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Design, Synthesis, Biological Evaluation, and Docking Studies of ( S )‐Phenylalanine Derivatives with a 2‐Cyanopyrrolidine Moiety as Potent Dipeptidyl Peptidase 4 Inhibitors
Author(s) -
Liu Yang,
Wu Yizhe,
Wu Haoshu,
Tang Li,
Wu Peng,
Liu Tao,
Hu Yongzhou
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.12139
Subject(s) - moiety , docking (animal) , phenylalanine , chemistry , stereochemistry , dipeptidyl peptidase , ic50 , rational design , dipeptidyl peptidase 4 , molecular model , enzyme , biochemistry , combinatorial chemistry , in vitro , amino acid , biology , medicine , nursing , diabetes mellitus , type 2 diabetes , genetics , endocrinology
A novel series of ( S )‐phenylalanine derivatives with a 2‐cyanopyrrolidine moiety were designed and synthesized through a rational drug design strategy. Biological evaluation revealed that most tested compounds were potent dipeptidyl peptidase 4 ( DPP ‐4) inhibitors; among them, the cyclopropyl‐substituted phenylalanine derivative 11h displayed the most potent DPP ‐4 inhibitory activity with an IC 50 value of 0.247 μ m . In addition, molecular docking analysis of the representative compounds 11h , 11k , and 15a were performed, which not only revealed the impact of binding modes on DPP ‐4 inhibitory activity but also provided additional methodological values for design and optimization.