| 主权项 |
1. A method of slowing progression of cancer and/or ameliorating one or more symptoms of cancer in a subject with cancer, comprising administering an effective amount of a compound represented by the following structural formula: or a pharmaceutically acceptable salt thereof, wherein:
ring A is optionally substituted with one or more substituents represented by Ra and ring B is optionally and independently substituted with one or more substitutents represented by Rb;ring C is a 5-membered heteroaromatic ring wherein one of X1-X3 is N, one of X1-X3 is NR5, and one of X1-X3 is N or CR6;Y is independently N or CH or CRa;each of Ra and Rb independently is:
halogen, —C(O)OR1, —C(O)R1, —C(S)R1, —OC(O)R1—, —C(O)NR1R2, —C(S)NR1R2, —OC(O)NR1R2, —S(O)R1, —S(O)2R1, —SO3R1, —SO2NR1R2, —OR1, —SR1, —NR1R2, —NR2C(O)R1, —NR2S(O)R1, —NR2C(O)OR1, —NR2C(O)ONR1R2, —N(R2)C(O)NR1R2, —NR2SO2NR1R2, —NR2SO2R1; —NO2, —CN, —NCS; or two ortho Ra groups taken together form —O—[CH2]p—O—, —S—[CH2]p—S— or —[CH2]q—; orC1-10 aliphatic group optionally substituted with one or more substituents selected from the group consisting halogen, nitro, cyano, —N(R21)2, —C(O)N(R21)2, —C(O)N(R21)2, —NR21C(O)R21, —SO2R22, —SO2N(R21)2, —NR21SO2R22, —NR21C(O)OR21, —OC(O)N(R21)2, —NR21C(O)N(R21)2, —NR21C(O)N(R21)2, —NR21SO2N(R21)2, —OR21, —SR21, C1-10 haloalkoxy, —C(O)R21, —C(O)OR21 and —OC(O)R21; or(C0-10alkylene)-Ar1, (C2-10 alkenylene)-Ar1, wherein Ar1 is a C6-14 aryl group or a 5-14 membered heteroaryl group, each optionally and independently substituted with one or more substituents selected from the group consisting of halogen, nitro, cyano, C1-10 alkyl, C1-10 haloalkyl, (C1-10 haloalkoxy)C1-10alkyl, (C1-10 alkoxy)C1-10alkyl, C1-10 hydroxyalkyl, C1-10 aminoalkyl, (C1-10 alkylamino)C1-10alkyl, (C1-10 dialkylamino)C1-10alkyl, —N(R21)2, —C(O)N(R21)2, —C(O)N(R21)2, —NR21C(O)R21, —SO2R22, —SO2N(R21)2, —NR21SO2R22, —NR21C(O)N(R21)2, —NRC(O)ON(R)2, —NR21SO2N(R21)2, —OR21, —SR21, C1-10haloalkoxy, —C(O)R21, —C(O)OR21, —OC(O)R21, phenyl and 5-6 membered heteroaryl, wherein said phenyl and said 5-6 membered heteroaryl are each independently and optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy and C1-3 haloalkoxy;each R1 independently is:i) hydrogen;ii) a C6-14 aryl group or a 5-14 membered heteroaryl group, each optionally and independently substituted with one or more substituents selected from the group consisting of halogen, —NO2, —CN, —NCS, C1-C10 aliphatic, (C1-10-alkylene)-Ar10, (C2-10 alkenylene)-Ar10, —C(O)OR10, —C(O)R10, —C(S)R10, —OC(O)R10, —C(O)N(R11)2, —C(S)N(R11)2, —OC(O)N(R11)2, —S(O)R12, —S(O)2R12, —SO3R12, —SO2N(R11)2, —OR10, —SR10, —N(R11)2, —NR11C(O)R10, —NR11S(O)R12, —NR11C(O)OR12, —N(R11)C(O)N(R11)2, —NR11SO2N(R11)2 and —NR11SO2R12; oriii) a C1-10 aliphatic group optionally substituted with one or more substituents selected from the group consisting of halogen, —NO2, —CN, —NCS, Ar10, —C(O)OR10, —C(O)R10, —C(S)R10, —OC(O)R10, —C(O)N(R11)2, —C(S)N(R11)2, —OC(O)N(R11)2, —S(O)R12, —S(O)2R12, —SO3R12, —SO2N(R11)2, —OR10, —SR10, —N(R11)2, —NR11C(O)R10, —NR11S(O)R12, —NR11C(O)OR12, —N(R11)C(O)N(R11)2, —NR11SO2N(R11)2 and —NR11SO2R12,
provided that R1 is other than hydrogen when Ra or Rb is —S(O)R1, —S(O)2R1, —SO3R1, —NR2S(O)R1 or —NR2SO2R1; andeach R2 independently is —H or C1-C6 alkyl, or, taken together with NR1, forms a non-aromatic heterocyclic group optionally substituted with one or more substituents selected from the group consisting of ═O, ═S, halogen, nitro, cyano, hydroxy, C1-6alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, amino, C1-6 alkylamino, C1-6 dialkylamino, C1-6 aminoalkyl, (C1-6 alkylamino)C1-6 alkyl, (C1-6 dialkylamino)C1-6 alkyl, (phenyl)C1-6 alkyl, (5-6 membered heteroaryl)C1-6 alkyl, C1-6alkoxy, C1-6haloalkoxy, C1-6alkylcarbonyloxy, C1-6 alkoxycarbonyl, C1-6alkylcarbonyl, phenyl and 5-6 membered heteroaryl;R3 is —H, halogen, C1-6 alkyl or C1-6 haloalkyl;each of R4 and R5 independently is —H, C1-6 alkyl, phenyl, —C(O)(C1-6 alkyl), —C(O)(phenyl), —C(O)O(C1-6alkyl), —C(O)O(phenyl), —S(O)2(C1-6alkyl) or —S(O)2(phenyl), wherein each alkyl in the groups represented by R4 and R5 independently is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, —C(O)NH2, phenyl, 5-6 membered heteroaryl, C1-6 alkoxy, C1-6alkylamino, C1-6dialkylamino and C1-6haloalkoxy, and wherein each phenyl in the groups represented by R4 and R5 independently is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy and C1-6 haloalkoxy;R6 is hydrogen, halogen, nitro, cyano, R′, —OR, —SR, —N(R)2, —C(O)R, —C(O)OR, —OC(O)R, —C(O)N(R)2, —OC(O)N(R)2, —NRC(O)R, —NRC(O)OR, —SOR′, —SO2R′, —SO3R′, —SO2N(R)2, —NRS(O)R′, —NRSO2R′, —NRC(O)N(R)2, —NRC(O)ON(R)2, or —NRSO2N(R)2;each R10 independently is:i) hydrogen;ii) a C6-14 aryl group or a 5-14 membered heteroaryl group, each optionally and independently substituted with one or more substituents selected from the group consisting of halogen, nitro, cyano, hydroxy, C1-10 alkyl, C1-10 haloalkyl, (C1-10 haloalkoxy)C1-10alkyl, (C1-10 alkoxy)C1-10alkyl, C1-10 hydroxyalkyl, C1-10 aminoalkyl, (C1-10 alkylamino)C1-10alkyl, (C1-10 dialkylamino)C1-10 alkyl, (phenyl)C1-10 alkyl, (5-6 membered heteroaryl)C1-10 alkyl, amino, C1-10 alkylamino, C1-10 dialkylamino, C1-10 alkoxy, C1-10 haloalkoxy, C1-10 alkylcarbonyloxy, C1-10 alkoxycarbonyl and C1-10 alkylcarbonyl; oriii) a C1-10 alkyl group optionally substituted with one or more substituents selected from the group consisting of halogen, nitro, cyano, hydroxy, C1-10 haloalkyl, C1-10alkoxy, C1-10haloalkoxy, amino, C1-10alkylamino, C1-10 dialkylamino, C1-10 alkylcarbonyloxy, C1-10 alkoxycarbonyl, C1-10 alkylcarbonyl and phenyl, said phenyl being optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy and C1-3 haloalkoxy;each R11 independently is R10, —CO2R10, —SO2R10 or —C(O)R10, or—N(R11)2 taken together is a non-aromatic heterocyclic group optionally substituted with one or more substituents selected from the group consisting of ═O, ═S, halogen, nitro, cyano, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, amino, C1-6 alkylamino, C1-6 dialkylamino, C1-6 aminoalkyl, (C1-6 alkylamino)C1-6 alkyl, (C1-6 dialkylamino)C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylcarbonyloxy, C1-6 alkoxycarbonyl and C1-6 alkylcarbonyl; andeach R12 independently is R10 provided that R12 is not hydrogen;each R21 independently is hydrogen, C1-6 alkyl, phenyl or 5-6 membered heteroaryl, wherein each of the phenyl and heteroaryl groups represented by R21 is independently and optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy and C1-3 haloalkoxy, and wherein the alkyl group represented by R21 is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy and C1-3 haloalkoxy; orN(R21)2 forms a non-aromatic heterocyclic group optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, ═O, C1-3alky, C1-3haloalkyl, C1-3alkoxy, C1-3haloalkoxy and amino; andeach R22 independently C1-6 alkyl, phenyl or 5-6 membered heteroaryl, wherein each of the phenyl and heteroaryl groups represented by R22 is independently and optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, C1-3alkyl, C1-3haloalkyl, C1-3alkoxy and C1-3haloalkoxy, and wherein the alkyl group represented by R22 is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy and C1-3 haloalkoxy;each R independently is hydrogen, C1-10 aliphatic, phenyl or 5-6 membered heteroaryl, wherein the aliphatic group represented by R is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, phenyl, 5-6 membered heteroaryl, C1-6 alkoxy, C1-6 haloalkoxy, and wherein each of the phenyl and heteroaryl groups represented by R, and the phenyl and