QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS AND CARMINATIVE ACTIVITY .2. STERIC CONSIDERATIONS

The unexplained variation in the relationships between carminative activities and octanol-water distribution coefficients of various classes of compounds was explained. The steric substituent constant (Es) value, van der Waals volume, and molecular connectivity were introduced into a previously derived correlation. Each parameter brought about an improvement, and molecular connectivity was the most successful. Correlations containing molecular connectivity terms explained the excess variation. The results were in agreement with a mechanism in which carminative activity depended on the availability of the O atom in the functional group of the molecule and was reaction between the O atom and the receptor. [Carminative activity was expressed as the ability to produce a 50% inhibition (ID50) of a standard response to carbachol in the guinea pig isolated ileum preparation.].