), 6.g6 (d, 1H), 6. 91 (d, 2H), 5.9g (d, 1H), 4.33 (m, 2H), 4.03 (m, 1H), 3.87 (m, 2H), 3.31 (m, 5H), 2.88 (m, 6H), 2.07 (m, 2H), 1.18 (m, 6H).

EXAMPLE 400 This example is prepared by substituting diethanolamine for isopropylamine in Example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 8.58 (d, 1H), 8.30 (m, 1H), 8.01 (s, 1H), 7.93 (dd, 1H), 7.82 (d, 2H), 7.41 (m, 11H), 7.10 (d, 1H), 6.93 (d, 2H), 4.50 (m, 1H), 4.23 (m, 1H), 3.75 (m, 4H), 3.49 (m, 4H), 3.28 (m, 4H) ), 3.33 (m, 7H), 2.59 (m, 2H), 2.23 (m, 2H).

EXAMPLE 401A A mixture of 1-bromo-2- (trifluoromethoxy) -benzene (5 g) and chlorosulfonic acid (30 ml) at 85 ° C is stirred for 18 hours, treated with crushed ice, and extracted with ethyl acetate. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, and concentrated. The material concentrated in IPA (200 ml) at 0 ° C is treated with 38% ammonium hydroxide (50 ml), stirred for 18 hours and concentrated. The concentrated material is treated with ethyl acetate (200 ml) and water. The extract is washed with water and brine and 56S Dry (Na2SO4), filter, and concentrate.

EXAMPLE 401B This example is prepared by replacing Example 401A with the example 4 - (((1 R) -3- (dimethylamino) -1- ((phenyl-Isulfanyl) methyl) propyl) amine) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 401C This example is prepared by substituting example 401 B for example 164B in example 164C. 1 H NMR (500 MHz, DMSO-d 6) d 11.82 (m, 1 H), 11.12 (m, 1 H), 10.18 (m, 1 H), 7.82 (d, 1 H), 7.56 (d, 2 H), 7.31 (m, 4H), 7.08 (m, 6H), 6.73 (d, 2H), 5.86 (d, 1H), 4.15 (m, 2H), 3.68 (m, 2H), 3.58 (m, 1H), 3.08 (m, 4H), 2.81 (m, 4H), 2.66 (m, 2H), 2.31 (m, 6H), 1. 85 (m, 2H).

EXAMPLE 402 This example is prepared by substituting example 388F and methyl isopropylamine for example 35A and sopropylamine, respectively, in Example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 11.86 (m, 1 H), 11.40 (m, 1 H), 10.38 (m, 1 H), 8.14 (m, 1 H), 7.85 (d, 1 H), 7.81 (d, 1H), 7.76 (d, 2H), 7.53 (m, 4H), 7.28 (m, 7H), 6.83 (m, 3H), 6.03 (m, 1H), 4.33 (m, 2H), 4.02 (m, 1H) ), 3.87 (m, 2H), 3.32 (m, 6H), 3.04 (m, 2H), 2.86 (m, 2H), 2.57 (m, 3H), 2.18 (m, 2H), 1.18 (m, 6H) .

EXAMPLE 403 This example is prepared by substituting example 388F and diethylamine for Example 35A and isopropylamine, respectively, in Example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 11.96 (m, 1 H), 11.28 (m, 1H), 10.30 (m, 1H), 8.11 (m, 1H), 7.94 (s, 1H), 7.81 (d, 1H), 7.76 (d, 2H), 7.53 (m, 4H), 7.28 (m, 7H), 6.g3 (m, 3H), 6.06 (m, 1H), 4. 33 (m, 2H), 4.02 (m, 1H), 3.87 (m, 2H), 3.24 (m, 4H), 3.14 (m, 2H), 3.04 (m, 4H), 2.88 (m, 4H), 2.13 (m, 2H), 1.17 (m, 6H).

EXAMPLE 404 This example is prepared by substituting 2,5-dimethylpyrrolidine for isopropylamine in Example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 12.10 (m, 1 H), 11.41 (m, 1H), 10.55 (m, 1H), 9.88 (m, 1H), 8.54 (s, 1H), 8.31 (d, 1H), 8.14 (m, 1H), 7.86 (dd, 1H), 7.77 (d, 2H), 7.53 (m, 4H), 7.24 (m, 8H), 6. 93 (d, 2H), 4.33 (m, 2H), 3.88 (m, 2H), 3.26 (m, 7H), 2.83 (d, 2H), 2.16 (m, 4H), 1.65 (m, 2H), 1.36 (m, 6H).

EXAMPLE 405 This example is prepared by substituting Example 398F and 7M NH3 in methanol for example 35A and isopropylamine, respectively, in Example 35B. 1 H NMR (500 MHz, DMSO-d6) d 7.S2 (s, 1 H), 7.87 (d, 1 H), 7.72 (d, 2H), 7.51 (dd, 1 H), 7.2S (m, 7H), 6.77 (m, 2H), 6.68 (m, 1 H), 4.40 (m, 1 H), 3.87 (m, 2H), 3.38 (m, 4H), 3.12 (m, 4H), 2.84 (t , 2H), 2.40 (m, 2H), 1.99 (m, 2H).

EXAMPLE 406A This example is prepared by replacing 4-bromo-2-trifluoromethylbenzenesulfonamide with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D .

EXAMPLE 406B This example is prepared by substituting example 406A for example 164B in example 164C. 1 H NMR (500 MHz, DMSO-d 6) d 7.87 (d, 1 H), 7.79 (d, 2 H), 7.48 (dd, 1 H), 7.26 (m, 1 1 H), 6.78 (m, 3 H) , 6.56 (m, 2H), 3.64 (m, 2H), 3.12 (m, 5H), 3.06 (m, 2H), 2.80 (m, 4H), 2.36 (m, 6H), 2.01 (m, 2H), 1.74 (m, 2H).

EXAMPLE 407A This example is prepared by replacing 4-bromo-3-fluorobenzenesulfonamide with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 407B This example is prepared by substituting example 407A for example 164B in example 164C. 1 H NMR (500 MHz, DMSO-d 6) d 7.68 (d, 2 H), 7.48 (dd, 1 H), 7.42 (d, 1 H), 7.25 (m, 12 H), 6.77 (m, 2 H), 6.44 (t, 1 H), 5.80 (d, 1 H), 3.63 (m, 2H), 3.10 (m, 9H), 2.78 (m, 4H), 2.36 (m, 6H), 1.88 (m, 1 H), 1.87 (m, 1 H).

EXAMPLE 847398A This example is prepared by replacing 4-bromo-2-trifluoromethoxybenzenesulfonamide with 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 847398B This example is prepared by substituting example 847388A for example 164B in example 164C. 1 H NMR (500 MHz, DMSO-d 6) d 7.73 (d, 2 H), 7.62 (d, 1 H), 7.51 (d, 1 H), 7.31 (m, 12 H), 6.81 (m, 2 H), 6.33 (m, 2H), 3.61 (m, 2H), 3.33 (m, 2H), 3.17 (m, 6H), 3.03 (m, 4H), 2.73 (m, 1H), 2.40 (m, 6H), 1.38 (m, 1H ), 1.87 (m, 1H).

EXAMPLE 409A This example is prepared by replacing 4-bromo-2,5-difluorobenzenesulfonamide with 4 - (((1R) -3- (dimethylamino) -1- ((phenylisulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 409B This example is prepared by substituting example 408A for example 164B in example 164C. 1 H NMR (500 MHz, DMSO-d 6) d 7.73 (d, 2 H), 7.51 (d, 1 H), 7.31 (m, 10 H), 6.80 (d, 2 H), 6.20 (m, 2 H), 6.10 (m, 2H), 3.58 (m, 1H), 3.33 (m, 4H), 3.14 (m, 6H), 2.34 (m, 2H), 2.85 (m, 2H), 2.40 (m, 6H), 2.01 (m, 1H) ), 1.30 (m, 1H).

EXAMPLE 410A This example is prepared by replacing 4-bromo-3-methylbenzenesulfonamide with 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 410B This example is prepared by substituting example 41 OA for example 164B in example 164C. 1 H NMR (500 MHz, DMSO-d 6) d 7.72 (d, 2 H), 7.51 (d, 1 H), 7.28 (m, 10 H), 6.83 (d, 2 H), 6.34 (d, 2 H), 5.75 (s, 2H), 5.52 (d, 1H), 3.72 (m, 1H), 3.33 (m, 2H), 3.15 (m, 8H), 2.64 (m, 2H), 2.54 (m, 2H), 2.40 (m, 6H) ), 2.05 (s, 3H), 1.38 (m 1H), 1.87 (m, 1H).

EXAMPLE 411 This example is prepared by substituting example 307C and example 23D for example 2C and 4 - (((1 R) -3- (dimethylamine) ~ 1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively , in the 2D example. 1 H NMR (300 MHz, DMSO-d 6) d 8.44 (s, 1 H), 8.14 (m, 1H), 7.81 (m, 1H), 7.71 (d, 2H), 7.25 (m, 7H), 6.34 (d, 1H), 6.77 (d, 2H), 4.11 (m, 1H), 3.58 (m, 2H) ), 3.13 (m, 6H), 2.76 (s, 2H), 2.22 (m, 8H), 1.66 (m, 4H), 1.19 (m, 12H), 0.89 (m, 4H).

EXAMPLE 412 This example is prepared by substituting (2R, 5R) - (-) - trans-2,5-dimeti-pyrrolidine, which is prepared as described in J. Org. Chem. 1999, 64, 1979-1985, by isopropylamine in Example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 8.45 (d, 1 H), 8.17 (m, ? H), 7.84 (dd, 1H), 7.72 (d, 2H), 7.51 (d, 1H), 7.27 (m, 8H), 6.99 (d, 1H), 6.79 (d, 2H), 4.14 (m, 2H), 3.88 (m, 2H), 3.74 (m, 1H), 3.38 (s, 2H), 3.28 (m, 6H), 2.87 (m, 2H), 2.40 (m, 6H), 2.09 (m, 4H), 1.24 (m, 4H).

EXAMPLE 413 This example is prepared by substituting (2S, 5S) - (+) - trans-2,5-dimethylpyrrolidine, which is prepared as described in J. Org. Chem. 1999, 64, 1979-1985, by isopropylamine in Example 35B. 1 H NMR (500 MHz, DMSO-d 6) d 8.45 (d, 1 H), 8.17 (m, 1H), 7.84 (dd, 1H), 7.72 (d, 2H), 7.51 (d, 1H), 7.27 (m, 8H), 6.94 (m, 1H), 6.79 (d, 2H), 4.11 (m, 2H), 3.88 (m, 2H), 3.74 (m, 1H), 3.38 (s, 2H), 3.27 (m, 6H), 2.87 ( m, 2H), 2.40 (m, 6H), 2.09 (m, 4H), 1.24 (m, 4H).

