Naphthridine derivatives as PI3K inhibitors for the treatment of cancer and immune-inflammatory disease

摘要

Compounds of formulae (I) and (II): or a pharmaceutically acceptable salt thereof, wherein: R1 is a nitrogen-containing 5 to 7-membered heteroaryl or heterocycle; R2 and R3 are each independently (LQ)mY, are described. The compounds are PI3K inhibitors and are useful for the treatment of cancer and immune-inflammatory diseases.;

主权项

1. A compound of formula I or IIor a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of: R2 is (LQ)mY; each L is independently selected from the group consisting of: a direct bond, C1-C10 alkylene, C2-C10 alkenylene, C2-C10 alkynylene, arylene and C3-C10 cycloalkylene; each Q is independently selected from the group consisting of: a direct bond, heteroarylene, —O—, —NR6—, —C(O)—, —C(O)NR6—, —SO2—, —SO2—NR6—, —NH—C(O)—NR6—, —NH—SO2—NR6, —C(halogen)a(R6(2-a))—, —NR4R5—, and —C(O)NR4R5, where R4 and R5 together with the nitrogen to which they are attached form a 5 to 7-membered heterocycle linker; m is from 0 to 5; Y is independently selected from the group consisting of: H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl, C3-C10 cycloalkyl, heteroaryl, —OR6, —N(R6)2, —C(O)R6, —C(O)OR6, —C(O)N(R6)2, —SO2—R6, —SO2—N(R6)2, —NH—C(O)—N(R6)2, —NH—SO2—N(R6)2, halogen, —C(halogen)bR6(3-b); b is from 1 to 3; a is 1 or 2; R3 is selected from the group consisting of:
(a) aryl substituted with from one to five substituents independently selected from the group of C1-C3 hydroxyalkyl, —N(benzyl)2, C2-C10 alkenyl, C2-C10 alkynyl, aryl, C3-C10 cycloalkyl, heteroaryl, —OR6, —N(R6)2, —C(O)R6, —C(O)OR6, —C(O)N(R6)2, —SO2—R6, —SO2—N(R6)2, —NH—C(O)—N(R6)2, —NH—SO2—N(R6)2, halogen, and —C(halogen)bR6(3-b);(b) (C1-C10 alkylene)-NR6-aryl; and(c) a bicyclic heteroaryl containing at least one nitrogen atom; and each R6 is independently selected from the group consisting of H, C1-C10 alkyl, aryl or heteroaryl.