Inhibitors of IRAK4 activity

Patent metadata

Field	Value
Publication number	US-9586948-B2
Application number	US-201314434348-A
Country	US
Kind code	B2
Filing date	Oct 3, 2013
Priority date	Oct 8, 2012
Publication date	Mar 7, 2017
Grant date	Mar 7, 2017

Abstract

The present invention relates to inhibitors of IRAK4 of Formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.

First claim

What is claimed is:

1. A compound of Formula III:

wherein:
X is CH;
a is 0 or 1; b is 0 or 1 m is 0, 1 or 2;
R 1 is selected from: H, oxo, (C═O) a O b (C 1 -C 10 )alkyl, (C═O) a O b -aryl, (C═O) a O b (C 2 -C 10 )alkenyl, (C═O) a O b (C 2 -C 10 )alkynyl, CO 2 H, halo, OH, O b (C 1 -C 6 )perfluoroalkyl, (C═O) a NR 5 R 6 , CN, (C═O) a O b (C 3 -C 8 )cycloalkyl, S(O) m NR 5 R 6 , SH, and S(O) m -(C 1 -C 10 )alkyl, said alkyl, aryl, alkenyl, alkynyl, and cycloalkyl are optionally substituted with one or more substituents selected from R a ;
R 5 and R 6 are independently selected from: H, (C═O) a O b (C a -C 10 )alkyl, (C═O) a O b -aryl, (C═O) a O b (C 2 -C 10 )alkenyl, (C═O) a O b (C 2 -C 10 )alkynyl, CO 2 H, O b (C 1 -C 6 )perfluoroalkyl, (C═O) a N(R a ) 2 , CN, (C═O) a O b (C 3 -C 8 )cycloalkyl, S(O) m N(R a ) 2 , SH, and S(O) m -(C 1 -C 10 )alkyl, said alkyl, aryl, alkenyl, alkynyl, and cycloalkyl are optionally substituted with one or more substituents selected from R a ;
R a is independently selected from R b , OH, (C 1 -C 6 )alkoxy, halogen, cyclopropyl, CO 2 H, CN, O a (C═O) b (C 1 -C 6 )alkyl, oxo, and N(R b ) 2 ; and
R b is independently selected from H and (C 1 -C 6 )alkyl;
or a pharmaceutically acceptable salt or a stereoisomer thereof.

2. A compound which is selected from:
N-(3-carbamoyl-1-methyl-1H-pyrazol-4-yl)-2′-((cyclopropylmethyl)amino)-[2,4′-bipyridine]-6-carboxamide;
tert-butyl(6-((3-carbamoyl-1 -methyl-1H-pyrazol-4-yl)carbamoyl)[2,4′-bipyridin]-2′-yl)carbamate;
2′-amino-N-(3-carbamoyl-1-methyl-1H-pyrazol-4-yl)[2,4′-bipyridine]-6-carboxamide;
N-(3-carbamoyl-1-methyl-1H-pyrazol-4-yl)-2,4′-bipyridine-6-carboxamide;
N-(3-carbamoyl-1-methyl-1H-pyrazol-4-yl)-2′-((2-methoxyethyl)amino)-[2,4′-bipyridine]-6-carboxamide;
N-(3-carbamoyl-1-methyl-1H-pyrazol-4-yl)-2′-((2,2-difluoroethyl)amino)-[2,4′-bipyridine]-6-carboxamide; and
N-(3-carbamoyl-1-methyl-1H-pyrazol-4-yl)-2′-((2,2,2-trifluoroethyl)amino)-[2,4′-bipyridine]-6-carboxamide;
or a pharmaceutically acceptable salt or stereoisomer thereof.

3. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 1 .

Assignees

• Merck Sharp & Dohme

Inventors

• Seganish W Michael
• Hanisak Jennifer
• Li Guoqing
• Zhang Rui
• Tang Haiqun

Classifications

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D409/14 Primary

  containing three or more hetero rings · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title