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

Sampath Kumar Anandan, Heather Kay Webb, Dawn Chen, Yi Xin Wang, Basker R. Aavula, Sylvaine Cases, Ying Cheng, Zung N. Do, Upasana Mehra, Vinh Tran, Jon Vincelette, Joanna Waszczuk, Kathy White, Kenneth R. Wong, Le Ning Zhang, Paul D. Jones, Bruce D. Hammock, Dinesh V. Patel, Randall Whitcomb, D. Euan MacIntyre & 2 others James Sabry, Richard Gless

Research output: Contribution to journal › Article

44 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)983-988
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number3
DOIs
StatePublished - Feb 1 2011

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Epoxide Hydrolases
Urea
Rodentia
Blood pressure
Hypertension
Blood Pressure
Glucose
Glucose Tolerance Test
Nutrition
Angiotensin II
Insulin Resistance
Rats
Blood
Obesity
Pharmacology
Insulin
Diet
1-(1-acetyl-piperidine-4-yl)-3-adamantan-1-yl-urea

Keywords

  • AngII hypertension model
  • AR9281
  • Diabetes
  • DIO model
  • Efficacy
  • sEH inhibitor

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

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. / 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.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 3, 01.02.2011, p. 983-988.

Research output: Contribution to journal › Article

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 2011, '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', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 3, pp. 983-988. https://doi.org/10.1016/j.bmcl.2010.12.042
Anandan SK, Webb HK, Chen D, Wang YX, Aavula BR, Cases S et al. 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. Bioorganic and Medicinal Chemistry Letters. 2011 Feb 1;21(3):983-988. https://doi.org/10.1016/j.bmcl.2010.12.042
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 (AR9281) as a potent, selective, and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia. In: Bioorganic and Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 3. pp. 983-988.
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