EXAMPLE 414 This example is prepared by substituting (2S, 5R) -cis-2,5-dimethylpyrrolidine, which is prepared as described in J. Org. Chem. 199g, 64, i g79-1985, by isopropylamine in Example 35B. 1 H NMR (500 MHz, DMSO-de) d 8.46 (d, 1 H), 8.16 (m, 1 H), 7.83 (dd, 1 H), 7.72 (d, 2 H), 7.51 (d, 1 H) , 7.27 (m, 8H), 6.97 (m, 1 H), 6.80 (d, 2H), 4.12 (m, 2H), 3.49 (m, 1 H), 3.39 (s, 2H), 3.28 (m, 8H ), 2.40 (m, 6H), 2.12 (m, 4H), 1.57 (m, 2H), 1.21 (m, 4H).

EXAMPLE 415A A mixture of 4-bromo-3- (trifluoromethyl) -benzenesulfonyl chloride (0.46 g), concentrated sulfuric acid (6 ml), and 90% nitric acid (3 ml) at 1 10 ° C is stirred for 18 hours, It is poured into ice water and extracted with ethyl acetate. The extract is washed with water and brine, dried (Na 2 SO), filtered, and concentrated.

EXAMPLE 415B Example 415A (0.5 g) in IPA (25 ml) and THF (25 ml) at -78 ° C is treated with 38% ammonium hydroxide (10 ml), stirred for 3 hours, acidified with 12 M HCl, and concentrates. The concentrated material is treated with ethyl acetate and water. The extract is washed with water and brine and dried (Na 2 SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 25% ethyl acetate / hexane.

EXAMPLE 415C A mixture of example 415B (0.235 g), example 164A (0.224 g) and DIEA (1 ml) in dimethylacetamide (10 ml) at 50 ° C is stirred for 18 hours, treated with ethyl acetate, washed with aqueous NaHCO 3, water, and brine, and dried (MgSO 4). , filter, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / dichloromethane saturated with NH3.

EXAMPLE 415D This example is prepared by replacing Example 415C with 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfanyl) methyI) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-d6) d 8.41 (d, 1 H), 8.20 (d, 1 H), 7.83 (dd, 1 H), 7.75 (d, 2H), 7.51 (dd, 1 H), 7.37 (, 8H), 7.06 (d, 2H), 6.78 (d, 2H), 6.50 (m , 1 H), 3.33 (s, 2H), 3.23 (m 1 H), 3.05 (m, 7H), 2.63 (m, 4H), 2.40 (m, 6H), 2.07 (m, 2H).

EXAMPLE 416 This example is prepared by replacing Example 415C and Example 307C with 4 - (((1 R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide and Example 2C, respectively , in the 2D example. 1 H NMR (400 MHz, DMSO-d 6) d 8.31 (d, 1 H), 8.10 (d, 1 H), 7.65 (d, 2 H), 7.27 (d, 2 H), 7.04 (m, 8 H), 6.68 (d, 2H), 6.44 (m, 1H), 3.04 (m, 4H), 2.82 (m, 1H), 2.69 (m, 2H), 2.41 (m, 6H), 2.20 (m, 4H), 2.08 (m, 4H) ), 1.98 (m, 2H), 1.56 (m, 4H).

EXAMPLE 417 This example is prepared by replacing Example 415C and Example 318C with 4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide and Example 2C, respectively, in the example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.18 (d, 1 H), 7.98 (d, 1H), 7.52 (d, 2H), 7.15 (d, 2H), 6.94 (m, 8H), 6.56 (d, 2H), 6.42 (m, 1H), 2.90 (m, 4H), 2.69 (m, 1H ), 2.56 (m, 2H), 2.29 (m, 6H), 2.19 (m, 4H), 2.10 (m, 4H), 1.82 (m, 1H), 1.74 (m, 1H), 1.56 (m, 4H) , 1.48 (m, 2H), 1.32 (m, 4H).

EXAMPLE 418A Treat 3-fluoro-4-nitrobenzenesulfonyl chloride (1 g) in IPA (50 ml) at -15 ° C with 38% NH 4 OH (10 ml), stir for 18 hours and concentrate. The concentrated material is separated between ethyl acetate and water. The aqueous layer is extracted with ethyl acetate. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, and concentrated.

EXAMPLE 418B This example is prepared by replacing Example 418A and Example 164A with 4-fluoro-3-nitrobenzene sulfonamide and Example 21C, respectively, in Example 21D.

EXAMPLE 418C This example is prepared by substituting Example 418B for 4 - (((1R) -3- (dimethylamino) -1 - ((f-enylsulfanyl) -methyl) -propyl) -amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500 MHz, DMSO-de) d 7.89 (d, 1H), 7.95 (d, 2H), 7.60 (s, 1H), 7.51 (dd, 1H), 7.37 (m, 4H), 7.30 (d, 4H), 7.24 (dd, 1H), 7.14 (t, 2H), 7.08 (t, 1H), 7.02 (dd, 1H), 6.79 (d, 2H), 4.13 (m, 1H), 3.49 (dd, 1H), 3.39 (d, 2H), 3.36 (dd, 1H), 3.13 (m, 4H), 3.04 (m, 2H), 2.63 (m, 4H), 2.40 ( m, 6H), 2.10 (m, 2H).

EXAMPLE 419A This example is prepared by substituting 4-bromo-3,5-difluorobenzenesulfonyl chloride for 3-fluoro-4-nittobenzenesulfonyl chloride in Example 418A.

EXAMPLE 419B This example is prepared by substituting Example 418A for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D.

EXAMPLE 419C This example is prepared by substituting example 418B for example 164B in example 164C. 1 H NMR (500 MHz, DMSO-d 6) d 12.10 (m, 1 H), 1 1 .43 (m, 1 H), 10.48 (m, 1 H), 8.55 (m, 1 H), 8.14 (m, 2H), 7.77 (m, 2H), 7.33 (m, 12H), 6.33 (m, 2H), 6.03 ( d, 2H), 4.34 (m 1 H), 3.88 (m, 2H), 3. 36 (m, 4H), 3.1 3 (m, 2H), 2.84 (m, 2H), 2.70 (m, 6H), 2.08 (m, 2H).

EXAMPLE 420A A mixture of 2-cyclo-3-nitrobenzoic acid (5 g) and chlorosulfonic acid (30 ml) at 150 ° C is stirred for 72 hours, treated with ice, and extracted with ethyl acetate. The extract is washed with water and brine, dried (Na2SO4), filtered, and concentrated. The material concentrated in IPA / THF 1: 1 (200 ml) at -78 ° C is treated with 38% ammonium hydroxide (30 ml), stirred for 2 hours, acidified with 12 M HCl, and concentrated. The concentrated material is treated with water and ethyl acetate. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, and concentrated.

EXAMPLE 420B Example 420A (4.5 g) in methanol (300 ml) is treated with concentrated sulfuric acid (3 ml), stirred at reflux for 18 hours, and concentrated. The concentrated material is treated with water and ethyl acetate. The extract is washed with water and brine and dried (Na 2 SO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20% ethyl acetate / hexane.

EXAMPLE 420C This example is prepared by substituting Example 420B and Example 164A for 4-fluoro-3-nitrobenzenesulfonamide and Example 21 C, respectively, in Example 21 D.

EXAMPLE 420D This example is prepared by replacing Example 420C and Example 307C with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide and Example 2C, respectively , in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 8.34 (s, 1 H), 8.28 (d, 1 H), 7.72 (d, 2 H), 7.36 (d, 2 H), 7.13 (m, 7 H), 6.76 (d, 2H), 3.80 (s, 3H), 3.10 (m, 4H), 2.75 (m, 2H), 2.27 (m, 4H), 2.18 (m, 6H), 1.98 (m, 2H), 1.88 (m, 2H), 1.65 (m, 4H).

EXAMPLE 421 This example is prepared by substituting Example 420C for 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfonyl) methyl 1) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D . 1 H NMR (500 MHz, DMSO-d6) d 8.27 (s, 1 H), 8.20 (d, 1 H), 7.66 (d, 2H), 7.43 (d, 2H), 7.16 (m, 1 1 H), 6.71 (d, 2H), 3.74 (s, 3H), 3.05 (m, 6H), 2.82 ( m, 2H), 2.43 (m, 6H), 2.32 (m, 4H), 1.35 (m, 2H), 1.85 (m, 2H).

EXAMPLE 422 Example 421 (60 mg) in THF (100 mL), methanol (100 mL), and water (100 mL) is treated with lithium hydroxide monohydrate (10 mg), stirred at 25 ° C for 18 hours, and concentrate The concentrated material is purified by high pressure liquid chromatography on a C8 Symmetry Waters column (25 mm x 100 mm, particle size 7 μm) with 10-100% acetonitrile / 0.1% aqueous TFA in a lapse of 8 minutes at a flow rate of 40 ml / minute. 1 H NMR (500 MHz, DMSO-d 6) d 8.55 (m, 1 H), 3.13 (m, 1 H), 8.46 (s, 1 H), 8.33 (s, 1 H), 7.73 (d, 2 H) , 7.72 (m, 1 H), 7.52 (m, 4H), 7.43 (m, 2H), 7.33 (m, 2H), 7.03 (m, 4H), 6.33 (m, 2H), 6.33 (d, 2H) , 4.21 (m, 1 H), 3.17 (m, 6H), 2.33 (m, 2H), 2.73 (m, 6H), 2.12 (m, 2H), 2.05 (m, 2H).

EXAMPLE 423 This example is prepared by replacing Example 420D by Example 421 in Example 422. 1 H NMR (500 MHz, DMSO-d6) d 3.57 (m, 1 H), 3.21 (m, 1 H), 8.47 (s, 1 H), 8.33 (s, 1 H), 7.80 (d, 2H), 7.40 (m, 4H), 7.1 5 (d, 2H), 7.03 (m, 4H), 7.01 (m, 2H), 6.85 (d , 2H), 3.17 (m, 6H), 2.73 (m, 6H), 2.26 (m, 4H), 2.21 (m, 4H), 2.14 (m, 2H), 2.03 (m, 2H), 1.70 ( m, 4H).

