Soluble epoxide hydrolase inhibitors and uses thereof
The present invention features compounds having soluble epoxide hydrolase inhibitory activity. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions, such as cardiovascular diseases, respiratory diseases, inflammation, and diabetes.
1. A compound having the structure:
wherein one of X 1 or X 2 is N and the other is CH;
R 1 is hydrogen, C 1 -C 6 acyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 heteroalkyl, C 2 -C 6 heteroalkenyl, C 2 -C 6 heteroalkynyl, C 3 -C 10 carbocyclyl, C 6 -C 10 aryl, C 6 -C 10 aryl C 1 -C 6 alkyl, C 2 -C 9 heterocyclyl, or C 2 -C 9 heterocyclyl C 1 -C 6 alkyl;
R 2 is hydrogen or C 1 -C 6 alkyl;
R 3 is C(O)NHR 4 ; and
R 4 is hydrogen, C 1 -C 6 acyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 heteroalkyl, C 2 -C 6 heteroalkenyl, C 2 -C 6 heteroalkynyl, C 3 -C 10 carbocyclyl, C 6 -C 10 aryl, C 6 -C 10 aryl C 1 -C 6 alkyl, C 2 -C 9 heterocyclyl, C 2 -C 9 heterocyclyl C 1 -C 6 alkyl;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein said compound has the structure:
3. The compound of claim 1 , wherein R 4 is C 3 -C 10 carbocyclyl or C 6 -C 10 aryl C 1 -C 6 alkyl.
4. The compound of claim 3 , wherein R 4 is C 3 -C 10 carbocyclyl.
5. The compound of claim 4 , wherein said C 3 -C 10 carbocyclyl is cyclohexyl.
6. The compound of claim 3 , wherein R 4 is C 6 -C 10 aryl C 1 -C 6 alkyl.
7. The compound of claim 6 , wherein said C 6 -C 10 aryl C 1 -C 6 alkyl is benzyl.
8. The compound of claim 1 , wherein R 2 is C 1 -C 6 alkyl.
9. The compound of claim 8 , wherein said C 1 -C 6 alkyl is methyl.
10. The compound of claim 1 , wherein X 1 is N and X 2 is CH.
11. The compound of claim 1 , wherein X 1 is CH and X 2 is N.
12. The compound of claim 1 , wherein R 1 is C 2 -C 9 heterocyclyl C 1 -C 6 alkyl.
13. A compound having the structure:
or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.