SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIP STUDIES IN A SERIES OF 2-SUBSTITUTED 1,3-DIOXOLANES MODIFIED AT THE CATIONIC HEAD

To develop ligands that may be useful in exploring muscarinic receptor heterogeneity, we synthesized a series of analogues of 2-diphenyl-[1, 3]-dioxolan-4-ylmethyl-dimethylamine oxalate and methiodide bearing a modified cationic head. These compounds, when tested on tissues contai ning the three subtypes M-1, M-2, and M-3, behaved as muscarinic antag onists whose results showed that different substituents on the quatern ary and tertiary nitrogen affect affinity and selectivity in different ways. In particular, comparison of the affinities of these ligands wi th those of the reference compounds points out that compounds bearing an ethyl substituent improve the affinity of the molecule at the three subtypes, while compounds bearing a phenethyl substituent are more se lective for the M-3 sites. (C) 1997 Published by Elsevier Science Ltd.