Hansch and Free-Wilson analyses

D QSAR Models Hansch and Free-Wilson Analyses... 

The proper application of Hansch and Free-Wilson analyses and the associated problems can best be illustrated with a well-investigated example. The antiadrenergic activities of meta-, para-, and met<2,/><2ra-disubstituted A/A-dimethyl-a-bromophene-thylamines have been investigated by Hansch and Lien [27], Unger and Hansch [28], Cammarata [29], and Kubinyi and Kehrhahn [30]. Table 1 presents the substituents, experimentally observed activity values, the parameter values for n,a+ and Efeta, as well as biological activity values calculated from Eqs. (14) and (16), respectively. To perform a Hansch analysis, the biological data are taken as Y values and an... 

A comparison of the results from Hansch and Free Wilson analyses offers some information, whether a certain Hansch model can be considered to be acceptable or not. In most cases the Free Wilson analysis of a data set shows whether a linear additive model is suited for the analysis only in certain cases is a good fit obtained for nonlinear relationships, especially if there are only few degrees of freedom [22, 390, 391]. 

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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