IP Library › Granted Patent US 12,466,815

Granted Patent B2

US 12,466,815 · App. 18/212,444 · Granted Nov 11, 2025

Carboxamide compounds and uses thereof

Inventors: Oleg Vechorkin (Wilmington, DE); Jun Pan (Media, PA); Alexander Sokolsky (Philadelphia, PA); Evan Styduhar (Media, PA); Qinda Ye (Claymont, DE); Wenqing Yao (Chadds Ford, PA)

Assignee: Incyte Corporation

C07D403/14 C07D239/26 C07D401/12 C07D401/14 C07D403/12 C07D413/12 C07D413/14 C07D487/04 C07D487/08

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 12,466,815
App. No.: 18/212,444
Granted: Nov 11, 2025
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Disclosed are compounds of Formula (I′) methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

Claims (441)

1 . A compound of Formula (I′):

or a pharmaceutically acceptable salt thereof, wherein:

Cy A is C 3-12 cycloalkyl or 4-12 membered heterocycloalkyl; wherein the 4-12 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of the 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-12 cycloalkyl and 4-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R A ,

A is N or CR 16 ;

R 16 is selected from H, D, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , OR a16 , SR a16 , C(O)R b16 , C(O)NR c16 R d16 , C(O)OR a16 , OC(O)R b16 , OC(O)NR c16 R d16 , NR c16 R d16 , NR c16 C(O)R b16 , NR c16 C(O)OR a16 , NR c16 C(O)NR c16 R d16 , NR c16 S(O)R b16 , NR c16 S(O) 2 R b16 , NR c16 S(O) 2 NR c16 R a16 , S(O)R b16 , S(O)NR c16 R d16 , S(O) 2 R b16 , S(O) 2 NR c16 R d16 and BR h16 R i16 ; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

R 1 is selected from H, D, halo, CN, C 1-6 alkyl, OR a15 and NR c15 R d15 ; wherein the C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R g ;

R 2 is selected from H, D, Cy 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NOR a )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , S(O) 2 NR c R d and BR h R i ; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ;

Cy 2 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ;

Z is N or CR 3 ;

R 3 is selected from H, D, Cy 3 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c14 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , C(═NR e4 )R b4 , C(═NOR a4 )R b4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , S(O) 2 NR c4 R d4 and BR h4 R i4 ; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 13 ;

Cy 3 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 13 ;

each R 4 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, NO 2 , OR a8 , SR a8 , C(O)R b8 , C(O)NR c8 R d8 , C(O)OR a8 , OC(O)R b8 , OC(O)NR c8 R dg , NR c8 R d8 , NR c8 C(O)R b8 , NR c8 C(O)OR a8 , NR c8 C(O)NR c8 R d8 , C(═NR e8 )R b8 , C(═NOR a8 )R b8 , C(═NR e8 )NR c8 R d8 , NR c8 C(═NR e8 )NR c8 R d8 , NR c8 S(O)R b8 , NR c8 S(O) 2 R b8 , NR c8 S(O) 2 NR c8 R d8 , S(O)R b8 , S(O)NR c8 R d8 , S(O) 2 R b8 , S(O) 2 NR c8 R d8 , and BR h8 R i8 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 5 ;

each R 5 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, OR a9 , SR a9 , C(O)R b9 , C(O)NR c9 R d9 , C(O)OR a9 , NR c9 R d9 , NR c9 C(O)R b9 , NR c9 C(O)OR a9 , NR c9 S(O)R b9 , NR c9 S(O) 2 R b9 , NR c9 S(O) 2 NR c9 R d9 , S(O)R b9 , S(O)NR c9 R d9 , S(O) 2 R b9 , S(O) 2 NR c9 R d9 and BR h9 R i9 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 6 ;

each R 6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a10 , SR a10 , C(O)R b10 , C(O)NR c10 R a10 , C(O)OR a10 , NR c10 R a10 , NR c10 C(O)R b10 , NR c10 C(O)OR a10 , NR c10 S(O)R b10 , NR c10 S(O) 2 R b10 , NR c10 S(O) 2 NR c10 R d10 , S(O)R b10 , S(O)NR c10 R d10 , S(O) 2 R b10 , and S(O) 2 NR c10 R d10 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R A is selected from H, D, Cy 1 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , OR a11 , SR a11 , C(O)R b11 , C(O)NR c11 R d11 , C(O)OR a11 , OC(O)R b11 , OC(O)NR c11 R d11 , NR c11 R d11 , NR c11 C(O)R b11 , NR c11 C(O)OR a11 , NR c11 C(O)NR c11 R d11 , C(═NR e11 )R b11 , C(═NOR a11 )R b11 , C(═NR e11 )NR c11 R a11 , NR c11 C(═NR e11 )NR c11 R d11 , NR c11 S(O)R b11 , NR c11 S(O) 2 R b11 , NR c11 S(O) 2 NR c11 R d11 , S(O)R b11 , S(O)NR c11 R d11 , S(O) 2 R b11 , S(O) 2 NR c11 R d11 and BR h11 R i11 ; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 7 ;

Cy 1 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 7 ;

each R 7 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, NO 2 , OR a12 , SR a12 , C(O)R b12 , C(O)NR c12 R d12 , C(O)OR a12 , OC(O)R b12 , OC(O)NR c12 R d12 , NR c12 R d12 , NR c12 C(O)R b12 , NR c12 C(O)OR a12 , NR c12 C(O)NR c12 R d12 , C(═NR e12 )R b12 , C(═NOR a12 )R b12 , C(═NR e12 )NR e2 R d12 , NR c12 C(═NR e12 )NR c12 R d12 , NR c12 S(O)R 12 , NR c12 S(O) 2 R b12 , NR c12 S(O) 2 NR c12 R d12 , S(O)R b12 , S(O)NR c12 R d12 , S(O) 2 R b12 , S(O) 2 NR c12 R d12 and BR h12 R i12 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 8 ;

each R 8 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, OR a13 , SR a13 , C(O)R b13 , C(O)NR c13 R d13 , C(O)OR a13 , NR c13 R d13 , NR c13 C(O)R b13 , NR c13 C(O)OR a13 , NR c13 S(O)R b13 , NR c113 S(O) 2 R b13 , NR c113 S(O) 2 NR c13 R d13 , S(O)R b13 , S(O)NR c13 R d13 , S(O) 2 R b13 , S(O) 2 NR c13 R d13 and BR h13 R i13 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 9 ;

each R 9 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a14 , SR a14 , C(O)R b14 , C(O)NR c14 R d14 , C(O)OR a14 , 1R c14 R d14 , NR c14 C(O)R b14 , NR c14 C(O)OR a14 , NR c14 S(O)R b14 , NR c14 S(O) 2 R b14 , NR c14 S(O) 2 NR 14 R d14 , S(O)R b14 , S(O)NR c14 R d14 , S(O) 2 R b14 and S(O) 2 NR 14 R d14 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e1 )R b1 , C(═NOR a1 )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , S(O) 2 NR c1 R d1 and BR h1 R i1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a , NR c2 S(O)R b2 , NR 2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , S(O) 2 NR c2 R 2 and BR h2 R i2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;

each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c13 R d3 , C(O)OR a3 , NR c13 R d3 , NR c13 C(O)R b3 , NR c13 C(O)OR a3 , NR c13 S(O)R b3 , NR c13 S(O) 2 R b3 , NR c13 S(O) 2 NR c13 R d3 , S(O)R b3 , S(O)NR c13 R d3 , S(O) 2 R b3 and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R 13 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, NO 2 , OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 C(O)NR c5 R d5 , C(═NR e5 )R b5 , C(═NOR a5 )R b5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , NR c15 S(O)R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , S(O) 2 NR c5 R d5 and BR h5 R i5 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 14 ;

each R 14 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, OR a6 , SR a6 , C(O)R b6 , C(O)NR c16 R d6 , C(O)OR a6 , NR c16 R d6 , NR c16 C(O)R b6 , NR c16 C(O)OR a6 , NR c16 S(O)R b6 , NR c16 S(O) 2 R b6 , NR c16 S(O) 2 NR c16 R d6 , S(O)R b6 , S(O)NR c16 R d6 , S(O) 2 R b6 , S(O) 2 NR c16 R d6 and BR h6 R i6 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 15 ;

each R 15 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)OR a7 , NR c7 S(O)R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 and S(O) 2 NR c7 R d7 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R a , R c and R d is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ;

or any R c and R d attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ;

each R b is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ;

each R c is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R h and R i is independently selected from OH and C 1-6 alkoxy;

or any R h and R i attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

or any R c1 and R d1 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 11 ;

each R b1 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

each R e1 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R h1 and R i1 is independently selected from OH and C 1-6 alkoxy;

or any R h1 and R i1 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a2 , R c2 and R d2 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;

or any R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 12 ;

each R b2 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;

each R h2 and R i2 is independently selected from OH and C 1-6 alkoxy;

or any R h2 and R i2 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a3 , R c3 and R d3 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R b3 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R a4 , R c4 and R d4 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 13 ;

