Biological Activity of Organic Compounds

Systematic studies of the effects of structure on the biological activities of organic compounds and the analysis of the results are comprised in the term Quantitative Structure-Activity Relationships (QSAR). Many of the treatments employed in the correlation analysis of data in this field closely resemble those used for linear free-energy relationships, e.g. the Hammett equation and extensions thereof, and so the study of the biological properties of organic compounds is often regarded as a part of physical organic chemistry. In recent years, some historical study of work in 

QSAR has begun. A few papers are known to the present author, but it has not been practicable to carry out a systematic search of the literature. 

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Absorption, metaboHsm, and biological activities of organic compounds are influenced by molecular interactions with asymmetric biomolecules. These interactions, which involve hydrophobic, electrostatic, inductive, dipole—dipole, hydrogen bonding, van der Waals forces, steric hindrance, and inclusion complex formation give rise to enantioselective differentiation (1,2). Within a series of similar stmctures, substantial differences in biological effects, molecular mechanism of action, distribution, or metaboHc events may be observed. Eor example, (R)-carvone [6485-40-1] (1) has the odor of spearrnint whereas (5)-carvone [2244-16-8] (2) has the odor of caraway (3,4). 

The extensive investigation of the biological activity of organic compounds that is so characteristic of the last few decades, has also revealed active compounds in the isoxazole series. The main advances have been achieved in recent years. 

Zahradnik R. Correlation of the biological activity of organic compounds by means of the linear free energy relations. Experimentia 1962 18 534-6. 

Biological activity of organic compounds elicited by the introduction of double bonds... 

These descriptors account for heteroatoms and multiple bonds, possess high discriminating power, and correlate well with a number of physico-chemical properties and the biological activities of organic compounds. 

In the following decades, various a scales were derived for different systems and several attempts were made to derive such relationships also for biological activities of organic compounds. Bruice et al. [10] formulated group contributions to biological activity values in a series of thyroid hormone analogs, which may be considered as a first Free-Wilson-type analysis. Zahradnik and Chvapil [11] and Zahradnik [12,13] tried to apply the concept of the Hammett equation also to biological data (Eq. (5)) ... 

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