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Design, Synthesis and Biological Evaluation of Imidazo[1,2‐a]pyridine Derivatives as Novel DPP ‐4 Inhibitors
Author(s) -
Li Qing,
Zhou Muxing,
Han Li,
Cao Qing,
Wang Xinning,
Zhao LeiLei,
Zhou Jinpei,
Zhang Huibin
Publication year - 2015
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.12560
Subject(s) - chemistry , pyridine , docking (animal) , moiety , stereochemistry , lead compound , combinatorial chemistry , ring (chemistry) , structure–activity relationship , in vitro , biochemistry , medicinal chemistry , organic chemistry , medicine , nursing
A new series of DPP ‐4 inhibitors with imidazo[1,2‐a]pyridine scaffold were designed by exploiting scaffold hopping strategy and docking study. Based on docking binding model, structural modifications of 2‐benzene ring and pyridine moieties of compound 5a led to the identification of compound 5d with 2, 4‐dichlorophenyl group at the 2‐position as a potent ( IC 50 = 0.13 μ m ), selective ( DPP ‐8/ DPP ‐4 = 215 and DPP ‐9/ DPP ‐4 = 192) and in vivo efficacious DPP ‐4 inhibitor. Further, molecular docking revealed that compound 5d could retain key binding features of DPP ‐4 with the pyridine moiety of imidazo[1,2‐a]pyridine ring providing an additional π − π interaction with Phe357 of DPP ‐4. Compound 5d might be a promising lead for further development of novel DPP ‐4 inhibitor treating T2 DM .