Quantitative structure-activity relations among steroids. Investigations of the use of steric parameters

Abstract

The importance of steric factors in quantitative structure-activity relationships involving steroid hormones is discussed. A variety of steric parameters, such as parachlor, molecular volume, van der Waals volume, and including difference and squared steric terms, is explored in an attempt to find preferred forms for such expressions. Improved correlations for 6-substituted 16-methylene-17.alpha.-acetoxy-4,6-pregnadiene-3,20-dione derivatives were found in which activity is related to .pi. and a squared or difference steric factor. The activity of 9.alpha.-substituted cortisols correlates well with .sigma.I and a simple steric factor, provided that the 9.alpha.-hydroxylated compound is excluded from the series.