Synthesis and SAR of N-substituted dibenzazepinone derivatives as novel potent and selective alpha(V)beta(3) antagonists

Bioorg Med Chem Lett. 2002 Feb 11;12(3):441-6. doi: 10.1016/s0960-894x(01)00773-9.

Abstract

Synthesis and SARs of new integrin alpha(V)beta(3) antagonists based on an N-substituted dibenzazepinone scaffold are described. Variation of spacer and guanidine mimetic led to potent compounds exhibiting an IC(50) towards alpha(V)beta(3) in the nanomolar range, high selectivity versus integrin alpha(IIb)beta(3) and efficacy in functional cellular assays.

MeSH terms

  • Dibenzazepines / chemical synthesis*
  • Dibenzazepines / pharmacology*
  • Drug Design
  • Drug Evaluation, Preclinical
  • Fibrinolytic Agents / chemical synthesis*
  • Fibrinolytic Agents / pharmacology
  • Guanidine / chemistry
  • Indicators and Reagents
  • Mass Spectrometry
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Receptors, Vitronectin / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Dibenzazepines
  • Fibrinolytic Agents
  • Indicators and Reagents
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Vitronectin
  • Guanidine