Synthesis of phenylpyridine derivatives and their biological evaluation toward dipeptidyl peptidase-4

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-[(1 H -1,2,4-triazol-1-yl)methyl]pyridine-2-carboxylic acid was identified as a potent (IC 50 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.