Heterocyclic amides as kinase inhibitors

Patent metadata

Field	Value
Publication number	US-10590085-B2
Application number	US-201615575235-A
Country	US
Kind code	B2
Filing date	May 19, 2016
Priority date	May 19, 2015
Publication date	Mar 17, 2020
Grant date	Mar 17, 2020

Abstract

Disclosed are compounds having the formula (I):

wherein R 1 , R 2 , and R 3 are as defined herein, and methods of making and using the same.

First claim

What is claimed is:

1. A compound according to Formula (I):

wherein:
R 1 is (C 1 -C 4 )alkoxy-CH 2 —, phenyl(C 1 -C 4 )alkoxy-CH 2 —, or a substituted or unsubstituted (C 2 -C 4 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 4 )alkyl-group, or a substituted or unsubstituted 5-6 membered heterocycloalkyl group further optionally substituted by halogen or (C 1 -C 4 )alkyl,
wherein said substituted (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-alkyl-, or 5-6 membered heterocycloalkyl group is substituted by 1, 2 or 3 substituents independently selected from hydroxyl, (benzyloxy)carbonyl)amino, cyano, halogen, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkyl-CO—, cyano(C 1 -C 4 )alkyl-CO—, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl-CO—, (C 1 -C 4 )alkoxy-CO—, (C 1 -C 4 )alkylNHCO—, ((C 1 -C 4 )alkyl)((C 1 -C 4 )alkyl)NCO—, halo(C 1 -C 4 )alkyl-CO—, optionally substituted (C 3 -C 6 )cycloalkyl-CO—, optionally substituted (C 3 -C 6 )cycloalkyl-(C 1 -C 4 )alkyl-CO—, optionally substituted phenyl-CO—, optionally substituted phenyl-SO 2 —, optionally substituted phenyl(C 1 -C 4 )alkyl-CO—, optionally substituted 5-6 membered heteroaryl-CO—, and optionally substituted 9-10 membered heteroaryl-CO—,
wherein said optionally substituted (C 3 -C 6 )cycloalkyl-CO—, optionally substituted (C 3 -C 6 )cycloalkyl-(C 1 -C 4 )alkyl-CO—, optionally substituted phenyl-CO—, optionally substituted phenyl-SO 2 -, optionally substituted phenyl(C 1 -C 4 )alkyl-CO—, optionally substituted 5-6 membered heteroaryl-CO—, or optionally substituted 9-10 membered heteroaryl-CO— is optionally substituted by 1 or 2 substituents independently selected from halogen, cyano, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkyl-CO—, halo(C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl-CO—, (C 3 -C 6 )cycloalkyl and 5-6 membered heterocycloalkyl; or

said substituted (C 2 -C 4 )alkynyl, (C 3 -C 6 )cycloalkyl or 5-6 membered heterocycloalkyl group is substituted by an optionally substituted phenyl, 5-6 membered heteroaryl or 9-membered heteroaryl group,
wherein said phenyl, 5-6 membered heteroaryl or 9-membered heteroaryl group is optionally substituted by 1 or 2 substituents independently selected from halogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl-CO—, halo(C 1 -C 4 )alkyl, and halo(C 1 -C 4 )alkyl-CO—;

R 2 is a substituted or unsubstituted phenyl, (C 3 -C 6 )cycloalkyl, 5-6 membered oxygen-containing heterocycloalkyl, 5-6 membered heteroaryl, 9-membered heteroaryl, 9-10 membered carbocyclic-aryl, or 9-10 membered heterocyclic-aryl group,
wherein said substituted phenyl, (C 3 -C 6 )cycloalkyl, 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl, 9-membered heteroaryl, 9-10 membered carbocyclic-aryl, or 9-10 membered heterocyclic-aryl group is substituted by 1, 2 or 3 substituents independently selected from halogen, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, halo(C 1 -C 4 )alkoxy, and cyano;

R 3 is H or halogen;
or a salt thereof,
provided the compound is not:
cyclohexyl(5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)methanone.

