Furo- and thieno-pyridine carboxamide compounds useful as pim kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9556197-B2
Application number	US-201414465910-A
Country	US
Kind code	B2
Filing date	Aug 22, 2014
Priority date	Aug 23, 2013
Publication date	Jan 31, 2017
Grant date	Jan 31, 2017

Abstract

The present disclosure describes furo- and thieno-pyridine carboxamide compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.

First claim

What is claimed is:

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
X is S or O;
A 5 is C—R 5 ;
Cy A is a pyridinyl ring, wherein the pyridinyl ring is unsubstituted or substituted with 1, 2, or 3 R A ;
each R A is independently selected from R A1 , halogen, C 1-6 haloalkyl, CN, 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)NR c1 R d1 , NR c1 C(═O)OR a1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , S(═O)R b1 , S(═O)NR c1 R d1 , S(═O) 2 R b1 , NR c1 S(═O) 2 R b1 and S(═O) 2 R c1 R d1 ;
each R A1 is independently selected from C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein each C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl forming R A1 is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen, CN, 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)NR c1 R d1 , NR c1 C(═O)OR a1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , S(═O)R b1 , S(═O)NR c1 R d1 , S(═O) 2 R b1 , NR c1 S(═O) 2 R b1 and S(═O) 2 NR c1 R d1 ;
Cy B is a 3-aminopiperidin-1-yl, wherein said piperidinyl is optionally substituted with 1, 2, 3, or 4 R B ;
each R B is independently selected from R B1 , R B2 , halogen, C 1-6 haloalkyl, CN, OR a2 , SR a2 , C(═O)R b2 , C(═O)NR c2 R d2 , C(═O)R a2 , OC(═O)R b2 , OC(═O)NR c2 R d2 , NR c2 R d2 , NR c2 C(═O)R b2 , NR c2 C(═O)NR c2 R d2 , NR c2 C(═O)OR a2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , S(═O)NR c2 R d2 , S(═O) 2 R b2 , NR c2 S(═O) 2 R b2 and S(═O)NR c2 R d2 ,
each R B1 is independently selected from C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein each of said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl of R B1 is unsubstituted or substituted with 1, 2, 3, 4 or 5 R B3 ;
each R B2 is independently selected from C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl, wherein each of said C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl forming R B2 is unsubstituted or substituted with 1, 2, 3, 4 or 5 R B4 ;

