Amphipathic 3-phenyl-7-propylbenziscoxazoles;: human PPaR γ, δ and α agonists

被引：48

作者：

Adams, AD

Yuen, W

Hu, Z

Santini, C

Jones, AB

MacNaul, KL

Berger, JP

Doebber, TW

Moller, DE

机构：

[1] Merck & Co Inc, Merck Res Labs, Dept Basic Chem, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Merck Res Labs, Dept Mol Endocrinol, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 05期

关键词：

D O I：

10.1016/S0960-894X(02)01029-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of amphipathic 3-phenylbenzisoxazoles were found to be potent agonists of human PPARalpha, gamma and delta. The optimization of acid proximal structure for in vitro and in vivo potency is described. Results of po dosed efficacy studies in the db/db mouse model of type 2 diabetes showed efficacy equal or superior to Rosiglitazone in correcting hyperglycemia and hyper-triglyceridemia. Good functional receptor selectivity for PPARalpha and gamma over PPARdelta can be obtained. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：931 / 935

页数：5

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