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ID: ALA1667772
Journal: Bioorg Med Chem Lett
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.
Authors: Anandan SK, Webb HK, Chen D, Wang YX, Aavula BR, Cases S, Cheng Y, Do ZN, Mehra U, Tran V, Vincelette J, Waszczuk J, White K, Wong KR, Zhang LN, Jones PD, Hammock BD, Patel DV, Whitcomb R, MacIntyre DE, Sabry J, Gless R.
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.
CiteXplore: 21211973