Substituted alpah-methylbenzyl and tricyclic arylalkyl lactamimides as inhibitors of blood platelet aggregation.
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.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D003864:Depression, Chemical; D006801:Humans; D007094:Imides / Q000138:chemical synthesis / Q000494:pharmacology; D007769:Lactams / Q000138:chemical synthesis / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010977:Platelet Factor 3 / Q000378:metabolism
D001593:Benzyl Compounds; D007094:Imides; D007769:Lactams; D010977:Platelet Factor 3; D000244:Adenosine Diphosphate