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1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:wherein
X is A1 is C or N and when A1 is N, R3 is absent; A2 is N, O, or S and when A2 is O or S, R3 is absent; X1 is NR7 or CR7; X2 is N, NR8, CR8, O, or S; X3 is NR8, CR8, O, or S; X4 is C or N; Y1 is N or CH; Y2 is N or CR6; Y3 is N, or CR11; R1 is Q0-T0, in which Q0 is NR1a, O or S, R1a being H, OH, C1-C6 alkyl, or C1-C6 alkoxyl, and T0 is H or RS0, in which RS0 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, and RS0 is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, oxo, C(O)OH, C(O)O—C1-C6 alkyl, cyano, C1-C6 alkyl, 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 of R2, R3, and R4, independently, is -Q1-T1, in which Q1 is a bond or C1-C3 alkyl linker optionally substituted with halo, cyano, hydroxyl or C1-C6 alkoxy, and T1 is H, halo, hydroxyl, C(O)OH, cyano, azido, or RS1, in which RS1 is C1-C3 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, C1-C6 thioalkyl, C(O)O—C1-C6 alkyl, CONH2, SO2NH2, —C(O)—NH(C1-C6 alkyl), —C(O)—N(C1-C6 alkyl)2, —SO2—NH(C1-C6 alkyl), —SO2—N(C1-C6 alkyl)2, C3-C8 cycloalkyl, C6-C10 aryl, C6-C10 aryloxy, amino, mono-C1-C6 alkylamino, di-C1-C6 alkylamino, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, and RS1 is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, oxo, C(O)OH, C(O)O—C1-C6 alkyl, cyano, C1-C6 alkyl, 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; or neighboring R1 and R2, together with the atoms to which they are attached, form a 5- or 6-membered heteroaryl having 0 to 2 additional heteroatoms or a 5 to 12-membered heterocycloalkyl ring having 0 to 2 additional heteroatoms; or neighboring R1 and R4, together with the atoms to which they are attached, form a 5- or 6-membered heteroaryl having 0 to 2 additional heteroatoms or a 5 to 12-membered heterocycloalkyl ring having 0 to 2 additional heteroatoms; or neighboring R2 and R3, together with the atoms to which they are attached, form C5-C8 cycloalkyl, C6-C10 aryl, or a 5- or 6-membered heteroaryl having 1 to 3 heteroatoms, or a 5 to 12-membered heterocycloalkyl ring having 1 to 3 heteroatoms; or neighboring R3 and R4, together with the atoms to which they are attached, form C5-C8 cycloalkyl, C6-C10 aryl, or a 5- or 6-membered heteroaryl having 1 to 3 heteroatoms, or a 5 to 12-membered heterocycloalkyl ring having 1 to 3 heteroatoms; in which each of the ring structures formed by R1 and R2, by R1 and R4, by R2 and R3, or by R3 and R4, independently is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C(O)OH, C(O)O—C1-C6 alkyl, C(O)O—C1-C6 haloalkyl, cyano, C1-C6 alkoxyl, C1-C6 haloalkoxyl, amino, mono-C1-C6 alkylamino, alkylamino, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl; 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, 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-T2, 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, C1-C6 alkylene-C3-C8 cycloalkyl, C6-C10 aryl, C1-C6 alkylene-C6-C10 aryl, 4 to 12-membered heterocycloalkyl, C1-C6 alkylene-4 to 12-membered heterocycloalkyl, 5- or 6-membered heteroaryl, or C1-C6 alkylene-5- or 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, O—C1-C4 alkylene-C1-C4 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 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; 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, Y1, 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. |