EXAMPLE 424 Example 420D (100 mg) in 7M NH3 in methanol at 70 ° C is stirred for 48 hours in a sealed flask, and concentrated. The concentrated material is purified by high pressure liquid chromatography on a C8 Symmetry Waters column (25 mm x 100 mm, particle size 7 μm) with 10-100% acetonitrile / 0.1% aqueous TFA in a lapse of 8 minutes at a flow rate of 40 ml / minute. 1 H NMR (500 MHz, DMSO-de) d 3.46 (m, 1 H), 8.52 (m, 1 H), 8.45 (d, 1 H), 7.38 (s, 1 H), 7.87 (s, 1 H ), 7.78 (d, 2H), 7.41 (m, 4H), 7.16 (d, 2H), 7.13 (m, 4H), 6.36 (d, 2H), 3.30 (m, 1 H), 3.53 (m, 2H) ), 3.35 (m, 4H), 3.27 (m, 4H), 3.17 (m, 6H), 2.77 (m, 6H), 2.26 (m, 4H), 2.21 (m, 4H), 2.10 (m, 2H) , 1.71 (m, 4H).

EXAMPLE 425 This example is prepared by replacing Example 421 with Example 420D in Example 424. 1 H NMR (500 MHz, DMSO-d6) d 3.42 (m, 1 H), 8.52 (m, 1 H), 8.46 (d, 1 H), 7.83 (s, 1 H), 7.87 (s, 1 H), 7.78 (d, 2 H), 7.53 (m, 4 H), 7.41 (d, 2 H), 7.34 (m, 1 H), 7.14 (m, 4H), 6.34 (d, 2H), 3.31 (m, 1 H), 3.36 (m, 4H), 3.28 (m, 4H), 3.16 (m, 6H), 2.77 (m, 6H), 2.1 1 (m, 2H).

EXAMPLE 426A 2-Fluoro-3- (trifluoromethyl) -benzoic acid (5 g) in concentrated sulfuric acid (50 ml) at 0 ° C is treated with urea nitrate, which is prepared as described in Textbook of Practice! Organic Chemistry; 1371, page 442, (5 g), is stirred for 30 minutes and at 25 ° C for 12 hours, poured into crushed ice and extracted with ethyl acetate. The extract is washed with water and brine, dried (Na 2 SO), filtered, and concentrated. The material concentrated in methanol (300 ml) and concentrated sulfuric acid (3 ml) is refluxed for 18 hours and concentrated. The concentrated material is treated with water and ethyl acetate, and the organic layer is washed with water and brine, and dried (Na2SO4), filtered, and concentrated.

EXAMPLE 426B Example 426A (6 g) and 10% Palladium on carbon (0.6 g) in ethyl acetate (200 ml) at 25 ° C are stirred under H2 (4.22 kg / cm2) for 2 hours, filtered and concentrated.

EXAMPLE 426C This example is prepared by substituting example 426B for example 848030A in example 848080B.

EXAMPLE 426D This example is prepared by substituting Example 426C and Example 164A for 4-fluoro-3-nitrobenzenesulfonamide and Example 21 C, respectively, in Example 21 D.

EXAMPLE 426E This example is prepared by replacing Example 426D and Example 307C with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide and Example 2C, respectively , in the 2D example. 1 H NMR (400 MHz, DMSO-d 6) d 8.33 (d, 1 H), 8.16 (d, 1H), 7.72 (d, 2H), 7.36 (d, 2H), 7.30 (m, 1H), 7.20 (d, 2H), 7.12 (m, 4H), 6.77 (d, 2H), 3.81 (s, 3H), 3.62 (m, 1H), 3.12 (m, 8H), 2.85 (m, 2H), 2.77 (m, 2H), 2.61 (m, 6H) ), 2.28 (m, 4H), 2.18 (m, 4H), 2.10 (m, 2H), 1.91 (m, 2H), 1.66 (m, 4H).

EXAMPLE 427 This example is prepared by replacing Example 426D and Example 312D with 4 - (((1R) -3- (dimethylamino) -1- ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide and Example 2C, respectively, in the 2D example. 1 H NMR (400 MHz, DMSO-d 6) d 8.38 (d, 1 H), 8.15 (d, 1 H), 7.72 (d, 2 H), 7.40 (d, 2 H), 7.30 (m, 1 H), 7.20 (m, 4H), 7.12 (m, 2H), 6.77 (d, 2H), 4.16 (s, 2H), 3.81 (s, 3H), 3.7S (t, 2H), 3.62 (m, 1H), 3.12 (m, 8H), 2.S5 (m, 2H), 2.88 (m, 4H), 2.60 (m, 6H), 2.30 (m, 4H), 2.05 (m, 2H), 1.91 (m, 2H).

EXAMPLE 428 This example is prepared by replacing Example 426D with 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (400 MHz, DMSO-d 6) d 8.40 (d, 1 H), 8.16 (d, 1 H), 7.73 (d, 2 H), 7.50 (d, 2 H), 7.47 (m, 4 H), 7.24 (m, 6H), 6.79 (d, 2H), 3.81 (s, 3H), 3.61 (m, 1 H), 3.38 (s, 2H), 3.12 (m, 8H), 2.95 (m, 2H), 2.61 (m, 6H), 2.40 (m, 4H), 2.10 (m, 2H), 1.91 (m, 2H).

EXAMPLE 429A This example is prepared by substituting Fmoc-D-Glu (0-tert-butyl) -OH for Fmoc-D-Asp (0-tert-butyl) -OH in Example 27A.

EXAMPLE 429B This example is prepared by substituting example 429A for example 27A in example 27B.

EXAMPLE 429C This example is prepared by substituting example 429B for example 27B in example 29A.

EXAMPLE 429D This example is prepared by substituting example 429C and (2S, 5R) -cis-2,5-dimethylpyrrolidine, which is prepared as described in J. Org. Chem. 1999, 64, 1979-1985, for example 29A and di-isopropylamine, respectively, in Example 29B.

EXAMPLE 429E This example is prepared by substituting example 429D for example 27B in example 398B.

EXAMPLE 429F This example is prepared by substituting example 429E for example 18E in example 18F.

EXAMPLE 429G This example is prepared by substituting example 429F for example 21 C in example 21 D.

EXAMPLE 429H This example is prepared by replacing Example 429G and Example 307C with 4 - (((1 R) -3- (dimethylamino) -1- ((phenylisulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide and Example 2C, respectively , in the 2D example. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1H), 10.17 (m, 1H), 8.01 (m, 1H), 8.53 (d, 1H), 8.32 (d, 1H), 7.87 (dd, 1H), 7.78 (d, 2H), 7.41 (d, 2H), 7.18 (m, 6H), 6.S6 (d, 2H), 4.18 (m, 1H), 3.30 (m, 2H), 3.60 (m, 2H), 3.03 (m, 2H), 2.78 (m, 2H), 2.26 (m, 4H), 2.03 (m, 2H), 1.68 (m, 8H), 1.28 (d, 6H).

EXAMPLE 430 This example is prepared by replacing Example 429G and Example 312D with 4 - (((1R) -3- (dimethylamino) -1- ((phenylisulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide and Example 2C, respectively, in the 2D example. 1 H NMR (300 MHz, DMSO-d 6) d 12.11 (m, 1H), 10.54 (m, 1H), 3.00 (m, 1H), 8.53 (d, 1H), 8.32 (d, 1H), 7.88 (dd, 1H), 7.78 (d, 2H), 7.45 (d, 2H), 7.18 (m, 6H), 6.36 (d, 2H), 4.38 (s, 2H), 4.18 (m, 1H), 3.84 (t, 2H), 3.66 (m, 2H), 3.03 (m, 2H), 2.75 (m, 2H), 2.46 (m, 4H), 2.03 (m, 2H), 1.68 (m, 8H ), 1.28 (d, 6H).

EXAMPLE 431 This example is prepared by substituting 2-tert-butoxycarbonylaminobenzoyl chloride for 2-bromobenzoyl chloride in Example 106B. 1 H NMR (500 MHz, DMSO-d 6) d 9.48 (s, 1 H), 9.28 (brs, 1H), 8.55 (d, 1H), 8.28 (d, 1H), 7.88 (dd, 1H), 7.77 (d, 2H), 7.24 (d, 2H), 7.16 (dd, 2H), 7.12 (d, 1H), 6.96 (d, 2H), 6.63 (d, 1H), 6.58 (s, 1H), 6.50 (d, 1H), 4.18 (m, 1H) ), 3.40 (m, 4H), 3.35 (m, 2H), 3.20- 3.08 (m, 4H), 2.73 (s, 6H), 2.54 (s, 2H), 2.14 (m, 2H), 1.48 (s, 9H).

EXAMPLE 432 This example is prepared by substituting 2-dimethylaminobenzoyl chloride for 2-bromobenzoyl chloride in Example 106B. 1 H NMR (500 MHz, DMSO-d 6) d 9.26 (br s, 1 H), 8.55 (d, 1 H), 8.28 (d, 1 H), 7.87 (dd, 1 H), 7.77 (d, 2 H), 7.23 (d, 2H), 7.15 (dd, 2H), 7.11 (d, 1H), 6.96 (d, 2H), 6.79 (d, 1H), 6.69 (s, 1H), 6.65 (d, 1H), 4.17 (m, 1H) ), 3.40 (m, 4H), 3.35 (m, 2H), 3.15 (m, 4H), 2.91 (s, 6H), 2.74 (s, 6H), 2.54 (s, 2H), 2.14 (m, 2H) .

EXAMPLE 433A This example is prepared by substituting (2S, 4R) -3 - ((benzyloxy) carbonyl) -4-methyl-2-phenyl-1,3-oxazolidin-5-one, (which is prepared as described in Helv. Chim. Acta 1991, by (2R, 4S) -3 - ((benzyloxy) carbonyl) -4-methyl-2-phenyl-1,3-oxazoIidin-5-one in Example 25A.

EXAMPLE 433B This example is prepared by substituting example 433A plo 25A in example 21 B.

EXAMPLE 433C This example is prepared by substituting example 433B plo 25B in example 21 C.

EXAMPLE 433D This example is prepared by substituting example 433C plo 18A in example 18B.

EXAMPLE 433E This example is prepared by substituting example 433D plo 25D in example 21 E.

EXAMPLE 433F This example is prepared by substituting example 433E plo 25E in example 21 F. 582 EXAMPLE 433G This example is prepared by substituting example 433F for example 18B in example 18C.

EXAMPLE 433H This example is prepared by substituting example 433G for example 25G in example 25H.

EXAMPLE 433I This example is prepared by substituting example 433H for example 1C in example 1D. 1 H NMR (500 MHz, DMSO-d 6) d 8.51 (d, 1 H), 8.31 (s, 1H), 7.82 (dd, 1H), 7.81 (d, 2H), 7.60 (d, 1H), 7.47 (m, 4H), 7.42 (m, 3H), 7.32 (m, 4H), 7.16 (dd, 2H) ), 7.08 (dd, 1H), 6.86 (d, 2H), 4.25 (m, 1H), 3.77 (d, 2H), 3.45 (d, 1H), 3.21 (m, 4H), 2.85 (m, 1H) , 2.67 (s, 6H), 2.54 (m, 1H), 2.45 (m, 4H), 2.27 (m, 1H), 1.58 (s, 3H).

