CHOLINE ACETYLTRANSFERASE INHIBITORS . CONFIGURATIONAL AND ELECTRONIC FEATURES OF STYRYLPYRIDINE ANALOGS

A variety of molecular modifications were made of styrylpyridine prototype choline acetylase (choline acetyl- Iransferase) inhibitors. Among these, enzyme inhibitory activity is favored by the presence of an aromatic ring system conjugated to a pyrido ring through an exocyclic unsaturated bond in such a manner as to provide an over-all coplanar molecule with minimal third dimensional structure. Optimum size appears to be provided by linkage of fused bicyclic and of monocyclic ring systems through either a double or triple bond. One of the cyclic structures should contain at least a weakly basic moiety; quaternizaliim generally increases choline acetylase inhibitory potency. Acetylcholinesterase inhibitory activities of most of these compounds are relatively low and bear no relationship to the activities against choline acetylase. © 1969, American Chemical Society. All rights reserved.