title: 1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors.
abstract: Adamantyl ureas are good soluble epoxide hydrolase (sEH) inhibitors; however they have limited solubility and rapid metabolism, thus limiting their usefulness in some therapeutic indications. Herein, we test the hypothesis that nodal substitution on the adamantane will help solubilize and stabilize the compounds. A series of compounds containing adamantane derivatives and isoxazole functional groups were developed. Overall, the presence of methyl on the nodal positions of adamantane yields higher water solubility than previously reported urea-based sEH inhibitors while maintaining high inhibition potency. However, it did not improve microsomal stability.
authors.affiliation: Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA; Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (Branch) Volgograd State Technical University, Volzhsky, Russia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Burmistrov
authors.affiliation: Department of Entomology and Nematology, and UC Davis 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 Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (Branch) Volgograd State Technical University, Volzhsky, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Danilov
authors.affiliation: Department of Entomology and Nematology, and UC Davis 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: N.D. Zelinsky Institute of Organic Chemistry (ZIOC) of Russian Academy of Sciences, Moscow, Russia.
authors.forename: Igor
authors.initials: I
authors.lastname: Dalinger
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry (ZIOC) of Russian Academy of Sciences, Moscow, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Vatsadze
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry (ZIOC) of Russian Academy of Sciences, Moscow, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Shkineva
authors.affiliation: Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (Branch) Volgograd State Technical University, Volzhsky, Russia.
authors.forename: Gennady M
authors.initials: GM
authors.lastname: Butov
authors.affiliation: Department of Entomology and Nematology, and UC Davis 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 / Q000737:chemistry* / Q000494:pharmacology; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology; D008861:Microsomes / Q000737:chemistry / Q000187:drug effects; D012995:Solubility; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007555:Isoxazoles; D014508:Urea; D004851:Epoxide Hydrolases; D000218:Adamantane
keywords: Adamantane; Inhibitor; Isocyanate; Isoxazole; Soluble epoxide hydrolase; Urea