EXAMPLE 434 This example is prepared by substituting example 25H for example 1C in example 1D. 1 H NMR (500 MHz, DMSO-d 6) d 10.20 (br s, 1 H), 8.48 (d, 583 1H), 8.26 (s, 1H), 7.87 (dd, 1H), 7.78 (d, 2H), 7.56 (d, 1H), 7.42 (m, 4H), 7.38 (m, 3H), 7.28 (d, 1H) ), 7.25 (m, 3H), 7.05 (dd, 2H), 6.87 (dd, 1H), 6.83 (d, 2H), 3.74 (m, 1H), 3.45 (s, 2H), 3.33 (d, 1H) , 3.28 (m, 1H), 3.20 (m, 4H), 3.16 (m, 1H), 2.37 (, 1H), 2.67 (s, 6H), 2.54 (m, 1H), 2.40 (m, 4H), 2.25 (m, 1H), 1.54 (s, 3H).

EXAMPLE 435A 2-Fluorobenzonitrile (0.325 ml) in isoindoline / NMP (1 ml / 2 ml) at 180 ° C is stirred for 10 minutes in a microwave reactor, poured into diethyl ether (50 ml) and washed with 1 M HCl and brine. . The solution is dried (Na 2 SO), filtered, and concentrated.

EXAMPLE 435B Example 435A (200 mg) in toluene (5 ml) at 25 ° C is treated with 1M DIBAL in dichloromethane (1.1 ml), stirred for 30 minutes, treated with methanol (3 ml), poured into 1 M HCl ( 50 ml), and extracted with ethyl acetate. The extract is washed with brine and dried (Na 2 SO), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 10% ethyl acetate / hexanes. 584 EXAMPLE 435C This example is prepared by substituting example 435B for example 130D in example 130E. 1 H NMR (500MHz, DMSO-d6) d 10.05 (br s, 1 H), 8.45 (d, 1 H), 8.21 (d, 1 H), 7.81 (dd, 1 H), 7.73 (d, 2H), 7.34 (m, 4H), 7.23 (m, 4H), 7.18 (m, 2H), 7.07 ( m, 1 H), 6.83 (m, 2H), 6.81 (d, 2H), 4.62 (AB quartet, 4H), 4.03 (m, 1 H), 3.62 (s, 1 H), 3.34 (m, 2H) , 3.28 (m, 1 H), 3.20 (m, 2H), 2.31 (dd, 2H), 2.84 (m, 1 H), 2.67 (s, 6H), 2.55 (m, 4H), 2.03 (m, 1 H), 2.02 (m, 1 H), 1.71 (m, 1 H).

EXAMPLE 436A This example is prepared by substituting cyclohexylamine for isoindoline in Example 435A.

EXAMPLE 436B This example is prepared by substituting example 436A for example 435A in example 435B.

EXAMPLE 436C This example is prepared by substituting Example 436B for 2- (methylsulfanyl) -benzaldehyde in Example 128E. 5 1 H NMR (400MHz, DMSO-d 6) d 9.70 (br s, 1H), 8.52 (d, 1H), 8.22 (d, 1H), 7.84 (dd, 1H), 7.76 (d, 2H), 7.26 (d, 2H), 7.19 (m, 2H), 7.11 (m, 2H), 6.97 (dd, 1H), 6.89 (d, 2H), 6.58 (d, 1H), 6.49 (m, 1H), 4.19 (m, 1H) ), 3.51 (m, 1H), 3.38 (d, 2H), 3.34 (m, 5H), 3.11 (m, 4H), 2.70 (s, 6H), 2.47 (m, 3H), 2.17 (m, 2H) , 1.88 (m, 2H), 1.62 (m, 2H), 1.53 (m, 1H), 1.37 (m, 2H), 1.22 (m, 4H).

EXAMPLE 437A This example is prepared by substituting isopropylamine for isoindoline in Example 435A.

EXAMPLE 437B This example is prepared by substituting example 437A for example 435A in example 435B.

EXAMPLE 437C This example is prepared by substituting Example 437B for 2- (methylsulfanyl) -benzaldehyde in Example 128E. 1 H NMR (400MHz, DMSO-d 6) d 9.82 (br s, 1H), 8.52 (d, 1H), 8.22 (d, 1H), 7.84 (dd, 1H), 7.78 (d, 2H), 7.25 (d, 2H), 7.18 (m, 2H), 7.13 (m, 2H), 6.99 (m, 1H), 6.92 (d, 2H), 6.60 (d, 1H), 6.51 (dd, 1H), 4.21 (m, 1H) ), 3.49 (m, 3H), 3.39 (d, 2H), 3.31 (m, 5H), 3.11 (m, 4H), 3.08 (d, 2H), 2.71 (s, 6H), 2.51 (m, 1H) , 2.16 (m, 2H), 1.14 (d, 6H).

EXAMPLE 438A This example is prepared by replacing benzylamine with β-indindoline in Example 435A.

EXAMPLE 438B This example is prepared by substituting example 438A for example 435A in example 435B.

EXAMPLE 438C This example is prepared by substituting Example 438B for 2- (methylsulfanyl) -benzaIdehyde in Example 128E. 1 H NMR (400MHz, DMSO-d 6) d 10.18 (br s, 1H), 8.52 (d, 1H), 8.25 (d, 1H), 7.84 (dd, 1H), 7.78 (d, 2H), 7.37 (d, 2H), 7.29 (dd, 2H), 7.24 (m, 2H), 7.19 (m, 2H), 7.12 (m, 3H), 7.07 (m, 1H), 6.95 (d, 2H), 6.56 (dd, 1H) ), 6.52 (d, 1H), 4.35 (s, 2H), 4.25 (m, 1H), 3.39 (d, 2H), 3.35 (m, 4H), 3.18 (m, 1H), 3.05 (m, 8H) , 2.68 (s, 6H), 2.51 (m, 1H), 2.19 (m, 2H).

EXAMPLE 439A This example is prepared by substituting piperidine for isoindoline in Example 435A.

EXAMPLE 439B This example is prepared by substituting example 439A for example 435A in example 435B.

EXAMPLE 439C This example is prepared by substituting Example 439B for 2- (methylsulfanyl) -benzaldehyde in Example 128E. 1 H NMR (400MHz, DMSO-d6) d 8.49 (d, 1 H), 8.19 (m, 1 H), 7.82 (dd, 1 H), 7.75 (d, 2 H), 7.41 (m, 1 H), 7.35 (m, 3 H), 7.30 (d, 2 H), 7.22 (m, 3 H), 7.15 (m, 1 H), 7.02 (m, 2H), 6.87 (d, 1 H), 4.12 (m, 1 H), 3.60 (m, 2H), 3.42 (m, 1 H), 3.37 (d, 2H) ), 3.31 (m, 5H), 3.22 (m, 2H), 3.08 (m, 2H), 2.82 (m, 4H), 2.69 (s, 6H), 2.59 (m, 2H), 2.10 (m, 2H) , 1.65 (m, 4H), 1.51 (m, 2H), 1.21 (m, 4H).

EXAMPLE 440 This example is prepared by substituting 4-cyclohexylamino-3-nitro-benzenesulfonamide, which is prepared as described in WO02 / 24636, by 4 - (((1 R) -3- (dimethylamino) -1- ((f-enyl) sulfide. anil) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (500MHz, DMSO-d 6) d 11.90 (brs, 1H), 8.61 (d, 1H), 8.60 (dd, 1H), 7.94 (dd, 1H), 7.74 (d, 2H), 7.59 (d, 1H) ), 7.41 (dd, 2H), 7.38 (m, 4H), 7.25 (d, 1H), 7.22 (d, 1H), 6.89 (d, 2H), 3.58 (m, 2H), 3.25 (m, 3H), 2.47 (m, 4H), 1.85 (d, 2H), 1.69 (m, 3H), 1. 61 (m, 2H), 1.19 (m, 4H), 0.99 (m, 2H).

EXAMPLE 441 This example is prepared by substituting 4-cyclohexylmethylamino-3-nitrobenzenesulfonamide, which is prepared as described in WO02 / 24636, by 4 - (((1R) -3- (dimethylamino) -l - ((phenylsulfanyl) methyl) p ropil) amino) -3-nitrobenzenesulfonamide in Example 1D. 1 H NMR (500 MHz, DMSO-d 6) d 11.90 (br s, 1 H), 8.70 (d, 1 H), 8.36 (dd, 1 H), 7.99 (dd, 1 H), 7.78 (d, 2 H), 7.50 (d, 1H), 7.45 (dd, 2H), 7.42 (m, 4H), 7.35 (d, 1H), 7.32 (d, 1H), 6.94 (d, 2H), 3.76 (m, 2H), 3.69 (m, 2H) ), 3.38 (m, 1H), 2.58 (m, 4H), 1.99 (d, 2H), 1.74 (m, 3H), 1.62 (m, 1.45 (m, 6H), 1.29 (m, 2H).

EXAMPLE 442 This example is prepared by replacing example 90C and 58S 4 - (((1R) -3- (4-morpholin il) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02 / 24636, for example 2C and 4 - (((1R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amine) -3-nitrobenzenesulfonamide, respectively, in the example 2D . 1 H NMR (400MHz, DMSO-de) d 11.43 (br s, 1H), 8.54 (d, 1H), 8.38 (d, 1H), 7.83 (dd, 1H), 7.73 (d, 2H), 7.41 (dd, 2H), 7.35 (m, 2H), 7.28 (m, 6H), 7.17 (m, 4H), 6.80 (d, 2H), 4.13 (m, 1H), 3.62 (m, 4H), 3.33 (m, 2H) ), 3.30 (m, 2H), 3.02 (s, 3H), 2.30 (s, 2H), 2.85 (dd, 2H), 2.65 (m, 6H), 2.08 (m, 1H), 1.38 (m, 1H) , 1.47 (d, 2H), 1.18 (m, 2H).

EXAMPLE 443 This example is prepared by substituting the SOC example and 3-Nitro-4 - ((2- (phenylsulfanyl) ethyl) amino) -benzenesulfonamide, which is prepared as described in WO 02/24636, by example 2C and 4 - (((1 R) -3- (dimethylamino) -1- ((f-enylsulf- nyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in Example 2D. 1 H NMR (400MHz, DMSO-d 6) d 11.35 (br s, 1H), 8.75 (dd, 1H), 8.60 (d, 1H), 7.31 (dd, 1H), 7.73 (d, 2H), 7.41 (dd, 2H), 7.36 (m, 3H), 7.28 (m, 6H), 7.17 (m, 3H), 6.80 (d, 2H), 3.66 (m, 2H), 3.38 (m, 2H), 3.28 (m, 2H) ), 3.02 (s, 3H), 2. SO (s, 2H), 2.86 (dd, 2H), 1.45 (m, 2H), 1.18 (m, 2H).

