《生命科学》 2012, 24(7): 626-633

取代环丁烷结构的非肽类胰高血糖素样肽-1受体激动剂

刘　青，何　敏，周彩红，王明伟^*

(中国科学院上海药物研究所/国家新药筛选中心，上海 201203)

摘　要：摘　要：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。
关键词：胰高血糖素样肽-1 ；环丁烷结构；糖尿病

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

LIU Qing， HE Min， ZHOU Cai-Hong， WANG Ming-Wei^*

(The National Center for Drug Screening， Shanghai Institute of Materia Medica， Chinese Academy of Sciences， Shanghai 201203， China)

Abstract: Abstract: 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.
Key words: glucagon-like peptide-1 (GLP-1); cyclobutane derivatives; diabetes