Pyrrole inhibitors of ERK protein kinase, synthesis thereof and intermediates thereto
The present invention relates to compounds useful of inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is a C 1-6 aliphatic group, wherein R 1 is optionally substituted with up to 2 groups independently selected from —OR or —C 1-3 haloalkyl;
each R is independently hydrogen or C 1-4 aliphatic;
R 2 is R, fluoro, or chloro;
m is 0, 1, or 2; and
R 3 is hydrogen, C 1-3 aliphatic, fluoro, or chloro; wherein
each aliphatic group is, independently, a saturated or unsaturated straight or branched hydrocarbon chain or monocyclic non-aromatic hydrocarbon.
2. The compound according to claim 1 , wherein R 1 is C 1-4 aliphatic optionally substituted with —OR or —C 1-3 haloalkyl.
3. The compound according to claim 2 , wherein R 1 is C 1-4 aliphatic optionally substituted with —OH, —CHF 2 , —CH 2 F, or —CF 3 .
4. The compound according to claim 3 , wherein R 1 is isopropyl, 2-butyl, cyclopropyl, or ethyl, wherein each moiety is optionally substituted with —OH or —CF 3 .
5. The compound according to claim 1 , wherein R 2 is hydrogen, C 1-3 aliphatic, or chloro.
6. The compound according to claim 1 , wherein R 3 is hydrogen, methyl, or chloro.
7. A compound selected from the group consisting of:
8. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
9. The compound according to claim 1 , wherein:
R 1 is isopropyl or 2-butyl, wherein R 1 is optionally substituted with one —OH;
R 2 is H or Cl;
m is 1; and
R 3 is Cl or methyl.
10. The compound
11. A composition comprising a compound according to claim 10 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
12. A pharmaceutically acceptable salt of the Compound
13. A composition comprising a pharmaceutically acceptable salt of compound 1-9 according to claim 12 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.