Discovery of potent and orally bioavailable heterocycle-based beta3-adrenergic receptor agonists, potential therapeutics for the treatment of obesity |
| |
| Authors: | Lafontaine Jennifer A Day Robert F Dibrino Joe Hadcock John R Hargrove Diane M Linhares Michael Martin Kelly A Maurer Tristan S Nardone Nancy A Tess David A Dasilva-Jardine Paul |
| |
| Institution: | Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton, CT 06340, USA. jennifer.lafontaine@pfizer.com |
| |
| Abstract: | A novel series of heterocycle-based analogs were prepared and evaluated for their in vitro and in vivo biological activity as human beta(3)-adrenergic receptor (AR) agonists. Several analogs demonstrated potent agonist activity at the beta(3)-AR, functional selectivity against beta(1)- and beta(2)-ARs, and favorable pharmacokinetic profiles in vivo. Compound 17 increased oxygen consumption in rats, a measure of energy expenditure, with an ED(20%) of 2mg/kg. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
