一种基于氢键描述符和结构相似性预测人类肠道药物吸收的新方法

O. Raevsky, K. Schaper, P. Artursson, J. McFarland
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引用次数: 24

摘要

提出了一种预测药物在人体肠道吸收的新方法。它是基于药物类化合物的结构相似性和氢键性质(ΣC值)。研究了100种不同结构药物的氢键描述子与人体胃肠道吸收的关系。从被动转运药物的s型关系可以看出,ΣC值小于14的药物完全吸收,而ΣC值大于18的药物吸收不良。在某些情况下,由于特殊的结构特征,其他输运机制占上风,吸收阈值可能有很大的不同。因此,在QSAR分析中不包括整套化合物,而是考虑通过相似性计算估计的1到5种结构相关药物(感兴趣药物的最近邻居)的小子集。在假设的子集内,假设被动输运分量的贡献和氢键因子对吸收的相应影响是相似的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Novel Approach for Prediction of Intestinal Absorption of Drugs in Humans based on Hydrogen Bond Descriptors and Structural Similarity
A new approach to predict the intestinal absorption of drugs in humans is presented. It is based on structural similarity and hydrogen bonding properties (ΣC values) of drug-like compounds. The relationship between gastrointestinal absorption in humans and hydrogen bond descriptors for 100 structurally diverse drugs was studied. From the sigmoid relationship for passively transported drugs it could be concluded that those with ΣC values less than 14 were completely absorbed, whereas those with ΣC values higher than 18 were poorly absorbed. In cases where other transport mechanisms prevail due to special structural features, an absorption threshold can be significantly different. So, instead of including the whole set of compounds in the QSAR analyses, small subsets of 1 to 5 structurally related drugs (nearest neighbors of a drug of interest) estimated by means of similarity calculations were considered. The contribution of the passive transport component and the corresponding influence of hydrogen bond factors on absorption was assumed to be similar within the postulated subsets.
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