Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:24

Article

Burmistrov, Vladimir^2,3  Morisseau, Christophe¹  Lee, Kin Sing Stephen¹  Shihadih, Diyala S.¹  Harris, Todd R.¹  Butov, Gennady M.^2,3  Hammock, Bruce D.¹ 

[1] Univ Calif Davis, Ctr Comprehens Canc, Dept Entomol & Nematol, Davis, CA 95616 USA

[2] Volgograd State Tech Univ, Volzhsky Polytech Inst Branch, Dept Chem & Gen Chem Technol, Volzhsky, Russia

[3] Volgograd State Tech Univ, Volgograd, Russia

关键词: Soluble epoxide hydrolase;    Inhibitor;    Adamantane;    Isocyanate;    Diurea;   

DOI  :  10.1016/j.bmcl.2014.03.016

来源: Elsevier

【 摘 要 】

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 mu M 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 (K-i = 3.1 nM) and a moderately long residence time on the enzyme (k(off) = 1.05 x 10(-3) s(-1); t(1/2) = 11 min). (C) 2014 Elsevier Ltd. All rights reserved.

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