or any R c4 and R d4 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 13 ;

each R b4 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 13 ;

each R e4 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R h4 and R i4 is independently selected from OH and C 1-6 alkoxy;

or any R h4 and R i4 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a5 , R c5 and R d5 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 14 ;

or any R c5 and R d5 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 14 ;

each R b5 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 14 ;

each R c5 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R h5 and R i5 is independently selected from OH and C 1-6 alkoxy;

or any R h5 and R i5 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a6 , R c6 and R d6 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 15 ;

or any R c6 and R d6 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 15 ;

each R b6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 15 ;

each R h6 and R i6 is independently selected from OH and C 1-6 alkoxy;

or any R h6 and R i6 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a7 , R c7 and R d7 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R b7 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R a8 , R c8 and R d8 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 5 ;

or any R c8 and R d8 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 5 ;

each R b8 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 5 ;

each R e8 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R h8 and R i8 is independently selected from OH and C 1-6 alkoxy;

or any R h8 and R i8 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a9 , R c9 and R d9 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 6 ;

or any R c9 and R d9 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 6 ;

each R b9 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 6 ;

each R h9 and R i9 is independently selected from OH and C 1-6 alkoxy;

or any R h9 and R i9 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a10 , R c10 and R d10 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R b10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R a11 , R c11 and R d11 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 7 ;

or any R c11 and R d11 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 7 ;

each R b11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 7 ;

each R e11 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R h11 and R i11 is independently selected from OH and C 1-6 alkoxy;

or any R h11 and R i11 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a12 , R c12 and R d12 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 8 ;

or any R c12 and R d12 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 8 ;

each R b12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 8 ;

each R e12 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R h12 and R i12 is independently selected from OH and C 1-6 alkoxy;

or any R h12 and R i12 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a13 , R c13 and R d13 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 9 ;

or any R c13 and R d13 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 9 ;

each R b13 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 9 ;

each R h13 and R i13 is independently selected from OH and C 1-6 alkoxy;

or any R h13 and R i13 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R a14 , R c14 and R d14 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R b14 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R a15 , R c15 and R d15 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R a16 , R c16 and R d16 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R b16 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R h16 and R i16 is independently selected from OH and C 1-6 alkoxy;

or any R h16 and R i16 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl; and

each R g is independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-2 alkylene, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-3 alkoxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkoxy, HO—C 1-3 alkoxy, HO—C 1-3 alkyl, cyano-C 1-3 alkyl, H 2 N—C 1-3 alkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino; and

n is 0, 1, 2, 3 or 4.

2 . A compound of Formula (I′):

or a pharmaceutically acceptable salt thereof, wherein:

Cy A is 4-12 membered heterocycloalkyl; wherein the 4-12 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of the 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R A ;

A is N or CR 16 ;

R 16 is selected from H, D, C 1-6 alkyl, halo, CN and OR a16 ;

R 1 is selected from H, D, halo, CN, C 1-6 alkyl and OR a15 ; wherein the C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R g ;

R 2 is selected from H, D, Cy 2 , C 1-6 alkyl, C 1-6 haloalkyl, halo, CN; wherein said C 1-6 alkyl, is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ;

Cy 2 is selected from 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ;

Z is N or CR 3 ;

R 3 is selected from H, D, Cy 3 , halo and CN;

Cy 3 is 6-10 membered heteroaryl; wherein the 6-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S;

each R 4 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN and OR a8 ;

R A is selected from H, D, Cy 1 , C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a11 , C(O)NR c11 R d11 , and NR c11 R d11 ; wherein said C 1-6 alkyl, is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 7 ;

Cy 1 is selected from C 3-10 cycloalkyl and 5-10 membered heteroaryl; wherein the 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 7 ;

each R 7 is independently selected from C 1-6 alkyl, halo, D, CN, OR a12 and NR e12 R d12 ;

each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a1 , C(O)NR c1 R d1 and NR c1 R d1 ; wherein said C 1-6 alkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

each R 11 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN and OR a ;

each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl and C 3-10 cycloalkyl; wherein said C 1-6 alkyl and C 3-10 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

each R a2 , R e2 and R d2 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl;

each R a8 , R c8 and R d8 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl;

each R a11 , R c11 and R d11 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 7 ;

each R a12 , R c12 and R d12 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl;

each R a15 , R c15 and R d15 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

R a16 is independently selected from H and C 1-6 alkyl;

each R g is independently selected from OH, CN, halo, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, amino, C 1-6 alkylthio, C 1-6 alkylsulfonyl; and

n is 0, 1, 2 or 3.

3 . A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

A is N or CF;

R 1 is selected from H, D, halo, CN, C 1-6 alkyl, OR a15 and NR c15 R d15 ; wherein the C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R g ;

R 3 is selected from H, D, Cy 3 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , C(═NR e4 )R b4 , C(═NOR a4 )R b4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , S(O) 2 NR c4 R d4 and BR h4 R i4 ; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 13 ;

each R 4 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, NO 2 , OR a8 , SR a8 , C(O)R b8 , C(O)NR c8 R d8 , C(O)OR a8 , OC(O)R b8 , OC(O)NR c8 R d8 , NR c8 R d8 , NR c8 C(O)R b8 , NR c8 C(O)OR a8 , NR c8 C(O)NR c8 R d8 , C(═NR e8 )R b8 , C(═NOR a8 )R b8 , C(═NR e8 )NR c8 R d8 , NR c8 C(═NR e8 )NR c8 R d8 , NR c8 S(O)R b8 , NR c8 S(O) 2 R b8 , NR c8 S(O) 2 NR c8 R d8 , S(O)R b8 , S(O)NR c8 R d8 , S(O) 2 R b8 , S(O) 2 NR c8 R d8 and BR h8 R i8 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 5 ;

each R 5 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, OR a9 , SR ag , C(O)R b9 , C(O)NR c9 R d9 , C(O)OR a9 , NR c9 R d9 , NR c9 C(O)R b9 , NR c9 C(O)OR a9 , NR c9 S(O)R b9 , NR c9 S(O) 2 R b9 , NR c9 S(O) 2 NR c9 R d9 , S(O)R b9 , S(O)NR c9 R d9 , S(O) 2 R b9 , S(O) 2 NR c9 R d9 and BR h9 R i9 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 6 ;

each R 6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a10 , SR a10 , C(O)R b10 , C(O)NR c10 R d10 , C(O)OR a10 , NR c10 R d10 , NR c10 C(O)R b10 , NR c10 C(O)OR a10 , NR c10 S(O)R b10 , NR c10 S(O) 2 R b10 , NR c10 S(O) 2 NR c10 R d10 , S(O)R b10 , S(O)NR c10 R d10 , S(O) 2 R b10 , and S(O) 2 NR c10 R d10 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

R A is selected from H, D, Cy 1 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , OR a11 , SR a11 , C(O)R b11 , C(O)NR c11 R d11 , C(O)OR a11 , OC(O)R b11 , OC(O)NR c11 R d11 , NR c11 R d11 , NR c11 C(O)R b11 , NR c11 C(O)OR a11 , NR c11 C(O)NR c11 R a11 , C(═NR e11 )R b11 , C(═NOR a11 )R b11 , C(═NR e11 )NR c11 R d11 , NR c11 C(═NR e11 )NR c11 R d11 , NR c11 S(O)R b11 , NR c11 S(O) 2 R b11 , NR c11 S(O) 2 NR c11 R d11 , S(O)R b11 , S(O)NR c11 R d11 , S(O) 2 R b11 , S(O) 2 NR c11 R d11 and BR h11 R i11 ; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 7 ;

each R 7 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, NO 2 , OR a12 , SR a12 , C(O)R b12 , C(O)NR c12 R a12 , C(O)OR a12 , OC(O)R b12 , OC(O)NR c12 R d12 , NR c12 R d12 , NR c12 C(O)R b12 , NR c12 C(O)OR a12 , NR c12 C(O)NR c12 R d12 , C(═NR e12 )R b12 , C(═NOR a12 )R b12 , C(═NR e12 )NR c12 R d12 , NR c12 C(═NR e12 )NR c12 R d12 , NR e12 S(O)R b12 , NR e12 S(O) 2 R b12 , NR c12 S(O) 2 NR c12 R d12 , S(O)R b12 , S(O)NR c12 R d12 , S(O) 2 R b12 , S(O) 2 NR c12 R d12 and BR h12 R i12 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 8 ;

each R 8 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, OR a13 , SR a13 , C(O)R b13 , C(O)NR c13 R d13 , C(O)OR a13 , NR c13 R d13 , NR c13 C(O)R b13 , NR c13 C(O)OR a13 , NR c13 S(O)R b13 , NR c113 S(O) 2 R b13 , NR c13 S(O) 2 NR c13 R d13 , S(O)R b13 , S(O)NR c13 R d13 , S(O) 2 R b13 , S(O) 2 NR c13 R d13 and BR h13 R i13 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 9 ;

