Hansch method

Other problems with the Hansch method are that biological systems are often too crude as models for its application, or the electronic effects operative in a drug molecule are not sufficiently understood or precise. Finally, the method requires considerable time and expense, even in the hands of an expert. Difficulties notwithstanding, the Hansch approach took both chemists and pharmacologists out of the dark age of pure empiricism and allowed them to consider simultaneously the effects of a large number of variables of drug activity—a feat unattainable with classical methods. 

Topliss Decision Tree Method. This method is quicker and easier to use than the Hansch method. The Topliss scheme is an empirical method in which each compound is tested before an analog is planned, and is compared in terms of its physical properties with analogs already planned. Like the Free-Wilson method, the Topliss decision tree is no longer extensively used. The 2D- and 3D-QSAR methods are gradually supplanting the ID methods. 

Multidimensional linear regression analysis is the most often employed statistical method for QSARs, This popularity is coupled to the acceptance of the Hansch method for QSAR analyses. The techniques and pitfalls of regression analysis have been well described.(44,45)... 

Thus far, this chapter has extolled the virtues of Hansch analysis. The method is simple to understand, easy to execute, and can lead to QSAR equations that may provide insight into the activity of a lead compound. The Hansch method has many clear and appealing... 

The fundamental point which differentiates between the two methods is the following the Hansch method seeks for correlations between... 

To apply the Free-Wilson method, one must have a series of closely related structures whereas the Hansch method may be applied to series of compounds with quite different structure, provided one has data for one or more physical parameters for all of the compounds in question. When one has only 8-12 compounds, only the Hansch method may be used. 

It should be pointed out here that the Hansch method, too, assumes that each substituent plays a constant and additive role from compound to compound, and it, too, is limited by the almost irreducible standard deviation of about 0.2 or 0.25 log 1/C units (8). In a recently published paper, Cammarata treats the relationships and assumptions involved in the Hansch and Free-Wilson methods from a systematic point of view (8). 

Besides providing mathematical relationships correlating structural changes to herbicidal activity variations among TFMS series members, Hansch analyses brought to light other facts which undoubtedly would have been overlooked had the TFMS herbicides not been examined by the Hansch method. In particular, the stepwise regression procedure demonstrated that ... 

Most QSARs are based on the Hansch method, where biological response is expressed as a linear function of hydrophobic, electronic, and steric properties (refer to equation below and Figure 10 k = rate constant for substituted compound = rate constant for unsubstituted compound) ... 

The Hansch method (114) relates the observed biological activity to extrathermodynamic parameters (see above, section A) that are assumed to represent the electronic, steric and hydro-phobic properties of the compounds responsible for the biological... 

It has been suggested (9) that both the Hansch and the Free-Wilson methods be used in QSAR analysis, but in general the methods are used exclusively. The Hansch method is best applied to a congeneric series in which a systematic change in a single substituent is made. The need for reliable physicochemical parameters for the substituents on the studied molecules is usually restrictive. The Free-Wilson method, on the other hand, is not limited by the physicochemical parameters (since only indicator variables are used) but needs large variations in substitution patterns to avoid singularities. Clearly the methods compliment each other. 

The Hansch method, known as quantitative structure-activity relationships (QSAR), has evolved to embrace a variety of techniques. A glance at the recently published proceedings of the European QSAR Conference [1] shows how much of an impact the methods of pharmacophore discovery have on the computational aspects of medicinal chemistry. Indeed, looking up publications that cite various pharmacophore discovery methods papers, it is surprising to see that the total has rapidly accelerated in the past few years, demanding that a review such as this sort through hundreds of papers. 

In the widely used Hansch method, it is assumed that within a series of related compounds the biological activity depends on the effective concentration, the speed of transport to the interaction point, and the interaction ability. In general, the Hansch equation is... 

In view of the complexify of the molecules studied, the method of calculation is simplified in the following way a series of sub-structures with different substituted group R (right part in Fig. 9.7) are used for the computation of molecular mechanics and quantum chemical methods. This kind of simplification is similar to the process of Hansch method considering the effects of various substituted groups. The difference of our method with Hansch method is that we did not treat the contribution of atomic groups separately, but treat the every substructure as a whole... 

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