Computer-aided studies of the structure-activity relationships between the structure of some steroids and their...

The relationship between variation in structure and variation in antiinflammatory activity was investigated for 125 steroids whose antiinflammatory activity had previously been determined by using the McKenzie-Stoughton human vasoconstrictor assay. Eighty-eight of the compounds were used in the training stages of analysis. A two-class problem was developed by classifying the compounds as low-to-no potency (37 compounds) or potent-to-very potent (51 compounds) on the basis of their activity relative to that of hydrocortisone butyrate. Thirty-eight different structural variations occurred at six different sites on the steroid nucleus. These variations were coded by a total of 10 descriptors--three indicator descriptors and seven descriptors that coded for the lipophilicity of the substituents at specific sites of variation. Linear discriminant analysis, principal components plots, K nearest neighbor analysis, and statistical measurements of class separation all confirmed that the more potent compounds existed in a region of the data space different from the less potent compounds. This structure-activity relationship was applied to the prediction of the activities of 37 compounds that were not used in the preliminary analysis with good results.