title: Synthesis and SAR of conformationally restricted inhibitors of soluble epoxide hydrolase.
abstract: A series of conformationally restricted inhibitors of human soluble epoxide hydrolase (sEH) has been developed. Inhibition potency of the described compounds ranges from 4.2 microM to 1.1 nM against recombinant sEH. N-(1-Acetylpiperidin-4-yl)-N'-(adamant-1-yl) urea (5a) was found to be a potent inhibitor (IC(50) = 7.0 nM) that was also orally bioavailable in canines.
authors.affiliation: Department of Entomology and Cancer Research Center, One Shields Avenue, University of California, Davis, 95616, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Jones
authors.forename: Hsing-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Zung N
authors.initials: ZN
authors.lastname: Do
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001682:Biological Availability; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D014508:Urea; D004851:Epoxide Hydrolases