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使用比较分子场分析（CoMFA）方法从三维结构直接预测可乐定样咪唑啉、2-取代咪唑和1-甲基-2-取代咪唑的解离常数（pKa值）。

Direct prediction of dissociation constants (pKa's) of clonidine-like imidazolines, 2-substituted imidazoles, and 1-methyl-2-substituted-imidazoles from 3D structures using a comparative molecular field analysis (CoMFA) approach.

作者信息

Kim K H, Martin Y C

机构信息

Computer Assisted Molecular Design Project, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.

出版信息

J Med Chem. 1991 Jul;34(7):2056-60. doi: 10.1021/jm00111a020.

DOI:10.1021/jm00111a020
PMID:2066976
Abstract

The applicability of a comparative molecular field analysis (CoMFA) method to reproduce and predict the pKa values of 28 clonidine-like imidazoline analogues and 16 2-substituted imidazoles has been investigated with the GRID force field. Molecular fields calculated with an H+ probe and AM1 partial atomic charges produced a correlation with a small standard deviation and a high correlation coefficient with cross validation. It was concluded that the CoMFA treatment of electrostatic effects is suitable for predicting pKa values and thus for the examination of the electronic effects in 3D quantitative structure-activity relationships.

摘要

利用GRID力场研究了比较分子场分析（CoMFA）方法在重现和预测28种可乐定样咪唑啉类似物及16种2-取代咪唑的pKa值方面的适用性。用H⁺探针和AM1部分原子电荷计算得到的分子场与交叉验证后的小标准偏差和高相关系数产生了相关性。得出结论，CoMFA对静电效应的处理适用于预测pKa值，从而适用于三维定量构效关系中电子效应的研究。

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