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) |
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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 |
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