heteroaryl substituents for the aliphatic group represented by R independently are optionally and independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, orN(R)2 forms a non-aromatic heterocyclic group optionally substituted with one or more substituents selected from the group consisting of ═O, ═S, halogen, nitro, cyano, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, amino, C1-6 alkylamino, C1-6 dialkylamino, C1-6 aminoalkyl, (C1-6 alkylamino)C1-6 alkyl, (C1-6 dialkylamino)C1-6 alkyl, (phenyl)C1-6 alkyl, (5-6 membered heteroaryl)C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylcarbonyloxy, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyl, phenyl and 5-6 membered heteroaryl; andeach R′ independently is C1-10 aliphatic, phenyl, 5-12 membered heteroaryl or 9-12 membered heterocyclyl group, wherein the aliphatic group represented by R′ is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, nitro, cyano, amino, phenyl, 5-12 membered heteroaryl, 9-12 membered heterocyclyl group, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-6 alkylamino, C1-6 dialkylamino, —C(O)H, —C(O)(C1-C6 alkyl), —C(O)(C1-C6 haloalkyl), —C(O)(phenyl), —C(O)(non-aromatic heterocyclic group), —C(O)O(C1-C6 alkyl), —C(O)O(C1-C6 haloalkyl), —C(O)O(phenyl), —OC(O)(C1-C6 alkyl), —OC(O)(C1-C6 haloalkyl), —OC(O)(phenyl), —S(O)2(C1-C6 alkyl), —S(O)2(C1-C6 haloalkyl) and —S(O)2(phenyl), and wherein each of the phenyl, heteroaryl and heterocyclyl groups represented by R′, and the phenyl, heteroaryl and heterocyclyl groups in the substituents for the aliphatic group represented by R′ independently are optionally substituted with one or more substituents selected from the group consisting of halogen, —OH, —SH, nitro, cyano, amino, C1-6 alkylamino, C1-6 dialkylamino, (C1-6 dialkylamino)C1-6 dialkylamino, C1-C6 alkyl, C1-C6 haloalkyl, —O(C1-6alkyl), —O-(non-aromatic heterocyclic group), —S(C1-6alkyl), —O(C1-6haloalkyl), (C1-6 haloalkoxy)C1-6 alkyl, (C1-6 alkoxy)C1-6 alkyl, C1-6 hydroxyalkyl, (C1-6 aminoalkyl), (C1-6 alkylamino)C1-6 alkyl, (C1-6 dialkylamino)C1-6 alkyl, (C1-6 dialkylamino)C1-6 alkoxy, (phenyl)C1-6 alkyl, (5-6 membered heteroaryl)C1-6 alkyl, (non-aromatic heterocyclic group)C1-6 alkyl (optionally substituted with halogen, —OH, C1-6 hydroxyalkyl, C1-6 alkyl, (C1-6 alkoxy)C1-6 alkyl, C1-6 acyl, C5-7 cycloalkyl, C1-6 alkylamino, C1-6 dialkylamino or non-aromatic heterocyclic group), (5-6 membered heteroaryl)C1-6 alkoxy, (non-aromatic heterocyclic group)C1-6 alkoxy, —C(O)(C1-C6 alkyl), —C(O)(C1-C6 haloalkyl), —C(O)(phenyl), —C(O)(non-aromatic heterocyclic group), —C(O)O(C1-C6 alkyl), —C(O)O(C1-C6 haloalkyl), —C(O)O(phenyl), —OC(O)(C1-C6 alkyl), —OC(O)(C1-C6 haloalkyl), —OC(O)(phenyl), —S(O)2NH2, —S(O)2(C1-C6 alkyl), —S(O)2(C1-6 haloalkyl), and —S(O)2(phenyl);each Ar10 independently is a C6-14 aryl group or a 5-14 membered heteroaryl group, each optionally and independently substituted with one or more substituents selected from the group consisting of halogen, nitro, cyano, —OH, —SH, —O(C1-10 alkyl), —S(C1-10 alkyl), C1-10 alkyl, C1-10 haloalkyl, (C1-10 haloalkoxy)C1-10alkyl, (C1-10 alkoxy)C1-10alkyl, C1-10 hydroxyalkyl, (C1-10 aminoalkyl, (C1-10 alkylamino)C1-10alkyl, (C1-10 dialkylamino)C1-10alkyl, (phenyl)C1-10 alkyl, (5-6 membered heteroaryl)C1-10 alkyl, amino, C1-10 alkylamino, C1-10 dialkylamino, C1-10 haloalkoxy, C1-10 alkylcarbonyloxy, C1-10 alkoxycarbonyl and C1-10 alkylcarbonyl;each p is 1, 2 or 3; andeach q is 2, 3, 4 or 5,wherein the cancer is selected from the group consisting of neuroblastoma, glioblastoma multiforme, lymphoma, leukemia, osteosarcoma, germinoma, glioma, fibrosarcoma, gastrointestinal sarcoma, fibrous histiocytoma, round cell sarcoma, synovial sarcoma, cervical cancer,anogenital cancer, head and neck cancer, and oropharyngeal cancer. |
