Compositions and treatments for inhibiting kinase and/or HMG-CoA reductase
View Patent ↗The present invention provides compositions of matter, kits and methods for their use in the treatment of MAP kinase-related conditions and/or HMG-CoA reductase-related conditions. In particular, the invention provides compositions for treating inflammatory and/or cardiovascular conditions in an animal subject by inhibiting p38α MAP kinase and/or HMG-CoA reductase, as well as providing formulations and modes of administering such compositions. The invention further provides methods for the rational design of inhibitors of MAP kinase, HMG-CoA reductase, or both for use in the practice of the present invention.
1. A compound comprising formula V:
wherein R 1 is
n being 0, 1, 2, or 3;
R 2 is optionally substituted alkyl, aryl, or heteroaryl;
R 4 is optionally substituted
and R 5 is optionally substituted aryl or heteroaryl, or a salt thereof, with the proviso that when R 4 is the pyridinyl ring optionally substituted with one or more substituents selected from halogen atoms and hydroxyl, C 1-3 alkyl, C 1-3 alkoxy and trifluoromethyl groups, then the bridging group of R 1 is —CH 2 CH 2 —.
2. The compound as recited in claim 1 wherein R 2 is a C 3-4 branched alkyl group.
3. The compound as recited in claim 1 wherein R 2 is isopropyl.
4. The compound as recited in claim 1 wherein R 2 is t-butyl.
5. The compound as recited in claim 1 wherein R 2 is —CF 3 .
6. The compound as recited in claim 1 wherein R 2 is phenyl.
7. The compound as recited in claim 1 wherein R 2 is
8. The compound as recited in claim 1 wherein R 2 is
9. The compound as recited in claim 1 wherein R 4 is
10. The compound as recited in claim 1 wherein R 4 is
11. The compound as recited in claim 1 wherein R 4 is
12. The compound as recited in claim 1 wherein R 4 is
13. The compound as recited in claim 1 wherein R 4 is
14. The compound as recited in claim 1 wherein R 4 is
15. The compound as recited in claim 1 wherein R 4 is
16. The compound as recited in claim 1 wherein R 4 is
17. The compound as recited in claim 1 wherein R 4 is
18. The compound as recited in claim 1 wherein R 4 is
19. The compound as recited in claim 1 wherein R 5 is an optionally substituted phenyl group.
20. The compound as recited in claim 1 wherein R 5 is 4-fluorophenyl.
21. The compound as recited in claim 1 wherein R 5 is 3-trifluoromethylphenyl.
22. A compound comprising at least one structure selected from:
a salt or a solvate thereof.
23. A compound comprising at least one structure selected from:
a salt or a solvate thereof.
24. A compound comprising at least one structure selected from:
a salt or a solvate thereof.
25. A compound comprising at least one structure selected from:
a salt or a solvate thereof.
26. A compound comprising formula V:
wherein R 1 is
being 0, 1, 2, or 3;
R 2 is optionally substituted alkyl, aryl, or heteroaryl;
R 4 is optionally substituted
and R 5 is optionally substituted aryl or heteroaryl, or a salt thereof,
with the proviso that when R 4 is the pyridinyl ring, said pyridinyl ring is substituted with one or more optionally substituted amino groups.
27. A compound comprising formula Va:
wherein R 1 is
being 0, 1, 2, or 3;
R 2 is optionally substituted alkyl, aryl, or heteroaryl;
the pyrimidinyl ring is optionally substituted;
and R 5 is optionally substituted aryl or heteroaryl, or a salt thereof.
28. A compound comprising formula Vb:
wherein R 1 is
n being 0, 1, 2, or 3;
R 2 is optionally substituted alkyl, aryl, or heteroaryl;
the pyridinyl ring is optionally substituted, with the proviso that when the pyridinyl ring is unsubstituted or substituted with one or more substituents selected from halogen atoms and hydroxyl, C 1-3 alkyl, C 1-3 alkoxy and trifluoromethyl groups, then the bridging group of R 1 is —CH 2 —CH 2 —; and R 5 is optionally substituted aryl or heteroaryl, or a salt thereof.
29. A pharmaceutical composition comprising an effective amount of at least one compound as recited in claim 1 with a pharmaceutically acceptable carrier.
30. The compound as recited in claim 1 wherein said R 1 has the following stereochemistry: