Discovery of 5-aryloxy-2,4-thiazolidinediones as potent GPR40 agonists.

Zhou, Changyou; Tang, Cheng; Chang, Eric; Ge, Min; Lin, Songnian; Cline, Eric; Tan, Carina P; Feng, Yue; Zhou, Yun-Ping; Eiermann, George J; Petrov, Aleksandr; Salituro, Gino; Meinke, Peter; Mosley, Ralph; Akiyama, Taro E; Einstein, Monica; Kumar, Sanjeev; Berger, Joel; Howard, Andrew D; Thornberry, Nancy; Mills, Sander G; Yang, Lihu

Zhou, Changyou; Tang, Cheng; Chang, Eric; Ge, Min; Lin, Songnian; Cline, Eric; Tan, Carina P; Feng, Yue; Zhou, Yun-Ping; Eiermann, George J; Petrov, Aleksandr; Salituro, Gino; Meinke, Peter; Mosley, Ralph; Akiyama, Taro E; Einstein, Monica; Kumar, Sanjeev; Berger, Joel; Howard, Andrew D; Thornberry, Nancy; Mills, Sander G; Yang, Lihu.

Afiliação

Zhou C; Merck Research Laboratories, Rahway, NJ 07065, USA.

Bioorg Med Chem Lett ; 20(3): 1298-301, 2010 Feb 01.

Article em En | MEDLINE | ID: mdl-20064714

ABSTRACT

ABSTRACT

Systematic structure-activity relationship (SAR) studies of a screening lead led to the discovery of a series of thiazolidinediones (TZDs) as potent GPR40 agonists. Among them, compound C demonstrated an acute mechanism-based glucose-lowering in an intraperitoneal glucose tolerance test (IPGTT) in lean mice, while no effects were observed in GPR40 knock-out mice.

Assuntos

Descoberta de Drogas/métodos; Receptores Acoplados a Proteínas G/agonistas; Tiazolidinedionas/química; Animais; Camundongos; Camundongos Knockout; Ligação Proteica/fisiologia; Receptores Acoplados a Proteínas G/metabolismo; Relação Estrutura-Atividade; Tiazolidinedionas/agonistas; Tiazolidinedionas/farmacologia

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tiazolidinedionas / Receptores Acoplados a Proteínas G / Descoberta de Drogas Idioma: En Ano de publicação: 2010 Tipo de documento: Article

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