each R 9 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a14 , SR a14 , C(O)R b14 , C(O)NR c14 R d14 , C(O)OR a14 , NR 14 R d14 , NR c14 C(O)R b14 , NR c14 C(O)OR a14 , NR c14 S(O)R b4 , NR c14 S(O) 2 R b14 , NR c14 S(O) 2 NR 14 R d14 , S(O)R b14 , S(O)NR c14 R d14 , S(O) 2 R b14 and S(O) 2 NR c14 R d14 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 13 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e1 )R b1 , C(═NOR a1 )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 S(O)R b1 , NR c11 S(O) 2 R b1 , NR c11 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , S(O) 2 NR c1 R d1 and BR h1 R i1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d , S(O) 2 R b2 S(O) 2 NR c2 R d2 and BR h2 R i2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;

each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R 13 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, NO 2 , OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 C(O)NR c5 R d5 , C(═NR e5 )R b5 , C(═NOR a5 )R b5 , C(═NR 5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , NR c5 S(O)R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , S(O) 2 NR c5 R d5 and BR h R i5 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 14 ;

each R 14 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, D, CN, OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R a6 , C(O)OR a6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 S(O)R b6 , NR c6 S(O) 2 R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , S(O) 2 NR c6 R d6 and BR h6 R i6 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 15 ;

each R e is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R h and R i is independently selected from OH and C 1-6 alkoxy;

each R h1 and R 1 is independently selected from OH and C 1-6 alkoxy;

or any R h1 and R 1 attached to the same B atom are C 2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C 1-6 alkyl;

each R h2 and R i2 is independently selected from OH and C 1-6 alkoxy;

each R h4 and R i4 is independently selected from OH and C 1-6 alkoxy;

each R e5 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R h5 and R i5 is independently selected from OH and C 1-6 alkoxy;

each R h6 and R i6 is independently selected from OH and C 1-6 alkoxy;

each R h8 and R i8 is independently selected from OH and C 1-6 alkoxy;

each R h9 and R i9 is independently selected from OH and C 1-6 alkoxy;

each R h11 and R i11 is independently selected from OH and C 1-6 alkoxy;

each R h12 and R i12 is independently selected from OH and C 1-6 alkoxy;

each R h13 and R i13 is independently selected from OH and C 1-6 alkoxy;

each R g is independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-2 alkylene, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-3 alkoxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkoxy, HO—C 1-3 alkoxy, HO—C 13 alkyl, cyano-C 1-3 alkyl, H 2 N—C 1-3 alkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino; and

n is 0, 1, 2, 3 or 4.

4 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein:

Cy A is 4-12 membered heterocycloalkyl; wherein the 4-12 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of the 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R A ,

A is N;

R 1 is selected from H, D, halo, CN, C 1-6 alkyl and OR a15 ; wherein the C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R g ;

R 2 is selected from H, D, Cy 2 , C 1-6 alkyl, C 1-6 haloalkyl, halo, CN; wherein said C 1-6 alkyl, is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ;

Cy 2 is selected from 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ;

R 3 is selected from H, D, Cy 3 , halo and CN;

Cy 3 is 5-10 membered heteroaryl; wherein the 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the 5-10 membered heteroaryl is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 13 ;

each R 4 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN and OR a8 ; wherein said C 1-6 alkyl, is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 5 ;

each R 5 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a9 and NR c9 R d9 ;

R A is selected from H, D, Cy 1 , C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a11 , C(O)NR c11 R d11 and NR c11 R d11 , wherein said C 1-6 alkyl, is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 7 ,

Cy 1 is 5-10 membered heteroaryl; wherein the 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 7 ;

each R 7 is independently selected from C 1-6 alkyl, halo, D, CN, OR a12 and NR c12 R d12 ;

each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a1 , C(O)NR c1 R d1 and NR c1 R d1 , wherein said C 1-6 alkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

each R 11 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN and OR a2 ;

each R 13 is independently selected from C 1-6 alkyl and C 1-6 haloalkyl;

each R a2 , R c2 and R d2 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl;

each R

a8 , R c8 and R d8 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl;

each R a9 , R c9 and R d9 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl;

each R a11 , R c11 and R d11 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl;

wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 7 ;

each R a12 , R c12 and R d12 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl;

each R a15 , R c15 and R d15 is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl;

wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R g is independently selected from OH, CN, halo, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, amino, C 1-6 alkylthio, C 1-6 alkylsulfonyl; and

n is 0, 1, 2 or 3.

5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is 4-12 membered heterocycloalkyl; wherein the 4-12 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of the 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R A .

6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R A is independently selected from Cy 1 , C 1-6 alkyl, OR a11 , C(O)NR c11 R d11 , and NR c11 R d11 , wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 7 .

7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R A is independently selected from methyl and ethyl; wherein said methyl and ethyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 7 .

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R A is independently selected from OH, NH 2 , aminomethyl, hydroxymethyl, methoxymethyl, pyridinyl, ethyl, hydroxyethyl, and propylcarbamoyl.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R A is independently Cy 1 .

10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is selected from C 3-10 cycloalkyl and 5-10 membered heteroaryl; wherein the 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 7 .

11 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is pyridinyl.

12 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 7 is independently selected from C 1-6 alkyl, halo, D, CN, OR a12 and NR c12 R d12 .

13 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is selected from 2,5-diazabicyclo[2.2.1]heptan-2-yl; 3-aminopyrrolidin-1-yl; 2-(aminomethyl)pyrrolidin-1-yl; 2-(hydroxymethyl)pyrrolidin-1-yl; 2-(methoxymethyl)pyrrolidin-1-yl; 4-amino-2-(hydroxymethyl)pyrrolidin-1-yl; 4-hydroxy-2-methylpyrrolidin-1-yl; 2-(pyridin-2-yl)pyrrolidin-1-yl; hexahydropyrrolo[3,4-b]pyrrol-1 (2H)-yl; 2-methylpiperazin-1-yl; 2-(hydroxymethyl)piperazin-1-yl; 3-(hydroxymethyl)morpholino; 5-ethyl-2,5-diazabicyclo[2.2.1]heptan-2-yl; (2-hydroxyethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl); 5-(propylcarbamoyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl; 4-hydroxy-2-(hydroxymethyl)pyrrolidin-1-yl; 2-(hydroxymethyl)-5-methylpiperazin-1-yl; 6-(hydroxymethyl)-4,7-diazaspiro[2.5]octan-7-yl; 4-amino-2-(1-hydroxycyclopropyl)pyrrolidin-1-yl; 4-amino-2-(2-hydroxypropan-2-yl)pyrrolidin-1-yl; 4-amino-2-(hydroxymethyl-d2)pyrrolidin-1-yl; 3-(hydroxymethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl; 4-amino-2-methylpiperidin-1-yl; piperidin-4-yl; 4-(dimethylamino)-2-(hydroxymethyl)pyrrolidin-1-yl; 2-(hydroxymethyl)-4-(isopropylamino)pyrrolidin-1-yl; 4-(hydroxymethyl)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl; 2-(hydroxymethyl)morpholino; 2-(2-((dimethylamino)methyl)morpholino; 2-(cyanomethyl)morpholino; 3-oxotetrahydro-3H-oxazolo[3,4-a]pyrazin-7 (1H)-yl; 3-(hydroxymethyl)piperazin-1-yl; 3-(methoxymethyl)azetidin-1-yl; 2-(hydroxymethyl)azetidin-1-yl; 2-((dimethylamino)methyl)azetidin-1-yl; 4-methylpiperazin-1-yl; and 4-(2-hydroxyethyl)piperazin-1-yl.

14 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is selected from 2,5-diazabicyclo[2.2.1]heptan-2-yl; 3-aminopyrrolidin-1-yl; 2-(aminomethyl)pyrrolidin-1-yl; 2-(hydroxymethyl)pyrrolidin-1-yl; 2-(methoxymethyl)pyrrolidin-1-yl; 4-amino-2-(hydroxymethyl)pyrrolidin-1-yl; 4-hydroxy-2-methylpyrrolidin-1-yl; 2-(pyridin-2-yl)pyrrolidin-1-yl; hexahydropyrrolo[3,4-b]pyrrol-1 (2H)-yl; 2-methylpiperazin-1-yl; 2-(hydroxymethyl)piperazin-1-yl; 3-(hydroxymethyl)morpholino; 5-ethyl-2,5-diazabicyclo[2.2.1]heptan-2-yl; (2-hydroxyethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl); and 5-(propylcarbamoyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl.

15 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is 4-amino-2-(hydroxymethyl)pyrrolidin-1-yl.

16 . The compound of claim 1 , wherein Cy A is selected from cyclopentyl and cyclohexyl, wherein the cyclopentyl and cyclohexyl are optionally substituted with NH 2 .

17 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from H, D, halo, CN, C 1-6 alkyl and OR a15 ; wherein the C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R g .

18 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from H, D, F, CN, methyl, hydroxymethyl and methoxy.

19 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is H.

20 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is F.

21 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from H, D, Cy 2 , C 1-6 alkyl, halo, and S(O) 2 R b , wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 .

22 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from isopropyl, F, Cl, Br, and S(O) 2 CH 3 .

