A series of biaryl chromans exhibiting potent and selective agonism for the GPR40 receptor with positive allosteric modulation of endogenous ligands (AgoPAM) were discovered as potential therapeutics for the treatment of type II diabetes. Optimization of physicochemical properties through modification of the pendant aryl rings resulted in the identification of compound AP5, which possesses an improved metabolic profile while demonstrating sustained glucose lowering.

中文翻译：

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新型和选择性的Biaryl-Chroman GPR40 AgoPAM的构效关系。

已发现一系列对GPR40受体表现出强效和选择性激动作用的联芳基苯并吡喃衍生物具有内源性配体的正变构调节作用（AgoPAM），可作为治疗II型糖尿病的潜在疗法。通过修饰芳基侧链来优化理化性质导致鉴定出化合物AP5，该化合物具有改善的代谢特性，同时显示出持续的葡萄糖降低。