Cycloalkyl-Linked Diheterocycle Derivatives

摘要

The present invention relates to compounds of formula (I);or pharmaceutically acceptable salts thereof, wherein A, L, D, R1-R15, w, x, y, and z are defined herein. The novel cycloalkyl-linked diheterocycle derivatives that are useful in the treatment of abnormal cell growth, such as cancer, in mammals. The present invention also relates to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

主权项

1. A compound of formula (I)wherein
A and D are independently 5 or 6-membered heteroaryl optionally substituted by one or two R7 groups; L is —(C4-C10 cycloalkyl)- optionally substituted by one to three substituents selected from the group consisting of halogen, cyano, C1-C4 alkyl, hydroxy, and C1-C4 alkoxy; R1 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, —C(O)R10a, or 5-6 membered heteroaryl, wherein the C3-C6 cycloalkyl and the 5-6 membered heteroaryl are independently optionally substituted by one or two R15 groups; R2 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, —C(O)R10b, or 5-6 membered heteroaryl, wherein the C3-C6 cycloalkyl and the 5-6 membered heteroaryl are independently optionally substituted by one or two R15 groups; R3, R4, R5 and R6 are each independently hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy or C3-C6 cycloalkyl; each R7 is each independently hydrogen, halogen, cyano, C1-C2 alkyl, hydroxy, C1-C2 alkoxy, or —N(R11)(R12), wherein the C1-C2 alkyl and the C1-C2 alkoxy are each independently optionally substituted by halogen or hydroxy; R10a and R10b are each independently hydrogen, C1-C4 alkyl, —[C(R13)(R14)]z—(C4-C10 cycloalkyl), —[C(R13)(R14)]z-(4-6 membered heterocycloalkyl), —[C(R13)(R14)]z—(C6-C10 aryl), or —[C(R13)(R14)]z-(5-10 membered heteroaryl), wherein the C1-C4 alkyl, the C4-C10 cycloalkyl, the 4-6 membered heterocycloalkyl, the C6-C10 aryl, and the 5-10 membered heteroaryl in R10a and R10b are each independently optionally substituted by one, two or three halogen, cyano, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, —(CH2)w—N(R11)(R12), —(CH2)w—C(O)N(R11)(R12), —C(O)OR11, —N(R11)C(O)R12, —S(O)2R11, or —S(O)N(R11)(R12) groups; each R11, R12, R13, R14 and R15 is independently hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, or 3-6 membered heterocycloalkyl, wherein the C1-C4 alkyl, the C3-C6 cycloalkyl, and the 3-6 membered heterocycloalkyl are each independently optionally substituted by one, two or three substituents selected from the group consisting of halogen, cyano, hydroxy, and methoxy; w is 0, 1, 2 or 3; x is 0 or 1; y is 0 or 1, provided that at least one of x and y is 0; and z is 0, 1, 2 or 3; or a pharmaceutically acceptable salt thereof.