Discovery of carmegliptin: a potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

  • Bioorg Med Chem Lett. 2010 Feb 1;20(3):1109-13. doi: 10.1016/j.bmcl.2009.12.024.
Patrizio Mattei  1 ,  Markus Boehringer ,  Patrick Di Giorgio ,  Holger Fischer ,  Michael Hennig ,  Joerg Huwyler ,  Buelent Koçer ,  Bernd Kuhn ,  Bernd M Loeffler ,  Alexander Macdonald ,  Robert Narquizian ,  Etienne Rauber ,  Elena Sebokova ,  Urs Sprecher
Affiliations
  • 1. F Hoffmann-La Roche Ltd, Pharma Research, CH-4070 Basel, Switzerland. [email protected]
PMID: 20031405 DOI: 10.1016/j.bmcl.2009.12.024
Abstract

Design, synthesis, and SAR are described for a class of DPP-IV inhibitors based on aminobenzo[a]quinolizines with non-aromatic substituents in the S1 specificity pocket. One representative thereof, carmegliptin (8p), was chosen for clinical development. Its X-ray structure in complex with the enzyme and early efficacy data in animal models of type 2 diabetes are also presented.

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