Substituted (aryloxy)alkanoic acids as antagonists of slow-reacting substance of anaphylaxis
作者:Ronald A. LeMahieu、Mathew Carson、Ru-Jen Han、William C. Nason、Margaret O'Donnell、Deborah L. Brown、Herman J. Crowley、Ann F. Welton
DOI:10.1021/jm00384a029
日期:1987.1
chain to substituted (aryloxy)alkanoic acids was prepared. The compounds were evaluated for their ability to antagonize SRS-A-induced contractions of guinea pig ilea and LTE-induced bronchoconstriction in the guinea pig. The results showed that the compounds were all less potent than FPL-55712 in vitro, yet surprisingly, most were more potent by the inhalation route of administration. Some of the most
制备了一系列化合物,其中标准SRS-A拮抗剂FPL-55712的4-乙酰基-3-羟基-2-丙基苯氧基部分通过多亚甲基或聚醚链与取代的(芳氧基)链烷酸相连。评价化合物拮抗SRS-A诱导的豚鼠回肠收缩和LTE诱导的豚鼠支气管收缩的能力。结果表明,这些化合物在体外均不如FPL-55712有效,但令人惊讶的是,大多数化合物在吸入途径下更有效。选择了一些最有效的类似物进行进一步的药理评估,与PAF或组胺相比,通过吸入,白三烯具有选择性拮抗作用。与FPL-55712相比,化合物28和37对LTE的效力更高(分别为40倍和80倍),