Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragmental Methods: An Analysis of ALOGP and CLOGP Methods

TLDR: In this article, an extensive reparametrization of the atomic log P values and a detailed comparison of the performance of ALOGP and CLOGP methods on the Pomona Medchem database were presented.

Abstract: Molecular hydrophobicity (lipophilicity), usually quantified as log P (the logarithm of 1-octanol/water partition coefficient), is an important molecular characteristic in drug discovery. ALOGP and CLOGP are two of the most widely used methods for the estimation of log P. This work describes an extensive reparametrization of the atomic log P values and a detailed comparison of the performance of ALOGP and CLOGP methods on the Pomona Medchem database. Only the “star list” compounds having precisely measured log P values were used in this analysis. While the overall results with both methods are similar, analysis shows that the CLOGP method is better for very small molecules in the range of 1−20 atoms. The two methods are almost comparable in the range of 21−45 atoms, while the ALOGP method has better accuracy for molecules with more than 45 atoms. Although the rms deviation and the correlation coefficient for CLOGP predictions were marginally better than those for corresponding ALOGP predictions, the latte...