THE INFLUENCE OF VARIOUS SPATIAL GROUPS ON CHOLINOLYTIC ACTIVITY

¹ Pharmacology Section, Sterling-Winthrop Research Institute, Rensselaer, New York

The influence of various sterical and spatial factors on cholinolytic activity has been considered.

Asymmetry on the terminal carbon atom is optimal for cholinolytic activity in compounds with or without an ester component. The symmetric molecules are less effective.

In a series of paired compounds where the interchange of a phenyl or cyclohexyl ring was the only variable, compound containing the phenyl rings are definitely more effective as cholinolytic agents.

Some higher homologs of the piperidine ring substituted in the cationic head have been studied and these are clearly less potent.

Selected gen (N-oxide) derivatives have been compared with the tertiary analogs. The N-oxide substitution is not favorable for cholinolytic activity.

The possible influences of the above spatial variations have been discussed in light of a multiple-point attachment hypothesis.