23 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is Cy 2 .

24 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 2 is selected from 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 .

25 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, 4-10 membered heterocycloalkyl, halo, CN, OH, OR a1 , C(O)NR c1 R d1 and NR c1 R d1 , wherein said C 1-6 alkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 .

26 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from OH, F, CN, methyl, hydroxymethyl, methylcarbamoyl, methoxy, morpholino, and cyclobutylamino.

27 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is OR a2 .

28 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is OH.

29 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 2 is selected from 1-methyl-1H-pyrazol-4-yl; 6-(hydroxymethyl)pyridin-3-yl; 6-(methylcarbamoyl)pyridin-3-yl; 1-methyl-6-oxo-1,6-dihydropyridin-3-yl; 2-methylpyridin-3-yl; 4-methoxypyridin-3-yl; 4-cyanopyridin-3-yl; 1,3,5-trimethyl-1H-pyrazol-4-yl; morpholino; azetidin-1-yl; 2-(methoxymethyl)azetidin-1-yl); 3-cyanopyridin-4-yl; 3-methoxypyridin-4-yl; 2-cyano-6-fluorophenyl; 3-cyanopyridin-2-yl; 4-cyano-1-methyl-1H-pyrazol-5-yl; tetrahydro-2H-pyran-4-yl; 5-cyano-2-(pyrrolidin-1-yl)pyridin-4-yl; and 1-cyanocyclopropyl.

30 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 2 is selected from 1-methyl-1H-pyrazol-4-yl; 6-(hydroxymethyl)pyridin-3-yl; 6-(methylcarbamoyl)pyridin-3-yl; 1-methyl-6-oxo-1,6-dihydropyridin-3-yl; 2-methylpyridin-3-yl; 4-methoxypyridin-3-yl; 4-cyanopyridin-3-yl; 1,3,5-trimethyl-1H-pyrazol-4-yl; morpholino; and azetidin-1-yl.

31 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 2 is selected from 3-cyanopyridin-4-yl; 4-cyanopyridin-3-yl; and 3-cyanopyridin-2-yl.

32 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is CR 3 .

33 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is N.

34 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is selected from H, D, F, Br, and CN.

35 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H.

36 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is Cy 3 .

37 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 3 is 5-10 membered heteroaryl; wherein the 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the 5-10 membered heteroaryl is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 13 .

38 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 13 is independently C 1-6 alkyl.

39 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 13 is methyl.

40 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 3 is selected from pyridin-3-yl and 1-methyl-1H-pyrazol-4-yl.

41 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, halo, D, CN, and OR a8 ; wherein said C 1-6 alkyl, is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 5 .

42 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, and OR a8 .

43 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently selected from halo and OR a8 .

44 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently selected from halo.

45 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently selected from F and methoxy.

46 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 5 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a9 , and NR c9 R d9 .

47 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 5 is independently selected from D and F.

48 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 2.

49 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is N.

50 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is CR 16 .

51 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 16 is H, CN, or OR a16 .

52 . The compound of claim 1 , having Formula IA:

or a pharmaceutically acceptable salt thereof.

53 . The compound of claim 1 , having Formula IB:

or a pharmaceutically acceptable salt thereof.

54 . The compound of claim 1 , having Formula IC:

or a pharmaceutically acceptable salt thereof.

55 . The compound of claim 1 , having Formula IIA:

or a pharmaceutically acceptable salt thereof.

56 . The compound of claim 1 , having Formula IIB:

or a pharmaceutically acceptable salt thereof.

57 . The compound of claim 1 , having Formula IIC:

or a pharmaceutically acceptable salt thereof.

58 . The compound of claim 1 , having Formula IID:

or a pharmaceutically acceptable salt thereof.

59 . The compound of claim 1 , having Formula III:

or a pharmaceutically acceptable salt thereof.

60 . The compound of claim 1 , having Formula IV:

or a pharmaceutically acceptable salt thereof.

61 . The compound claim 1 , having Formula V:

or a pharmaceutically acceptable salt thereof.

62 . The compound of claim 1 , having Formula VI:

or a pharmaceutically acceptable salt thereof.

63 . The compound of claim 1 selected from:

N-(2-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(S)—N-(2-(3-aminopyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(R)—N-(2-(2-(aminomethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(R)—N-(5-fluoro-2-(2-(hydroxymethyl)pyrrolidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(R)—N-(5-fluoro-2-(2-(methoxymethyl)pyrrolidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(5-fluoro-2-((2S,4S)-4-hydroxy-2-methylpyrrolidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(5-fluoro-2-(2-(pyridin-2-yl)pyrrolidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(5-fluoro-2-(hexahydropyrrolo[3,4-b]pyrrol-1 (2H)-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(R)—N-(5-fluoro-2-(2-methylpiperazin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(R)—N-(5-fluoro-2-(2-(hydroxymethyl)piperazin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(5-fluoro-2-(3-(hydroxymethyl)morpholino)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-3-bromo-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-3-cyanophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-3-(pyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-3-(1-methyl-1H-pyrazol-4-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-4-(hydroxymethyl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-bromo-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-4-(6-(hydroxymethyl)pyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-4-(6-(methylcarbamoyl)pyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-4-(2-methylpyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(2-methylpyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(4-methoxypyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-4-morpholinophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(4-(azetidin-1-yl)-2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-4-(morpholinomethyl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-((cyclobutylamino)methyl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1R,4R)-5-ethyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(5-fluoro-2-((1R,4R)-5-(2-hydroxyethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(1R,4R)-5-(4-fluoro-2-(2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamido)phenyl)-N-propyl-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide;

N-(2-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-methoxyphenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-(hydroxymethyl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide; and

N-(2-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-cyanophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

or a pharmaceutically acceptable salt thereof.

64 . The compound of claim 1 selected from:

N-(4-(Azetidin-1-yl)-2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)-4-((S)-2-(methoxymethyl)azetidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)-4-(3-cyanopyridin-4-yl)-3-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(3-cyanopyridin-4-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(2-methylpyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(3-methoxypyridin-4-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(3-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-2′-cyano-6′-fluorobiphenyl-4-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(3-cyanopyridin-2-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyano-1-methyl-1H-pyrazol-5-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-isopropylphenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(4-(3-Cyanopyridin-4-yl)-2-((2S,4S)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(4-(4-Cyanopyridin-3-yl)-2-((2S,5R)-2-(hydroxymethyl)-5-methylpiperazin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(4-(4-Cyanopyridin-3-yl)-2-((2S,5S)-2-(hydroxymethyl)-5-methylpiperazin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(S)—N-(4-(4-Cyanopyridin-3-yl)-2-(6-(hydroxymethyl)-4,7-diazaspiro[2.5]octan-7-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(1-hydroxycyclopropyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(2-hydroxypropan-2-yl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl-d2)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(4-(4-Cyanopyridin-3-yl)-2-((1S,3R,4S)-3-(hydroxymethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(4-(4-Cyanopyridin-3-yl)-2-((1S,4S)-1-(hydroxymethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-methylpiperidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-6-(2-fluoro-6-methoxyphenyl) picolinamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-5-cyano-6-(2-fluoro-6-methoxyphenyl) picolinamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-6-(2-fluoro-6-methoxyphenyl)-5-methoxypicolinamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methylphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-chloro-6-fluorophenyl)pyrimidine-4-carboxamide; and

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-6-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyridin-3-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

or a pharmaceutically acceptable salt thereof.

65 . The compound of claim 1 selected from:

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(3-cyano-2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2,3-difluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-(methoxy-d3)-3-methylphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxy-4-methylphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(3,6-difluoro-2-methylphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2,3-difluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(3,6-difluoro-2-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(3-cyano-2-fluoro-6-(methoxy-d3)phenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(3,6-difluoro-2-(methoxy-d3)phenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2,3-difluoro-6-(methoxy-d3)phenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-(methoxy-d3)phenyl-5-d)pyrimidine-4-carboxamide;

2-(2-Fluoro-6-methoxyphenyl)-N-(2-(piperidin-4-yl)phenyl)pyrimidine-4-carboxamide;

N-(2-(cis) 4-Aminocyclohexyl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-(trans) 4-Aminocyclohexyl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-(3-Aminocyclohexyl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-(3-aminocyclopentyl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((cis)-4-Aminocyclohexyl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((trans)-4-Aminocyclohexyl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((cis)-4-Aminocyclohexyl)-4-(4-cyano-1-methyl-1H-pyrazol-5-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((trans)-4-aminocyclohexyl)-4-(4-cyano-1-methyl-1H-pyrazol-5-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((cis)-4-Aminocyclohexyl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(methylsulfonyl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-methylphenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-(Dimethylamino)-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(5-Fluoro-2-((2S,4S)-2-(hydroxymethyl)-4-(isopropylamino)pyrrolidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(tetrahydro-2H-pyran-4-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-chlorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(5-cyano-2-(pyrrolidin-1-yl)pyridin-4-yl)phenyl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(1-cyanocyclopropyl)phenyl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-(difluoromethoxy)-6-fluorophenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-(methoxy-d3)phenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-cyclopropyl-6-fluorophenyl)pyrimidine-4-carboxamide;

