title: 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 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).
authors.affiliation: Department of Chemistry and General Chemical Technology, Volzhsky Polytechnic Institute (branch) Volgograd State Technical University, Volzhsky, Russia; Volgograd State Technical University, Volgograd, Russia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Burmistrov
authors.affiliation: Department of Entomology and Nematology, Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.affiliation: Department of Entomology and Nematology, Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Kin Sing Stephen
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Entomology and Nematology, Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Diyala S
authors.initials: DS
authors.lastname: Shihadih
authors.affiliation: Department of Entomology and Nematology, Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Harris
authors.affiliation: Department of Chemistry and General Chemical Technology, Volzhsky Polytechnic Institute (branch) Volgograd State Technical University, Volzhsky, Russia; Volgograd State Technical University, Volgograd, Russia.
authors.forename: Gennady M
authors.initials: GM
authors.lastname: Butov
authors.affiliation: 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.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014508:Urea; D004851:Epoxide Hydrolases; D000218:Adamantane
keywords: Adamantane; Diurea; Inhibitor; Isocyanate; Soluble epoxide hydrolase