Design, Synthesis, and in Vitro Evaluation of Novel Aminomethyl-pyridines as DPP-4 Inhibitors

摘要: A collection of novel aminomethyl-pyridines was designed, synthesized, and investigated as potential inhibitors DPP-4. Optimization the screening hit afforded a number 5-aminomethyl-pyridines with inhibitory activity in nanomolar range. Selected DPP-4 were further evaluated for their selectivity over closely related peptidase DPP-8. 5-Aminomethyl-4-(2,4-dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid cyanomethyl-amide showed high potency excellent [IC50: 10 (DPP-4) 6600 nM (DPP-8)] no toxicity mammalian cell culture.