Highly potent and selective alphaVbeta3-receptor antagonists: solid-phase synthesis and SAR of 1-substituted 4-amino-1H-pyrimidin-2-ones

Bioorg Med Chem Lett. 2003 Jan 20;13(2):165-9. doi: 10.1016/s0960-894x(02)00931-9.

Abstract

Solid-phase synthesis and SAR of alpha(V)beta(3)-receptor antagonists based on a N(1)-substituted 4-amino-1H-pyrimidin-2-one scaffold are described. The most potent compounds exhibited IC(50) values towards alpha(V)beta(3) in the nano- to subnanomolar range and high selectivity versus related integrins like alpha(IIb)beta(3). For selected examples efficacy in functional cellular assays was demonstrated.

MeSH terms

  • Combinatorial Chemistry Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Guanidines / pharmacology
  • Indicators and Reagents
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Ligands
  • Molecular Mimicry
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Guanidines
  • Indicators and Reagents
  • Integrin alphaVbeta3
  • Ligands
  • Pyrimidinones