Discovery of potent dipeptidyl peptidase IV inhibitors derived from beta-aminoamides bearing substituted [1,2,3]-triazolopiperidines for the treatment of type 2 diabetes

作者：Shan, Zhenwei; Peng, Min; Fan, Houxing; Lu, Qingtao; Lu, Peng; Zhao, Chuansheng; Chen, Yilang^*

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(6): 1731-1735.

DOI：10.1016/j.bmcl.2011.01.086

• Dipeptidyl peptidase IV inhibitors
• Type 2 diabetes
• Triazolopiperidine

A series of novel [1,2,3]-triazolopiperidine derivatives 5a-5y were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes, most of the compounds exhibited excellent in vitro potency (IC50 < 50 nM) against DPP-4. Among these, compound 5d with potent in vitro activity against DPP-4 and good pharmacokinetic profiles exhibited pronounced in vivo efficacy in an oral glucose tolerance test (OGTT) in ICR mice. On the base of these properties, compound 5d was selected as a potential new candidate for the treatment of type 2 diabetes.

• 出版日期2011-3-15
• 单位湖南中医药大学; 山东中医药大学