To better evaluate, in the context of QSAR studies, new validation techniques such as bootstrapping and crossvalidation and the new analytic technique of partial least squares (PLS), seventeen QSAR results taken from nine recent publications were reexamined using these techniques. The results indicate that bootstrapping and crossvalidation are more powerful indicators of possible chance correlation than are the classical tests based on assumed normal independent distribution of variables. Although PLS will not detect all correlations existing within a set of data, its conservative behavior is particularly valuable when the candidate physicochemical descriptors are numerous and non-orthogonal.

Crossvalidation, Bootstrapping, and Partial Least Squares Compared with Multiple Regression in Conventional QSAR Studies

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...

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

Determination of hydrophobic parameters by reversed-phase liquid chromatography: theory, experimental techniques, and application in studies on quantitative structure-activity relationships

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jps.2600760902

Hydrophobicity and central nervous system agents: on the principle of minimal hydrophobicity in drug design.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jps.2600620102

Lipophilic Character and Biological Activity of Drugs II: The Parabolic Case

Partition data of penicillins determined by means of reversed-phase thin-layer chromatography.

Determination of lipophilicity by means of reversed-phase thin-layer chromatography: I. Basic aspects and relationship between slope and intercept of TLC equations

Influence of lipophilic character on the antibacterial activity of cephalosporins and penicillins.

The experimental Rm values for a series of phenols were obtained by a reversed-phase TLC system. The extrapolation from a range of linear relationship between experimental Rm values and acetone concentration provided a set of extrapolated Rm values. This were used for studying the relationship between structure and activity in vitro and in vivo. The possibility to obtain by means of the extrapolation technique the Rm values in a standard system for serveral series of chemotherapeutic agents is pointed out.

Rm values of phenols. Their relationship with log P values and activity.

Determination of lipophilicity by means of reversed-phase thin-layer chromatography: II. Influence of the organic modifier on the slope of the thin-layer chromatographic equation

A.M. Barbaro

Papers

Partition data of penicillins determined by means of reversed-phase thin-layer chromatography.

Determination of lipophilicity by means of reversed-phase thin-layer chromatography: I. Basic aspects and relationship between slope and intercept of TLC equations

Influence of lipophilic character on the antibacterial activity of cephalosporins and penicillins.

Rm values of phenols. Their relationship with log P values and activity.

Determination of lipophilicity by means of reversed-phase thin-layer chromatography: II. Influence of the organic modifier on the slope of the thin-layer chromatographic equation