取代环丁烷结构的非肽类胰高血糖素样肽-1受体激动剂

Substituted cyclobutane derivatives as non-peptidic GLP-1 receptor agonists

应用胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)及其类似物治疗2型糖尿病是代谢性疾病研究领域近年来的热点,尤其是胰高血糖素样肽-1独特的作用机制倍受业界的关注。它能同时作用于2型糖尿病的多个发病环节,在有效降低血糖的同时,避免低血糖的发生并能减轻体重。但这类药物因其多肽性质而存在诸多的使用限制(如需反复注射)。简要介绍一类取代环丁烷结构的新型非肽类胰高血糖素样肽-1受体小分子激动剂的发现过程、基本药理学特征和体内抗糖尿病和抗肥胖症效应。

Application of glucagon-like peptide-1 （GLP-1） to treat type 2 diabetes has become a focal point in the study of metabolic diseases in recent years. Of particular interest is the unique mechanisms of action relative to GLP-1. It exerts multiple effects on the pathogenesis of type 2 diabetes. While effectively lowering blood glucose levels, it does not cause hypoglycemia but reduces body weight. However, GLP-1 and its peptidic mimetics require frequent injections that limits their wide use. This paper briefly reviews the discovery and pharmacological characterization of a class of novel cyclobutane derivatives as non-peptidic GLP-1 receptor agonists including in vivo efficacies on diabetes and obesity.