Potent non-urea inhibitors of soluble epoxide hydrolase
AssigneeThe Trustees of Columbia University in the City of New York
InventorsDonald W. Landry, Yuli Xie, Yidong Lu, Gangli Gong, Shi-Xian Deng, Kirsten Alison Rinderspacher
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Abstract
The present invention relates to compounds that exhibit vasodilatory and anti-inflammatory effects by inhibiting the activity of soluble epoxide hydrolase (sEH). The present invention is also directed to methods of identifying such compounds, and use of such compounds for the treatment of diseases related to dysfunction of vasodilation, inflammation, and/or endothelial cells. In particular non-limiting embodiments, components of the invention may be used to treat hypertension.
Claims21
A compound of Formula 1:
- wherein R1 and R2 are independently selected for each occurrence from the group consisting of Phosphorus, substituted or unsubstituted benzothiazol, substituted or unsubstituted pyridyl, substituted or unsubstituted naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic, —C(O)R3 and —S(O)2R3;
- wherein R3 is independently selected for each occurrence from the groups consisting of substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl;
- substituted or unsubstituted aryl;
- substituted or unsubstituted arylalkyl;
- substituted or unsubstituted heteroaryl;
- substituted or unsubstituted heterocyclic, substituted or unsubstituted naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted thienyl, substituted or unsubstituted benzothienyl, substituted or unsubstituted pyridyl, substituted or unsubstituted indol, substituted or unsubstituted isoquinolyl, substituted or unsubstituted quinolyl, and substituted or unsubstituted benzothiazol;
- and further wherein, when R2 is
- and R1 is a substituted phenyl, wherein the substituent is an unsubstituted alkyl, the alkyl is at least a C3 alkyl;
- and pharmaceutically acceptable salts and prodrugs thereof.
A method for inhibiting the activity of a soluble epoxide hydrolase which comprises contacting the soluble epoxide hydrolase with a compound of Formula I in an amount effective to inhibit soluble epoxide hydrolase activity, wherein Formula I is:
- wherein R1 and R2 are independently selected for each occurrence from the group consisting of Phosphorus, substituted or unsubstituted benzothiazol, substituted or unsubstituted pyridyl, substituted or unsubstituted naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic, —C(O)R3 and —S(O)2R3;
- wherein R3 is independently selected for each occurrence from the groups consisting of substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl;
- substituted or unsubstituted aryl;
- substituted or unsubstituted arylalkyl;
- substituted or unsubstituted heteroaryl;
- substituted or unsubstituted heterocyclic, substituted or unsubstituted naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted thienyl, substituted or unsubstituted benzothienyl, substituted or unsubstituted pyridyl, substituted or unsubstituted indol, substituted or unsubstituted isoquinolyl, substituted or unsubstituted quinolyl, and substituted or unsubstituted benzothiazol;
- and pharmaceutically acceptable salts and prodrugs thereof.
21-58. (canceled)
Dependencies are inferred from the claim text.