二肽基肽酶Ⅳ抑制剂的研究进展

Research progress of dipeptidyl peptidase Ⅳ inhibitors

二肽基肽酶Ⅳ(DPP-Ⅳ)抑制剂通过抑制内源性的胰高血糖素样肽-1(GLP-1)的降解,提高GLP-1的水平,进而促进葡萄糖依赖的胰岛素分泌和抑制胰高血糖素产生,从而控制血糖的稳定。DPP-Ⅳ抑制剂具有不影响体重和不增加低血糖风险的优势,在2型糖尿病的治疗中发挥着越来越重要的作用。从结构特点上划分,DPP-Ⅳ抑制剂可分为肽类模拟物和非肽类。本文根据DPP-Ⅳ抑制剂的结构特点对此类抑制剂的最新研究进展进行综述,并对其构效关系进行分析。

The dipeptidyl peptidase-IV（DPP-IV ） is a validated target for the treatment of type 2 diabetes. DPP-IV inhibitors significantly lower blood glucose levels in patients with type 2 diabetes without common side effects of body weight gain, hypoglycemia and gastrointestinal disturbances. Therefore, DPP-IV inhibi- tors play an increasingly important role in the treatment of type 2 diabetes. Based on their structural features the DPP-IV inhibitors can be divided into peptidomimetic series and non-peptidomimic series. Peptidomimic series can be subdivided into the glycine-based inhibitors and fl-alanine-based inhibitors; Non-peptidomimic series are further classified by chemical groups： xanthine, pyrimidine, pyridine, quinoline, isoquinoline, benzoquinolizine and azolopyrimidine. This review will summarize the latest research progress and discuss on concluded structure-activity relationships（SAR） of DPP-1V inhibitors according to the structure features.