(4-piperidin-1-yl)phenyl amides:: Potent and selective human β3 agonists

被引：19

作者：

Hu, BH ^{[1
]}

Ellingboe, J

Han, S

Largis, E

Mulvey, R

Oliphant, A

Sum, FW

Tillett, J

机构：

[1] Wyeth Ayerst Res, Chem Sci, Pearl River, NY 10965 USA

[2] Wyeth Ayerst Res, Cardiovasc Metab Dis Res, Pearl River, NY 10965 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 09期

关键词：

D O I：

10.1021/jm000544b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In search of potent and selective human beta (3) agonists as potential drugs for the treatment of human obesity and type II diabetes, a series of (4-piperidin-1-yl)phenyl amides was prepared and evaluated for their biological activity on the human beta (3)-adrenergic receptor. The leucine derivative 26e and the reverse amide 33b were found to be the two most potent and selective compounds in this study. With EC50 values of 0.008 and 0.009 muM, respectively, at the beta (3) receptor, nearly completely abolished intrinsic activity at either the beta (1) or beta (2) receptor, and significant thermogenesis effects on human beta (3)-adrenergic receptor transgenic mice, 26e and 33b are among the most potent and selective human beta (3) agonists known to date.

引用

页码：1456 / 1466

页数：11

共 26 条

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