EXAMPLE 444A 4-Chloro-3- (trifluoromethyl) -benzenesulfonyl chloride (5 g) in THF (100 ml) is treated with saturated NH 4 OH at 0 ° C, stirred for 30 minutes and concentrated. The material concentrated in ethyl acetate is washed with water and brine, and dried (Na 2 SO 4), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 30% ethyl acetate in hexanes.

EXAMPLE 444B A mixture of example 444A (1.5 g) and 2- (phenylsulfanyl) ethanamine (1.06 g) in DMSO (17 ml) is treated with TEA (0.87 ml), heated at 145 ° C for 18 hours, cool to 25 ° C, pour into ethyl acetate, wash with water, brine, dry (Na S04), filter, and concentrate. The concentrated material is subjected to flash chromatography on silica gel with 50% ethyl acetate / hexanes.

EXAMPLE 444C This example is prepared by substituting Example 444B for 4 - (((1 R) -3- (dimethylamino) -1 - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500MHz, DMSO-d6) d 7.88 (d, 1 H), 7.77 (d, 1 H), 7.73 (d, 2H), 7.51 (d, 1 H), 7.43 (s, 4H), 7.40 (dd, 2H), 7.35 (m, 4H), 7.21 (m, 2H), 6.78 (d, 2H), 6.70 (d, 1 H), 3.41 (m, 2H), 3.33 (s, 1 H), 3.16 (m, 2H), 3.13 (m, 4H), 2.50 (s, 1 H), 2.40 (m, 4H).

EXAMPLE 445A This example is prepared by substituting Example 444A for 4-fluoro-3-nitrobenzenesulfonamide, which is prepared as described in WO02 / 24636, in Example 20D.

EXAMPLE 445B This example is prepared by substituting example 445A for example 18E in example 18F.

EXAMPLE 445C This example is prepared by substituting Example 445B for 4 - (((1 R) -3- (d-methylamino) -1 - ((phenylsulfonyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide in Example 2D. 1 H NMR (500MHz, DMSO-d6) d 10.30 (br s, 1 H), 7.34 (d, 1 H), 7.73 (d, 1 H), 7.74 (d, 2H), 7.53 (d, 1 H), 7.47 (s, 4H), 7.38 (m, 2H), 7.32 (m, 2H), 7.26 (m, 3H), 7.18 (m, 1 H), 6.87 (d, 3H), 3.83 (m, 1 H), 3.42 (s, 2H), 3.23 (m , 2H), 3.17 (m, 4H), 3.02 (m, 4H), 2.40 (m, 4H), 2.16 (m, 2H), 1.89 (m, 4H), 1.28 (m, 2H).

EXAMPLE 446A 4-Chloronicotinic acid (5 g) in methanol / ethyl acetate 1: 1 (200 ml) is treated with 2M trimemethyldiazomethane (25 ml) and concentrated.

EXAMPLE 446B A mixture of example 446A (4.88 g), 4-chlorobenzanboronic acid (5.15 g), KF (5.45 g), Pd (dba) 3 (260 mg), and tri-tert-butylphosphine in THF (80 ml) at 25 ° C. C is stirred for 3 days, filtered and concentrated. The concentrated material is subjected to flash chromatography on silica gel with 20% ethyl acetate / hexanes.

EXAMPLE 446C Example 446B (3.4 g) in THF (50 ml) at 0 ° C is treated with 1 M LiAlH in THF (14 ml), stirred at 25 ° C for 1 hour, quenched with water (5 ml) and NaOH 1 M (20 ml), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with ethyl acetate.

EXAMPLE 446D Example 446C (530 mg) in acetonitrile (15 ml) at 0 ° C is treated with pyridine (0.315 ml) and dibromotriphenylphosphorane (1.32 g), stirred at 25 ° C for 1 hour, and poured into saturated Na 2 CO 3. (100 ml) and ethyl acetate. The extract is washed with brine and dried (Na S0), filtered, and concentrated. The concentrated material is subjected to flash chromatography on silica gel with ethyl acetate / hexanes 1: 1.

EXAMPLE 446E This example is prepared by substituting Example 446D for 2-bromobenzyl bromide in Example 2A.

EXAMPLE 446F This example is prepared by substituting example 446E for example 1 B in example 1 C.

EXAMPLE 446G This example is prepared by substituting example 446F for example 1C in example 1 D. 1 H NMR (500MHz, DMSO-d6) d 8.64 (s, 1 H), 8.55 (d, 1H), 8.52 (d, 1H ), 8.23 (d, 1H), 7.85 (dd, 1H), 7.74 (d, 2H), 7.58 (d, 2H), 7.54 (d, 2H), 7.31 (d, 1H), 7.26 (d, 1H) , 7.17 (dd, 2H), 7.13 (d, 1H), 7.12 (m, 1H), 6.88 (d, 2H), 4.18 (m, 1H), 3.47 (s, 2H), 3.32 (m, 4H), 3.11 (m, 4H), 2.71 (s, 6H), 2.42 (m, 4H), 2.16 (m, 2H).

EXAMPLE 447 This example is prepared by substituting example 446F and 4 - (((1R) -3- (4-morpholinyl) -1 - ((f-enylsulfanyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide, which is prepared as described in WO 02/24636, for example 2C and 4 - (((1R) -3- (dimethylamino) -l - ((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide, respectively, in the 2D example. 1 H NMR (500 MHz, DMSO-d 6) d 8.65 (s, 1 H), 8.56 (d, 1 H), 8.52 (d, 1 H), 8.34 (d, 1 H), 7.83 (dd, 1 H), 7.74 (d, 2 H) ), 7.58 (d, 2H), 7.54 (d, 2H), 7.31 (d, 1H), 7.27 (d, 1H), 7.18 (dd, 2H), 7.13 (d, 1H), 7.11 (m, 1H) , 6.88 (d, 2H), 4.18 (m, 1H), 3.63 (s, 4H), 3.22 (s, 4H), 3.08 (m, 4H), 2.75-2.55 (m, 6H), 2.42 (m, 4H) ), 2.10 (m, 1H), 1.88 (m, 1H).

EXAMPLE 448A This example is prepared by substituting 2,6-difluorobenzotrifluoride for 1-fluorobenzotrifluoride in Example 18D.

EXAMPLE 448B This example is prepared by substituting example 448A for example 18D in example 18E.

EXAMPLE 448C This example is prepared by substituting example 448B for example 18E in example 18F.

EXAMPLE 448D This example is prepared by substituting example 448C for example 1C in example 1D. 1 H NMR (500MHz, DMSO-d 6) d 7.82 (d, 2H), 7.76 (dd, 1H), 7.64 (d, 1H), 7.54 (d, 2H), 7.51 (d, 2H), 7.44 (m, 2H), 7.40 (d, 2H), 7.35 (dd, 2H), 7.31 (d, 1H) ), 7.25 (dd, 1H), 6.83 (d, 2H), 6.74 (d, 1H), 4.02 (m, 1H), 3.55 (m, 4H), 3.35 (m, 2H), 3.18 (m, 2H) , 3.06 (m, 2H), 2.74 (s, 6H), 2.52 (m, 4H), 2.21 (m, 2H).

