Design,Synthesis and SAR Studies of Novel and Potent Dipeptidyl Peptidase 4 Inhibitors

• 作者: Na Luo Xiaoyu Fang Mingbo Su Xinwen Zhang Dan Li Honglin Li Shiliang Li Zhenjiang Zhao
• 来源期刊: 中国化学（英文版）
• 年，卷（期）: 2021,（1）
• 所属期刊栏目: Concise Reports
• 页码范围: 115-120
• 页数: 6页
• 语种: 英文
• DOI: 10.1002/cjoc.202000342

摘要

Dipeptidyl peptidase 4(DPP-4)is a clinically validated target for the treatment of type 2 diabetes mellitus(T2DM).To discover novel and potent DPP-4 inhibitors,three series of compounds were designed and synthesized in this study based on our previously identi-fied novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine.Among the designed compounds,41d-1 was the most po-tent one with an IC50 value of 16.00 nM.Besides,41d-1(5 mg/kg)displayed a moderate glucose tolerance capability in ICR mice.Structure-activity-relationship(SAR)studies were discussed in detail,which is constructive for our further optimization.