Synthesis and SAR of benzyl and phenoxymethylene oxadiazole benzenesulfonamides as selective β3 adrenergic receptor agonist antiobesity agents

被引：22

作者：

Biftu, T ^{[1
]}

Feng, DD

Liang, GB

Kuo, H

Qian, XX

Naylor, EM

Colandrea, VJ

Candelore, MR

Cascieri, MA

Colwell, LF

Forrest, MJ

Hom, GJ

MacIntyre, DE

Stearns, RA

Strader, CD

Wyvratt, MJ

Fisher, MH

Weber, AE

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Biochem & Physiol, Rahway, NJ 07065 USA

[3] Merck Res Labs, Dept Drug Metab, Rahway, NJ 07065 USA

[4] Merck Res Labs, Dept Pharmacol, Rahway, NJ 07065 USA

[5] Merck Res Labs, Dept Comparat Med, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 13期

关键词：

D O I：

10.1016/S0960-894X(00)00268-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Benzyl and phenoxymethylene substituted oxadiazoles are potent and orally bioavailable beta(3) adrenergic receptor (AR) agonists. The 4-trifluormethoxy substituted 5-benzyl oxadiazole 5f has an EC50 of 8 nM in the beta(3) AR agonist assay with 100-fold selectivity over beta(1) and beta(2) AR binding inhibition activity. Its oral bioavailability in dogs is 30 +/- 4%, with a half-life of 3.8 +/- 0.4 h. In the anesthetized rhesus, 5f evoked a dose-dependent glycerolemia (ED50Gly = 0.15 mg/kg): Under these conditions a heart rate increase of 15% was observed at a dose level of 10 mg/kg. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.

引用

页码：1431 / 1434

页数：4

共 4 条

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