N-(1-(substituted-phenyl)ethyl)-9H-purin-6-amines as PI3K inhibitors

摘要

The present invention provides N-(1-(substituted-phenyl)ethyl)-9H-purin-6-amines derivatives that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.

主权项

1. A compound of Formula IIa:or a pharmaceutically acceptable salt thereof; wherein:
R1 is methyl or ethyl; R2 is selected from C1-6 alkyl, —O—(C1-6 alkyl), —O—(C1-4 alkylene)n-(4-7 membered heterocycloalkyl), and phenyl; wherein said phenyl is optionally substituted by 1, 2, 3, or 4 independently selected halo groups; Cy3 is selected from phenyl, a piperidine ring, a pyrrolidin-2-one ring, a 1,3-oxazolidin-2-one ring, an isoxazole ring, a pyrazole ring, a tetrazole ring, a triazole ring, a pyridine ring, a pyrimidine ring, an azetidine ring, a pyrrole ring, a tetrahydrofuran ring, and a morpholin-2-one ring; each of which is optionally substituted with 1, 2, 3, or 4 independently selected R3a groups; R4 is selected from H, halo, C1-3 alkyl, CN, cyano-C1-6 alkyl, and C1-6 haloalkyl; R5 is selected from C1-3 alkyl, halo, and CN; each R3a is independently selected from halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, (4-7 membered heterocycloalkyl)-C1-3 alkyl, (5-6 membered heteroaryl)-C1-3 alkyl, ORa, C(O)Rb, C(O)ORa, C(O)NRcRd, NRcRd, NRcC(O)Rb, and S(O)2Rb; wherein said C1-6 alkyl, C3-7 cycloalkyl, and 4-7 membered heterocycloalkyl are each optionally substituted by 1, 2, 3, or 4 groups independently selected from OH, CN, halo, C1-6 alkyl, C1-6 haloalkyl, cyano-C1-6 alkyl, HO—C1-6 alkyl, C1-4 alkoxy-C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, and C3-7 cycloalkyl; each Ra, Rc, and Rd is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl, C3-7 cycloalkyl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, CN, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, and amino; each Rb is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl; each of which is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, CN, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, and amino; and n is 0 or 1.