SYNTHESIS OF PHENYLPYRIDINE DERIVATIVES AND THEIR BIOLOGICAL EVALUATION TOWARD DIPEPTIDYL PEPTIDASE-4

Authors

  • Yan Zhu State Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives
  • Xiangguo Meng College of Pharmacy, Shanghai University of Medicine & Health Sciences
  • Zhengyan Cai State Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives
  • Qun Hao State Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives
  • Weicheng Zhou State Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives

DOI:

https://doi.org/10.1007/3668

Keywords:

DPP4 inhibitors, phenylpyridines, type 2 diabetes mellitus

Abstract

A novel series of pyridine-based derivatives was synthesized and evaluated for their inhibitory activity against dipeptidyl peptidase-4 (DPP4). 5-Aminomethyl-6-(2,4-dichlorophenyl)-4-[(1H-1,2,4-triazol-1-yl)methyl]pyridine-2-carboxylic acid was identified as a potent (IC50 0.57 nM) and selective DPP4 inhibitor (DPP8 / DPP4 = 238). A docking study of this compound revealed a hydrogen-bonding interaction with the Arg125 residue of the enzyme providing a potential target residue for further structural optimization.

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Published

2017-04-04

Issue

Vol. 53 No. 3 (2017): Privileged heterocyclic scaffolds in chemical biology and drug discovery: synthesis and bioactivity

Section

Original Papers