Prediction of drug solubility from Monte Carlo simulations

被引：305

作者：

Jorgensen, WL

Duffy, EM

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[2] Pfizer Inc, Div Cent Res, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 11期

基金：

美国国家科学基金会;

关键词：

D O I：

10.1016/S0960-894X(00)00172-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Monte Carlo statistical mechanics simulations have been carried out for 150 organic solutes in water. Physically significant descriptors such as the solvent-accessible surface area, numbers of hydrogen bonds, and indices for cohesive interactions in solids are correlated with pharmacologically important properties including octanol/water partition coefficient (log P) and aqueous solubility (log S), The regression equation for log S only requires five descriptors to provide a correlation coefficient, r(2), of 0.9 and rms error of 0.7 for the 150 solutes. The descriptors can form a basis for structural modifications to guide an analogue's properties into desired ranges. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：1155 / 1158

页数：4

共 15 条

[1]

ABRAHAM MH, 1999, J PHARM SCI, V89, P968

[2]

Buchwald P, 1998, CURR MED CHEM, V5, P353

[3] Prediction of properties from simulations: Free energies of solvation in hexadecane, octanol, and water [J].