Relationship between physiological action and chemical constitution

Relationship between physiological action and chemical constitution in the fluoroacetate series 133... 

Relationship between Physiological Action and Chemical Constitution in the Fluoroacetate Series1... 

In 1868 two Scottish scientists, Crum Brown and Fraser [4] recognized that a relation exists between the physiological action of a substance and its chemical composition and constitution. That recognition was in effect the birth of the science that has come to be known as quantitative structure-activity relationship (QSAR) studies a QSAR is a mathematical equation that relates a biological or other property to structural and/or physicochemical properties of a series of (usually) related compounds. Shortly afterwards, Richardson [5] showed that the narcotic effect of primary aliphatic alcohols varied with their molecular weight, and in 1893 Richet [6] observed that the toxicities of a variety of simple polar chemicals such as alcohols, ethers, and ketones were inversely correlated with their aqueous solubilities. Probably the best known of the very early work in the field was that of Overton [7] and Meyer [8], who found that the narcotic effect of simple chemicals increased with their oil-water partition coefficient and postulated that this reflected the partitioning of a chemical between the aqueous exobiophase and a lipophilic receptor. This, as it turned out, was most prescient, for about 70% of published QSARs contain a term relating to partition coefficient [9]. 

Easson, L. H., Stedman, E., Studies on the relationship between chemical constitution and physiological action. V. Molecular dissymmetry and physiological activity. Biochem. J. 1933, 27, 1257-1266. 

The concept of specific receptors and sites of drug action has many origins. However, the work of Thomas Fraser and Alexander Crum Brown of Edinburgh University described in their publication of 1869, "On The Connection Between Chemical Constitution and Physiological Action", provides both a definition of structure-activity relationships and a pioneering example of chemist-pharmacologist collaboration (13). 

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