N-(2-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-ethoxy-6-fluorophenyl)pyrimidine-4-carboxamide;

N-(4-(4-Cyanopyridin-3-yl)-2-((1S,4S)-4-(hydroxymethyl)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(S)—N-(4-(4-Cyanopyridin-3-yl)-2-(2-(hydroxymethyl)morpholino)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(S)—N-(4-(4-Cyanopyridin-3-yl)-2-(2-((dimethylamino)methyl)morpholino)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(R)—N-(2-(2-(Cyanomethyl)morpholino)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(R)—N-(4-(4-Cyanopyridin-3-yl)-2-(3-oxotetrahydro-3H-oxazolo[3,4-a]pyrazin-7 (1H)-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(S)—N-(5-Fluoro-2-(3-(hydroxymethyl)piperazin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(4-(4-Cyanopyridin-3-yl)-2-(3-(methoxymethyl)azetidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(S)—N-(4-(4-Cyanopyridin-3-yl)-2-(2-(hydroxymethyl)azetidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

(R)—N-(4-(4-Cyanopyridin-3-yl)-2-(2-((dimethylamino)methyl)azetidin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(4-(4-Cyanopyridin-3-yl)-2-(4-methylpiperazin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

N-(4-(4-Cyanopyridin-3-yl)-2-(4-(2-hydroxyethyl)piperazin-1-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide; and

(S)—N-(5-Fluoro-2-(3-(hydroxymethyl)piperazin-1-yl)-4-isopropylphenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;

or a pharmaceutically acceptable salt thereof.

66 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 19, 2023

From: VECHORKIN, OLEG; PAN, JUN; SOKOLSKY, ALEXANDER; STYDUHAR, EVAN; YE, QINDA; YAO, WENQING

To: INCYTE CORPORATION

Reel/Frame 064311/0274 →

Continuity (6)

Continuation 17015797 · Sep 9, 2020

Division 16278865 · Feb 19, 2019

Provisional Application 62750371 · Oct 25, 2018

Provisional Application 62672772 · May 17, 2018

Provisional Application 62632702 · Feb 20, 2018

Related Publication 20240150326A1 · May 9, 2024

References Cited (400)

US 5250534A · Bell et al. · 1993 [cited by applicant]

US 6200980B1 · Piazza et al. · 2001 [cited by applicant]

US 6333330B1 · Bunnage et al. · 2001 [cited by applicant]

US 6458951B2 · Bunnage et al. · 2002 [cited by applicant]

US 6512002B2 · Lee et al. · 2003 [cited by applicant]

US 6670366B1 · Bunnage et al. · 2003 [cited by applicant]

US 6743799B2 · Westbrook et al. · 2004 [cited by applicant]

US 6756373B1 · Allerton et al. · 2004 [cited by applicant]

US 6770645B2 · Denton et al. · 2004 [cited by applicant]

US 6784185B2 · Allerton et al. · 2004 [cited by applicant]

US 6916927B2 · Bunnage et al. · 2005 [cited by applicant]

US 7105532B2 · Rawlings · 2006 [cited by applicant]

US 7166293B2 · Teng et al. · 2007 [cited by applicant]

US 7259165B2 · Bernotas et al. · 2007 [cited by applicant]

US 7345178B2 · Nunes et al. · 2008 [cited by applicant]

US 7429609B2 · Ohi et al. · 2008 [cited by applicant]

US 7576087B2 · Bernotas et al. · 2009 [cited by applicant]

US 7919487B2 · Sun et al. · 2011 [cited by applicant]

US 7968719B2 · Zoller et al. · 2011 [cited by applicant]

US 8106190B2 · Kuramochi et al. · 2012 [cited by applicant]

US 8450335B2 · Singh et al. · 2013 [cited by applicant]

US 8546403B2 · Whitten et al. · 2013 [cited by applicant]

US 8637507B2 · Zhou et al. · 2014 [cited by applicant]

US 8722691B2 · He et al. · 2014 [cited by applicant]

US 8987273B2 · Rehwinkel et al. · 2015 [cited by applicant]

US 9090593B2 · Wang et al. · 2015 [cited by applicant]

US 9260425B2 · Do et al. · 2016 [cited by applicant]

US 9284319B2 · Eis et al. · 2016 [cited by applicant]

US 9320737B2 · Eis et al. · 2016 [cited by applicant]

US 9718818B2 · DeMong et al. · 2017 [cited by applicant]

US 9730929B2 · Eis et al. · 2017 [cited by applicant]

US 10266530B2 · Vechorkin et al. · 2019 [cited by applicant]

US 10280164B2 · Ye et al. · 2019 [cited by applicant]

US 10435405B2 · Vechorkin et al. · 2019 [cited by applicant]

US 10722495B2 · Vechorkin et al. · 2020 [cited by applicant]

US 10745388B2 · Vechorkin et al. · 2020 [cited by applicant]

US 10752635B2 · Sokolsky et al. · 2020 [cited by applicant]

US 10800761B2 · Vechorkin et al. · 2020 [cited by applicant]

US 10899755B2 · Hummel et al. · 2021 [cited by applicant]

US 10934288B2 · Vechorkin et al. · 2021 [cited by applicant]

US 11014929B2 · Vechorkin et al. · 2021 [cited by applicant]

US 11066394B2 · Jia et al. · 2021 [cited by applicant]

US 11242343B2 · Liu et al. · 2022 [cited by applicant]

US 11299473B2 · Hummel et al. · 2022 [cited by applicant]

US 11406624B2 · Sokolsky et al. · 2022 [cited by applicant]

US 11492354B2 · Sokolsky et al. · 2022 [cited by applicant]

US 11542265B2 · Vechorkin et al. · 2023 [cited by applicant]

US 11731958B2 · Vechorkin et al. · 2023 [cited by applicant]

US 11787784B2 · Jia et al. · 2023 [cited by applicant]

US 11795166B2 · Vechorkin et al. · 2023 [cited by applicant]

US 11866426B2 · Hummel et al. · 2024 [cited by applicant]

US 11891388B2 · Liu et al. · 2024 [cited by applicant]

US 20020013327A1 · Lee et al. · 2002 [cited by applicant]

US 20030162782A1 · Grossman et al. · 2003 [cited by applicant]

US 20030186996A1 · Teng et al. · 2003 [cited by applicant]

US 20040063730A1 · Eggenweiler et al. · 2004 [cited by applicant]

US 20040077681A1 · Rawlings et al. · 2004 [cited by applicant]

US 20040147546A1 · Tanaka et al. · 2004 [cited by applicant]

US 20040157866A1 · Takasugi et al. · 2004 [cited by applicant]

US 20040167030A1 · Bernotas et al. · 2004 [cited by applicant]

US 20040204417A1 · Perez et al. · 2004 [cited by applicant]

US 20050070557A1 · Fryburg et al. · 2005 [cited by applicant]

US 20050075795A1 · Pandit · 2005 [cited by applicant]

US 20050119278A1 · Teng et al. · 2005 [cited by applicant]

US 20050137226A1 · Ji et al. · 2005 [cited by applicant]

US 20050208582A1 · Ohi et al. · 2005 [cited by applicant]

US 20050261339A1 · Ohi et al. · 2005 [cited by applicant]

US 20060106032A1 · Kuo et al. · 2006 [cited by applicant]

US 20070087988A1 · Sawasdikosol et al. · 2007 [cited by applicant]

US 20070161673A1 · Barker et al. · 2007 [cited by applicant]

US 20070185152A1 · Yamashita et al. · 2007 [cited by applicant]

US 20070270412A1 · Bell et al. · 2007 [cited by applicant]

US 20080280891A1 · Kelly et al. · 2008 [cited by applicant]

US 20100035891A1 · Bunnage et al. · 2010 [cited by applicant]

US 20100087464A1 · Mi et al. · 2010 [cited by applicant]

US 20100216798A1 · Nakai et al. · 2010 [cited by applicant]

US 20120129852A1 · Duan et al. · 2012 [cited by applicant]

US 20120225869A1 · Liu et al. · 2012 [cited by applicant]

US 20120295884A1 · Altmann et al. · 2012 [cited by applicant]

US 20130039906A1 · Do et al. · 2013 [cited by applicant]

US 20130040949A1 · Gray et al. · 2013 [cited by applicant]

US 20130281433A1 · Babaoglu et al. · 2013 [cited by applicant]

US 20140225073A1 · Lee et al. · 2014 [cited by applicant]

US 20140249135A1 · Burger et al. · 2014 [cited by applicant]

US 20140288045A1 · Ren et al. · 2014 [cited by applicant]

US 20140288069A1 · Eis et al. · 2014 [cited by applicant]

US 20140350017A1 · Williams et al. · 2014 [cited by applicant]

US 20140364605A1 · Li et al. · 2014 [cited by applicant]

US 20150038485A1 · Eis et al. · 2015 [cited by applicant]

US 20150191462A1 · Hommel et al. · 2015 [cited by applicant]

US 20150239868A1 · Pais et al. · 2015 [cited by applicant]

US 20150239889A1 · Nakajima et al. · 2015 [cited by applicant]

US 20150243908A1 · Lee et al. · 2015 [cited by applicant]

US 20150274639A1 · Williams et al. · 2015 [cited by applicant]

US 20150328188A1 · Orlemans et al. · 2015 [cited by applicant]

US 20160013427A1 · Kim et al. · 2016 [cited by applicant]

US 20160046648A1 · Petrukhin et al. · 2016 [cited by applicant]

US 20160068529A1 · Kc et al. · 2016 [cited by applicant]

US 20160068547A1 · Kc et al. · 2016 [cited by applicant]

US 20160068548A1 · Kc et al. · 2016 [cited by applicant]

US 20160068551A1 · Kc et al. · 2016 [cited by applicant]

US 20160200722A1 · DeMong et al. · 2016 [cited by applicant]

US 20180072718A1 · Liu et al. · 2018 [cited by applicant]

US 20180072719A1 · Ye et al. · 2018 [cited by applicant]

US 20180072720A1 · Vechorkin et al. · 2018 [cited by applicant]

US 20180072741A1 · Vechorkin et al. · 2018 [cited by applicant]

US 20180228786A1 · Sokolsky · 2018 [cited by applicant]

US 20190076401A1 · Vechorkin et al. · 2019 [cited by applicant]

US 20190106419A1 · Vechorkin et al. · 2019 [cited by applicant]

US 20190256500A1 · Vechorkin et al. · 2019 [cited by applicant]

US 20190256520A1 · Sokolsky · 2019 [cited by applicant]

US 20190315717A1 · Hummel et al. · 2019 [cited by applicant]

US 20190315743A1 · Liu et al. · 2019 [cited by applicant]

US 20190343814A1 · Sokolsky · 2019 [cited by applicant]

US 20190382380A1 · Vechorkin et al. · 2019 [cited by applicant]

US 20200048241A1 · Hummel et al. · 2020 [cited by applicant]

US 20200087301A1 · Vechorkin et al. · 2020 [cited by applicant]

US 20200172545A1 · Vechorkin et al. · 2020 [cited by applicant]

US 20200283434A1 · Liu et al. · 2020 [cited by applicant]

US 20210002288A1 · Sokolsky · 2021 [cited by applicant]

US 20210040071A1 · Jia et al. · 2021 [cited by applicant]

US 20210094934A1 · Vechorkin et al. · 2021 [cited by applicant]

US 20210171518A1 · Hummel et al. · 2021 [cited by applicant]

US 20210371425A1 · Vechorkin et al. · 2021 [cited by applicant]

US 20210380581A1 · Vechorkin et al. · 2021 [cited by applicant]

US 20220162195A1 · Jia et al. · 2022 [cited by applicant]

US 20220227752A1 · Liu et al. · 2022 [cited by applicant]

US 20240287059A1 · Vechorkin et al. · 2024 [cited by applicant]

US 20240383889A1 · Liu et al. · 2024 [cited by applicant]

CN 101801981 · 2010 [cited by applicant]

CN 101918371 · 2010 [cited by applicant]

CN 102206172 · 2011 [cited by applicant]

CN 102503959 · 2012 [cited by applicant]

CN 102516263 · 2012 [cited by applicant]

CN 103570709 · 2014 [cited by applicant]

CN 105452226 · 2016 [cited by applicant]

CN 107922431 · 2018 [cited by applicant]

CO 2022002563 · 2022 [cited by applicant]

DE 102004054666 · 2006 [cited by applicant]

EP 2543372 · 2013 [cited by applicant]

EP 2824099 · 2015 [cited by applicant]

ES 2445405 · 2014 [cited by applicant]

ES 2640063 · 2017 [cited by applicant]

IN 187433 · 2002 [cited by applicant]

JP H03287584 · 1991 [cited by applicant]

JP 2000038350 · 2000 [cited by applicant]

JP 2007055940 · 2007 [cited by applicant]

JP 2010111624 · 2010 [cited by applicant]

JP 2010520228 · 2010 [cited by applicant]

JP 2010533716 · 2010 [cited by applicant]

JP 2011246389 · 2011 [cited by applicant]

KR 963644 · 1996 [cited by applicant]

KR 20140019055 · 2014 [cited by applicant]

KR 20180015255 · 2018 [cited by applicant]

MX 9910322 · 2003 [cited by applicant]

MY 146643 · 2012 [cited by applicant]

TW I771319 · 2022 [cited by applicant]

WO WO1989008263 · 1989 [cited by applicant]

WO WO1997019065 · 1997 [cited by applicant]

WO WO1997046537 · 1997 [cited by applicant]

WO WO2000043394 · 2000 [cited by applicant]

WO WO2001019827 · 2001 [cited by applicant]

WO WO2001019828 · 2001 [cited by applicant]

WO WO2001021576 · 2001 [cited by applicant]

WO WO2001046124 · 2001 [cited by applicant]

WO WO2002000196 · 2002 [cited by applicant]

WO WO2002016348 · 2002 [cited by applicant]

WO WO2002019975 · 2002 [cited by applicant]

WO WO2002050073 · 2002 [cited by applicant]

WO WO2002090347 · 2002 [cited by applicant]

WO WO2003037432 · 2003 [cited by applicant]

WO WO2003049681 · 2003 [cited by applicant]

WO WO2004072069 · 2004 [cited by applicant]

WO WO2004096810 · 2004 [cited by applicant]

WO WO2004108133 · 2004 [cited by applicant]

WO WO2005004799 · 2005 [cited by applicant]

WO WO2005011681 · 2005 [cited by applicant]

WO WO2005028475 · 2005 [cited by applicant]

WO WO2005051906 · 2005 [cited by applicant]

WO WO2005066167 · 2005 [cited by applicant]

WO WO2005073199 · 2005 [cited by applicant]

WO WO2005073232 · 2005 [cited by applicant]

WO WO2003101968 · 2005 [cited by applicant]

WO WO2005085227 · 2005 [cited by applicant]

WO WO2005085248 · 2005 [cited by applicant]

WO WO2005085249 · 2005 [cited by applicant]

WO WO2006013095 · 2006 [cited by applicant]

WO WO2006028958 · 2006 [cited by applicant]

WO WO2006038001 · 2006 [cited by applicant]

WO WO2006045010 · 2006 [cited by applicant]

WO WO2006050097 · 2006 [cited by applicant]

WO WO2006053109 · 2006 [cited by applicant]

WO WO2006053121 · 2006 [cited by applicant]

WO WO2006053227 · 2006 [cited by applicant]

WO WO2006074428 · 2006 [cited by applicant]

WO WO2006105289 · 2006 [cited by applicant]

WO WO2006128172 · 2006 [cited by applicant]

WO WO2007019344 · 2007 [cited by applicant]

WO WO2007019345 · 2007 [cited by applicant]

WO WO2007019346 · 2007 [cited by applicant]

WO WO2007019417 · 2007 [cited by applicant]

WO WO2007020050 · 2007 [cited by applicant]

WO WO2007023110 · 2007 [cited by applicant]

WO WO2007023111 · 2007 [cited by applicant]

WO WO2007023114 · 2007 [cited by applicant]

WO WO2007030582 · 2007 [cited by applicant]

WO WO2007056280 · 2007 [cited by applicant]

WO WO2007063925 · 2007 [cited by applicant]

WO WO2007065924 · 2007 [cited by applicant]

WO WO2007080382 · 2007 [cited by applicant]

WO WO2007093402 · 2007 [cited by applicant]

WO WO2007112093 · 2007 [cited by applicant]

WO WO2007114848 · 2007 [cited by applicant]

WO WO2007137030 · 2007 [cited by applicant]

WO WO2008008059 · 2008 [cited by applicant]

WO WO2008008539 · 2008 [cited by applicant]

WO WO2008012027 · 2008 [cited by applicant]

WO WO2008045627 · 2008 [cited by applicant]

WO WO2008070313 · 2008 [cited by applicant]

WO WO2008089307 · 2008 [cited by applicant]

WO WO2008089310 · 2008 [cited by applicant]

WO WO2008113856 · 2008 [cited by applicant]

WO WO2009019167 · 2009 [cited by applicant]

WO WO2009024341 · 2009 [cited by applicant]

WO WO2009032651 · 2009 [cited by applicant]

WO WO2009038784 · 2009 [cited by applicant]

WO WO2009058348 · 2009 [cited by applicant]

WO WO2009100130 · 2009 [cited by applicant]

WO WO2009139834 · 2009 [cited by applicant]

WO WO2009152356 · 2009 [cited by applicant]

WO WO2010029300 · 2010 [cited by applicant]

WO WO2010035217 · 2010 [cited by applicant]

WO WO2010035219 · 2010 [cited by applicant]

WO WO2010035221 · 2010 [cited by applicant]

WO WO2010046780 · 2010 [cited by applicant]