Claims

1. - A compound having the formula (I) (I), or a salt, prodrug, salt of a pharmaceutically acceptable prodrug or metabolite thereof, wherein A1 is N or C (A2); one or two or three or each of A2, B1, D1 and E1 are independently selected from R1, OR1, SR1, S (0) R1, S02R1, C (0) R \ C (0) OR1, OC (0) R1, NHR1, N (R1) 2, C (0) NHR1, C (0) N (R1) 2, NHC (0) R1, NHC (0) OR1, NR1C (0) NHR1, NR1C ( 0) N (R1) 2, S02NHR1, S02N (R1) 2, NHS02R1, NHS02NHR1 or N (CH3) S02N (CH3) R1, and the remainder are independently selected from H, F, Cl, Br, I , CN, CF3, C (0) OH, C (0) NH2 or C (0) OR1A; and Y1 is H, CN, N02, C (0) OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R7, OR17, C (0) R17, C (0) OR17, SR17, NH2, NHR17, N (R17) 2, NHC (0) R17, C (0) NH2, C (0) NHR17 , C (0) N (R17) 2, NHS (0) R17 or NHS02R17; or B1 and Y1, together with the atoms to which they are attached, are midazole or triazole; and one or two or each of A2, D1 and E1 are independently selected from R1, OR1, SR1, S (0) R1, S02R1, C (0) R \ C (0) OR1, OC (0 ) R1, NHR1, N (R1) 2, C (0) NHR1, C (0) N (R1) 2, NHC (0) R1, NHC (0) OR1, NHC (0) NHR1, N (CH3) C (0) N (CH3) R1, S02NH R1, S02N (R1) 2, NHS02R1, NHS02NHR1 or N (CH3) S02N (CH3) R1, and the remaining ones are independently selected from H, F, Cl, Br, I, CF3, C (0) OH, C (0) NH2 or C (0) OR1 TO; R1 is R2, R3, R4 or R5; R1 A is Ci-Ce alkyl, C3-C6 alkenyl or C3-C6 alkynyl; R2 is phenyl which is not fused or fused with arene, heteroarene or R2A; R2A is cycloalkane or heterocycloalkane; R3 is heteroaryl which is not fused or fused with benzene, heteroarene or R3A; R3A is cycloalkane or heterocycloalkane; R 4 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is not fused or fused with arene, heteroarene or R 4A; R 4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R5 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or is substituted with one or two or three substituents that are independently selected from R6, NC (R6A) (R6B), R7, OR7, SR7 , S (0) R7, S02R7, NHR7, N (R7) 2, C (0) R7, C (0) NH2, C (0) NHR7, NHC (0) R7, NHS02R7, NHC (0) OR7, S02NH2 , S02NHR7, S02N (R7) 2, NHC (0) NH2, NHC (0) NHR7, NHC (0) CH (CH3) NHC (0) CH (CH3) NH2, NHC (0) CH (CH3) NHC (0 CH (CH3) NHR1, OH, (O), C (0) OH, (O), N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R6 is C2-C5 spiroalkyl, each of which is unsubstituted or substituted by OH, (O), N3, CN, CF3, CF2CF3, F, Cl, Br, l, NH2, NH (CH3) or N (CH3) 2; R6A and R6B are independently selected from alkyl or, together with the N to which they are attached, R6C; R6C is aziridin-1-yIo, azetidin-1-yl, pyrroidin-1-yl or piperidin-1-yl, each having a CH2 portion not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH; R7 is R8, R9, R10 or R11; R8 is phenyl which is not fused or fused with arene, heteroarene or R8A; R8A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R9 is heteroaryl which is not fused or fused with arene, heteroarene or R9A; R9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R10 is C3-C? 0 cycloalkyl or C4-C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH independently selected and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R10A; R10A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R1 1 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted by one or two or three substituents which are independently selected from R12, OR12, NHR12, N (R12) 2, C ( 0) NH2, C (0) NHR12, C (0) N (R12) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R12 is R13, R14, R15 or R16; R13 is phenyl which is not fused or fused with arene, heteroarene or R13A; R13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R14 is heteroaryl, each of which is not fused or fused to arene, heteroarene or R14A; R14A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R15 is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene, each of which is not fused or fused with arene, heteroarene or R15A; R15A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R16 is alkyl, alkenyl or alkynyl; R17 is R18, R19, R20 or R21; R18 is phenyl which is not fused or fused with arene, heteroarene or R18A; R18A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R 9 is heteroaryl which is not fused or fused with arene, heteroarene or R19A; R19A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R20 is C3-C10 cycloalkyl or C4-C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R20A; R20A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R21 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or is substituted with one or two or three substituents that are independently selected from R22, OR22, NHR22, N (R22) 2, C (0) ) NH2, C (0) NHR22, C (0) N (R22) 2, OH, (O), C (0) OH, N3) CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R22 is R23, R24 or R25; R23 is phenyl which is not fused or fused with arene, heteroarene or R23A; R23A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R24 is heteroarene which is not fused or fused with arene, heteroarene or R24A; R24A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R25 is C3-C6 cycloalkyl or C4-C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R25A; R25A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; Z1 is R26 or R27, each of which is substituted with R28, R29 or R30, each of which is substituted with F, Cl, Br, l, CH2R37, CH (R31) (R37), C (R31) (R31A) (R37), C (0) R37, OR37, SR37, S (0) R37, S02R37, N HR37 or N (R32) R37; R26 is phenyl which is not fused or fused with arene or heteroarene; R27 is heteroarene which is not fused or is fused with arene or heteroarene; R28 is phenyl which is not fused or fused to arene, heteroarene or R28A; R28A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R29 is heteroaryl or R29A; R29A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R30 is cycloalkyl or cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH independently selected and one or two CH portions not replaced or replaced with N, and each of which is not fused or is fused with arene, heteroarene or R30A; R 30A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R31 and R31 A are independently F, Cl, Br or alkyl or are taken together and are spiroalkyl of C-C5; R32 is R33, C (0) R33 or C (0) OR33; R33 is R34 or R35; R34 is phenyl which is not fused or fused with aryl, heteroaryl or R34A; R34A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R35 is alkyl which is unsubstituted or substituted with R36; R36 is phenyl which is not fused or fused with arene, heteroarene or R36A; R36A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R37 is R38, R39 or R40, each of which is substituted with F, Cl, Br, l, R41, OR41, N HR41, N (R41) 2, NHC (0) OR41, SR41, S (0) R41 or S02R41; R38 is phenyl which is not fused or fused with arene, heteroarene or R38A; R38A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R39 is heteroaryl which is not fused or fused to arene, heteroarene or R39A; R39A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R40 is C3-Cs cycloalkyl or C-C-cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R40A; R40A cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R41 is R42, R43, R44 or R45; R42 is phenyl which is not fused or fused with arene, heteroarene or R42A; R42A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R43 is heteroaryl which is not fused or fused to arene, heteroarene or R43A; R43A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R44 is C3-C6 cycloalkyl or C-C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R44A; R44A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R 45 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted by one or two substituents that are independently selected from R46, OR46, NHR46, N (R46) 2, C (0) NH2 , C (0) NHR46, C (0) N (R46) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R46 is R47, R48 or R49; R47 is phenyl which is not fused or fused with arene, heteroarene or R47A; R47A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R48 is heteroaryl or R48A; R48A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R49 is C3-Ce cycloalkyl or C4-C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R49A; R49A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; wherein each preceding cyclic portion, independently, is not substituted, not further substituted, substituted or further substituted with one or two or three or four or five substituents that are independently selected from R50, OR50, SR50, S (0) R50, S02R50, C (0) R50, CO (0) R50, OC (0) R50, OC (0) OR50, NH2, NHR50, N (R50) 2, C (0) NH2, C ( 0) NHR50, C (O) N (R50) 2, C (0) N HOH, C (0) NHOR50, C (0) NHS02R50, C (0) NR 5S02R50, S02NH2, S02NHR50, SO2N (R50) 2, CF3, CF2CF3, C (0) H, C (0) OH, C (N) NH2, C (N) NHR50, C (N) N (R50) 2, OH, (O), N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I; R50 is R51, R52, R53 or R54; R51 is phenyl which is not fused or fused with arene, heteroarene or R51 A; R51 A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R52 is heteroaryl or R52A; R52A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R53 is C3-C6 cycloalkyl or C4-C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N, and each of which is not fused or fused with arene, heteroarene or R53A; R53A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R54 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R55, OR55, SR55, S (0) R55, S02R55, NH R55, N (R55) 2, C (0) R55, C (0) NH2, C (0) NHR55, NHC (0) R55, NHS02R55, NHC (0) OR55, S02N H2, SO2NHR55, S02N (R55) 2 , NHC (0) NH2, NHC (0) NHR55, OH, (O), C (0) OH, (O), N3, CN, NH2, CF3, OCF3, CF2CF3, OCF2CF3, F, Cl, Br or I; R55 is alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R56; R56 is C3-C6 cycloalkyl or C4-C6 cycloalkyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected from independently and one or two CH portions not replaced or replaced with N.

