Applications of Free Wilson Analysis and Related Models

Applications of Free Wilson Analysis and Related Models 

The Free Wilson model never became as popular as the Hansch model, due to the limitations inherent in its applicability and predictive ability. Only a few hundred studies [390, 391] have been published since 1964. 

From a Free Wilson analysis of antimalarial 2-phenylquinolinylmethanols (46), including 40 substituents in 6 different positions (n = 69 r = 0.905 s = 0.359 34 variables, corresponding to 69—34 — 1 = 34 degrees of freedom), Hansch equations could be derived for the group contributions in different positions of the molecule, e.g. in the 4 -position (eq. 187), 7-position (eq. 188), and the 8-position (eq. 189) [810]. 

These analyses aided in the stepwise derivation of Hansch equations for the antimalarial activities of structurally related phenanthreneaminoalkylcarbinols (47) (eq. 190) [778] and finally led to the derivation of eq. 175 (chapter 7.4) for a much larger group of analogs [779]. 

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S. Applications of Free Wilson Analysis and Related Models... 

QSARs include statistical methods to relate biological activities (most often expressed by logarithms of equipotent molar activities) with structural elements (Free Wilson analysis), physicochemical properties (Hansch analysis), or fields (3D QSAR). The parameters used in a QSAR model are also called (molecular) descriptors. Classical QSAR analyses (Hansch and Free Wilson analyses) consider only 2D structures. Their main field of application is in substituent variation of a common scaffold. 3D-QSAR analysis (CoMFA) has a much broader scope. It starts from 3D structures and correlates biological activities with 3D-property fields (McKinney et al. 2000). 

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