Thiazolyl- or thiadiazolyl-substituted pyridyl compounds useful as kinase inhibitors
Compounds having the following formula (I) or an enantiomer, diastereomer or a pharmaceutically-acceptable salt thereof, wherein X is N or C—R 7 , are useful as kinase modulators, including IRAK-4 modulation.
1. A compound having the following formula:
or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein
X is N;
R is —C(═O)—R 1 , —C(═O)O—R 1 or —C(═O)NR 11 —R 1 ;
R 1 is piperidinyl substituted with 0-3 R 1a ;
R 1a is hydrogen, —OCF 3 , —CN, —(CH 2 ) r OR b , —(CH 2 ) r C(O)R b , —(CH 2 ) r C(O)OR b , —(CH 2 ) r OC(O)R b , —(CH 2 ) r NR 11 R 11 , —(CH 2 ) r C(O)NR 11 R 11 , —(CH 2 ) r NR b C(O)R c , —(CH 2 ) r NR b C(O)OR c , —S(O) p NR 11 R11, —NR b S(O) p R c , —S(O) 2 R c , or C 1-6 alkyl substituted with 0-2 R a ;
R 2 is benzo[d]thiazolyl;
R 3 is propyl substituted with 0-3 R 3a ;
R 3a is —OH or phenyl;
R 11 at each occurrence is hydrogen;
R a is R d , F, Cl, Br, OCF 3 , CF 3 , CHF 2 , or CN;
R b is R e , C 1-6 alkyl, or C 1-6 haloalkyl;
R c is CH 3 ;
R d is hydrogen;
R e is hydrogen;
p is 0, 1, or 2; and
r is 0, 1, or 2.
2. The compound of claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 2 is
3. The compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 3 is —CH(CH 3 ) 2 .
4. The compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 1a is —OH or —NH 2 .
5. The compound according to claim 1 or a stereoisomer or pharmaceutically acceptable salt thereof, wherein:
R is —C(═O)—R 1 ;
R 1 is piperidinyl substituted with 0-1 R 1a ; and
R 1a is hydrogen, —OH, or —NH 2 .
6. The compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein said compound is selected from
7. A pharmaceutical composition comprising one or more compounds according to claim 1 and a pharmaceutically acceptable carrier or diluent.