Baggaley K H, English P D, Jennings L J, Morgan B, Nunn B, Tyrrell A W
J Med Chem. 1985 Nov;28(11):1661-7. doi: 10.1021/jm00149a021.
A series of substituted 1,2-benzisothiazol-3-ones was synthesized, and the compounds were tested for ability to inhibit platelet aggregation induced by adenosine diphosphate and collagen in rats and guinea pigs ex vivo. Alkyl substituents at the 2-position bearing a basic group were necessary for ex vivo activity. Several of the compounds were potent inhibitors of adenosine diphosphate induced first-phase aggregation, but adverse toxicological findings terminated their further development. Preliminary studies suggested that inhibition of aggregation was not attributable to inhibition of prostanoid synthesis or to raised levels of cyclic 3',5'-adenosine monophosphate.
合成了一系列取代的1,2-苯并异噻唑-3-酮，并在体外对这些化合物抑制大鼠和豚鼠体内由二磷酸腺苷和胶原蛋白诱导的血小板聚集的能力进行了测试。2-位带有碱性基团的烷基取代基对于体外活性是必需的。几种化合物是二磷酸腺苷诱导的第一阶段聚集的有效抑制剂，但不良的毒理学结果终止了它们的进一步开发。初步研究表明，聚集的抑制并非归因于前列腺素合成的抑制或环3',5'-单磷酸腺苷水平的升高。
