Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2012 Nov 1;22(21):6628-31. doi: 10.1016/j.bmcl.2012.08.110. Epub 2012 Sep 7.

Abstract

Dipeptidyl peptidase IV (DPP-4) inhibitors have been shown to enhance GLP-1 levels and thereby improve hyperglycemia in type II diabetes. From a small fragment hit, using structure-based design, we have discovered a new class of non-covalent, potent and selective DPP-4 inhibitors.

Publication types

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

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Activation / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / chemistry*
  • Pyrimidinones / pharmacology*

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Pyrimidinones