Peptidyl-urea based inhibitors of soluble epoxide hydrolases

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Abstract

We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (KI = 15 nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor structures could accept large groups that could lead to better orally available drugs.

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Acknowledgments

This study was supported in part by NIEHS Grant ES02710, NIEHS Superfund Grant P42 ES04699, NIEHS Center Grant P30 ES05707, and NHLBI STTR Grant R41 HL078016.

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