title: 1-(1-acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea (AR9281) as a potent, selective, and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia.
abstract: 1-(1-Acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea 14a (AR9281), a potent and selective soluble epoxide hydrolase inhibitor, was recently tested in a phase 2a clinical setting for its effectiveness in reducing blood pressure and improving insulin resistance in pre-diabetic patients. In a mouse model of diet induced obesity, AR9281 attenuated the enhanced glucose excursion following an intraperitoneal glucose tolerance test. AR9281 also attenuated the increase in blood pressure in angiotensin-II-induced hypertension in rats. These effects were dose-dependent and well correlated with inhibition of the sEH activity in whole blood, consistent with a role of sEH in the observed pharmacology in rodents.
authors.affiliation: Arête Therapeutics, Inc., 7000 Shoreline Court, South San Francisco, CA 94080, United States. anandan30@yahoo.com
authors.forename: Sampath-Kumar
authors.initials: SK
authors.lastname: Anandan
authors.forename: Heather Kay
authors.initials: HK
authors.lastname: Webb
authors.forename: Dawn
authors.initials: D
authors.lastname: Chen
authors.forename: Yi-Xin Jim
authors.initials: YX
authors.lastname: Wang
authors.forename: Basker R
authors.initials: BR
authors.lastname: Aavula
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Cases
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Zung N
authors.initials: ZN
authors.lastname: Do
authors.forename: Upasana
authors.initials: U
authors.lastname: Mehra
authors.forename: Vinh
authors.initials: V
authors.lastname: Tran
authors.forename: Jon
authors.initials: J
authors.lastname: Vincelette
authors.forename: Joanna
authors.initials: J
authors.lastname: Waszczuk
authors.forename: Kathy
authors.initials: K
authors.lastname: White
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Wong
authors.forename: Le-Ning
authors.initials: LN
authors.lastname: Zhang
authors.forename: Paul D
authors.initials: PD
authors.lastname: Jones
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
authors.forename: Dinesh V
authors.initials: DV
authors.lastname: Patel
authors.forename: Randall
authors.initials: R
authors.lastname: Whitcomb
authors.forename: D Euan
authors.initials: DE
authors.lastname: MacIntyre
authors.forename: James
authors.initials: J
authors.lastname: Sabry
authors.forename: Richard
authors.initials: R
authors.lastname: Gless
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000284:Administration, Oral; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D007333:Insulin Resistance; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C557705:1-(1-acetyl-piperidine-4-yl)-3-adamantan-1-yl-urea; D000959:Antihypertensive Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D014508:Urea; D004851:Epoxide Hydrolases; D000218:Adamantane