摘要
根据咪唑类和吡啶类TXA_2合成酶抑制剂的构效关系和作用机制,设计合成了20个4-{[2-(1H-咪唑基)-1-(4-取代苯基)乙氧基]甲基}苯甲酸类化合物。初步体外药理试验结果表明,所有化合物都有不同程度的抑制TXA_2合成酶能力,从而抑制花生四烯酸(AA)诱导的血小板聚集。化合物15的抑酶活性最强,以IC_(50)值相比,其活性为Dazoxiben的55.6%。并初步探讨了这类化合物的构效关系。
Analogues of 4- {[ 2 - ( 1H - imidazol - 1 - yl ) - 1 - (4 - substituted-phenyl) ethoxy ] methyl} benzoic acids were synthesized for searching of more potent and selective thromboxane synthetase inhibitors. All title compounds are first reported.Results of preliminary pharmacological tests showed that all title compounds have activity against thromboxane synthetase, i.e. inhibiting platelet aggregation induced by AA in vitro with rabbit. Compound 15 is the most potent. Its activity is 55.6% of that of Dazoxiben in comparison of IC_(50). The change of group substituted on benzene would af fect inhibitory activity to thrcmboxane synthtase. Esters are more potent than the parent acids. This is probably due to the greater platelet permeability of the more lipophilic ester prior to intraplatelet deesterification.NBS was applied to the preparation of p- bromonethylbenzoic ester. This method increased the yield and simplified operating process.
出处
《药学学报》
CAS
CSCD
北大核心
1991年第10期741-746,共6页
Acta Pharmaceutica Sinica
