Benzoheterocyclic compounds and use thereof

摘要

Disclosed are compound of formula (I) and pharmaceutically accepted salts and prodrugs thereof, wherein each of R1, R2, R3, R4, R5, R6, X1 and X2 is as defined in the description. These compounds are protein kinases inhibitors, especially the inhibitors of Mek, which are useful in the treatment of cancers and inflammation of mammals. Disclosed are the treatment methods of cancers and inflammation of mammals as well as pharmaceutical compositions comprising the compounds described herein. The preparation of benzoheterocyclic compounds are disclosed. Disclosed are the preparation of potential drug candidates, such as benzooxazol, benzothiazol, benzothiadiazol and the like.;

主权项

1. A compound of the formula (I):or a salt, prodrug or solvate thereof, wherein:
X1 is CR11 or N; X2 is O, S or carbonyl; R1, R2, R4 and R5 are independently hydrogen, halo, nitro, azido, hydroxy, C1-C10 alkoxy, halo-substituted C1-C10 alkoxy, acyloxy, C1-C10 alkylthio, halo-substituted C1-C10 alkylthio, amino, carboxy, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C10 cycloalkyl; R3 is hydrogen, halo, cyano, nitro, azido, hydroxy, C1-C10 alkoxy, halo-substituted C1-C10 alkoxy, acyloxy, mercapto, C1-C10 alkylthio, halo-substituted C1-C10 alkylthio, —SO2Ra, —SO2N(Rc)Rd, —N(Rc)Rd, —C(O)ORb, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C10 cycloalkyl; Ra is C1-C10 alkyl or C6-C14 aryl; each Rb, Rc and Rd is independently hydrogen or C1-C10 alkyl; R6 is —C(O)N(R8)OR7 or —NHSO2R10; R7 is C1-C10 alkyl substituted with at least one hydroxy group; R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl C1-C10 alkyl or C1-C10 alkyl C3-C10 cycloalkyl; R10 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl C1-C10 alkyl or C1-C10 alkyl C3-C10 cycloalkyl; and R11 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl or C3-C10 cycloalkyl C1-C10 alkyl; wherein each C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C10 cycloalkyl moiety may be unsubstituted or substituted with one or more groups independently selected from the group consisting of hydroxy, oxo, halo, cyano, nitro, trifluoromethyl, azido, amino, carboxy and mercapto.