Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors.

Autor: Burmistrov V; Department of Chemistry and General Chemical Technology, Volzhsky Polytechnic Institute (branch) Volgograd State Technical University, Volzhsky, Russia; Volgograd State Technical University, Volgograd, Russia., Morisseau C; Department of Entomology and Nematology, Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA., Lee KS; Department of Entomology and Nematology, Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA., Shihadih DS; Department of Entomology and Nematology, Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA., Harris TR; Department of Entomology and Nematology, Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA., Butov GM; Department of Chemistry and General Chemical Technology, Volzhsky Polytechnic Institute (branch) Volgograd State Technical University, Volzhsky, Russia; Volgograd State Technical University, Volgograd, Russia., Hammock BD; Department of Entomology and Nematology, Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA. Electronic address: bdhammock@ucdavis.edu.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2014 May 01; Vol. 24 (9), pp. 2193-7. Date of Electronic Publication: 2014 Mar 20.
DOI: 10.1016/j.bmcl.2014.03.016
Abstrakt: 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.)
Databáze: MEDLINE
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