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

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

SUBMITTER: Kaczanowska K

PROVIDER: S-EPMC4007959 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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

Kaczanowska Katarzyna K Wiesmüller Karl-Heinz KH Schaffner Arnaud-Pierre AP

ACS medicinal chemistry letters 20101005 9

A collection of novel aminomethyl-pyridines was designed, synthesized, and investigated as potential inhibitors of DPP-4. Optimization of the screening hit afforded a number of 5-aminomethyl-pyridines with inhibitory activity in the nanomolar range. Selected DPP-4 inhibitors were further evaluated for their selectivity over the closely related peptidase DPP-8. 5-Aminomethyl-4-(2,4-dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid cyanomethyl-amide showed high potency and excellent DPP-4 selec ...[more]

PMID: 24900243

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