Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 2: design of potent antagonists containing the 3-azaspiro[5.5]undecanes

Bioorg Med Chem Lett. 2001 May 21;11(10):1293-6. doi: 10.1016/s0960-894x(01)00216-5.

Abstract

The synthesis and biological activity of novel glycoprotein IIb-IlIa anatagonists containing 3-azaspiro[5.5]undec-9-yl nucleus are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the monoazaspirocyclic structure as central template for nonpeptide RGD mimics.

MeSH terms

  • Administration, Oral
  • Animals
  • Aza Compounds / chemical synthesis
  • Aza Compounds / pharmacokinetics
  • Aza Compounds / pharmacology
  • Biological Availability
  • Blood Platelets / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Vitronectin / antagonists & inhibitors
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / pharmacokinetics
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Aza Compounds
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Vitronectin
  • Spiro Compounds