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

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

  • ACS Med Chem Lett. 2010 Oct 5;1(9):530-5. doi: 10.1021/ml100200c.
Katarzyna Kaczanowska 1,  Karl-Heinz Wiesmüller 1,  Arnaud-Pierre Schaffner 1
Affiliations

Affiliation

  • 1 EMC microcollections GmbH, Sindelfinger Str. 3, D-72070 Tübingen, Germany.
PMID: 24900243 DOI: 10.1021/ml100200c
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.

Keywords

Aminomethyl-pyridines; DPP-4; DPP-8; diabetes; incretins; structure−activity relationship.

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