| 主权项 |
1. A method of treating a subject with a cancer selected from breast cancer, prostate cancer, colon cancer, renal cell carcinoma, glioblastoma multiforme cancer, bladder cancer, melanoma, bronchial cancer, lymphoma, and liver cancer, comprising administering to the subject an effective amount of a compound having structural formula I: or a pharmaceutically acceptable salt thereof, wherein: Z is ═C(R2)— or ═N—; each of X1 and X2 is independently selected from ═N— and ═C(R3)—; X3 is selected from ═N— and ═C(R6)—; no more than one of X1, X2, and X3 is ═N—; each R1 and R2 is independently selected from hydrogen, halo, —OH, —CN, C1-C4 alkyl, —O—(C1-C4 alkyl), —N(R7)2, —(C0-C4 alkylene)-aryl, —(C0-C4 alkylene)-heteroaryl, —(C0-C4 alkylene)-heterocyclyl, and —(C0-C4 alkylene)-carbocyclyl; or
one R1 and R2 are taken together with atoms to which they are bound to form an aryl, heteroaryl, heterocyclyl, or carbocyclyl ring; each R3 and R6 is independently selected from hydrogen, halo, —CN, —(C0-C4 alkylene)-R8, —(C2-C6 alkenyl or alkynyl)-R9, —(C1-C4 alkylene)-O—R9, —(C1-C4 alkylene)-O—(C1-C4 alkylene)-R8, —O—(C0-C4 alkylene)-R9, —O—(C2-C4 alkylene)-O—R8, —O—(C1-C4 alkylene)-R9, —(C0-C4 alkylene)-N(R7)2, —(C0-C4 alkylene)-C(O)—O—R9, —(C0-C4 alkylene)-O—C(O)—R9, —(C0-C4 alkylene)-C(O)—N(R7)2, —(C0-C4 alkylene)-N(R9)—C(O)—R9, —O—(C1-C4 alkylene)-C(O)—N(R7)2, —O—(C2-C4 alkylene)-N(R9)—C(O)—(R7), —(C0-C4 alkylene)-S(O)—R8, —(C0-C4 alkylene)-S(O)2—R8 and —(C0-C4 alkylene)-S(O)2—N(R7)2; or
two R3 are taken together with the carbon atoms to which they are bound to form an aryl, heteroaryl, heterocyclyl, or carbocyclyl fused to the ring comprising X1, X2 and X3; Rx is Q, —S(O)2-Q, —C(O)-Q, or —CH(R4)(R5); Q is selected from aryl, heteroaryl, heterocyclyl, and carbocyclyl; R4 is selected from C2-C6 alkyl, —CH2—O—(C1-C4 alkyl) and —(C0-C6 alkylene)-Q, wherein one or two methylene units in the alkyl or alkylene portion of R4 are optionally and independently replaced by —O—, —S—, —S(═O)—, —S(═O)2—, or —N(R10)—; or
one methylene unit of R4 is taken together with X2 or X3, when the X2 or X3 is ═C(R3)—, and the intervening atoms to form a heteroaryl or heterocyclyl fused to the ring comprising X1, X2, and X3; R5 is selected from hydrogen, —(C0-C6 alkylene)-Q, and C1-C6 alkyl, wherein one or two methylene units in R5 are optionally and independently replaced by —O—, —S—, —S(═O)—, —S(═O)2—, or —NR10—; each R7 is independently selected from —(C0-C4 alkylene)-R9, —(C0-C4 alkylene)-O—R9, —S(O)2—R8, —C(═O)—R8, —C(═O)—N(R9)2, —(C1-C4 alkylene)-O—C(═O)—R8 and —(C0-C4 alkylene)-C(═O)—O—R9; or
two R7 are taken together with the nitrogen atom to which they are commonly bound to form an optionally substituted heterocyclyl or heteroaryl ring; R8 is selected from C1-C4 alkyl, aryl, heteroaryl, carbocyclyl and heterocyclyl; R9 is selected from hydrogen and R8; R10 is selected from hydrogen, C1-C4 alkyl, —S(═O)2—R9, —C(═O)—R8, —C(═O)—N(R9)(R12), and —C(═O)—O—R11; R11 is selected from unsubstituted C1-C4 alkyl and C1-C4 haloalkyl; R12 is selected from hydrogen, unsubstituted C1-C4 alkyl and C1-C4 haloalkyl; wherein unless otherwise designated any alkyl, alkylene, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl or carbocyclyl portion of the compound is optionally substituted; and wherein:
when X3 is ═N—, X2 is ═C(CH3)—, X1 is ═C(H)—, and Rx is 2-fluorophenyl; then R1 and R2 are not taken together with atoms to which they are bound to form when each R1 is methyl, Z is ═C(H)—, each of X2 and X3 is ═C(CH3)—, and X1 is ═C(H)—; then Rx is other than unsubstituted cyclohexyl, benzyl, pyridin-3-yl, or pyridin-2-yl;when each R1 is methyl, Z is ═C(H)—, X3 is ═N—, and Rx is phenyl or 4-fluorophenyl; then the R3 of X and the R3 of X2 are not taken together to form unsubstituted C5-C7 cycloalkyl fused to the ring comprising X1, X2 and X3;when X1 is ═N—, R5 is hydrogen, and R4 is taken together with X3 to form wherein “1” represents the portion of the ring bound to X2, and “2” represents the portion of the ring bound to the ring carbon adjacent to X3; then X2 is other than ═C(cyclopropyl)-, ═C(C(CH3)3)—, or ═C(CH2CH(CH3)2)—, wherein the cyclopropyl is unsubstituted;when X2 is ═N—, X3 is ═C(H)—, each R1 is methyl, Z is ═C(H)—, and Rx is 4-methylphenyl, unsubstituted phenyl, or unsubstituted benzyl; then X1 is other than ═C(3-methylphenyl)-, ═C(3-methoxyphenyl)-, ═C(phenyl)-, ═C(4-chlorophenyl), ═C(thien-2-yl)-, or ═C(pyridin-3-yl); andwhen X2 is ═N—, X1 is ═C(H)—, each R1 is methyl, Z is ═C(H)—, and Rx is pyridin-2-yl, 2,4-dichlorophenyl or 3-methylphenyl; then X3 is other than ═C(CH3)—, ═C(CH2CH3)—, or ═C(cyclopropyl)-;when X2 is ═N—, X1 is ═C(CH3)—, and X3 is ═C(CH3)—, the Rx is other than 2,4-difluorophenyl or 3-chloro-4-cyanophenyl; andthe compound is other than: |
