Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2008 Apr 1;18(7):2362-7. doi: 10.1016/j.bmcl.2008.02.071. Epub 2008 Mar 4.

Abstract

A novel series of non-covalent, benzimidazole-based inhibitors of DPP-4 has been developed from a small fragment hit using structure-based drug design. A highly versatile synthetic route was created for the development of SAR, which led to the discovery of potent and selective inhibitors with excellent pharmaceutical properties.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / pharmacology*
  • Crystallography, X-Ray
  • Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Drug Design*
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / pharmacology*
  • Models, Chemical
  • Rats
  • Structure-Activity Relationship

Substances

  • Benzimidazoles
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • benzimidazole

Associated data

  • PDB/3CCC