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 language | English (US) |
|---|---|
| Pages (from-to) | 983-988 |
| Number of pages | 6 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 21 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 1 2011 |
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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
}
TY - JOUR
T1 - 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
AU - Anandan, Sampath Kumar
AU - Webb, Heather Kay
AU - Chen, Dawn
AU - Wang, Yi Xin
AU - Aavula, Basker R.
AU - Cases, Sylvaine
AU - Cheng, Ying
AU - Do, Zung N.
AU - Mehra, Upasana
AU - Tran, Vinh
AU - Vincelette, Jon
AU - Waszczuk, Joanna
AU - White, Kathy
AU - Wong, Kenneth R.
AU - Zhang, Le Ning
AU - Jones, Paul D.
AU - Hammock, Bruce D.
AU - Patel, Dinesh V.
AU - Whitcomb, Randall
AU - MacIntyre, D. Euan
AU - Sabry, James
AU - Gless, Richard
PY - 2011/2/1
Y1 - 2011/2/1
N2 - 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.
AB - 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.
KW - AngII hypertension model
KW - AR9281
KW - Diabetes
KW - DIO model
KW - Efficacy
KW - sEH inhibitor
UR - http://www.scopus.com/inward/record.url?scp=78751648188&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78751648188&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2010.12.042
DO - 10.1016/j.bmcl.2010.12.042
M3 - Article
C2 - 21211973
AN - SCOPUS:78751648188
VL - 21
SP - 983
EP - 988
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 3
ER -