T. Biftu, G. Scapin, Suresh B. Singh
Jun 15, 2007
Citations
4
Influential Citations
66
Citations
Journal
Bioorganic & medicinal chemistry letters
Abstract
Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile.