Fahrenholtz K E, Silverzweig M Z, Germane N, Crowley H J, Simko B A, Dalton C
J Med Chem. 1979 Aug;22(8):948-53. doi: 10.1021/jm00194a012.
A number of indoles containing the 2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl side chain have been prepared by standard methods. Alternate, novel syntheses of indole-2-carboxamides and indole-2-carbonitriles have been developed. The title compound, 7e, was found to be a potent inhibitor of bovine prostaglandin synthetase in vitro and to lower serum prostaglandin levels after oral or intraperitoneal administration to rats. Consistent with prostaglandin synthetase inhibition, 7e prevented arachidonic acid induced diarrhea in mice and also collagen, ADP, or epinephrine induced platelet aggregation in human platelet-rich plasma. In contrast to many prostaglandin synthetase and platelet-aggregation inhibitors, 7e had neither ulcerogenicity nor systemic antiinflammatory activity in rats.
通过标准方法制备了多种含有2,2,2-三氟-1-羟基-1-(三氟甲基)乙基侧链的吲哚。已开发出吲哚-2-羧酰胺和吲哚-2-腈的替代新颖合成方法。发现标题化合物7e在体外是牛前列腺素合成酶的有效抑制剂，并且在对大鼠口服或腹腔注射后可降低血清前列腺素水平。与前列腺素合成酶抑制作用一致，7e可预防花生四烯酸诱导的小鼠腹泻，还可预防胶原蛋白、ADP或肾上腺素诱导的人富含血小板血浆中的血小板聚集。与许多前列腺素合成酶和血小板聚集抑制剂不同，7e在大鼠中既没有致溃疡作用也没有全身抗炎活性。
