Method of treating arthritis

A method for treating arthritis in a mammal comprising administering to a mammal in need of such a treatment a therapeutically effective amount of a compound having Formula (I)

• or a therapeutically acceptable salt thereof, wherein
• A1 is N or C(A2);
• one or two or three or each of A2, B1, D1 and E1 are independently selected 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 or N(CH3)SO2N(CH3)R1, and the remainder are independently selected H, F, Cl, Br, I, CN, CF3, C(O)OH, C(O)NH2 or 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;
• 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 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, NHC(O)NHR1, N(CH3)C(O)N(CH3)R1, SO2NHR1, SO2N(R1)2, NHSO2R1, NHSO2NHR1 or N(CH3)SO2N(CH3)R1, and the remainder are independently selected H, F, Cl, Br, I, CF3, CF2CF3, CF2CF2CF3, C(O)OH, C(O)NH2 or C(O)OR1A;
• R1 is R2, R3, R4 or R5;
• R1A is alkyl, C3-C6-alkenyl or C3-C6-alkynyl;
• R2 is phenyl which is unfused or fused with benzene, 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 benzene, 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 of independently selected R6, NC(R6A)(R6B), 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, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I;
• R6 is C2-C5-spiroalkyl which is unsubstituted or substituted with OH, (O), N3, CN, CF3, CF2CF3, F, Cl, Br, I, NH2, NH(CH3) or N(CH3)2;
• R6A and R6B are independently selected 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 of which has one CH2 moiety unreplaced or replaced with O, C(O), CNOH, CNOCH3, S, S(O), SO2 or NH;
• R7 is R8, R9, R10 or R11;
• R8 is phenyl which is unfused or fused with benzene, heteroarene or R8A;
• R8A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R9 is heteroaryl which is unfused or fused with benzene, heteroarene or R9A;
• R9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R10 is C3-C10-Cycloalkyl, C4-C10-Cycloalkenyl, C3-C10-heterocycloalkyl or C4-C10-heterocycloalkenyl, each of which is unfused or fused with benzene, 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 of 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;
• R12 is R13, R14, R15 or R16;
• R13 is phenyl which is unfused or fused with benzene, heteroarene or R13A;
• R13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R14 is heteroaryl, each of which is unfused or fused with benzene, 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 benzene, 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 benzene, heteroarene or R18A;
• R18A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R19 is heteroaryl which is unfused or fused with benzene, heteroarene or R19A;
• R19A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R20 is C3-C10-cycloalkyl, C4-C10-cycloalkenyl, C3-C10-heterocycloalkyl or C4-C10-heterocycloalkenyl, each of which is unfused or fused with benzene, 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 of 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;
• R22 is R23, R24 or R25;
• R23 is phenyl which is unfused or fused with benzene, heteroarene or R23A;
• R23A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R24 is heteroarene which is unfused or fused with benzene, heteroarene or R24A;
• R24A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R25 is C3-C6-cycloalkyl, C4-C6-cycloalkenyl, C3-C6-heterocycloalkyl or C4-C6-heteroycloalkenyl, each of which is unfused or fused with benzene, 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, 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 unfused or fused with benzene or heteroarene;
• R27 is heteroarene which is unfused or fused with benzene or heteroarene;
• R28 is phenyl which is unfused or fused with benzene, 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, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R30A;
• R30A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R31 and R31A are independently selected F, Cl, Br or independently selected alkyl or are taken together and are C2-C5-spiroalkyl;
• R32 is R33, C(O)R33 or C(O)OR33;
• R33 is R34 or R35;
• R34 is phenyl which is unfused 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 unfused or fused with benzene, 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, R41, OR41, NHR41, N(R41)2, NHC(O)OR41, SR41, S(O)R41 or SO2R41;
• R38 is phenyl which is unfused or fused with benzene, heteroarene or R38A;
• R38A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R39 is heteroaryl which is unfused or fused with benzene, heteroarene or R39A;
• R39A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R40 is C3-C5-cycloalkyl, C4-C5-cycloalkenyl, C3-C5-heterocycloalkyl or C4-C5-heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R40A;
• R40A cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R41 is R42, R43, R44 or R45;
• R42 is phenyl which is unfused or fused with benzene, heteroarene or R42A;
• R42A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R43 is heteroaryl which is unfused or fused with benzene, heteroarene or R43A;
• R43A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R44 is C3-C6-cycloalkyl, C4-C6-cycloalkenyl, C3-C6-heterocycloalkyl or C4-C6-heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R44A;
• R44A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• R45 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two independently selected R46, OR46, NHR46, N(R46)2, C(O)NH2, C(O)NHR46, C(O)N(R46)2, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br or I substituents;
• R46 is R47, R48 or R49;
• R47 is phenyl which is unfused or fused with benzene, 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-C6-cycloalkyl, C4-C6-cycloalkenyl, C3-C6-heterocycloalkyl or C4-C6-heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R49A;
• R49A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
• wherein each foregoing cyclic moiety is independently unsubstituted, further unsubstituted, substituted or further substituted with one or two or three or four or five of 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;
• R50 is R51, R52, R53 or R54;
• R51 is phenyl which is unfused or fused with benzene, 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, C4-C6-cycloalkenyl, C3-C6-heterocycloalkyl or C4-C6-heteroycloalkenyl, each of which is unfused or fused with benzene, 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 or 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;
• and
• R55 is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, C3-C6-cycloalkyl, C4-C6-cycloalkyl, C3-C6-heterocycloalkyl or C4-C6-heterocycloalkyl.