title: 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.
authors.affiliation: EMC microcollections GmbH, Sindelfinger Str. 3, D-72070 Tübingen, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kaczanowska
authors.affiliation: EMC microcollections GmbH, Sindelfinger Str. 3, D-72070 Tübingen, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wiesmüller
authors.affiliation: EMC microcollections GmbH, Sindelfinger Str. 3, D-72070 Tübingen, Germany.
authors.forename: Arnaud-Pierre
authors.initials: AP
authors.lastname: Schaffner
keywords: Aminomethyl-pyridines; DPP-4; DPP-8; diabetes; incretins; structure−activity relationship