Design and synthesis of a series of indole glycoprotein IIb/IIIa inhibitors

Eur J Med Chem. 2002 Jan;37(1):45-62. doi: 10.1016/s0223-5234(01)01325-3.

Abstract

Synthesis of 1,3-disubstituted indoles derivatives as potential glycoprotein (GP) IIb/IIIa antagonists was reported. Substitution of the indolic nitrogen atom by piperidino or benzamidino moieties was used as mimics of an arginine residue. The acid carboxylic group was linked to the indole scaffold in position-3 via a methylene unit (compounds 4, 9, 10). Introduction of a beta-alanine chain was carried out on the acids (17-22) which after deprotection and basic hydrolysis afforded the final compounds 39-46. The distance between the indole scaffold and the amide bond was modulated from no methylene unit (compound 39) to 1 (compounds 40, 41) or 2 methylene units (compounds 42-46). The presence of a tosylamino group on the beta-alanine chain (compound 56) slightly increased the inhibiting action on platelet aggregation initiated by collagen.

MeSH terms

  • Animals
  • Drug Design
  • Guinea Pigs
  • In Vitro Techniques
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Male
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Indoles
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex