Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Free-Wilson method

Free-Wilson method Freeze concentration Freeze drying... [Pg.422]

Nevertheless, Hansch analysis revolutionized drug molecule optimization and directly led to two other strategies for molecule optimization the Free-Wilson method and the Topliss decision tree. [Pg.142]

The Free-Wilson Method. This method also assumes that biological activity can be described by the additive properties of the substituents on a basic molecular structure. In the Fujita-Ban modification of this method... [Pg.142]

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. [Pg.143]

A key advantage of the Free-Wilson method over standard descriptors-based QSAR techniques is the estimation of activity contribution for individual R-group structures that are readily interpretable to medicinal chemists. [Pg.106]

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. [Pg.11]

The basic principles on which the Hansch multiple parameter method for structure-activity correlation depends are described. These are compared with the basic features of the Free-Wilson method for assigning additivity constants to structural features of related compounds. An example is given for which the two methods of analysis have led to similar structure-activity relationships. Factors which determine the particular method to use in a new situation are discussed. The Free-Wilson method is presented in considerable operational detail with special emphasis on the detection and avoidance of situations which lead to singularity problems in solution of the matrix. Favorable analyses, which result in additivity constants that can be correlated with known physical constants, may lead to predictions for new compounds not covered in the original matrix. [Pg.121]

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. [Pg.127]

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). [Pg.128]

Procedure. The Free-Wilson method is most useful when three or more positions of a molecule are subjected to variation although one can apply the method to cases where only two positions are involved, simple intuition can do about as well in such simple cases. As the complexity of the structural changes increases, this method becomes more and more valuable, and in very complicated systems with substituents at many positions, it can be extremely helpful. The following treatment will illustrate the method in general terms. The following generic formula repre-... [Pg.128]

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. [Pg.2]

In organic chemistry, decomposition of molecules into substituents and molecular frameworks is a natural way to characterize molecular structures. In QSAR, both the Hansch-Fujita " and the Free-Wilson classical approaches are based on this decomposition, but only the second one explicitly accounts for the presence or the absence of substituent(s) attached to molecular framework at a certain position. While the multiple linear regression technique was associated with the Free-Wilson method, recent modifications of this approach involve more sophisticated statistical and machine-learning approaches, such as the principal component analysis and neural networks. ... [Pg.9]

These special cases of multiple linear regression analysis have been developed for the determination of the impact of individual molecular substructures (independent variables) on one dependent variable. Both techniques are similar yet, the Free-Wilson method considers the retention of the unsubstituted analyte as base, while Fujita-Ban analysis uses the less substituted molecule as reference. These procedures have not been frequently employed in chromatography only their application in QSRR studies in RP TLC and HPLC have been reported. [Pg.353]

Kubinyi, H. (1990). The Free-Wilson Method and its Relationship to the Extrathermodynamic Approach. In Quantitative Drug Design. Vol. 4 (Ramsden, C.A., ed.), Pergamon Press, Qxford (UK), pp. 589-643. [Pg.603]

Liwo, A., Tarnowska, M., Grzonka, Z. and Tempczyk, A. (1992). Modified Free-Wilson Method for the Analysis of Biological Activity Data. Computers Chem., 16,1-9. [Pg.609]

Internal structural variables derived from purely structural information groups, as in the Free-Wilson method (5), global connectivity indices (6), ordered sites, such as in the DARC/ PELCO method (1),... [Pg.201]

The DARC/PELCO variable remains non ambiguous and exhaustive throughout the treatment and is explicit it makes it possible to retrieve, by a very simple procedure, the structure of the compound whose activity is predicted equal to a required value. Thus, like the structural variable used in the Free-Wilson method, the DARC/PELCO variable is capable of all types of prediction. [Pg.215]

The Free-Wilson method (198) and its modifications (212, 213) are all based on the linear additivity assumption. This was criticized by Bocek et al. (215, 216), and the possibility of interactions between substituents was introduced. For two substituents the Bocek-Kopecky interaction model can be expressed by equation 102... [Pg.69]

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. [Pg.71]

Despite several obvious ineonsistencies, the results indicate the importance of electron withdrawing groups at positions 7 and 2. Another study by Borea employingthe Free-Wilson method was based on the inhibition of [ HJdiazepam binding by a set of 39 benzodiazepines (112). In addition to corroborating the positive effect of electron withdrawing moieties at positions 7 and 2, the results of... [Pg.239]

Kubinyi, H. The Free-Wilson method and its relationship to the extrathermodynamic approach. In Comprehensive Medicinal... [Pg.510]

Kubinyi H. The Free-Wilson method and its relationship to the extrathermodynamic approach. In Ramsden CA, ed. Quantitative Drug DesignHansch C, Sammes PG, Taylor JB, eds. Comprehensive Medicinal Chemistry. The Rational Design, Mechanistic Study and Therapeutic Application of Chemical Compounds 1990 Vol. 4. Oxford Pergamon Press, 1990 589-643. [Pg.565]

There are numerous examples of traditional Hansch QSAR studies in the literature. Some include large sets of descriptors, while others explore just a few. If descriptor values are not readily available, indicator or dummy variables, denoting presence or absence of a certain structural feature, may be of help. This is the basis of the Free-Wilson method (see below). [Pg.359]

The Free-Wilson method has the advantage that one does not need to estimate physical property descriptors for the compounds. This property also makes it difficult, if not impossible, to forecast the bioactivity of untested substituents. Moreover, the assumption of a constant effect on the potency of a particular substituent at a particular position breaks down in the case of a nonlinear relationship of potency with log P. [Pg.74]

If the Free Wilson method is applied to the cx-bromophenethylamines (Table 12 chapter 4.1) and if the unsubstituted parent compound (12, X = Y = H) is selected as the reference compound. Table 13 results the regression analysis of these data leads to eq. 70 [390, 391, 393]. [Pg.63]

The DARC-PELCO approach [418—423] is a simple application of a hyperstructure concept to the Free Wilson method while the approach may be appropriate for extremely large data sets, e.g. for the derivation of lipophilicity contributions from partition coefficients, it is usdess for most structure-activity analyses, due to the much too large number of variables (compare eqs. 199 and 200, chapter 8) [390, 391]. The results from Hansch, Free Wilson, and DARC-PELCO analyses have been compared with each other [421, 422, 424] no advantages of the latter approach could be seen. [Pg.65]


See other pages where Free-Wilson method is mentioned: [Pg.327]    [Pg.384]    [Pg.408]    [Pg.142]    [Pg.41]    [Pg.100]    [Pg.422]    [Pg.327]    [Pg.125]    [Pg.30]    [Pg.122]    [Pg.69]    [Pg.70]    [Pg.349]    [Pg.31]    [Pg.735]    [Pg.327]    [Pg.62]   
See also in sourсe #XX -- [ Pg.142 ]

See also in sourсe #XX -- [ Pg.2 , Pg.9 , Pg.153 , Pg.154 ]

See also in sourсe #XX -- [ Pg.186 ]

See also in sourсe #XX -- [ Pg.41 , Pg.67 , Pg.184 ]




SEARCH



Free-Wilson

© 2024 chempedia.info