Molecular requirements of the recognition site of cholinergic receptors. 22. Resolution, absolute configuration, and cholinergic enantioselectivity of (+)- and (-)-cis-2-methyl-5-[(dimethylamino)methyl]-1,3-oxathiolane methiodide
- 1 September 1986
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 29 (9) , 1610-1615
- https://doi.org/10.1021/jm00159a009
Abstract
The potent cholinergic agonist (.+-.)-cis-2-methyl-5-[(dimethylamino)methyl]-1,3-oxathiolane methiodide [(.+-.)-1] was resolved into enantomeric forms. Their absolute configurations were established by a synthetic pathway that also allowed the synthesis of the corresponding diastereomeric (+)- and (-)-trans-2-methyl-5-[(dimethylamino)methyl]-1,3-oxathiolane methiodide [(+)- and (-)-10]. Compouned (+)-1, which is the most potent of the four isomers, showed the same absolute configuration as L-(+)-muscarine and (+)-cis-dioxolane. The four isomers were tested on guinea pig ileum and frog rectus abdominis, and their muscarinic and nicotonic potency (EPMR) and selectivity were determined. The relationships between stereoisomerism and potency are discussed.This publication has 1 reference indexed in Scilit:
- Recognition of cholinergic agonists by the muscarinic receptor. 1. Acetylcholine and other agonists with the NCCOCC backboneJournal of Medicinal Chemistry, 1983