WO WO2010080503 · 2010 [cited by applicant]

WO WO2010104306 · 2010 [cited by applicant]

WO WO2010107765 · 2010 [cited by applicant]

WO WO2010107768 · 2010 [cited by applicant]

WO WO2010111624 · 2010 [cited by applicant]

WO WO2010118367 · 2010 [cited by applicant]

WO WO2011019780 · 2011 [cited by applicant]

WO WO2011031628 · 2011 [cited by applicant]

WO WO2011050245 · 2011 [cited by applicant]

WO WO2011051535 · 2011 [cited by applicant]

WO WO2011062253 · 2011 [cited by applicant]

WO WO2011078143 · 2011 [cited by applicant]

WO WO2011079236 · 2011 [cited by applicant]

WO WO2011082400 · 2011 [cited by applicant]

WO WO2011082488 · 2011 [cited by applicant]

WO WO2011107186 · 2011 [cited by applicant]

WO WO2011133920 · 2011 [cited by applicant]

WO WO2011139107 · 2011 [cited by applicant]

WO WO2011139489 · 2011 [cited by applicant]

WO WO2011141756 · 2011 [cited by applicant]

WO WO2011147765 · 2011 [cited by applicant]

WO WO2011153553 · 2011 [cited by applicant]

WO WO2011157653 · 2011 [cited by applicant]

WO WO2011158108 · 2011 [cited by applicant]

WO WO2012048058 · 2012 [cited by applicant]

WO WO2012049277 · 2012 [cited by applicant]

WO WO2012078777 · 2012 [cited by applicant]

WO WO2012080376 · 2012 [cited by applicant]

WO WO2012109263 · 2012 [cited by applicant]

WO WO2012130780 · 2012 [cited by applicant]

WO WO2012141487 · 2012 [cited by applicant]

WO WO2012143144 · 2012 [cited by applicant]

WO WO2012151567 · 2012 [cited by applicant]

WO WO2012158810 · 2012 [cited by applicant]

WO WO2012163959 · 2012 [cited by applicant]

WO WO2013007708 · 2013 [cited by applicant]

WO WO2013021276 · 2013 [cited by applicant]

WO WO2013024002 · 2013 [cited by applicant]

WO WO2013024011 · 2013 [cited by applicant]

WO WO2013042137 · 2013 [cited by applicant]

WO WO2013064445 · 2013 [cited by applicant]

WO WO2013123215 · 2013 [cited by applicant]

WO WO2013130890 · 2013 [cited by applicant]

WO WO2013146942 · 2013 [cited by applicant]

WO WO2014003405 · 2014 [cited by applicant]

WO WO2014024125 · 2014 [cited by applicant]

WO WO2014047616 · 2014 [cited by applicant]

WO WO2014055955 · 2014 [cited by applicant]

WO WO2014100719 · 2014 [cited by applicant]

WO WO2014151616 · 2014 [cited by applicant]

WO WO2015026683 · 2015 [cited by applicant]

WO WO2015037965 · 2015 [cited by applicant]

WO WO2015038503 · 2015 [cited by applicant]

WO WO2015058163 · 2015 [cited by applicant]

WO WO2015061247 · 2015 [cited by applicant]

WO WO2015089327 · 2015 [cited by applicant]

WO WO2015089479 · 2015 [cited by applicant]

WO WO2015090235 · 2015 [cited by applicant]

WO WO2015091426 · 2015 [cited by applicant]

WO WO2015104662 · 2015 [cited by applicant]

WO WO2015117718 · 2015 [cited by applicant]

WO WO2015164956 · 2015 [cited by applicant]

WO WO2015192939 · 2015 [cited by applicant]

WO WO2015193506 · 2015 [cited by applicant]

WO WO2015193846 · 2015 [cited by applicant]

WO WO2015200680 · 2015 [cited by applicant]

WO WO2015200682 · 2015 [cited by applicant]

WO WO2016040180 · 2016 [cited by applicant]

WO WO2016040181 · 2016 [cited by applicant]

WO WO2016041618 · 2016 [cited by applicant]

WO WO2020151742 · 2016 [cited by applicant]

WO WO2016057500 · 2016 [cited by applicant]

WO WO2016083433 · 2016 [cited by applicant]

WO WO2016090300 · 2016 [cited by applicant]

WO WO2016124304 · 2016 [cited by applicant]

WO WO2016144351 · 2016 [cited by applicant]

WO WO2016144702 · 2016 [cited by applicant]

WO WO2016164285 · 2016 [cited by applicant]

WO WO2016174183 · 2016 [cited by applicant]

WO WO2016205942 · 2016 [cited by applicant]

WO WO2017009798 · 2017 [cited by applicant]

WO WO2017009806 · 2017 [cited by applicant]

WO WO2017023894 · 2017 [cited by applicant]

WO WO2017023972 · 2017 [cited by applicant]

WO WO2017027400 · 2017 [cited by applicant]

WO WO2017045955 · 2017 [cited by applicant]

WO WO2017058915 · 2017 [cited by applicant]

WO WO2017108744 · 2017 [cited by applicant]

WO WO2017120429 · 2017 [cited by applicant]

WO WO2018019204 · 2018 [cited by applicant]

WO WO2018049152 · 2018 [cited by applicant]

WO WO2019164846 · 2019 [cited by applicant]

WO WO2019207463 · 2021 [cited by applicant]

WO WO2019211451 · 2021 [cited by applicant]

WO WO2021026180 · 2021 [cited by applicant]

WO WO2019219517 · 2021 [cited by applicant]

ZA 2003005330 · 2003 [cited by applicant]

Alzabin et al., “Hematopoietic progenitor kinase 1 is a critical component of prostaglandin E2-mediated suppression of the anti-tumor immune response,” Cancer Immunol Immunother, 2010, 59(3):419-429. [cited by applicant]

Alzabin et al., “Hematopoietic progenitor kinase 1 is a negative regulator of dendritic cell activation,” J Immunol, 2009, 182(10):6187-6194. [cited by applicant]

Anonymous, “Crystalline APX,” IP.com #IPCOM000233879, Dec. 25, 2013, 3 pages. [cited by applicant]

Anonymous, “Crystalline ethyl 1-(4-methoxyphenyl)-6-(4-nitrophenyl)-7-oxo-,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate,” IP.com #IPCOM000233229D, Dec. 3, 2019, 4 pages. [cited by applicant]

Antoine et al., “Efficient synthesis of novel disubstituted pyrido[3,4-b]pyrazines for the design of protein kinase inhibitors,” Med Chem Common., 2016, 6:224-229. [cited by applicant]

Antunes et al., “In silico prediction of novel phosphodiesterase type-5 inhibitors derived from Sildenafil, Vardenafil and Tadalafil,” Bioorg Med Chem., Aug. 15, 2008, 16(16):7599-7606. [cited by applicant]

Atzrodt et al., “The Renaissance of H/D Exchange,” Angew. Chem. Int. Ed., 2007, 7744-7765. [cited by applicant]

Australian Office Action in Australian Application No. 2017322427, dated Dec. 16, 2020, 5 pages. [cited by applicant]

Bae et al., “Cancer Targeted Drug Delivery,” Springer: New York, 2013, p. v. [cited by applicant]

Ballell et al., “Fueling Open-Source Drug Discovery: 177 Small-Molecule Leads against Tuberculosis,” ChemMedChem., 2013, 8(2):313-321. [cited by applicant]

Balog et al., “The synthesis and evaluation of [2.2.1]-bicycloazahydantoins as androgen receptor antagonists,” Bioorg. Med. Chem. Lett., Dec. 20, 2004, 14(24):6107-6111. [cited by applicant]

Batliwalla et al., “Microarray analyses of peripheral blood cells identifies unique gene expression signature in psoriatic arthritis,” Mol Med, 2005, 11(1-12):21-29. [cited by applicant]

Benz, “The Jeremiah Metzger Lecture Cancer in the Twenty-First Century: An Inside View from an Outsider,” Trans Am Clin Climatol Assoc., 2017, 128:275-297. [cited by applicant]

Berge et al., “Pharmaceutical Salts,” J. Pharm. Sci., 1977, 66(1):1-19. [cited by applicant]

Blom et al., “Optimizing Preparative LC-MS Configurations and Methods for Parallel Synthesis Purification,” J. Combi. Chem., 2003, 5:670. [cited by applicant]

Blom et al., “Preparative LC-MS Purification: Improved Compound Specific Method Optimization,” J. Combi. Chem., 2004, 6:874-883. [cited by applicant]

Blom et al., “Two-Pump At Column Dilution Configuration for Preparative LC-MS,” J. Combi. Chem., 2002, 4: 295. [cited by applicant]

Boomer et al., “Functional Interactions of HPK1 With Adaptor Proteins” Journal of Cellular Biochemistry, 2005, 95:34-44. [cited by applicant]

Brioche et al., “Chiral Phosphoric Acid-Catalyzed Enantioselective Three-Component Aza-Diels-Alder Reactions of Aminopyrroles and Aminopyrazoles,” Advanced Synthesis & Catalysis, 2014, 356(8):1719-1724. [cited by applicant]

