Hansch recommendations

Hansch recommended a lateral validation of QSAR results, i.e., the comparison of models of closely related series of compounds in one biological test system (cf. equations 16 and 17) or trie comparison of the QSAR models derived for one series of compounds in several related biological test models (e.g., serine and cysteine proteases). If all models are of comparable quality, and if they show similar regression coefficients of the physicochemical terms, the results can be accepted. However, in most cases the required effort will be too large to do this routinely. In addition, even closely related enzymes or receptors may have significantly different binding sites. 

The Free-Wilson analysis provides more site-specific information than a Hansch analysis. It is recommended to carry out a Free-Wilson analysis first in order to obtain an idea of the importance of the substituent groups and of the sensitivity of the substitution sites. This type of analysis can be regarded as being qualitative, as it points to the important pharmacophores in the molecule. The information thus obtained may guide the selection of the appropriate physicochemical, topological... 

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