Substituted alpah-methylbenzyl and tricyclic arylalkyl lactamimides as inhibitors of blood platelet aggregation

J Med Chem. 1976 Apr;19(4):503-8. doi: 10.1021/jm00226a011.

Abstract

N-[1-(p-Phenoxyphenyl)ethyl]hexahydro-2H-azepin-2-imine hydrochloride (10) and N-[1-(2-dibenzothienyl)-ethyl]hexahydro-2H-azepin-2-imine hydrochloride (22) were found to inhibit in vitro aggregation of human blood platelets induced by ADP with minimal release of procoagulant platelet factor 3. The compounds were selected from a series of substituted alpha-methylbenzyl and tricyclic arylalkyl lactamimides that were free of hypoglycemic and diuretic effects. Compounds 10 and 22, as well as N-[1-(1-naphthyl)ethyl]hexahydro-2H-azepin-2-imine hydrochloride (I) and N-(2,2-diphenylpentyl)hexahydro-2H-azepin-2-imine hydrochloride (II), were evaluated for effects on ADP-induced platelet aggregation after repeated oral administration to guinea pigs. Compound II (RMI 12,366A) showed in vivo activity in this system 2 h after the last of four daily doses of 100 mg/kg po.

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Benzyl Compounds / chemical synthesis
  • Benzyl Compounds / pharmacology
  • Depression, Chemical
  • Humans
  • Imides / chemical synthesis
  • Imides / pharmacology
  • Lactams / chemical synthesis
  • Lactams / pharmacology*
  • Platelet Aggregation / drug effects*
  • Platelet Factor 3 / metabolism

Substances

  • Benzyl Compounds
  • Imides
  • Lactams
  • Platelet Factor 3
  • Adenosine Diphosphate