Inhibitors of epoxide hydrolases for the treatment of inflammation
The invention provides compounds that inhibit epoxide hydrolase in therapeutic applications for treating hypertension. A preferred class of compounds for practicing the invention have the structure shown by Formula 1 wherein Z is oxygen or sulfur, W is carbon phosphorous or sulfur, X and Y is each independently nitrogen, oxygen, or sulfur, and X can further be carbon, at least one of R 1 -R 4 is hydrogen, R 2 is hydrogen when X is nitrogen but is not present when X is sulfur or oxygen, R 4 is hydrogen when Y is nitrogen but is not present when Y is sulfur or oxygen, R 1 and R 3 is each independently C 1 -C 20 substituted or unsubstituted alkyl, cycloalkyl, aryl, acyl, or heterocyclic.
1. A method of treating inflammation in an inflammatory disorder of the lung in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of an inhibitor of soluble epoxide hydrolase (“sEH”), wherein said inhibitor of sEH is a compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof, whereby the inflammation is treated.
2. A method of treating inflammation in a subject with adult respiratory distress syndrome (“ARDS”), comprising administering to said patient a therapeutically effective amount of an inhibitor of soluble epoxide hydrolase (“sEH”), wherein said inhibitor is a compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof, whereby the inflammation in the subject with ARDS is treated.
3. A method of claim 1 , wherein said inflammatory disorder is systemic inflammatory response syndrome (“SIRS”).
4. The method of claim 1 , wherein the sEH is mammalian.
5. The method of claim 1 , wherein the sEH is human.
6. The method of claim 1 , wherein the inhibitor is administered orally or parentally.
7. The method of claim 1 , wherein the inhibitor is administered in a total daily dose from about 0.001 μM/kg to about 100 mg/kg body weight of the patient.
8. The method of claim 1 , wherein the inhibitor is formulated as a unit dosage form.
9. The method of claim 2 , wherein the inhibitor is administered orally or parentally.
10. The method of claim 2 , wherein the inhibitor is administered in a total daily dose from about 0.001 μM/kg to about 100 mg/kg body weight of the subject.
11. The method of claim 2 , wherein the inhibitor is formulated as a unit dosage form.