| 主权项 |
1. A compound of Formula (IIE):or a pharmaceutically acceptable salt thereof wherein:
each R2 is independently:
(a) -halo, —CN, —NO2, —OT3, —C(═O)T3, —C(═O)OT3, —C(═O)N(T1)(T2), —S(═O)2OH, —S(═O)T3, —S(═O)2T3, —S(═O)2N(T1)(T2), —N(T1)(T2), —N(T3)C(═O)T3, —N(T3)C(═O)N(T1)(T2), —N(T3)S(═O)2T3, or —N(T3)S(═O)2N(T1)(T2); or(b) —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C1-C6)alkoxy, —(C3-C7)cycloalkyl, —(C6-C14)bicycloalkyl, —(C8-C20)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C7-C14)bicycloalkenyl, —(C8-C20)tricycloalkenyl, -(5- or 6-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R8 groups; or(c) -phenyl, -naphthalenyl, —(C14)aryl, or -(5- or 6-membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R7 groups; a is an integer selected from 0, 1, and 2; each R4 is independently:
(a) —H; or(b) -halo, —CN, or —NO2; or(c) —X, —(C1-C6)alkyl-X, -(5- or 6-membered)heterocycle-X, or -(5- or 6-membered)heterocycle-(C1-C6)alkyl-X; or(d) —C(═Y)CN, —C(═Y)X, —C(═Y)T3, —C(═Y)YX, —C(═Y)YT3, —C(═Y)N(T1)(T2), —C(═Y)N(R9)CN, —C(═Y)N(R9)X, —C(═Y)N(R9)YH, —C(═Y)N(R9)YX, —C(═Y)N(R9)YCH2X, —C(═Y)N(R9)YCH2CH2X, or —C(═Y)N(R9)S(═O)2T3; or(e) —N(R9)X, —N(R9)—CH2X, —N(R9)—CH2CH2X, —N(R9)CH2N(R9)C(═N(R12))N(R12)2, —N(R9)—CH2CH2N(R9)C(═N(R12))N(R12)2, —N(T1)(T2), —N(T3)C(═Y)T3, —N(T3)C(═Y)YT3, —N(T3)C(═Y)N(T1)(T2), —N(T3)S(═O)2T3, or —N(T3)S(═O)2N(T1)(T2); or(f) —YH, —CH2YH, —CH2CH2YH, —YX, or —YT3; or(g) —S(═O)T3, —S(═O)2T3, —S(═O)N(T1)(T2), —S(═O)2N(T1)(T2), —S(═O)X, or —S(═O)2X; X is:
(a) —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C1-C6)alkoxy, —(C3-C7)cycloalkyl, —(C6-C14)bicycloalkyl, —(C8-C20)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C7-C14)bicycloalkenyl, —(C8-C20)tricycloalkenyl, -(5- or 6-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R8 groups; or(b) -phenyl, -naphthalenyl, —(C14)aryl, or -(5- or 6-membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R7 groups; each Y is independently O or S; Z is —[(C1-C10)alkyl optionally substituted by R1]h—, wherein h is 0 or 1; or —(C1-C10)alkyl-NR6C(═Y)—; each R1 is independently:
(a) -halo, —CN, —OH, —CH2OH, —CH2CH2OH, —NO2, —N(R6)7, —S(═O)NH2, —S(═O)2NH2, —C(═O)OV1, or —C(═O)CN; or(b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —O(C1-C6)alkyl, —(C3-C7)cycloalkoxy, —(C6-C14)bicycloalkyl, —(C8-C20)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C7-C14)bicycloalkenyl, —(C8—C20)tricycloalkenyl, or -(3- to 7-membered)heterocycle, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R9 groups; or(c) or
(d) -phenyl, -naphthalenyl, or —(C14)aryl, each of which is unsubstituted or substituted with an R7 group; or —Z—R1 is 3,3-diphenylpropyl- optionally substituted at the 3 carbon of the propyl with —CN, —C(═O)N(R6)2, —C(═O)OV1, or -tetrazolyl; or —Z—R1 is —(C1-C4)alkyl substituted with tetrazolyl; each R5 is independently —(C1-C4)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -(5- or 6-membered)heteroaryl, —(C1-C6)alkyl-C(═O)OR9, —OR9, —SR9, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, ═O, ═S, -halo, —N3, —NO2, —CH═N(R9), —N(R9)(C1-C6)alkyl-C(═O)OR9, —N(R9)2, —N(R9)OH, —N(R9)S(═O)R12, —N(R9)S(═O)2R12, —N(R9)C(═O)R12, —N(R9)C(═O)OR12, —C(═O)R9, —C(═O)OR9, —OC(═O)R9, —OC(═O)OR9, —S(═O)R9, or —S(═O)2R9; each R6 is independently —H, —(C1-C6)alkyl, or —(C3-C7)cycloalkyl, or two R6 groups attached to the same nitrogen atom can together form a 5- to 8-membered