Carboxamide compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-12466815-B2
Application number	US-202318212444-A
Country	US
Kind code	B2
Filing date	Jun 21, 2023
Priority date	Feb 20, 2018
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

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.

First claim

What is claimed is:

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

Assignees

• Incyte Corp

Inventors

• Vechorkin Oleg
• Pan Jun
• Sokolsky Alexander
• Styduhar Evan
• Ye Qinda
• Yao Wenqing

Classifications

• C07D487/08 Primary

  Bridged systems · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title