US2018362499A1PendingUtilityA1
Soluble epoxide hydrolase inhibitors and uses thereof
Est. expiryAug 28, 2034(~8.1 yrs left)· nominal 20-yr term from priority
A61K 31/4412A61P 29/00C07D 213/81C07D 401/12
56
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Claims
Abstract
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.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
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, C 2 -C 9 heterocyclyl C 1 -C 6 alkyl;
R 2 is hydrogen or C 1 -C 6 alkyl;
R 3 is hydrogen, hydroxyl, halogen, thiol, 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, —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 or 2 , wherein R 3 is —C(O)NHR 4 .
4 . The compound of claim 3 , wherein R 4 is C 3 -C 10 carbocyclyl or C 6 -C 10 aryl C 1 -C 6 alkyl.
5 . The compound of claim 4 , wherein R 4 is C 3 -C 10 carbocyclyl.
6 . The compound of claim 5 , wherein said C 3 -C 10 carbocyclyl is cyclohexyl.
7 . The compound of claim 4 , wherein R 4 is C 6 -C 10 aryl C 1 -C 6 alkyl.
8 . The compound of claim 7 , wherein said C 6 -C 10 aryl C 1 -C 6 alkyl is benzyl.
9 . The compound of any one of claims 1 to 8 , wherein R 2 is C 1 -C 6 alkyl.
10 . The compound of claim 9 , wherein said C 1 -C 6 alkyl is methyl.
11 . The compound of any one of claims 1 to 10 , wherein X 1 is N and X 2 is CH.
12 . The compound of any one of claims 1 to 10 , wherein X 1 is CH and X 2 is N.
13 . The compound of any one of claims 1 to 12 , wherein R 1 is C 2 -C 9 heterocyclyl C 1 -C 6 alkyl.
14 . The compound of claim 13 , wherein said C 2 -C 9 heterocyclyl C 1 -C 6 alkyl is pyrazolyl ethyl.
15 . The compound of claim 14 , wherein said pyrazoyl-ethyl is pyrazo-1-yl ethyl.
16 . A compound having the structure:
or a pharmaceutically acceptable salt thereof.
17 . A pharmaceutical composition comprising the compound of any one of claims 1 to 16 and a pharmaceutically acceptable excipient.
18 . A method for the treatment of a cardiovascular disease in a subject in need thereof, said method comprising administering to said subject an effective amount of the compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 .
19 . The method of claim 18 , wherein said cardiovascular disease is hypertension, cardiac hypertrophy, arteriosclerosis, coronary artery calcification, coronary heart disease, ischemia, or reperfusion injury.
20 . A method for the treatment of cancer in a subject in need thereof, said method comprising administering to said subject an effective amount of the compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 .
21 . A method for the treatment of pain in a subject in need thereof, said method comprising administering to said subject an effective amount of the compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 .
22 . A method for the treatment of a respiratory disease in a subject in need thereof, said method comprising administering to said subject an effective amount of the compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 .
23 . The method of claim 22 , wherein said respiratory disease is an obstructive lung disease.
24 . The method of claim 23 , wherein said obstructive lung disease is chronic obstructive pulmonary disease (COPD).
25 . The method of any one of claims 22 to 24 , wherein said subject is a smoker.
26 . The method of any one of claims 22 to 24 , wherein said subject is obese.
27 . A method for the treatment of inflammation in a subject in need thereof, said method comprising administering to said subject an effective amount of the compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 .
28 . A method for the treatment of diabetes in a subject in need thereof, said method comprising administering to said subject an effective amount of the compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 .
29 . A method of increasing the levels of epoxyeicosatrienoic acids in a subject, said method comprising administering to said subject an effective amount of the compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 .
30 . A method of decreasing the levels of dihydroxyeicosatrienoic acids in a subject, said method comprising administering to said subject an effective amount of the compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 .
31 . A method for the inhibition of soluble epoxide hydrolase in a cell, said method comprising contacting a cell with an effective amount of the compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 .Cited by (0)
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