The conformation-dependent lipophilicity of morphine glucuronides as calculated from their molecular lipophilicity potential

Bioorganic & Medicinal Chemistry Letters
1994.0

Abstract

A whole range of cor\$onners of morphine-6-0-glucuronide and morphine 3-0-glucuronia'e were exumined for their theoretical log P values using the molecular lipophilicity potential method. The results substantiate the "chameleonic" behavior of morphine glucuronides to exist in water as hydrophilic, extended co\$ormers, and in lipidic media as folded, more lipophilic conformers. Despite the Large variety of approaches developed to predict lipophilicity, many authors have noted the lack of a highly reliable, fully computerized method for log P prediction capable of accounting for variations in hpophihcity due to topological or conformational changes in a molecule. The conclusions of a very recent paper1 in this area prompt us to report an application of our molecular hpophihcity potential (MLP) method? a new tool to quantitate lipophilicity variations in the conformational space of drug molecules.

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