2. The compound of the formula (I) according to claim 1, wherein A1 is N or C (A2); A2 is H, F, CN, C (0) OH, C (0) NH2 or C (0) OR1A; B1 is R1, OR1, SR1, S (0) R1, S02R1, C (0) R1, C (0) OR1, OC (0) R1, NHR1, N (R1) 2, C (0) NHR1, C ( 0) N (R1) 2, NHC (0) R1, NHC (0) OR1, NR1C (0) NHR1, NR1C (0) N (R1) 2, S02NHR1, S02N (R1) 2, NHS02R1, NHS02NHR1 or N ( CH3) S02N (CH3) R1; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, C (O) OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R17, OR17, C (0) R17, C (0) OR17, SR17, NH2, NHR17, N (R17) 2, NHC (0) R17, C (0) NH2, C (0) NHR17, C (0) N (R17) 2, NHS (0) R17 or NHS02R17; or B1 and Y1, together with the atoms to which they are attached, are imidazole or triazole; R1 is R2, R3, R4 or R5; R1A is C1 alkyl; C2 alkyl, C3 alkyl, C alkyl, C5 alkyl, C6 alkyl; R2 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R3 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazoyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, siathiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole , pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 4 is C 3 cycloalkyl, C cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, C 4 cycloalkenyl, C 5 cycloalkenyl or C 6 cycloalkenyl, each having one or two CH 2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S0 or NH independently selected and one or two CH portions not replaced or replaced with N; R5 is Ci alkyl, C2 alkyl, C3 alkyl, C alkyl, C5 alkyl, Ce alkyl, C2 alkenyl, C3 alkenyl, C alkenyl, C5 alkenyl, C6 alkenyl, C3 alkynyl, C alkynyl, C5 alkynyl or Ce alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R6, R7, OR7, SR7, S (0 ) R7, S02R7, NH R7, N (R7) 2, C (0) R7, C (0) NH2, C (0) NHR7, NHC (0) R7, NHS02R7, NHC (0) OR7, S02NH2, S02NHR7, S02N (R7) 2, NHC (0) NH2, NHC (0) NHR7, NHC (0) CH (CH3) N HC (0) CH (CH3) NH2, OH, (O), C (0) OH, (O), N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R6 is spiroalkyl of C2, spiroalkyl of C3, spiroalkyl of C4 or spiroalkyl of C5, each of which is unsubstituted or substituted by OH, (O), N3, CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH (CH3) or N (CH3) 2; R7 is R8, R9, R10 or R1 1; R8 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R8A; R8A is C-cycloalkane, C5-cycloalkane, C6-cycloalkane, C4-cycloalkene, C5-cycloalkene or C6-cycloalkene, each having one or two CH2-portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R9 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2, 3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2, 3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1, 2, 3-triazole; R10 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C cycloalkyl, C8 cycloalkyl, Cg cycloalkyl, C cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl, CT cycloalkenyl, C cycloalkenyl, C8 cycloalkenyl, C9 cycloalkenyl, Cio cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R1 1 is Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, C6 alkyl, C2 alkenyl, C3 alkenyl, C4 alkenyl, C5 alkenyl, C6 alkenyl, C2 alkynyl , C3 alkynyl, C alkynyl, C5 alkynyl or C6 alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R12, OR12, NHR12, N (R12) 2, C (0) NH2, C (0) NHR12, C (0) N (R12) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R12 is R1 3, R14, R15 or R16; R13 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2, 3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R13A; R13A is C4 cycloalkane, C5 cycloalkane, C6 cycloalkane, C cycloalkene, C5 cycloalkene or C6 cycloalkene, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R 14 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl, 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R1 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O) , CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R 16 is C 1 alkyl C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, C 6 alkyl, C 2 alkenyl, C 3 alkenyl, C 4 alkenyl, C 5 alkenyl, C 6 alkenyl, C 3 alkynyl, C4 alkynyl, C5 alkynyl or C6 alkynyl; R17 is R18, R19, R20 or R21; R18 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2, 3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R19 is furanyl, midazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or , 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole , pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1, 2, 3-triazole; R 20 is C 3 cycloalkyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, C 7 cycloalkyl, C 8 cycloalkyl, C 9 cycloalkyl, C cycloalkyl, C 4 cycloalkenyl, Cs cycloalkenyl, C 6 cycloalkenyl, C 7 cycloalkenyl, Cycloalkenyl of Ce, cycloalkenyl of Cg, cycloalkenyl of C10, each has one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R21 is Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, Ce alkyl, C2 alkenyl, C3 alkenyl, C4 alkenyl, C5 alkenyl, C6 alkenyl, C2 alkynyl, C3 alkynyl, C4 alkynyl, C5 alkynyl or C6 alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R22, OR22, N HR22, N (R22) 2, C (0) N H2, C (0) NH R22, C (0) N (R22) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R22 is R23, R24 or R25; R23 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine , pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 24 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl, 1, 2,3-triazole, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R25 is C3 cycloalkyl, C cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C cycloalkenyl, C5 cycloalkenyl or C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; Z1 is R26 or R27, each of which is substituted with R28, R29 or R30, each of which is substituted with F, Cl, Br, I, CH2R37, CH (R31) (R37), C (R31) (R31A) (R37), C (0) R37, OR37, SR37, S (0) R37, S02R37, NHR37 or N (R32) R37; R26 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 27 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazoly, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R28 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R29 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazoly, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 30 is C 3 cycloalkyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, C cycloalkyl, C 8 cycloalkyl, Cg cycloalkyl, C cycloalkyl, Cu cycloalkyl, C 2 cycloalkyl, C 3 cycloalkyl, C 14 cycloalkyl, C cycloalkenyl, C 5 cycloalkenyl, C 6 cycloalkenyl, C 7 cycloalkenyl, C 8 cycloalkenyl, C 9 cycloalkenyl or C 10 cycloalkenyl, each having one or two CH 2 portions not replaced or replaced with O, C (O ), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R31 and R31A are independently F, Cl, Br, C ^ alkyl C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl or are taken together and are C2 spiroalkyl, C3 spiroalkyl , C4 spiroalkyl or C5 spiroalkyl; R32 is R33, C (0) R33 or C (0) OR33; R33 is R34 or R35; R34 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2, 3-oxadiazole, 1, 2,5-oxadiazoI, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R35 is Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl, each of which is unsubstituted or substituted by R36; R36 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R37 is R38, R39 or R40, each of which is substituted with F, Cl, Br, I, R41, OR41, NHR41, N (R41) 2, NHC (0) OR41, SR41, S (0) R41 or S02R41; R38 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R39 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R40 is C3 cycloalkyl, C cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C cycloalkenyl, C5 cycloalkenyl, C6 cycloalkenyl, C7 cycloalkenyl or C8 cycloalkenyl, each having a or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R41 is R42, R43, R44 or R45; R42 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazoI, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R42A; R42A is C4 cycloalkane, C5 cycloalkane) C6 cycloalkane, C cycloalkene, C5 cycloalkene or C6 cycloalkene, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S ( O), SO2 or NH selected independently and one or two CH portions not replaced or replaced with N; R43 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or , 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole , pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R44 is C3 cycloalkyl, C cycloalkyl, C5 cycloalkyl, Ce cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or Ce cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S0 or NH independently selected and one or two CH portions not replaced or replaced with N, and each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 45 is Ci alkyl, C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, C 6 alkyl, C alkenyl, C 3 alkenyl, C 4 alkenyl, C 5 alkenyl, C 6 alkenyl, C 2 alkynyl, C3 alkynyl, C4 alkynyl, C5 alkynyl or C6 alkynyl, each of which is unsubstituted or substituted by one or two substituents that are independently selected from R46, OR46, NHR46, N (R46 ) 2, C (0) N H2, C (0) N HR46, C (0) N (R46) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F , Cl, Br or I; R46 is R47, R4d or R49; R47 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2, 3-oxadiazole, 1, 2, 5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R48 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R49 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or Ce cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; in which the portions represented by B1 and Y1 together are substituted with alkyl of C ^ alkyl of C2, alkyl of C3, alkyl of C4, alkyl of C5 or alkyl of C6, each of which is substituted with one or two substituents which are independently selected from SR55 or N (R55) 2, in which R55 is independently selected from phenyl, C ^ alkyl C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl; the portions represented by R2, R3 and R4 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, S02R5 °, CO (0) R50 or OCF3, in which R50 is phenyl, alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl; the portions represented by R8, R9 and R10 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, C (0) NHS02R50, CO (0) R50, C (0) R50 , C (0) OH, C (0) NHOH, OH, NH2, F, Cl, Br or I, in which R50 is phenyl, tetrazolyl or R54, in which R54 is Ci alkyl, C2 alkyl, alkyl of C3, C-alkyl, C5-alkyl or C6-alkyl, each of which is unsubstituted or substituted by phenyl; the portions represented by R26 and R27 are also not substituted or substituted with one or two substituents that are independently selected from F, Br, Cl or I; the portions represented by R28, R29 and R30 are also unsubstituted or substituted with OR54, in which R54 is C2 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl, each of which is unsubstituted or substituted with R56, wherein R56 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl or C6 cycloalkyl, each having one or two CH2 portions replaced with independently selected O or NH and a CH portion not replaced or replaced with N; the portions represented by R38, R39 and R40 are unsubstituted or are substituted with one or two substituents that are independently selected from R54, F, Br, Cl or I, in which R54 is C4 alkyl, C2, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl; and the portions represented by R42, R43, R44 and R45 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, N (R50) 2, S02R50, CN, CF3, F, Cl, Br or I, in which R50 is phenyl or R54, in which R54 is C2 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl, each of which is unsubstituted or substituted by N (R55) 2 or R56, in which R55 is Ci alkyl, C2 alkyl, C3 alkyl, C alkyl, C5 alkyl or C6 alkyl and R56 is C3 cycloalkyl , C4 cycloalkyl, C5 cycloalkyl or Ce cycloalkyl, each has a CH2 portion not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two portions CH not replaced or replaced with N.

3. The compound of the formula (I) according to claim 2, wherein A1 is C (A2); A2 is H, F, CN, C (0) OH, C (0) NH2 or C (0) OR1A; B1 is R1, OR1, SR1, S (0) R1, S02R1, C (0) R1, C (0) OR1, OC (0) R1, NHR1, N (R1) 2, C (0) NHR1, C ( 0) N (R1) 2, NHC (0) R1, NHC (0) OR1, NR1C (0) NHR1, NR1C (0) N (R1) 2, S02NHR1, S02N (R1) 2, NHS02R1, NHS02NHR1 or N ( CH3) S02N (CH3) R1; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, C (O) OH, F, Cl, Br, CF3, OCF3, NH2, C (0) NH2 or B1 and Y1, together with the atoms to which these are bound, are midazole or triazole; R1 is R2, R3, R4 or R5; R1A is Ci alkyl, C alkyl, C3 alkyl, C4 alkyl, C5 alkyl, Ce alkyl; R2 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R3 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene; R 4 is C 3 cycloalkyl, C cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, C 4 cycloalkenyl, C 5 cycloalkenyl or C 6 cycloalkenyl, each having one or two CH 2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R5 is C2 alkyl, C2 alkyl, C3 alkyl, C alkyl, C5 alkyl, Ce alkyl, C2 alkenyl, C3 alkenyl, C4 alkenyl, C5 alkenyl, C6 alkenyl, C3 alkynyl, C4 alkynyl, C5 alkynyl or C6 alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R6, R7, OR7, SR7, S (0 ) R7, S02R7, NHR7, N (R7) 2, C (0) R7, C (0) NH2, C (0) NHR7, NHC (0) R7, NHS02R7, NHC (0) OR7, S02NH2, S02NHR7, S02N (R7) 2, NHC (0) NH2, NHC (0) NHR7, NHC (0) CH (CH3) NHC (0) CH (CH3) NH2, OH, (O), C (0) OH, (O), N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R6 is spiroalkyl of C2, spiroalkyl of C3, spiroalkyl of C4 or spiroalkyl of C5, each of which is unsubstituted or substituted by OH, (O), N3, CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH (CH3) or N (CH3) 2; R7 is R8, R9, R10 or R1 1; R8 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R8A; RdA is cycloalkane of C4, cycloalkane of C5, cycloalkane of C6, cycloalkene of C4, cycloalkene of C5 or cycloalkene of C6, each having one or two portions CH2 not replaced or replaced with O, C (O), S, S ( O), S0 or NH selected independently and one or two CH portions not replaced or replaced with N; R9 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene; R10 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, Cg cycloalkyl, C cycloalkyl, C cycloalkenyl, Cs cycloalkenyl, C6 cycloalkenyl, C cycloalkenyl, C8 cycloalkenyl, C9 cycloalkenyl, C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R 1 is C 2 alkyl C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, C 6 alkyl, C 2 alkenyl, C 3 alkenyl C 4 alkenyl, C 5 alkenyl, C alkenyl, C alkynyl , C3 alkynyl, C4 alkynyl, C5 alkynyl or C alkynyl, each of which is unsubstituted or substituted by one or two or three substituents that are independently selected from R12, OR12, NHR12 , N (R12) 2 l C (0) NH2, C (0) NH R12, C (0) N (R12) 2, OH, (O), C (O) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R12 is R13, R14, R1 5 or R16; R13 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R13A; R13A is C4 cycloalkane, C5 cycloalkane, Ce cycloalkane, C cycloalkene, C5 cycloalkene or C6v cycloalkene each have one or two CH2 portions not replaced or replaced with O, C (O), S, S (O ), S0 or NH selected independently and one or two CH portions not replaced or replaced with N; R 14 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl, 1, 2,3-triazoium, each of which is not fused or is fused with benzene; R15 is C3 cycloalkyl, C cycloalkyl, C5 cycloalkyl, Ce cycloalkyl, C cycloalkenyl, C5 cycloalkenyl or Ce cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R16 is C-alkyl? , C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, C6 alkyl, C2 alkenyl, C3 alkenyl, C alkenyl, C5 alkenyl, C6 alkenyl, C3 alkynyl, C4 alkynyl, alkynyl of C5 or alkynyl of C Z1 is R26 or R27, each of which is substituted with R28, R29 or R30, each of which is substituted with Cl, Br, CH2R37, C (R31) (R31A) (R37) ), C (0) R37, OR37, SR37, S (0) R37, S02R37, or NHR37; R26 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R 27 is furanyl, midazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or , 2, 3-triazolyl, each of which is not fused or is fused with benzene; R28 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazoIe, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R29 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or fused with benzene; R 30 is C 3 cycloalkyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, C 7 cycloalkyl, C 8 cycloalkyl, Cg cycloalkyl, C cycloalkyl, Cu cycloalkyl, C 2 cycloalkyl, C 13 cycloalkyl, Cycloalkyl C1, C4 cycloalkenyl, C5 cycloalkenyl, C6 cycloalkenyl, C7 cycloalkenyl, C8 cycloalkenyl, Cg cycloalkenyl or C10 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R31 and R31 A are independently F, Cl, Br, Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl or are taken together and are C2 spiroalkyl, C3 spiroalkyl , C4 spiroalkyl or C5 spiroalkyl; R37 is R38, R39 or R40, each of which is substituted with F, Cl, Br, I, R 4411,? ODR4411, M NUHDR4411,, SR41, S (0) R41 or S02R41; R38 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R39 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene; R40 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, Ce cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C cycloalkenyl, C5 cycloalkenyl, C6 cycloalkenyl, C7 cycloalkenyl or C8 cycloalkenyl, each have a or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S0 or NH independently selected and one or two CH portions not replaced or replaced with N; R41 is R42, R43, R44 or R45; R42 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1, 2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or R42A; R42A is C4 cycloalkane, C5 cycloalkane, Ce cycloalkane, C4 cycloalkene, C5 cycloalkene or Ce cycloalkene, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S ( O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; R43 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1,2,3-triazolyl, each of which is not fused or is fused with benzene; R44 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, Ce cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or C6 cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), CNOH, CNOCH3, S, S (O), S0 or NH independently selected and one or two CH portions not replaced or replaced with N, and each of which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,2-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R45 is C-alkyl? , C2 alkyl, C3 alkyl, C alkyl, C5 alkyl, C6 alkyl, C2 alkenyl, C3 alkenyl, C4 alkenyl, C alkenyl, C6 alkenyl, C2 alkynyl, C3 alkynyl, alkynyl of C, C5 alkynyl or C6 alkynyl, each of which is unsubstituted or substituted with one or two substituents that are independently selected from R46, OR46, NHR46, N (R6) 2, C (0) NH2, C (0) NHR46, C (0) N (R46) 2, OH, (O), C (0) OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I; R46 is R47, R48 or R49; R47 is phenyl which is not fused or is fused with benzene, furan, imidazole, isothiazole, isoxazole, 1,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine or 1,2,3-triazole; R48 is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazoyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thienyl, triazinyl or 1, 2,3-triazolyl, each of which is not fused or is fused with benzene; R49 is C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C4 cycloalkenyl, C5 cycloalkenyl or Ce cycloalkenyl, each having one or two CH2 portions not replaced or replaced with O, C (O), S, S (O), S02 or NH selected independently and one or two CH portions not replaced or replaced with N; in which the portions represented by B1 and Y1 together are substituted with C2 alkyl, C3 alkyl or C alkyl, each of which is substituted with one or two substituents that are independently selected from SR55 or N (R55) 2, in which R55 is independently selected from phenyl or Ci alkyl; the portions represented by R, R and R4 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, S02R50, CO (0) R50 or OCF3, in which R50 is phenyl, Ci alkyl, C2 alkyl, C3 alkyl or C4 alkyl; the portions represented by R8, R9 and R10 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, C (0) N HS02R5 °, CO (0) R50, C (0 ) R 5 °, C (0) OH, C (0) NHOH, OH, NH 2, F, Cl, Br or I, in which R 50 is phenyl, tetrazolyl or R 54, in which R 54 is C 1 alkyl C2 or C3 alkyl, each of which is unsubstituted or substituted by phenyl; the portions represented by R26 and R27 are also unsubstituted or substituted with one or two substituents that are independently selected from F, Br, Cl or i; the portions represented by R28, R29 and R30 are also unsubstituted or substituted with OR54, in which R54 is C ^ alkyl or C2 alkyl, each of which is unsubstituted or substituted by N (R55) 2 or R56, in which R55 is Ci-alkyl, C2-alkyl, C3-alkyl, C4-alkyl, C5-alkyl or C6-alkyl, and R56 is C5 or C6-cycloalkyl-cycloalkyl, each having one or two CH2-portions replaced with O or NH selected independently and a CH portion not replaced or replaced with N; the portions represented by R38, R39 and R40 are unsubstituted or are substituted with one or two substituents that are independently selected from C 1 F alkyl, Br, Cl or I; and the portions represented by R42, R43, R44 and R45 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, N (R50) 2, S02R5 °, CN, CF3 , F, Cl, Br or I, in which R50 is phenyl or R54, in which R54 is Ci alkyl, C2 alkyl or C3 alkyl, each of which is unsubstituted or substituted by N (alkyl) of C -?) 2 or Ce cycloalkyl having a CH portion replaced with O and a CH portion replaced with N.

