关键词: 5-HT₃受体拮抗剂, 三维药效团, 数据库搜索

Abstract: A three-dimensional pharmacophore model of 5-HT₃ Receptor Antagonists was developed based on 31 5-HT₃ Receptor Antagonists which antagonizes the von Bezold-Jarisch reflex evoked by 5-HT in anesthetized rats. The antagonists were selected with great diversity in both molecular structure and bioactivity as required by HypoGen program in the Catalyst software. The antagonists in training set show 5-HT₃ Receptor inhibiting activity with ED₅₀ values, and the range of values is 0.05—320 μg/kg i.v.. The best statistical hypothesis, consisting of four features, one hydrogen-bond acceptor, one hydrophobic region, one ring aromatic feature, one positive ionizable and six excluded volumes, has a correlation coefficient of 0.9031, a root-mean-square deviation of0.8976, a fixed cost of112.6, a null cost of 172.0, a configuration cost of 7.248. The pharmacophore model has a highly predictive ability, which was approved by the results of the activity estimated by mapping the compounds of training set with it. On the basis of Fischer method, the cross-validation provided a strong confidence on this hypothesis. This pharmacophore model can contribute to the finding and designing of new-type 5-HT₃ Receptor Antagonists.

Key words: 5-HT₃ receptor antagonists, Three-dimensional pharmacophore, Database searching