2-arylimidazo[1,2-B]pyridazine, 2-phenylimidazo[1,2-A]pyridine, and 2-phenylimidazo[1,2-A]pyrazine derivatives

摘要

Disclosed are compounds of formula (I):;
where X, Y, X, A, R1, R2, and R3 are defined herein. Also disclosed are pharmaceutically acceptable salts of the compounds, compositions containing the compounds, and methods of using the compounds to treat, e.g., cancer.

主权项

1. A compound according to formula: or a pharmaceutically acceptable salt thereof, wherein
R1 is pyridyl optionally substituted at a substitutable position with one or more of R8 wherein R8 is halogen, —CN, —OH, —SH, —NO2, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NH(C1-C6 alkyl)-OH, —NH(C1-C6 alkyl)-(C1-C6 alkoxy), —C1-C6 alkoxy-OH, —C1-C6 alkoxy-(C1-C6 alkoxy), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), (C1-C6 alkoxy)C1-C6 alkyl, amino(C1-C6 alkyl), —S(C1-C6 alkyl), —CO2H, —CO2(C1-C6 alkyl), —C(O)(C1-C6 alkyl), —SO2(C1-C6 alkyl), —SO2NH2, —SO2NH(C1-C6 alkyl), —SO2N(C1-C6 alkyl), —CON(H)OR80 where R80 is hydrogen or a hydroxy protecting group, —CONH2, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —NHCO(C1-C6 alkyl), —C(═NH)NH2, —C(═NH)NH—NH2, —C(═NOH)NH2, or —NHCO2(C1-C6 alkyl) wherein each alkyl, alkenyl, alkynyl, alkoxy is optionally substituted at a substitutable carbon with —CO2(C1-C6)alkyl or —CON(H)OR80; R2 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, aryl, heteroaryl, heterocyclyl, (C3-C8 cycloalkyl)C1-C6 alkyl, (aryl)C1-C6 alkyl, (heteroaryl)C1-C6 alkyl, (heterocyclyl)C1-C6 alkyl, (aryloxy)C1-C6 alkyl, or (heteroaryloxy)C1-C6 alkyl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl group is optionally substituted at a substitutable position with one or more of R10;
wherein R10 is halogen, —CN, —OH, —NO2, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), (C1-C6 alkoxy)C1-C6 alkyl, amino(C1-C6 alkyl), —CO2H, —CO2(C1-C6 alkyl), —SO2(C1-C6 alkyl), —CONH2, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CON(H)OR80, —NHCO(C1-C6 alkyl), or —NHCO2(C1-C6 alkyl), wherein each alkyl, alkenyl, alkynyl, alkoxy is optionally substituted at a substitutable carbon with one R102,
where R102 is —COR104 where R104 is —(C1-C6)alkoxy, —NHOR80, or —NR7R110,
where R110 is aryl or heteroaryl, each of which is optionally substituted with up to three of halogen, —CN, —OH, —SH, —NO2, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), (C1-C6 alkoxy)C1-C6 alkyl, amino(C1-C6 alkyl), or —S(C1-C6 alkyl); andR7 is hydrogen or C1-C8 alkyl optionally with C1-C4 alkoxycarbonyl; R3 is hydrogen, halogen, —CN, —OH, —SH, —NO2, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, aryl, heteroaryl, heterocyclyl, (aryl)C1-C6 alkyl, or (heteroaryl)C1-C6 alkyl; A is N(R7)C(O)—, —N(R7)C(O)O—, —C(O)N(R7)—, —N(R7)C(O)N(R7)—, OC(O)N(R7)—, —S(O)2N(R7)—, —OS(O)2N(R7)—, —N(R7)S(O)2—, or —OS(O)2O—;
R5 represents hydrogen, halogen, —CN, —OH, —SH, —NO2, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), (C1-C6 alkoxy)C1-C6 alkyl, amino(C1-C6 alkyl), C3-C8 cycloalkyl, aryl, heteroaryl, heterocyclyl, (aryl)C1-C6 alkyl, or (heteroaryl)C1-C6 alkyl wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl group is optionally substituted at a substitutable position with one or more of R10; each Z is independently N or CR6, provided only one Z is N; and
each R6 is independently hydrogen, halogen, —CN, —OH, —SH, —NO2, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), (C1-C6 alkoxy)C1-C6 alkyl, amino(C1-C6 alkyl), C3-C8 cycloalkyl, aryl, heteroaryl, heterocyclyl, (aryl)C1-C6 alkyl, or (heteroaryl)C1-C6 alkyl wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl group is optionally substituted at a substitutable position with one or more of R10.