each R B3 is independently selected from R B2 , halogen, C 1-6 haloalkyl, CN, OR a2 , SR a2 , C(═O)R b2 , C(═O)NR c2 R d2 , C(═O)OR a2 , OC(═O)R b2 , OC(═O)NR c2 R d2 , NR c2 R d2 , NR c2 C(═O)R b2 , NR c2 C(═O)NR c2 R d2 , NR c2 C(═O)OR a2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , S(═O)R b2 , S(═O)NR c2 R d2 , S(═O) 2 R b2 , NR c2 S(═O) 2 R b2 and S(═O) 2 NR c2 R d2 ;
each R B4 is independently selected from halogen, C 1-6 haloalkyl, CN, OR a2 , SR a2 , C(═O)R b2 , C(═O)NR c2 R d2 , C(═O)OR a2 , OC(═O)R b2 , OC(═O)NR c2 R d2 , NR c2 R d2 , NR c2 C(═O)R b2 , NR c2 C(═O)NR c2 R d2 , NR c2 C(═O)OR a2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , S(═O)R b2 , S(═O)NR c2 R d2 , S(═O) 2 R b2 , NR c2 S(═O) 2 R b2 and S(═O) 2 NR c2 R d2 ;
R 2 is H, halogen or NH 2 ;
R 5 is H, halogen, R 5A , C 1-6 haloalkyl, CN, OR a3 , SR a3 , C(═O)R b3 , C(═O)NR c3 R d3 , C(═O)OR a3 , OC(═O)R b3 , OC(═O)NR c3 R d3 , NR c3 R d3 , NR c3 C(═O)R b3 , NR c3 C(═O)NR c3 R d3 , NR c3 C(═O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(═O)R b3 , S(═O)NR c3 R d3 , S(═O) 2 R b3 , NR c3 S(═O) 2 R b3 or S(═O) 2 NR c3 R d3 ;
R 5A is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl or phenyl, wherein each of said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl or phenyl forming R 5A is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen, CN, OR a3 , SR a3 , C(═O)R b3 , C(═O)NR c3 R d3 , C(═O)OR a3 , OC(═O)R b3 , OC(═O)NR c3 R d3 , NR c3 R d3 , NR c3 C(═O)R b3 , NR c3 C(═O)NR c3 R d3 , NR c3 C(═O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(═O)R b3 , S(═O)NR c3 R d3 , S(═O) 2 R b3 , NR c3 S(═O) 2 R b3 and S(═O) 2 NR c3 R d3 ;
R 6 is H, halogen, R 6A , C 1-6 haloalkyl, CN, 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)NR c4 R d4 , NR c4 C(═O)OR a4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , S(═O)R b4 , S(═O)NR c4 R d4 , S(═O) 2 R b4 , NR c4 S(═O) 2 R b4 or S(═O) 2 NR c4 R d4 ;
R 6A is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 3-7 cycloalkyl-C 1-4 alkyl-, C 6-10 aryl-C 1-4 alkyl-, 5-10 membered heteroaryl-C 1-4 alkyl- or 4-10 membered heterocycloalkyl-C 1-4 alkyl-, wherein each of said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 3-7 cycloalkyl-C 1-4 alkyl-, C 6-10 aryl-C 1-4 alkyl-, 5-10 membered heteroaryl-C 1-4 alkyl- or 4-10 membered heterocycloalkyl-C 1-4 alkyl- forming R 6A is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents independently selected from C 1-6 alkyl, halogen, C 1-6 haloalkyl, CN, 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)NR c4 R d4 NR c4 C(═O)OR a4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 S(═O)R b4 , S(═O)NR c4 R d4 , S(═O) 2 R b4 , NR c4 S(═O) 2 R b4 and S(═O) 2 NR c4 R d4 ;
R 7 is H, halogen, R 7A , C 1-6 haloalkyl, CN, 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)NR c5 R d5 , NR c5 C(═O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(═O)R b5 , S(═O)NR c5 R d5 , S(═O) 2 R b5 , NR c5 S(═O) 2 R b5 or S(═O) 2 NR c5 R d5 ;
R 7A is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 3-7 cycloalkyl-C 1-4 alkyl-, C 6-10 aryl-C 1-4 alkyl-, 5-10 membered heteroaryl-C 1-4 alkyl- or 4-10 membered heterocycloalkyl-C 1-4 alkyl-, wherein each of said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 3-7 cycloalkyl-C 1-4 alkyl-, C 6-10 aryl-C 1-4 alkyl-, 5-10 membered heteroaryl-C 1-4 alkyl- or 4-10 membered heterocycloalkyl-C 1-4 alkyl- forming R 7A is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents independently selected from C 1-6 alkyl, halogen, C 1-6 haloalkyl, CN, OR a5 , SR a5 , C(═O)R b5 , (═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)NR c5 R d5 , NR c5 C(═O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(═O)R b5 , S(═O)NR c5 R d5 , S(═O) 2 R b5 , NR c5 S(═O) 2 R b5 and S(═O) 2 NR c5 R d5 ;
R a1 , R b1 , R c1 and R d1 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl;
R a2 , R b2 , R c2 and R d2 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl;
R a3 , R b3 , R c3 and R d3 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl;
R a4 , R b4 , R c4 and R d4 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C

Assignees

• Incyte Corp

Inventors

• Li Yun-Long
• Burns David M
• Feng Hao
• Huang Taisheng
• Mei Song
• Pan Jun
• Vechorkin Oleg
• Ye hai-fen
• Zhu Wenyu
• Rafalski Maria
• Wang Anlai
• Xue Chu-Biao

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title