The Invention of QSAR

The publication of the first QSAR paper in April 1962 was a landmark in medicinal chemistry. It suggested to the community that it is possible to forecast the biological potency of a compound before it is synthesized. This publication reported equation (3.1)  

The publication was novel in at least six respects (1) It provided a quantitative relationship between the biological potency and physical properties of a compound (2) It recognized the quantitative importance of hydrophobicity to affinity (3) It put the hydrophobic effect of a substituent, n, on a scale similar to that of the Hammett cr constant for electronic effects (4) It provided a mechanism to identify the optimum value of some property as it relates to potency, for example, the parabolic fit of n with (5) It considered the additive effect of different physical properties on potency (6) The fit to the equation used a computer. 

The work was formalized in a March 1964 publication, which correlated seven additional datasets to equation (3.2).  

They thereby demonstrated the generality of the method. They also emphasized that n appears to be an additive property, the value of which is relatively independent of the parent aromatic structure or the position of the substituent. Several of the publications by the Pomona group are recognized as citation classics in view of the number of citations they have received. 

Since the time of this publication, literally thousands of datasets have been correlated the database of the equations generated by the Pomona group (BioLoom) contains more than six thousand equations. In addition, such studies led to the commercialization of products. Most recently, the European Community in its Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) program states that for each chemical circulating in the European territory, a complete dossier on physico-chemical, biological, and toxicological properties must be compiled. For this purpose, validated QSAR methods are accepted.  

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