Bicyclic azaheterocyclobenzylamines as PI3K inhibitors

摘要

The present invention provides bicyclic azaheterocyclobenzylamines of Formula I:;
wherein the variables are defined herein, 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 II:or a pharmaceutically acceptable salt thereof, wherein:
V is CH2; T is CH2, or CH(CH3); Q is CH2, CH(CH3), or CH(CH2CH3); U is O; R1 is C1-3 alkyl; R3b is H, Cy, —(C1-3alkylene)-Cy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C(═O)Rb, C(═O)NRcRd, C(═O)ORa, S(═O)2Rb, or S(═O)2NRcRd; wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are optionally substituted by 1, 2, 3, or 4 independently selected R13b groups; R4 is H, halo, OH, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, or C1-4 haloalkoxy; R5 is halo, OH, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, or cyclopropyl; R6 is H; R8 is H, halo, —OH, —CN, C1-6 alkyl, or C1-6 haloalkyl; R10 is H or C1-4 alkyl; each R11 is independently selected from halo, OH, NO2, CN, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, carbamyl, C1-3 alkylcarbamyl, and di(C1-3 alkyl)carbamyl; each R13b is independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, ORa1, SRa1, C(═O)Rb1, C(═O)NRc1Rd1, C(═O)ORa1, OC(═O)Rb1, OC(═O)NRc1Rd1, NRc1Rd1, NRc1C(═O)Rb1, NRc1S(═O)Rb1, NRc1S(═O)2NRc1Rd1, S(═O)Rb1, S(═O)2Rb1, and S(═O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl are each optionally substituted with 1, 2, or 3 independently selected R11 groups; each Cy is independently selected from C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl, wherein said C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl are optionally substituted with 1, 2, 3, or 4 independently selected R13b groups; each Ra, Rc, and Rd is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and Cy; wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 independently selected R13b groups; each Rb is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and Cy; wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 independently selected R13b groups; or each Ra1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, or 3 independently selected R11 groups; and each Rb1 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, or 3 independently selected R11 groups.