Nonlinear structure-activity relationships

Kim, K.H. (1992c). 3D Quantitative Structure-Activity Relationships Nonlinear Dependence Described Directly from 3D Structures Using a Comparative Molecular Field Analysis (CoMFA) Approach. Quant.Struct.-Act.Relat., 11, 309-317. 

Hirst JD. Nonlinear quantitative structure-activity relationship for the inhibition of dihydrofolate reductase by pyrimidines. J Med Chem 1996 39(18) 3526-32. 

Kubinyi, H., Quantitative structure-activity relationships. IV. Nonlinear dependence of biological activity on hydrophobic character a new model, Arzneim. Forsch. (Drug Res.) 26, 1991-1997 (1976). 

In most cases, the MFTA models are built using the Partial Least Squares Regression (PLSR) technique that is suitable for the stable modeling based on the excessive and/or correlated descriptors (under-defined data sets). However, the MFTA approach is not limited to the PLSR models and can successfully employ other statistical learning techniques such as the Artificial Neural Networks (ANN) supporting the detection of the nonlinear structure-activity relationships. ... 

The 7/f-pyridocarbazoles (Schemes 38 and 39) have been exhaustively studied by Roques and co-workers (102). It is seen that, for highly active antitumor compounds, it is necessary to have high DNA binding and intercalation. The structure-activity relationships of these nonlinear pyridocarbazoles are discussed in Section XI. Some very elegant theoretical (232) and H-NMR studies (233) have shown that the concave side of 7ff-pyridocarbazoles, such as 414, protrudes into the major groove of a minihelical self-complementary tetranucleotide... 

For illustration, we shall consider here one of the nonlinear variable selection methods that adopts a k-Nearest Neighbor (kNN) principle to QSAR [kNN-QSAR (49)]. Formally, this method implements the active analog principle that lies in the foundation of the modern medicinal chemistry. The kNN-QSAR method employs multiple topological (2D) or topographical (3D) descriptors of chemical structures and predicts biological activity of any compound as the average activity of k most similar molecules. This method can be used to analyze the structure-activity relationships (SAR) of a large number of compounds where a nonlinear SAR may predominate. 

QSAR. Quantitative structure-activity relationships—the science of deriving quantitative linear or nonlinear mathematical relationships between physicochemical and topo-logical/topographical properties of chemical structures and their biological activity. Originally, regression analysis was the only tool used to derive QSAR equations. More re-... 

Hirst, J.D. (1996). Nonlinear Quantitative Structure-Activity Relationship for the Inhibition of Dihydrofolate Reductase by Pyrimidines. J.Med.Chem., 39, 3526-3532. 

Kimura, T, Miyashita, Y, Funatsu, K. and Sasaki, S.I. (1996). Quantitative Structure-Activity Relationships of the Synthetic Substrates for Elastase Enzyme Using Nonlinear Partial Least Squares Regression. J.Chem.Inf.Comput.Sci., 36,185-189. 

Kubinyi, H. (1977). Quantitative Structure-Activity Relationships. 7. The Bilinear Model, a New Model for Nonlinear Dependence of Biological Activity on Hydrophobic Character. J.Med. Chem., 20,625-629. 

Nonlinear Quantitative Structure-Activity Relationship Modeling For the... 

Domine D, Devillers J, Chastrette M. A nonlinear map of substituent constants for selecting test series and deriving structure-activity relationships I. Aromatic series. J Med Chem 1994 37 973-80. 

Kimura, T., Miyashita, Y, Eunatsu, K. and Sasaki, S.l. (1996) Quantitative structure-activity relationships of the synthetic substrates for elastase enzyme using nonlinear partial least squares regression. J. Chem. Inf. Comput. Sci., 36, 185—189. 

The parabolic Hansch model is a good approximation of observed nonlinear structure-activity relationships. However, whereas the left and right sides of a parabola are always nonlinear, many nonlinear lipophilicity relationships show linear left and right sides, as also observed for the function describing the rate constants of... 

Kubinyi H. Quantitative structure-activity relationships 7. The bilinear model, a new model for nonlinear dependence of biological activity on hydrophobic character. J Med Chem 1977 20 625-629. 

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