Imidazopyridazine compounds useful as modulators of IL-12, IL-23 and/or IFN alpha responses
Compounds of formula I or a stereoisomer or pharmaceutically-acceptable salt thereof, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.
1. A compound of the formula
wherein
R 1 is —NHR 2 ;
R 2 is C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;
R 3 is H, C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl or mono or bicyclic C 3 -C 8 cycloalkyl;
R 4 is H, C 1 -C 6 alkyl, mono or bicyclic C 3 -C 6 cycloalkyl, phenyl, or pyridyl, any of said groups other than H substituted with 0-4 R 7 ;
R 5 is H or C 1 -C 4 alkyl;
R 7 is H, halo, CN, CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CONH C 1 -C 6 alkyl, —CONH halo C 1 -C 6 alkyl, —CONH halo C 1 -C 6 alkoxy, heteroaryl, or aryl, said aryl and heteroaryl groups substituted with 0-2 R 8 ;
R 8 is H, halo, CF 3 , C 1 -C 4 alkyl or C 1 -C 4 alkoxy;
or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.
2. The compound according to claim 1
wherein
R 1 is —NHR 2 ;
R 2 is CH 3 or cyclopropyl;
R 3 is H, C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl or mono or bicyclic C 3 -C 8 cycloalkyl;
R 4 is H, C 1 -C 6 alkyl, mono or bicyclic C 3 -C 6 cycloalkyl, phenyl, or pyridyl, any of said groups other than H substituted with 0-4 R 7 ;
R 5 is H or C 1 -C 4 alkyl;
R 7 is H, halo, CN, CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CONH C 1 -C 6 alkyl, —CONH halo C 1 -C 6 alkyl, —CONH halo C 1 -C 6 alkoxy, heteroaryl, or aryl, said aryl and heteroaryl groups substituted with 0-2 R 8 ;
R 8 is H, halo, CF 3 , C 1 -C 4 alkyl or C 1 -C 4 alkoxy;
or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.
3. A pharmaceutical composition comprising one or more compounds according to claim 1 and a pharmaceutically acceptable carrier or diluent.