利用计算化学的定量结构-代谢关系（QSMR）：大鼠体内取代苯甲酸II相共轭反应的模式识别分析与统计预测

Quantitative structure-metabolism relationships (QSMR) using computational chemistry: pattern recognition analysis and statistical prediction of phase II conjugation reactions of substituted benzoic acids in the rat.

Cupid B C, Holmes E, Wilson I D, Lindon J C, Nicholson J K

Department of Chemistry, Birkbeck College, University of London, UK.

Xenobiotica. 1999 Jan;29(1):27-42. doi: 10.1080/004982599238795.

Abstract

Quantitative relationships between molecular physico-chemical properties of 22 substituted benzoic acids and the extent of excretion of their metabolites in rat urine have been investigated using computational chemistry and multivariate statistics. 2. A data set of 34 theoretically derived physico-chemical descriptors calculated was used to classify the benzoic acids according to their predominant urinary metabolic fate. 3. Quantitative structure-metabolism relationships were obtained by linear regression using combinations of physico-chemical descriptors allowing the prediction of % urinary excretion of glycine (r = 0.73) and glucuronide conjugates (r = 0.82) and % urinary excretion of the parent compound (r = 0.91).

摘要

利用计算化学和多元统计学方法，研究了22种取代苯甲酸的分子物理化学性质与其代谢产物在大鼠尿液中排泄程度之间的定量关系。2. 使用一组计算得出的34个理论物理化学描述符，根据苯甲酸在尿液中的主要代谢命运对其进行分类。3. 通过线性回归，结合物理化学描述符，得到了定量构效关系，可预测甘氨酸的尿排泄百分比（r = 0.73）、葡萄糖醛酸结合物的尿排泄百分比（r = 0.82）以及母体化合物的尿排泄百分比（r = 0.91）。