title: Peptidyl-urea based inhibitors of soluble epoxide hydrolases.
abstract: We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (K(I)=15nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor structures could accept large groups that could lead to better orally available drugs.
authors.affiliation: Department of Entomology and UCD Cancer Center, University of California, Davis, CA 95616, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.forename: Hsing-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Preston A
authors.initials: PA
authors.lastname: Baecker
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics*
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D014508:Urea; D004851:Epoxide Hydrolases