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 VI:
wherein R 1 is
being 0 or any integer;
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 2 is an alkyl from 1–3 carbon atoms, trifluoromethyl,
diakylamino where alkyl is 1–4 carbon atoms, pyrrolidino, piperidino, morpholino or piperazino, then R 4 is substituted.
2. The compound as recited in claim 1 wherein R 2 is an alkyl of from one to four carbon atoms.
3. The compound as recited in claim 1 wherein R 2 is dimethylamino.
4. The compound as recited in claim 1 wherein R 2 is 1-methylpropyl.
5. The compound as recited in claim 1 wherein R 2 is isopropyl.
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 hydrogen.
8. The compound as recited in claim 1 wherein R 4 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 5 is an optionally substituted phenyl group.
12. The compound as recited in claim 1 wherein R 5 is 3-trifluoromethylphenyl.
13. The compound as recited in claim 1 wherein R 5 is 4-fluorophenyl.
14. A compound comprising at least one structure selected from:
salt and/or a solvate thereof.
15. A compound comprising at least one structure selected from:
or a salt and/or a solvate thereof.
16. A compound comprising at least one structure selected from:
or a salt and/or a solvate thereof.
17. A compound comprising at least one structure selected from:
salt or a solvate thereof.
18. A compound comprising at least one structure selected from:
or a salt or a solvate thereof.
19. A compound comprising formula VI:
wherein R 1 is
n being 0 or any integer;
R 2 is optionally substituted alkyl, aryl, or heteroaryl;
R 4 is substituted
and R 5 is optionally substituted aryl or heteroaryl, or a salt thereof.
20. A compound comprising formula VIa
wherein R 1 is
n being 0 or any integer;
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,
with the proviso that when R 2 is an alkyl from 1–3 carbon atoms, trifluoromethyl, diakylamino in which alkyl is 1–4 carbon atoms, pyrrolidino, piperidino, morpholino or piperazino, then the pyrimidinyl ring is substituted.
21. A compound comprising formula VIb:
wherein R 1 is
n being 0 or any integer;
R 2 is optionally substituted alkyl, aryl, or heteroaryl;
the pyridinyl ring is optionally substituted;
and R 5 is optionally substituted aryl or heteroaryl, or a salt thereof,
with the proviso that when R 2 is an alkyl from 1–3 carbon atoms, trifluoromethyl, diakylamino in which alkyl is 1–4 carbon atoms, pyrrolidino, piperidino, morpholino or piperazino, then the pyridinyl ring is substituted.
22. A pharmaceutical composition comprising an effective amount of at least one compound as recited in claim 1 with a pharmaceutically acceptable carrier.