2. The compound, or salt thereof, according to claim 1 , wherein:
R 1 is a substituted or unsubstituted (C 4 -C 6 )cycloalkyl, (C 4 -C 6 )cycloalkyl-alkyl-, or 5-6 membered heterocycloalkyl group,
wherein said substituted (C 4 -C 6 )cycloalkyl, (C 4 -C 6 )cycloalkyl-alkyl-, or 5-6 membered heterocycloalkyl group is substituted by 1, 2 or 3 substituents independently selected from hydroxyl, (benzyloxy)carbonyl)amino, halogen, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl-CO—, halo(C 1 -C 4 )alkyl-CO—, and an optionally substituted 5-6 membered heteroaryl-CO—, wherein said optionally substituted 5-6 membered heteroaryl-CO— is optionally substituted by 1 or 2 substituents independently selected from (C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl-CO—, halo(C 1 -C 4 )alkyl, and halo(C 1 -C 4 )alkyl-CO—, or
said substituted (C 4 -C 6 )cycloalkyl or 5-6 membered heterocycloalkyl group is substituted by an optionally substituted phenyl, 5-6 membered heteroaryl or 9-membered heteroaryl optional substituted by 1 or 2 substituents independently selected from halogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl-CO—, halo(C 1 -C 4 )alkyl, and halo(C 1 -C 4 )alkyl-CO—;
R 2 is a substituted or unsubstituted phenyl, (C 3 -C 6 )cycloalkyl, 5-membered oxygen-containing heterocycloalkyl, 5-6 membered heteroaryl or 9-membered heteroaryl group,
wherein said substituted phenyl, (C 3 -C 6 )cycloalkyl, 5-membered heterocycloalkyl, 5-6 membered heteroaryl or 9-membered heteroaryl group is substituted by 1, 2 or 3 substituents independently selected from halo, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, and cyano; and
R 3 is H.

3. The compound, or salt thereof, according to claim 1 , wherein:
R 1 is a substituted or unsubstituted (C 4 -C 6 )cycloalkyl, (C 4 -C 6 )cycloalkyl-alkyl-, or 5-6 membered heterocycloalkyl group,
wherein said substituted (C 4 -C 6 )cycloalkyl, (C 4 -C 6 )cycloalkyl-alkyl-, or 5-6 membered heterocycloalkyl group is substituted by 1, 2 or 3 substituents independently selected from hydroxyl, (benzyloxy)carbonyl)amino, halogen, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl-CO—, halo(C 1 -C 4 )alkyl-CO—, and an optionally substituted 5-6 membered heteroaryl-CO—, wherein said optionally substituted 5-6 membered heteroaryl-CO— is optionally substituted by 1 or 2 substituents independently selected from (C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl-CO—, halo(C 1 -C 4 )alkyl, and halo(C 1 -C 4 )alkyl-CO—, or
said substituted (C 4 -C 6 )cycloalkyl or 5-6 membered heterocycloalkyl group is substituted by an optionally substituted phenyl, 5-6 membered heteroaryl or 9-membered heteroaryl optional substituted by 1 or 2 substituents independently selected from halogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl-CO—, halo(C 1 -C 4 )alkyl, and halo(C 1 -C 4 )alkyl-CO—;
R 2 is a substituted or unsubstituted phenyl, 5-6 membered oxygen-containing heterocycloalkyl, wherein said substituted 5-6 membered heterocycloalkyl is substituted by 1, 2 or 3 substituents independently selected from halo, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, and cyano; and R 3 is H.

4. The compound, or salt thereof, according to claim 1 , having Formula (II):

5. The compound, or salt thereof, according to claim 4 , wherein R 1 is a substituted or unsubstituted 5-6 membered heterocycloalkyl group.

6. The compound, or salt thereof, according to claim 4 , wherein R 1 is a substituted or unsubstituted 5-6 membered heterocycloalkyl group further optionally substituted by halogen or (C 1 -C 4 )alkyl.

7. The compound, or salt thereof, according to claim 4 , wherein R 1 is a substituted piperidinyl group, wherein the substituted piperidinyl group is substituted by a substituent selected from (C 1 -C 4 )alkyl-CO—, halo(C 1 -C 4 )alkyl-CO—, cyano(C 1 -C 4 )alkyl-CO—, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl-CO—, (C 1 -C 4 )alkylNHCO—, optionally substituted (C 3 -C 6 )cycloalkyl-CO—, optionally substituted (C 3 -C 6 )cycloalkyl-(C 1 -C 4 )alkyl-CO—, optionally substituted phenyl-CO—, optionally substituted phenyl-SO 2 —, optionally substituted phenyl(C 1 -C 4 )alkyl-CO—, optionally substituted 5-6 membered heteroaryl-CO—, and optionally substituted 9-10 membered heteroaryl-CO—, wherein said optionally substituted (C 3 -C 6 )cycloalkyl-CO—, optionally substituted (C 3 -C 6 )cycloalkyl-(C 1 -C 4 )alkyl-CO—, optionally substituted phenyl-CO—, optionally substituted phenyl-SO 2 —, optionally substituted phenyl(C 1 -C 4 )alkyl-CO—, optional

Assignees

• Glaxosmithkline Ip Dev Ltd

Inventors

• Anderson Niall Andrew
• Bandyopadhyay Deepak
• Daugan Alain Claude-Marie
• Donche Frederic G
• Eidam Patrick M
• Faucher Nicolas Eric
• George Nicolas S
• Harris Philip Anthony
• Jeong Jae U
• King Bryan W
• Sehon Clark A
• White Gemma Victoria
• Wisnoski David Duff

Classifications

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• A61K31/454 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K31/415

  1,2-Diazoles · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title