Structure-activity theories

If these conclusions are valid they have important implications for the design of tests to evaluate relative toxicity and also for structure/activity theories for example if the relationship between polarity and toxicity is strongly influenced by decay processes then it is important that these are given appropriate consideration in designing candidate compounds. The analysis presented above also gives a strong support for further pharmacodynamic studies of pesticide action... 

Because of the large number of dyestuffs and the fact that most of these colorants have not been tested for carcinogenicity, structure-activity theory may help predict possible candidates Tor study. 

As the authors indicated, the activity of these opioid aromatic ethers could not have been anticipated from any known structure-activity theory. ... 

The aim of this work is to review the structure-activity theories in the field of androgens and anabolic agents. It is written primarily for medicinal chemists and pharmacologists, but other research scientists, such as endocrinologists and biochemists, may also find it of value. 

The first chapter deals with metabolic factors affecting the biological activities of androgens. In the second chapter the structure-activity theories are reviewed. A new approach to the structure-activity relationship is offered in Chapter 3. The effects of structural and stereochemical changes on biological activities are extensively analyzed in this chapter. A new theory of steroid-receptor interaction concludes this chapter. 

Through a comparison of the insecticidal and toxicological data, structure-activity theories were developed which provided a means for the synthesis of safer compounds. A similar approach was used in the 2,4-D area. All manner of substituted phenoxy and benzoic acids and their derivatives were prepared. As a result, much was learned about the structural relationships for the auxin type action. This analog synthesis procedure has often been called "me too chemistry". The patent literature abounds with examples of such a strategy tried on almost everything that has shown a modicum of biological activity. 

The elucidation of the biochemistry of the vitamin D endocrine system has led to a renewed interest in the synthetic aspects of the field. Because of the limited availability of vitamin D metabolites from natural sources, the production of large quantities of metabolites and analogs is essential for detailed biomedical experimentation. Vitamin D analog synthesis has not only aided in determining the structural and stereochemical parameters of the natural metabolites, but has also helped to establish a foundation for structure-activity theories. 

All the techniques described above can be used to calculate molecular structures and energies. Which other properties are important for chemoinformatics Most applications have used semi-empirical theory to calculate properties or descriptors, but ab-initio and DFT are equally applicable. In the following, we describe some typical properties and descriptors that have been used in quantitative structure-activity (QSAR) and structure-property (QSPR) relationships. 

Hermann RB. Structure-activity correlations in the cephalosporin C series using extended Htickel theory and CNDO/2.1 Antibiot 1973 26 223-7. 

Menziani, M.C., Fanelli, F., Cocchi, M. and De Benedetti, P.G. (1996) The heuristic-direct approach to quantitative structure-activity relationship analysis of ligand-G protein coupled receptor complexes, in Membrane Protein Models Experiment, Theory and Speculation (ed. J. Findlay), Bios Science Publications, pp. 113-131. 

A., Navarro, M.T., Renz, M., and Valencia, S. (2009) Reactivity in the confined spaces of zeolites the interplay between spectroscopy and theory to develop structure-activity relationships for catalysis. Phys. Chem. Chem. Phys., 11, 2876-2884. 

Braumann, T. Determination of hydrophobic parameters by reversed-phase liquid chromatography theory, experimental techniques, and application in studies on quantitative structure-activity relationships, J. Chromatogr., 373 191-225, 1986. 

To overcome this weakness, we are developing a quantitative structure-activity strategy that is conceptually applicable to all chemicals. To be applicable, at least three criteria are necessary. First, we must be able to calculate the descriptors or Independent variables directly from the chemical structure and, presumably, at a reasonable cost. Second, the ability to calculate the variables should be possible for any chemical. Finally, and most importantly, the variables must be related to a parameter of Interest so that the variables can be used to predict or classify the activity or behavior of the chemical (j ) One important area of research is the development of new variables or descriptors that quantitatively describe the structure of a chemical. The development of these indices has progressed into the mathematical areas of graph theory and topology and a large number of potentially valuable molecular descriptors have been described (7-9). Our objective is not concerned with the development of new descriptors, but alternatively to explore the potential applications of a group of descriptors known as molecular connectivity indices (10). 

The underlying theory of Quantitative Structure-Activity Relationship (QSAR) is that biological activity is directly related to molecular structure. Therefore, molecules with similar structure will possess similar bioactivities for similar proteins/receptors/enzymes and the changes in structure will be represented through the changes in the bioactivities. The best general description of a QSAR model is... 

Graph theory is largely applied to the characterization of chemical structures, as well as to structure-property and structure-activity correlations, by means of so-called topological indices. These are numerical quantities based on various invariants or characteristics of molecular graphs. 

In this chapter, we discuss the fundamental principles of chemical reactivity and catalysis to understand the organic chemistry of catalysis and how to analyze it. We begin with transition state theory because it provides a simple framework for understanding much about reactivity and kinetics. We progress to structure-activity relationships and also discuss some fundamental concepts in analyzing mechanisms. 

Balasubramanian, K., Integration of Graph Theory and Quantum Chemistry for Structure-Activity Relationships. SAR QSAR Environ. Res., 1994 2, 59-77. 

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