ring, wherein the number of atoms in the ring includes the nitrogen atom, and in which one of the 5- to 8-membered ring carbon atoms is optionally replaced by O, S, or N(T3); each R7 is independently —(C1-C4)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —OR9, —SR9, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, -halo, —N3, —NO2, —CH═N(R9), —N(R9)2, —N(R9)OH, —N(R9)S(═O)R12, —N(R9)S(═O)2R12, —N(R9)C(═O)R12, —N(R9)C(═O)N(T1)(T2), —N(R9)C(═O)OR12, —C(═O)R9, —C(═O)N(T1)(T2), —C(═O)OR9, —OC(═O)R9, —OC(═O)N(T1)(T2), —OC(═O)OR9, —S(═O)R9, or —S(═O)2R9; each R8 is independently —(C1-C4)alkyl, —(C7-C6)alkenyl, —(C2-C6)alkynyl, -(5- or 6-membered)heteroaryl, —(C1-C6)alkyl-C(═O)OR9, —OR9, —SR9, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, ═O, ═S, -halo, —N3, —NO2, —CH═N(R9), —N(R9)(C1-C6)alkyl-C(═O)OR9, —N(R9)2, —N(R9)OH, —N(R9)S(═O)R12, —N(R9)S(═O)2R12, —N(R9)C(═O)R12, —N(R9)C(═O)N(T1)(T2), —N(R9)C(═O)OR12, —C(═O)R9, —C(═O)N(T1)(T2), —C(═O)OR9, —OC(═O)R9, —OC(═O)N(T1)(T2), —OC(═O)OR9, —S(═O)R9, or —S(═O)2R9; each R9 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -benzyl, -(3- to 6-membered)heterocycle, —C(halo)3, —CH(halo)2, or —CH2(halo); if h is 0, then R11 can be —H, —CN, —C(═O)OR9, or —C(═O)N(R6)2 or R11 can be —(C1-C4)alkyl which is unsubstituted or substituted with —OH, —(C1-C4)alkoxy, —N(R6)2, —C(═O)OR9, or —C(═O)N(R6)2; if h is 1, then R11 can be —H, —CN, —OH, -halo, —C(═O)OR9, or —C(═O)N(R6)2 or R11 can be —(C1-C4)alkyl which is unsubstituted or substituted with —OH, —(C1-C4)alkoxy, —N(R6)2, —C(═O)OR9, or —C(═O)N(R6)2; otherwise, wherein Z is —(C1-C10)alkyl-NR6C(═Y)—, then R11 can be —H, —CN, —C(═O)OR9, or —C(═O)N(R6)2 or R11 can be —(C1-C4)alkyl which is unsubstituted or substituted with —OH, —(C1-C4)alkoxy, —N(R6)2, —C(═O)OR9, or —C(═O)N(R6)2; each R12 is independently —H or —(C1-C4)alkyl; m is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11; e and f are each an integer independently selected from 0, 1, 2, 3, 4, and 5 provided that 2≦(e+≦5; j and k are each an integer independently selected from 0, 1, 2, 3, and 4 provided that 1≦(j+k)≦4; each p is an integer independently selected from 0 and 1; each T1 and T2 is independently —H or —(C1-C10)alkyl which is unsubstituted or substituted with 1, 2 or 3 independently selected R5 groups and, optionally, in which any —(C1-C10)alkyl carbon atom except the carbon atom bonded directly to the atom to which T1 or T2 is attached is independently replaced by O, S, or N(R6), or T1 and T2 can together form a 5- to 8-membered ring wherein the number of atoms in the ring includes the nitrogen atom to which T1 and T2 are bonded, said 5- to 8-membered ring is unsubstituted or substituted with 1, 2 or 3 independently selected R5 groups and, optionally, any carbon atom in said 5- to 8-membered ring is independently replaced by O, S, or N(R6); each T3 is independently —H or —(C1-C10)alkyl which is unsubstituted or substituted with 1, 2 or 3 independently selected R5 groups and, optionally, in which any —(C1-C10)alkyl carbon atom except the carbon atom bonded directly to the atom to which T3 is attached is independently replaced by O, S, or N(R12); each V1 is independently —H, —(C1-C6)alkyl, —(C3-C7)cycloalkyl, -phenyl, or benzyl; and each halo is independently —F, —Cl, —Br, or —I; provided that if Z is —[(C1-C10)alkyl optionally substituted by R1]h— and h is 0 then R4 is not COOH. |
