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Design, Synthesis, Structure–Activity Relationships, and Docking Studies of 1‐(γ‐1,2,3‐Triazol Substituted Prolyl)‐( S )‐3,3‐Difluoropyrrolidines as a Novel Series of Potent and Selective Dipeptidyl Peptidase‐4 Inhibitors
Author(s) -
Zhang Lei,
Su Mingbo,
Li Jingya,
Ji Xun,
Wang Jiang,
Li Zeng,
Li Jia,
Liu Hong
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12058
Subject(s) - dipeptidyl peptidase , dipeptidyl peptidase 4 , proteases , chemistry , biochemistry , docking (animal) , enzyme , in vitro , combinatorial chemistry , stereochemistry , biology , diabetes mellitus , type 2 diabetes , medicine , nursing , endocrinology
Dipeptidyl peptidase‐4 inhibitors hold great potential for the treatment of type 2 diabetes. A series of 1‐(γ‐1,2,3‐triazol substituted prolyl)‐( S )‐3,3‐difluoropyrrolidines were designed, synthesized, and evaluated as novel dipeptidyl peptidase‐4 inhibitors. Most of the compounds exhibited good in vitro potency against dipeptidyl peptidase‐4. Among these, compounds 7j , 7q, and 7s displayed good dipeptidyl peptidase‐4 activity and excellent selectivity versus other proteases including dipeptidyl peptidase‐8, dipeptidyl peptidase‐9, and FAP. The possible binding modes of compounds 7j , 7q, and 7s with dipeptidyl peptidase‐4 were also explored by molecular docking simulation.