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

Influence of the mobile phase composition on the reversed-phase thin-layer chromatographic behaviour of a series of prostaglandins

Thin-layer chromatographic study of the lipophilicity of triazine herbicides: Influence of different organic modifiers

Rm values, retention times and octanol—water partition coefficients of a series of 5-nitroimidazoles

In recent times there has been a growing interest in the determination of chromatographic parameters of lipophilicity with regard to their use in the study of quantitative structure-activity relationship (1, 2). Very good correlations had been shown between the chromatographic parameters and the log P or π values as a measure of the partition coefficient between octanol and water (2). The reversed phase TLC Rm values in two different chromatographic systems and the reversed-phase HPLC log k′ values of a series of dermorphin-related oligopeptides have been previously determined (3, 4). The purpose of the present work was to study the relationship between log k′ values on one hand and Rm or Σπ values on the other one in view of QSAR studies. In fact the discovery of enkephalin and endorphins with high affinities for opioid receptors added new dimensions to the study of structure-activity relationship of opioid agonists (5, 6, 7, 8).

A.M. Barbaro

Papers

Influence of the mobile phase composition on the reversed-phase thin-layer chromatographic behaviour of a series of prostaglandins

Thin-layer chromatographic study of the lipophilicity of triazine herbicides: Influence of different organic modifiers

Rm values, retention times and octanol—water partition coefficients of a series of 5-nitroimidazoles

Determination of Lipophilic Character of a Series of Dermorphin-Related Oligopeptioes by Means of Reversed-Phase HPLC

Thin-layer chromatography of sulphonamides on silica gel G and polyamide layers by means of a polar mobile phase.