Quantitative structure-activity Free-Wilson approach

Quantitative Structure-Activity Relationship (QSAR) approach was first developed by Cros (1863) and Brown and Fraser (1868). In the 1960s, C. Hansch, T. Fujita, S. M. Free Jr. and J. W. Wilson started what is now considered to be classical QSAR. A series of powerful advanced computer tools have now been introduced, increasing the capacity of QSAR. 

Kubinyi, H., Kehrhahn, . H. (1976) Quantitative structure-activity relationships. 1. The modified Free-Wilson approach. JMed Chem 19(5), 578-586. 

The Free-Wilson method of deriving quantitative structure-activity-relationships 101 uses implicit representations of physico-chemical properties and there are also numerous examples where indicator variables have been successfully included in the Hansch approach. 

The epoch of QSAR (Quantitative Structure-Activity Relationships) studies began in 1963-1964 with two seminal approaches the a-p-7i analysis of Hansch and Fujita " and the Free-Wilson method. The former approach involves three types of descriptors related to electronic, steric and hydrophobic characteristics of substituents, whereas the latter considers the substituents themselves as descriptors. Both approaches are confined to strictly congeneric series of compounds. The Free Wilson method additionally requires all types of substituents to be suflficiently present in the training set. A combination of these two approaches has led to QSAR models involving indicator variables, which indicate the presence of some structural fragments in molecules. 

Kubinyi, H. (1976a). Quantitative Structure-Activity Relationships. 2. A Mixed Approach, Based on Hansch and Free-Wilson Analysis. J.Med.Chem., 19,587-600. 

Kubinyi H, Kehrhahn OH. Quantitative structure-activity relationships 1. The modified free-Wilson approach. J Med Chem 1976 19 578-86. 

Due to the relationships between Hansch analysis and the Free Wilson model, indicator variables (chapter 3.8) have relatively early been included in Hansch analyses (e.g. [21, 427, 428]). Both models can be combined to a mixed approach, in a linear (eq. 78) and a nonlinear form (eq. 79), which offers the advantages of both, Hansch analysis and Free Wilson analysis, and widens their applicability in quantitative structure-activity relationships [22]. 

Quantitative structure-activity relationships (QSAR) correlate the dependence of various biological activities on different physicochemical properties (Hansch analysis, extrathermo-dynamic approach) or on the presence and absence of certain structural features (Free-Wilson analysis). " In addition, the concept of Hansch analysis is used to correlate different biological activities, e.g., in vitro and in vivo, with each other. ... 

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