Synthesis and antiplatelet evaluation of alpha-methylene-gamma-butyrolactone bearing 2-methylquinoline and 8-hydroxyquinoline moieties

Chem Pharm Bull (Tokyo). 1997 Nov;45(11):1777-81. doi: 10.1248/cpb.45.1777.

Abstract

In a search for inhibitors of platelet aggregation, some alpha-methylene-gamma-butyrolactones bearing 2-methylquinoline and 8-hydroxyquinoline moieties were synthesized and evaluated for antiplatelet activities against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. With the exception of 2-[[2,3,4,5-tetrahydro-4-methylene-5-oxo-2-(4-phenylphenyl)-2 -furanyl]methoxy]-8-hydroxyquinoline (8f), these alpha-methylene-gamma-butyrolactones completely inhibited the platelet aggregation induced by AA and Col. The 2-methylquinoline derivatives were also active against Thr- and PAF-induced aggregation, while their 8-hydroxyquinoline counterparts were relatively inactive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives
  • 4-Butyrolactone / chemical synthesis*
  • 4-Butyrolactone / pharmacology
  • Adenosine Triphosphate / blood
  • Animals
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Cattle
  • Crystallography, X-Ray
  • In Vitro Techniques
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology
  • Rabbits

Substances

  • Platelet Aggregation Inhibitors
  • Quinolines
  • Adenosine Triphosphate
  • 4-Butyrolactone