Quantitative structure-activity relationship history

Abraham, D.J. (Ed.). History of quantitative structure activity relationships. In Burger s Medicinal Chemistry and Drug Discovery, Volume 3. John Wiley Sons, Hoboken, NJ, 2003, 1-48. Chapters by Selassie, C.D. Tropsha, a. Recent trends in quantitative stmcture-activity relationships, 49-76 Marshall, G.R. Beusen, D.D. Molecular modeling in drug design, 77-168 ... 

This book intends to provide a starting point for those interested in the prediction of the toxicity and fate of chemicals to humans and the environment. SARs and, more frequently, quantitative structure-activity relationships (QS ARs) provide methods to predict these endpoints. A brief history of the area, the driving forces, and basis of the topic is provided in this chapter. Further chapters (2 to 7) describe the methods to develop predictive models the application of models to human health endpoints (Chapters 8 to 11) their application to environmental toxicity and fate (Chapters 12 to 17) and the use of predictive models (Chapter 19), adoption by the regulatory authorities (Chapter 19), and validation (Chapter 20). 

Abstract Cancer is an important area of interest in the life sciences because it has been a major killer disease throughout human history. Heterocyclic molecules are well known to play a critical role in health care and pharmaceutical drug design. A number of heterocyclic compounds are available commercially as anticancer drugs. Interest in the application of structure-activity relationships has steadily increased in recent decades. Thus, development of the quantitative structure-activity relationship (QSAR) model on the cytotoxicity data of heterocyclic compound series against various cancer ceU lines should be of great importance. In this chapter, an attempt has been made to collect the... 

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) HISTORY... 

Selassie C, Verma RP (2010) History of quantitative structure-activity relationships. In Abraham D (ed) Burger s medicinal chemistry, drug discovery and development. Wiley, New YotIc, pp 1—95... 

Throughout this chapter we will describe how wavelets can be used to analyze, clean, and encode molecular information in a dense and usable format, and we will show how wavelets provide a useful and stable means for representing molecular electronic property distributions for use in quantitative structure-activity relationship/quantitative structure-property relationship (QSAR/QSPR) modeling. Before that, however, some history of their place in signal analysis is appropriate. 

The history of quantitative structure-activity relationships dates back to the last century, when Crum-Brown and Fraser in 1865 postulated that there ought to be a relationship between physiological activities <1> and chemical structures C. Later, Richet correlated toxicities with aqueous solubility. Around 1900, Meyer and Overton found linear relationships between the narcotic potencies of organic compounds and their partitioning behavior. In the mid-1930s, Hammett defined a reaction constant p to describe the reactivity of aromatic systems R, expressed by rate constants k (or equilibrium constants K) and a parameter o to describe the electronic properties of aromatic substituents X (1 equation 1) (see Linear Free Energy Relationships (LFER)) ... 

Selassie, C. D. (2003). History of Quantitative Structure-Activity Relationships, In Abraham, D. J. (Ed.) Burger s Medicinal Chemistry and Drug Discovery, 6th ed., Wiley, New York, pp. 1 8. 

Hansch C (1969) A quantitative approach to biochemical structure-activity relationships. Acc Chem Res 2 232-239 Kubinyi H (2002) From narcosis to hyperspace The history of QSAR. Quant Struct Act Relat 21 348-356 Lemont KB, Lowell H (1999) Molecular Structure Description The Electrotopological State. Academic Press, San Diego, CA, USA... 

Approach was used in deriving mechanistic information about odor intensity as well as insight into how this biological activity may be predicted. This paper will first briefly describe the history of QSAR, the QSAR parameters used, and how substituents for QSAR studies are selected. Several examples of the Hansch Approach used in taste and odor quality studies will next be presented. The balance of the paper will deal with the development of quantitative structure odor intensity relationships which will further expand upon the earlier study reported by this author (11). For example, the use of relatively new QSAR steric parameters in correlations with odor intensity data, and correlations of log P with literature odor intensity data determined on animal panels will be presented. This will be followed by conclusions derived from those studies, and areas of future work. 

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