| 主权项 |
1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:wherein
X1 is NR7 or CR7; X2 is N, NRB, CR8, O, or S; X3 is NR8, CR8, O, or S; X4 is C or N; Y1 is CH; Y2 is N or CR6; Y3 is N or CR11; each of R5, R9, and R10, independently, is H or C1-C6 alkyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, COOH, C(O)O—C1-C6 alkyl, cyano, C1-C6 alkoxyl, amino, mono-C1-C6 alkylamino, di-C1-C6 alkylamino, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl; each R6 independently is H, halo, ORa, —NRaRb, —C(O)Ra, —C(O)ORa, —C(O)NRaRb, —NRbC(O)Ra, —S(O)2Ra, —S(O)2NRaRb, or RS2, in which each of Ra and Rb, independently is H or RS3 and each of RS2 and RS3, independently, is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl; or Ra and Rb, together with the N atom to which they are attached, form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatoms to the N atom; and each of RS2, RS3, and the 4 to 7-membered heterocycloalkyl ring containing Ra and Rb, is optionally substituted with one or more -Q2-T2, wherein Q2 is a bond or C1-C3 alkyl linker each optionally substituted with halo, cyano, hydroxyl or C1-C6 alkoxy, and T2 is H, halo, cyano, —ORc, —NRcRd, —(NRcRdRd′)+A−, —C(O)Rc, —C(O)ORc, —C(O)NRcRd, —NRdC(O)Rc, —NRdC(O)ORc, —S(O)2Rc, —S(O)2NRcRd, or RS4, in which each of Rc, Rd, and Rd′, independently is H or RS5, A− is a pharmaceutically acceptable anion, each of RS4 and RS5, independently, is C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, or Rc and Rd, together with the N atom to which they are attached, form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatoms to the N atom, and each of RS4, RS5, and the 4 to 7-membered heterocycloalkyl ring containing Rc and Rd, is optionally substituted with one or more -Q3-T3, wherein Q3 is a bond or C1-C3 alkyl linker each optionally substituted with halo, cyano, hydroxyl or C1-C6 alkoxy, and T3 is selected from the group consisting of H, halo, cyano, C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 7-membered heterocycloalkyl, 5 to 6-membered heteroaryl, ORe, COORe, —S(O)2Re, —NReRf, and —C(O)NReRf, each of Re and Rf independently being H or C1-C6 alkyl optionally substituted with OH, O—C1-C6 alkyl, or NH—C1-C6 alkyl; or -Q3-T3 is oxo; or -Q2-T2 is oxo; or any two neighboring -Q2-T25 together with the atoms to which they are attached form a 5- or 6-membered ring optionally containing 1-4 heteroatoms selected from N, O and S and optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, COOH, C(O)O—C1-C6 alkyl, cyano, C1-C6 alkoxyl, amino, mono-C1-C6 alkylamino, di-C1-C6 alkylamino, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 7-membered heterocycloalkyl, and 5 to 6-membered heteroaryl; provided that Q2-T2 is not H; each R7 independently is -Q4-T4, in which Q4 is a bond, C1-C4 alkyl linker, or C2-C4 alkenyl linker, each linker optionally substituted with halo, cyano, hydroxyl or C1-C6 alkoxy, and T4 is H, halo, cyano, NRgRh, —ORg, —C(O)Rg, —C(O)ORg, —C(O)NRgRh, —C(O)NRgORh, —NRgC(O)Rh, —S(O)2Rg, or RS6, in which each of Rg and Rh, independently is H or RS7, each of RS6 and RS7, independently is C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of RS6 and RS7 is optionally substituted with one or more Q5-T5, wherein Q5 is a bond, C(O), C(O)NRk, NRkC(O), NRk, S(O)2, NRkS(O)2, or C1-C3 alkyl linker, Rk being H or C1-C6 alkyl, and T5 is H, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, hydroxyl, cyano, C1-C6 alkoxyl, amino, mono-C1-C6 alkylamino, di-C1-C6 alkylamino, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl and T5 is optionally substituted with one or more substituents selected from the group consisting of halo, C1-C6 alkyl, hydroxyl, cyano, C1-C6 alkoxyl, amino, mono-C1-C6 alkylamino, di-C1-C6 alkylamino, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 7-membered heterocycloalkyl, and 5 to 6-membered heteroaryl except when T5 is H, halo, hydroxyl, or cyano; or -Q5-T5 is oxo; provided that -Q4-T4 is not H; and each of R8 and R11, independently, is H, halo, hydroxyl, COOH, cyano, RS8, ORS8, or COORS8, in which RS8 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, amino, mono-C1-C6 alkylamino, or di-C1-C6 alkylamino, and RS8 is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, COOH, C(O)O—C1-C6 alkyl, cyano, C1-C6 alkoxyl, amino, mono-C1-C6 alkylamino, and di-C1-C6 alkylamino; X is a monocyclic or bicyclic 5 to 10-membered saturated, unsaturated, or aromatic ring containing 2-4 heteroatom ring members and optionally substituted with one or more -Q7-T7, wherein Q7 is a bond or C1-C3 alkyl linker each optionally substituted with halo, cyano, hydroxyl or C1-C6 alkoxy, and T7 is H, —OR, —NRnRr, —C(O)Rn, —C(O)ORn, —C(O)NRnRr, —S(O)2Rn, —S(O)2NRnRr, or RS9, in which each of Rn and Rr, independently is H or RS10, each of RS9 and RS10, independently, is C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, or Rn and Rr, together with the N atom to which they are attached, form a 4 to 12-membered heterocycloalkyl ring having 0 or 1 additional heteroatom, and each of RS9, RS10, and the 4 to 12-membered heterocycloalkyl ring formed by R, and Rr, is optionally substituted with one or more -Q8-T8, wherein Q8 is a bond or C1-C3 alkyl linker each optionally substituted with halo, cyano, hydroxyl or C1-C6 alkoxy, and T8 is selected from the group consisting of halo, cyano, C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 12-membered heterocycloalkyl, 5- or 6-membered heteroaryl, ORs, COORs, —S(O)2Rs, —NRsRt, and —C(O)NRsRt, each of Rs and Rt independently being H or C1-C6 alkyl, or -Q8-T8 is oxo; or -Q7-T7 is oxo; or any two neighboring -Q7-T7 together with the atoms to which they are attached form a 5- or 6-membered ring optionally containing 1-4 heteroatoms selected from N, O and S and optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, COOH, C(O)O—C1-C6 alkyl, cyano, C1-C6 alkoxyl, amino, mono-C1-C6 alkylamino, di-C1-C6 alkylamino, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl; and n is 0, 1, 2, 3, 4, or 5; provided that at most one of X2 and X3 is O or S, at least one of X1, X2, X3, X4, Y2, and Y3 is N or NR7, and X1, X2, X3, X4, Y1, Y2, and Y3 are assigned such that themoiety in Formula (I) is a bicyclic heteroaryl system. |
