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Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors.

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 ?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 (Ki=3.1 nM) and a moderately long residence time on the enzyme (koff=1.05 × 10(-3) s(-1); t1/2=11 min).

SUBMITTER: Burmistrov V

PROVIDER: S-EPMC4019751 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors.

Burmistrov Vladimir V Morisseau Christophe C Lee Kin Sing Stephen KS Shihadih Diyala S DS Harris Todd R TR Butov Gennady M GM Hammock Bruce D BD

Bioorganic & medicinal chemistry letters 20140320 9

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). ...[more]

PMID: 24685540

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