Apoptosis promoters

A compound having formula (I)

• or a therapeutically acceptable salt thereof, wherein
• A1 is C(A2);
• one or two or three or each of A2, B1, D1 and E1 are independently selected from R1, OR1, SR1, S(O)R1, SO2R1, C(O)R1, C(O)OR1, OC(O)R1, NHR1, N(R1)2, C(O)NHR1, C(O)N(R1)2, NHC(O)R1, NHC(O)OR1, NR1C(O)NHR1, NR1C(O)N(R1)2, SO2NHR1, SO2N(R1)2, NHSO2R1, NHSO2NHR1 and N(CH3)SO2N(CH3)R1, and the remainder are independently selected from H, F, Cl, Br, I, CN, CF3, C(O)OH, C(O)NH2 and C(O)OR1A;
• and
• Y1 is H, CN, NO2, C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R17, OR17, C(O)R17, C(O)OR17, SR17, NH2, NHR17, N(R17)2, NHC(O)R17, C(O)NH2, C(O)NHR17, C(O)N(R17)2, NHS(O)R17 or NHSO2R17;
• R1 is R2, R3, R4 or R5;
• R1A is C1-C6-alkyl, C3-C6-alkenyl or C3-C6-alkynyl;
• R2 is phenyl which is unfused or fused with arene, heteroarene or R2A;
• R2A is cycloalkane or heterocycloalkane;
• R3 is heteroaryl which is unfused or fused with benzene, heteroarene or R3A;
• R3A is cycloalkane or heterocycloalkane;
• R4 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with arene, heteroarene or R4A;
• R4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R5 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three independently selected R6, R7, OR7, SR7, S(O)R7, SO2R7, NHR7, N(R7)2, C(O)R7, C(O)NH2, C(O)NHR7, NHC(O)R7, NHSO2R7, NHC(O)OR7, SO2NH2, SO2NHR7, SO2N(R7)2, NHC(O)NH2, NHC(O)NHR7, NHC(O)CH(CH3)NHC(O)CH(CH3)NH2, NHC(O)CH(CH3)NHC(O)CH(CH3)NHR1, OH, (O), C(O)OH, (O), N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I substituents;
• R6 is C2-C5-spiroalkyl, each of which is unsubstituted or substituted with OH, (O), N3, CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH(CH3) or N(CH3)2;
• R7 is R8, R9, R10 or R11;
• R8 is phenyl which is unfused or fused with arene, heteroarene or R8A;
• R8A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R9 is heteroaryl which is unfused 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 moieties unreplaced or replaced with a substituent independently selected from O, C(O), CNOH, CNOCH3, S, S(O), SO2 and NH and one or two CH moieties unreplaced or replaced with N, and each of which is unfused or fused with arene, heteroarene or R10A;
• R10A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R11 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three independently selected R12, OR12, NHR12, N(R12)2, C(O)NH2, C(O)NHR12, C(O)N(R12)2, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I substituents;
• R12 is R13, R14, R15 or R16;
• R13 is phenyl which is unfused or fused with arene, heteroarene or R13A;
• R13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R14 is heteroaryl, each of which is unfused or fused with arene, heteroarene or R14A;
• R14A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R15 is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene, each of which is unfused 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 unfused or fused with arene, heteroarene or R18A;
• R18A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R19 is heteroaryl which is unfused 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 moieties unreplaced or replaced with a substituent independently selected from O, C(O), CNOH, CNOCH3, S, S(O), SO2 and NH and one or two CH moieties unreplaced or replaced with N, and each of which is unfused 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 substituted with one or two or three independently selected R22, OR22, NHR22, N(R22)2, C(O)NH2, C(O)NHR22, C(O)N(R22)2, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I substituents;
• R22 is R23, R24 or R25;
• R23 is phenyl which is unfused or fused with arene, heteroarene or R23A;
• R23A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R24 is heteroarene which is unfused 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 moieties unreplaced or replaced with a substituent independently selected from O, C(O), CNOH, CNOCH3, S, S(O), SO2 and NH and one or two CH moieties unreplaced or replaced with N, and each of which is unfused or fused with arene, heteroarene or R25A;
• R25A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• Z1 is phenyl substituted with piperazinyl, where the piperazinyl is substituted with CH2R37;
• R37 is phenyl substituted with R41;
• and
• R41 is phenyl;
• wherein each foregoing cyclic moiety is independently unsubstituted, further unsubstituted, substituted or further substituted with one or two or three or four or five independently selected R50, OR50, SR50, S(O)R50, SO2R50, C(O)R50, CO(O)R50, OC(O)R50, OC(O)OR50, NH2, NHR50, N(R50)2, C(O)NH2, C(O)NHR50, C(O)N(R50)2, C(O)NHOH, C(O)NHOR50, C(O)NHSO2R50, C(O)NR55SO2R50, SO2NH2, SO2NHR50, SO2N(R50)2, CF3, CF2CF3, C(O)H, C(O)OH, C(N)NH2, C(N)NHR50, C(N)N(R50)2, OH, (O), N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I substituents;
• R50 is R51, R52, R53 or R54;
• R51 is phenyl which is unfused 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 moieties unreplaced or replaced with a substituent independently selected from O, C(O), CNOH, CNOCH3, S, S(O), SO2 and NH and one or two CH moieties unreplaced or replaced with N, and each of which is unfused 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 with one or two or three independently selected R55, OR55, SR55, S(O)R55, SO2R55, NHR55, N(R55)2, C(O)R55, C(O)NH2, C(O)NHR55, NHC(O)R55, NHSO2R55, NHC(O)OR55, SO2NH2, SO2NHR55, SO2N(R55)2, NHC(O)NH2, NHC(O)NHR55, OH, (O), C(O)OH, (O), N3, CN, NH2, CF3, OCF3, CF2CF3, OCF2CF3, F, Cl, Br or I substituents;
• R55 is alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R56;
• and
• R56 is C3-C6-cycloalkyl or C4-C6-cycloalkyl, each having one or two CH2 moieties unreplaced or replaced with a substituent independently selected from O, C(O), CNOH, CNOCH3, S, S(O), SO2 and NH and one or two CH moieties unreplaced or replaced with N.