4. The compound of formula (I) according to claim 3, wherein A1 is C (A2); A1 is H, F, CN, C (0) OH, C (0) NH2 or C (0) QCH3; B1 is R \ OR1, NHR1, N (R1) 2 or NR1 C (0) N (R1) 2; D1 is H, F, Cl or CF3; E1 is H, F or Cl; Y1 is H, CN, N02, F, Cl, CF3, OCF3, NH2, C (0) NH2, or B1 and Y1, together with the atoms to which they are attached, are imidazole or triazole; R1 is phenyl, pyrrolyl, cyclopentyl, cyclohexyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl or R5; R5 is Ci alkyl, C2 alkyl, C3 alkyl, C4 alkyl, Cs alkyl or C6 alkyl, each of which is unsubstituted or substituted with one or two or three substituents which are independently selected from spiroalkyl of C4, spiroalkyl of C5, R7, OR7, SR7, S02R7, NHR7, N (R7) 2, C (0) R7, C (0) NH2, C (0) NHR7, NHC (0) R7 , NHS02R7, NHC (0) OR7, NHC (0) NH2, NHC (0) CH (CH3) NHC (0) CH (CH3) NH2, OH, C (0) OH or NH2; R7 is phenyl, furanyl, imidazolyl, pyridinyl, tetrazolyl, thiazolyl, thienyl, 1,3-benzoxazolyl, 1,3-benzodioxolyl, 1,3-benzothiazole, cyclopropyl, cyclobutyl, cyclohexyl, azetidinyl, morpholinyl, piperazinyl, piperidinyl, thiomorpholinyl, thiomorpholinyl sulfone 7-azabicyclo [2.2.1] heptanyl, 8-azabicyclo [3.2.1] octanyl, 4,5-dihydro-1 H-imidazoyl 2-oxa-5-azabicynic [2.2.1] heptanil, 1, 4, 5,6-tetrahydropyrimidinyl or R 1 1; R1 1 is Ci alkyl, C2 alkyl, C3 alkyl or C4 alkyl, each of which is unsubstituted or substituted by one or two or three substituents which are independently selected from R12, OR12, N (R12) 2, C (0) N (R12) 2, OH, C (O) OH, NH2, CF3, F, Cl, Br or I; R 12 is 1,3-benzodioxolyl, pyridinyl, morpholinyl or alkyl of d; Z1 is phenyl or pyridinyl, each of which is substituted with cyclohexenyl, piperazinyl, piperidinyl, 1, 2,3,6-tetrahydropyridinyl or octahydropyrrolo [3,4-c] pyrrolyl, each of which is substituted with CH2R37, C (Spiroalkyl of C2) (R37) or C (0) R37; R37 is phenyl, naphthyl, imidazolyl, pyrazolyl, pyridinyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclo-octenyl or 3,6-dihydro-2H-pyranyl, each of which is substituted with F, Cl, Br, I, R41, NHR41, N (R41) 2, NHC (0) OR41 or SR41; R41 is phenyl, naphthyl, cyclohexyl, morpholinyl, piperidinyl, thienyl, pyridinyl, quinolinyl, benzofuranyl, 1,3-benzodioxolyl, isoindolinyl, 1,3-oxazolidin-2-onyI or R45; R 45 is Ci alkyl, C 2 alkyl, C 3 alkyl or C alkyl, each of which is unsubstituted or substituted by phenyl; in which the portions represented by B1 and Y1 together are substituted with C2 alkyl, C3 alkyl or C4 alkyl, each of which is substituted with one or two substituents that are independently selected from SR55 or N (R55) 2, in which R55 is independently selected from phenyl or alkyl of d; the portions represented by R1 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, S02R50, CO (0) R50 or OCF3, in which R50 is phenyl, alkyl of d, C2 alkyl, C3 alkyl or C alkyl; the portions represented by R7 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, C (0) NHS02R50, CO (0) R50, C (0) R50, C (0) ) OH, C (0) NHOH, OH, NH2, F, Cl, Br or I, in which R50 is phenyl, tetrazolyl or R54, in which R54 is alkyl of d, C2 alkyl or C3 alkyl, each one of which is unsubstituted or substituted with phenyl; the phenyl and pyridinyl portions of Z1 are unsubstituted or are further substituted with one or two substituents that are independently selected from F, Br, Cl or I; the cycloalkenyl portions of C6, piperazinyl, piperidinyl, 1, 2,3,6-tetrahydropyridinyl and octahydropyrrolo [3,4-cyryroline of Z1 are unsubstituted or are additionally substituted with OR54, in which R54 is Ci-alkyl or C2, each of which is unsubstituted or substituted by N (C?) Alkyl, morpholinyl, piperidinyl or piperidinyl; the portions represented by R37 are unsubstituted or substituted with one or two substituents that are independently selected from alkyl of d, F, Br, Cl or l; and the portions represented by R41 are unsubstituted or substituted with one or two substituents that are independently selected from R50, OR50, SR50, N (R50) 2, S02R50, CN, CF3, F, Cl, Br or I, in which R50 is phenyl or R54, in which R54 is alkyl of d, C2 alkyl or C3 alkyl, each of which is unsubstituted or is substituted with N (a) of d) 2 or morpholinyl.

5. A composition for treating bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, cancer of the esophagus, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, malignant tumors lymphoid originating in T cell or B cell, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer, said composition comprises an excipient and a therapeutically effective amount of the compound according to claim 1. 6.- A method to treat bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, malignant tumors lymphoid originating in T cell or B cell, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or splenic cancer in a patient, said method comprises administering to the patient a therapeutically effective amount of the compound according to claim 1. 7.- A method for treating bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, cancer colorectal cancer, cancer of the esophagus, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, malignant lymphoid tumors of origin in T cell or B cell, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer in a patient, said method comprises administering to the patient a therapeutically effective amount of the compound N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) -4 - (((1 R) -3- (d-imethylamino) -1- ((phenylsulfanyl) methyl) -propyl) amino) -3-nitrobenzenesulfonamide, or a therapeutically acceptable salt, prodrug or salt of a prodrug thereof. 8.- A method to treat bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, cancer! esophagus, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, malignant lymphoid tumors of T cell or B cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, lung cancer Small cell or spleen cancer in a patient, said method comprises administering to the patient a therapeutically effective amount of the compound according to claim 1 and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent. 9.- A method to treat bladder cancer, brain cancer, breast tissue cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, malignant tumors lymphoid originating in T cell or B cell, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or splenic cancer in a patient, said method comprises administering to the patient a therapeutically effective amount of the compound N- (4- (4 - ((4'-chloro- (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) -benzoyl) - 4 - (((1 R) -3- (d-imethylamino) -1- ((phenylsulfan I) methyl) -propyl) amino) -3-nitrobenzenesulfonamide, or a salt, prodrug or salt of a prodrug thereof therapeutically acceptable, and a therapeutically effective amount of an additional therapeutic agent or more than one additional therapeutic agent.