Synthesis and biological evaluation of non-peptide alpha(v)beta(3)/alpha(5)beta(1) integrin dual antagonists containing 5,6-dihydropyridin-2-one scaffolds

Bioorg Med Chem. 2007 Dec 1;15(23):7380-90. doi: 10.1016/j.bmc.2007.07.049. Epub 2007 Aug 22.

Abstract

Small constrained non-peptidic molecules consisting of a polyfunctionalized rigid core, carrying appendages corresponding to arginine and aspartic acid side chains, have been recently reported to be promising for drug development. In this work, the 5,6-dihydropyridin-2-one was envisaged as a scaffold to turn into potential integrin ligands, introducing a carboxylic acid and a basic appendage. The synthesis and the antiadhesion activity of a small library of peptidomimetics capable to recognize alpha(v)beta(3) and alpha(5)beta(1) integrins has been herein reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Integrin alpha5beta1 / antagonists & inhibitors*
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • K562 Cells
  • Ligands
  • Molecular Structure
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Pyridones / chemical synthesis*
  • Pyridones / chemistry
  • Pyridones / pharmacology*
  • Small Molecule Libraries
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Integrin alpha5beta1
  • Integrin alphaVbeta3
  • Ligands
  • Pyridines
  • Pyridones
  • Small Molecule Libraries