Byciclic dioxolanes as potential antimuscarinic agents

A series of rigid compounds - derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine methiodide (1b) - has been synthesized and tested to evaluate affinity and selectivity for M1, M2, and M3 muscarinic receptors. The stereochemistry of the annulation does not influence the activity; the optimal distance between nitrogen and the benzhydryl group seems to be that with the nitrogen in the rigid ring (2b) or the nitrogen directly bound at the cyclopentane nucleus (9b, 11b). The different structure-activity relationship between tertary amines (a series) and the corresponding quaternary salts (b series) suggest a different binding to the receptor sites.