Structure-activity relations for anticholinergic 2[1-aryl(or cyclohexyl)-1-hydroxy-1 -phenyl]methyl-1,3-dioxolans

Abstract

The syntheses and configurational assignments of some 4-dimethyl aminomethyl-2[1-aryl (or cyclohexyl)-1 -hydroxy-1-phenyl]methyl-1,3-dioxolans are described. The anticholinergic potency of the 4-dimethylaminomethyl-2[l-cyclohexyl-l-hydroxy-l-phenyl]methyl-1,3-dioxolans, both in tertiary and quaternary form, depends principally on the configuration of the benzylic carbon atom, secondly on the C-2 configuration and thirdly, and to a much lesser extent, if at all, on the C-4 configuration. The dioxolans, which are derived formally from 4-dimethylaminomethyl-2-methyl-1,3-dioxolan methiodide (or its tertiary analogue) by replacement of the 2-methyl substituent by a 2[l-aryl (or cyclohexyl)-l-hydroxy-l-phenyl]methyl group and the glycollates which are derived formally from acetylcholine (or its tertiary analogue) by corresponding substitution of the acetoxymethyl group have closely similar anticholinergic potencies.