Bioorganic and Medicinal Chemistry Letters p. 983 - 988 (2011)
Update date:2022-07-29
Topics:
Anandan, Sampath-Kumar
Webb, Heather Kay
Chen, Dawn
Wang, Yi-Xin
Aavula, Basker R.
Cases, Sylvaine
Cheng, Ying
Do, Zung N.
Mehra, Upasana
Tran, Vinh
Vincelette, Jon
Waszczuk, Joanna
White, Kathy
Wong, Kenneth R.
Zhang, Le-Ning
Jones, Paul D.
Hammock, Bruce D.
Patel, Dinesh V.
Whitcomb, Randall
MacIntyre, D. Euan
Sabry, James
Gless, Richard
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.
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