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 

机构地区：[1]Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,130 Meilong Road,Shanghai 200237,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zhuchongzhi Road,Shanghai 201203,China [3]Shandong Biopolar Dichang Pharmaceutical Co.,Ltd,RM2306,No.786 Linzi Avenue,Zibo,Shandong 255400,China

出　　处：《Chinese Journal of Chemistry》2021年第1期115-120,共6页中国化学（英文版）

基　　金：This work was supported by the National Key Research and Development Program(No.2016YFA0502304 to H.L.);the National Natural Science Foundation of China(No.81825020 to H.L,No.81803437 to SL.);the National Science&Technology Major Project"Key New Drug Creation and Manufacturing Program",China(No.2018ZX09711002);the Fundamental Research Funds for the Central Universities,Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund(the second phase)under Grant No.U1501501;Shiliang Li is sponsored by Shanghai Sailing Program(No.18YF1405100);Honglin Li is also sponsored by the National Program for Special Supports of Emi nent Professionals and the National Program for Support of Top-notch Young Professionals.

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 identified 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 IC_(50) value of 16.00 nM.

关 键 词：TypeⅡdiabetes Dipeptidyl peptidaseⅣ INHIBITORS Molecular docking Structure-activity relationship 

分 类 号：R587.2[医药卫生—内分泌]