Grisar J M, Claxton G P, MacKenzie R D
J Med Chem. 1976 Apr;19(4):503-8. doi: 10.1021/jm00226a011.
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.
发现盐酸N-[1-(对苯氧基苯基)乙基]六氢-2H-氮杂卓-2-亚胺（10）和盐酸N-[1-(2-二苯并噻吩基)乙基]六氢-2H-氮杂卓-2-亚胺（22）能在体外抑制由ADP诱导的人血小板聚集，同时凝血血小板因子3的释放最少。这些化合物是从一系列无降血糖和利尿作用的取代α-甲基苄基和三环芳基烷基内酰胺亚胺中筛选出来的。对化合物10和22以及盐酸N-[1-(1-萘基)乙基]六氢-2H-氮杂卓-2-亚胺（I）和盐酸N-(2,2-二苯基戊基)六氢-2H-氮杂卓-2-亚胺（II）进行了研究，观察其对豚鼠反复口服给药后ADP诱导的血小板聚集的影响。化合物II（RMI 12,366A）在每日口服100 mg/kg、连续四天给药，末次给药后2小时的该实验系统中显示出体内活性。
