Chapter 33. Physicochemical Parameters in Drug Design

Publisher Summary This chapter describes various aspects of physicochemical parameters in drug design. As pharmacological testing becomes more precisely defined in numerical values, the drug designer faces the challenge of explaining quantitative differences in physical chemical terms. Sorting out roles for the large number of variables can only be accomplished through computerized regression analysis. The slope of the equation indicates the dependence of inhibition on the hydrophobic character of the drug. The intercepts are different, indicating greater sensitivity of the Avena test. It is postulated that there should be an ideal lipophilic character for a set of drugs so that the members having this value would be least restricted in their random walk through biological tissue to the sites of action. Once the drug molecule reaches the site of action, there is a last partitioning step onto a receptor site, which may be highly important in determining BR and highly dependent on log P . The difference in brain concentration of epimeric analogs of meperidine is quantitatively related to their partition coefficients.

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