Caira, “Crystalline polymorphism of organic compounds,” Topics in current chemistry, Jan. 1998, 198:163-208. [cited by applicant]

Chessari et al., “Fragment-Based Drug Discovery Targeting Inhibitor of Apoptosis Proteins: Discovery of a Non-Alanine Lead Series with Dual Activity Against cIAP1 and XIAP,” J. Med. Chem., Jul. 18, 2015, 58(16):6574-658… [cited by applicant]

Cheung et al., “A Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing,” J Med Chem., Mar. 10… [cited by applicant]

Chilean Office Action in Chilean Application No. 2146-2020, dated Oct. 10, 2021, 18 pages. [cited by applicant]

Chinchilla and Najera, “Recent advances in Sonogashira reactions,” Chem. Soc. Rev., 2011, 40: 5084-5121. [cited by applicant]

Chinese Office Action in Chinese Application No. 201780068722.2, dated Jul. 15, 2021, 13 pages. [cited by applicant]

Chinese Office Action in Chinese Application No. 201980020899.4, dated Dec. 22, 2022, 11 pages (with English translation). [cited by applicant]

Chinese Office Action in Chinese Application No. 201980020899.4, dated Jul. 25, 2023, 8 pages (with English translation). [cited by applicant]

Chinese Office Action in Chinese Application No. 202080065915.4, dated Sep. 16, 2023, 11 pages (with English Translation). [cited by applicant]

Chinese Office Action in Chinese Application No. 2020800659154, dated Apr. 20, 2024, 10 pages (with English Translation). [cited by applicant]

Chinese Office Action in Chinese Application No. 202211268174.7, dated Apr. 25, 2024, 16 pages (with English Translation). [cited by applicant]

Choi et al., “In vitro metabolism of a novel phosphodiesterase-5 inhibitor DA-8159 in rat liver preparations using liquid chromatography/electrospray mass spectrometry,” Biomed Chromatogr., Sep. 2002, 16(6):395-399. [cited by applicant]

Colombian Office Action in Colombian Application No. NC2020/0011530, dated Oct. 26, 2022, 19 pages (with English translation). [cited by applicant]

Cordovilla et al., “The Stille Reaction, 38 Years Later,” ACS Catalysis, 2015, 5: 3040-3053. [cited by applicant]

Devegowda et al., “Novel 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one derivatives as potential anti-cancer agents,” Bioorg Med Chem Lett., Mar. 1, 2010, 20(5):1630-1633. [cited by applicant]

Di Bartolo et al., “A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76,” J. Exp. Med., Mar. 2007, 204(3): 681-691. [cited by applicant]

Dolgin, “Lung Cancer Outlook,” Nature, Nov. 19, 2020, 587:S16-S17. [cited by applicant]

Dong et al., “Pharmacophore identification, virtual screening and biological evaluation of prenylated flavonoids derivatives as PKB/Akt1 inhibitors,” Eur J Med Chem., Dec. 2011, 46(12):5949-5958. [cited by applicant]

Dong et al., “QSAR study of Akt/protein kinase B (PKB) inhibitors using support vector machine,” Eur J Med Chem., Oct. 2009, 44(10):4090-4097. [cited by applicant]

Dornow et al., “Syntheses of nitrogen-containing heterocycles. XXXVIII. Preparation and reaction of several substituted 3-nitropyridines, ” Chemische Berichte, 1966, 99(1):244-253 (Machine Translation). [cited by applicant]

Dumestre-Toulet et al., “Last performance with Viagra: post-mortem identification of sildenafil and its metabolites in biological specimens including hair sample,” Forensic Sci Int., Mar. 28, 2002, 126(1):71-76. [cited by applicant]

Edmondson et al., “Aminopiperidine-fused imidazoles as dipeptidyl peptidase-IV inhibitors,” Bioorg Med Chem Lett., Aug. 2009, 19(15):4097-4101. [cited by applicant]

El Sayed et al., “New route for the preparation of pyrazolo[4,3-c]pyridines,” Bulletin of the Chemical Society of Japan (1973), 46(6), 1801-1803. [cited by applicant]

El-Aziz et al., “Synthesis and in vitro anti-breast cancer activity of some novel 1,4-dihydropyridine derivatives,” Int J of Pharm Pharma Sci., 2013, 5(Suppl. 3):183-189. [cited by applicant]

Elgemeie et al., “A new general method for substituted 4-alkylthio-N-arylsulfonylamino-2-pyridones: Reaction of ketene-S,S-acetals with arylsulfonylhydrazides,” Phosphorus, Sulfur and Silicon and the Related Elements, 2… [cited by applicant]

Elgemeie et al., “Novel N-Substituted Amino-4-methylsulfanyl-2-pyridones and Deazapurine Analogues from Ketene Dithioacetals,” J Chem Res., 1998, 3:164-165. [cited by applicant]

Elgemeie et al., “Novel Nucleoside Analogues: First Synthesis of Pyridine-4-Thioglycosides and Their Cytotoxic Evaluation,” Nucleosides, Nucleotides and Nucleic Acids, Jun. 27, 2015, 34:659-673. [cited by applicant]

Elgemeie et al., “Novel synthesis of N-aroylaminated pyridones via reaction of ketene dithioacetals with cyanoaceto-N-aroylhydrazides,” Synth Comm., 2003, 33(2):253-258. [cited by applicant]

Elgemeie et al., “Synthesis of Novel Derivatives of 4-Methylthio-N-Aryl-2-Pyridone and Deazapurine Analogues: The Reaction of Ketene Dithioacetals with Substituted Acetanilides,” Phosphorus, Sulfur and Silicon, 2000, 16… [cited by applicant]

Erian, “2-Ary1-1,1-dicyano-3-phenylsulfonylpropenes in heterocyclic synthesis. A synthetic strategy towards heterocyclic sulfone,” Monatshefte fuer Chemie, Oct. 1998, 129(10):1049-1056. [cited by applicant]

Eurasian Office Action in Eurasian Application No. 201990665, Feb. 17, 2020, 5 pages. [cited by applicant]

Eurasian Office Action in Eurasian Application No. 202091983, dated Nov. 29, 2021, 4 pages. [cited by applicant]

Eurasian Office Action in Eurasian Application No. 202290492, dated Jan. 9, 2023, 9 pages (with English translation). [cited by applicant]

Extended European Search Report in European Application No. 22177485.4, dated Dec. 19, 2022, 8 pages. [cited by applicant]

Figueiredo et al., “A chemometric study of phosphodiesterase 5 inhibitors,” J Mol Graph Model., Jan. 2006, 24(4):227-232. [cited by applicant]

Gao, “Slidenafil” Handbook of Metabolic Pathways of Xenobiotics, 2014, 5:2151-2154. [cited by applicant]

Garson et al., “Models of ovarian cancer—Are we there yet?” Molecular and Cellular Endocrinology, Jul. 2005, 239(1-2):15-26. [cited by applicant]

Gerratana et al., “Do platinum salts fit all triple negative breast cancers?,” Cancer Treatment Reviews, Jul. 2016, 48:34-41. [cited by applicant]

Goodarzi et al., “Feature Selection and Linear/Nonlinear Regression Methods for the Accurate Prediction of Glycogen Synthase Kinase-3β Inhibitory Activities,” J. Chem. Inf. Model, 2009, 49(4):824-832. [cited by applicant]

Haas et al., “Recent Developments in Negishi Cross-Coupling Reactions,” ACS Catalysis, 2016, 6: 1540-1552. [cited by applicant]

Haning et al., “Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors,” Sep. 1, 2005, 15(17):3900-3907. [cited by applicant]

Hanson, “Diterpenoids of Terrestrial Origin”, National Product Reports, 2016, 33:1227-1238. [cited by applicant]

Hayat, “Autophagy: Cancer, other Pathologies, Inflammation, Immunity, Infection, and Aging,” Academic Press: San Diego, 2015, p. xxi. [cited by applicant]

He et al., “Predicting the Genotoxicity of Polycyclic Aromatic Compounds from Molecular Structure with Different Classifiers,” Chemical Research in Toxicology (2003), 16(12):1567-1580. [cited by applicant]

Ho et al., “Discovery of 4-phenyl-2-phenylaminopyridine based TNIK inhibitors,” Boorg Med Chem Lett, 2013, 23(2):569-573. [cited by applicant]

Howard et al., “Identification of potent phosphodiesterase inhibitors that demonstrate cyclic nucleotide-dependent functions in apicomplexan parasites,” ACS Chem Biol., Apr. 17, 2015, 10(4):1145-1154. [cited by applicant]

Howington et al., “Treatment of Stage I and II Non-small Cell Lung Cancer Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines,” Chest, May 20… [cited by applicant]

Hu et al., “Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors,” Bioorg Med Chem Lett., 2015, 25(22):5258-5264. [cited by applicant]

Hu et al., “Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade,” Genes Dev, 1996, 10(18): p. 2251-2264. [cited by applicant]