Heterocyclic compounds as immunomodulators

Patent metadata

Field	Value
Publication number	US-11608337-B2
Application number	US-202017032603-A
Country	US
Kind code	B2
Filing date	Sep 25, 2020
Priority date	May 6, 2016
Publication date	Mar 21, 2023
Grant date	Mar 21, 2023

Abstract

Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.

First claim

What is claimed is:

1. A compound of Formula (I):

or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
one of X 1 and X 3 is S and the other is N;
X 2 is C;
X 4 is N or CR 4 ;
X 5 is N or CR 5 ;
X 6 is N or CR 6 ;
Y is C;
Cy is C 6-10 aryl, C 3-10 cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl, each of which is optionally substituted with 1 to 5 independently selected R 7 substituents;
R 4 , R 5 and R 6 are each independently selected from H, C 1-4 alkyl, C 3-4 cycloalkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo, —CN, —OH, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, —NH 2 , —NH—C 1-4 alkyl, —N(C 1-4 alkyl) 2 , —NHOR 10 , —C(O)R 10 , —C(O)R 10 R 10 , —C(O)OR 10 , —OC(O)R 10 , —OC(O)NR 10 R 10 , —NR 10 C(O)R 10 , —NR 10 C(O)OR 10 , —NR 10 C(O)NR 10 R 10 , —C(═NR 10 )R 10 , —C(═NR 10 )NR 10 R 10 , —NR 10 C(═NR 10 )NR 10 R 10 , —NR 10 S(O)R 10 , —NR 10 S(O) 2 R 10 , —NR 10 S(O) 2 NR 10 R 10 , —S(O)R 10 , —S(O)NR 10 R 10 , —S(O) 2 R 10 , and —S(O) 2 NR 10 R 10 , wherein each R 10 is independently selected from H and C 1-4 alkyl optionally substituted with 1 or 2 groups independently selected from halo, —OH, —CN and C 1-4 alkoxy; and wherein the C 1-4 alkyl, C 3-4 cycloalkyl, C 2-4 alkenyl, C 2-4 alkynyl and C 1-4 alkoxy of R 4 , R 5 and R 6 are each optionally substituted with 1 or 2 substituents independently selected from halo, —OH, —CN and C 1-4 alkoxy;
R 9 is C 1-4 alkyl, halo, or —CN;
R 7 , R 13 and R 14 are each independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, —CN, —NO 2 , —OR a , —SR a , —NHOR a , —C(O)R a , —C(O)NR a R a , —C(O)OR a , —OC(O)R a , —OC(O)NR a R a , —NHR a , —NR a R a , —NR a C(O)R a , —NR a C(O)OR a , —NR a C(O)NR a R a , —C(═NR a )R a , —C(═NR a )NR a R a , —NR a C(═NR a )NR a R a , —NR a S(O)R a , —NR a S(O) 2 R a , —NR a S(O) 2 NR a R a , —S(O)R a , —S(O)NR a R a , —S(O) 2 R a , and —S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 7 , R 13 and R 14 are each optionally substituted with 1, 2, 3, or 4 R b substituents;
or two adjacent R 7 substituents on the Cy ring, taken together with the atoms to which they are attached, form a fused phenyl ring, a fused 5-, 6- or 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 3-6 cycloalkyl ring, wherein the fused 5-, 6- or 7-membered heterocycloalkyl ring and fused 5- or 6-membered heteroaryl ring each have 1-4 heteroatoms as ring members selected from N, O and S and wherein the fused phenyl ring, fused 5-, 6- or 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 3-6 cycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected R b substituents;
or two R 13 substituents attached to the same carbon atom, taken together with the carbon atom to which they are attached, form a C 3-6 cycloalkyl ring or 4-, 5-, 6- or 7-membered heterocycloalkyl ring, wherein the C 3-6 cycloalkyl ring and 4-, 5-, 6- or 7-membered heterocycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected R b substituents;
each R a is independently selected from H, CN, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R a are each optionally substituted with 1, 2, 3, 4, or 5 R d substituents;
each R d is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, halo, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, —CN, —NH 2 , —NHOR e , —OR e , —SR e , —C(O)R e , —C(O)NR e R e , —C(O)OR e , —OC(O)R e , —OC(O)NR e R e , —NHR e , —NR e R e , —NR e C(O)R e , —NR e C(O)NR e R e , —NR e C(O)OR e , —C(═NR e )NR e R e , —NR e C(═NR e )NR e R e , —S(O)R e , —S(O)NR e R e , —S(O) 2 R e , —NR e S(O) 2 R e , —NR e S(O) 2 NR e R e , and —S(O) 2 NR e R e , wherein the C 1-4 alkyl, C 3-10 cycloalkyl and 4-10 membered heterocycloalkyl of R d are each further optionally substituted with 1-3 independently selected R q substituents;
each R b substituent is independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, —CN, —OH, —NH 2 , —NO 2 , —NHOR c , —OR c , —SR c , —C(O)R c , —C(O)NR c R c , —C(O)OR c , —OC(O)R c , —OC(O)NR c R c , —C(═NR c )NR c R c , —NR c C(═NR c )NR c R c , —NHR c , —NR c R c , —NR c C(O)R c , —NR c C(O)OR c , —NR c C(O)NR c R c , —NR c S(O)R c , —NR c S(O) 2 R c , —NR c S(O) 2 NR c R c , —S(O)R c , —S(O)NR c R c , —S(O) 2 R c and —S(O) 2 NR c R c ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R b are each further optionally substituted with 1-3 independently selected R d substituents;
each R c is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R c are each optionally substituted with 1, 2, 3, 4, or 5 R f substituents;
each R f is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, halo, —CN, —NHOR g , —OR g , —SR g , —C(O)R g , —C(O)NR g R g , —C(O)OR g , —OC(O)R g , —OC(O)NR g R g , —NHR g , —NR g R g , —NR g C(O)R g , —NR g C(O)NR g R g , —NR g C(O)OR g , —C(═NR g )NR g R g , —NR g C(═NR g )NR g R g , —S(O)R g , —S(O)NR g R g , —S(O) 2 R g , —NR g S(O) 2 R g , —NR g S(O) 2 NR g R g , and —S(O) 2 NR g R g ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C

Assignees

• Incyte Corp

Inventors

• Li Zhenwu
• Wu Liangxing
• Yao Wenqing

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D498/04

  Ortho-condensed systems · CPC title

• C07D513/04

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title