Inhibitors of IRAK4 activity
View Patent ↗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.
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 .