title: Non-urea functionality as the primary pharmacophore in soluble epoxide hydrolase inhibitors.
abstract: Inhibition of soluble epoxide hydrolase has been proposed as a promising new pharmaceutical target for diseases involving hypertension and vascular inflammation. The most potent sEH inhibitors reported to date contain a urea or amide moiety as the central or 'primary' pharmacophore. We evaluated replacing the urea pharmacophore with other functional groups such as thiourea, sulfonamide, sulfonylurea, aminomethylene amide, hydroxyamide, and ketoamide to identify novel and potent inhibitors. The hydroxyamide moiety was identified as a novel pharmacophore affording potency comparable to urea.
authors.affiliation: Arête Therapeutics, Inc., 3912 Trust Way, Hayward, CA 94545, USA. skumar@aretetherapeutics.com
authors.forename: Sampath-Kumar
authors.initials: SK
authors.lastname: Anandan
authors.forename: Zung N
authors.initials: ZN
authors.lastname: Do
authors.forename: Heather K
authors.initials: HK
authors.lastname: Webb
authors.forename: Dinesh V
authors.initials: DV
authors.lastname: Patel
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gless
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D004851:Epoxide Hydrolases; D013890:Thiourea