Partition coefficients and biological activity

In 1899 Overton (13) and Meyer (1 ) correlated narcotic activity with lipid solubility (chloroform-water partition coefficients) of a wide variety of non-ionized compounds. They found that narcotic activity increased with increasing lipophilicity until lipid solubility became so high that the substance was virtually water insoluble. They also found that these compounds penetrated tissue cells as though the membranes were lipid in nature. This is the first reported correlation between partition coefficients and biological activity. A second major development in QSAR occurred in 1939 when Ferguson (15) was able to calculate toxic concentrations of a series of compounds from solubility and vapor pressure data. 

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