Bioorganic & Medicinal Chemistry Letters 2014-05-01

Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors.

Vladimir Burmistrov, Christophe Morisseau, Kin Sing Stephen Lee, Diyala S Shihadih, Todd R Harris, Gennady M Butov, Bruce D Hammock

Index: Bioorg. Med. Chem. Lett. 24(9) , 2193-7, (2014)

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Abstract

A series of inhibitors of the soluble epoxide hydrolase (sEH) containing two urea groups has been developed. Inhibition potency of the described compounds ranges from 2.0 μM to 0.4 nM. 1,6-(Hexamethylene)bis[(adamant-1-yl)urea] (3b) was found to be a potent slow tight binding inhibitor (IC50=0.5 nM) with a strong binding to sEH (Ki=3.1 nM) and a moderately long residence time on the enzyme (koff=1.05 × 10(-3) s(-1); t1/2=11 min).Copyright © 2014 Elsevier Ltd. All rights reserved.