An approach to QSAR of 16-substituted pregnenolones as microsomal enzyme inducers

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Abstract
In this study, we attempt to correlate quantitatively the structure of eight 16-substituted pregnenolones with microsomal enzyme inducing activity. We also performed some electrostatic potential calculations to get further insight into the properties of these substituents. It was found that pregnenolone-16α-carbonitrile is the most active steroidal inducer among the pregnenolone derivatives tested. The receptor-inducer interaction is facilitated by a favourable electronic effect of the 16α-substitutents. The orientation of the electronegative area at position 16 seems to influence activity. Lipophilic and volume effects of the 16α-substituents do not seem to be important for microsomal enzyme induction. However, substituent length has some influence on drug metabolising enzyme activity, probably interfering with receptor-inducer interactions.