CORRELATION OF GEOMETRICAL FEATURES OF MUSCARINIC ANTAGONISTS WITH ACTIVITY

Seven muscarinic antagonists have been studied by the molecular-mechan ics method; minimum-energy conformations were analyzed in a search for geometric descriptors correlating with their activity. Two pharmacoph ore descriptors were found to discriminate between the low-energy conf ormations of the most and least potent antagonists: the distances betw een the basic nonaromatic nitrogen atom and (1) the mean plane of the aromatic moiety (N-P1) and (2) the centre of the aromatic ring system (N-P). Analysis by Classification And Regression Trees (CART) confirme d the validity of these descriptors for activity classification.