Studies on the Cholinergic Receptor. 11. Monosubstituted and Bicyclic Derivatives of cis-2-Methyl-4-dimethylaminomethyl-1,3-dioxolane Methiodide

In continuation of our studies on rigid analogs of acetylcholine, some 7-aza-2,4-dioxa-cis-bicyclo[3.3.0]oclane methiodides (III) have been prepared. These are bicyclic analogs of the potent muscarinic agent cis-2-methyl-4-dimethylaminomethyl-1,3-dio.xoiane methiodide (VI). For comparative purposes the cis- and trans-2-methyl cis-4-dimethylaminomethyl-5-methyl-1,3-dioxolane methiodides (IV) have been prepared so that the effects of 5-methyl substitution could be determined. Muscarinic activities of these compounds were low but an inversion of geometric specificity, relative to cis- and trans-2-methyl-4-dimethylammomethyl-1,3-dioxolane methiodide, was noted with the 3,7-dimethyl-7-aza-2,4-dioxa-cis-bieyclo[3.3.0] octane methiodides, the exo isomer being more potent than the endo isomer by a factor of ten. This observation may be rationalized by assuming that the quaternary ammonium group constitutes the primary binding site in these compounds and thus determines the general mode of binding of the remaining molecular structure.