【文章名】Synthesis and Pharmacological Characterization of Chiral Pyrrolidinylfuran Derivatives: The Discovery of New Functionally Selective Muscarinic Agonists.
Synthesis and Pharmacological Characterization of Chiral Pyrrolidinylfuran Derivatives: The Discovery of New Functionally Selective Muscarinic Agonists.
[摘要]：Building on the previously and successfully applied hypothesis that stereochem. complication in the proximity of the crit. cationic head of a cholinergic agonist would result in subtype selective compds., we synthesized a series of chiral derivs. of furmethide and 5-methylfurmethide, e.g., I, with the aim of obtaining compds. that are useful for treating diseases derived from cholinergic receptor dysfunctions and/or useful for further characterizing subtypes of cholinergic receptors. Unlike their parent compds., the new mols. lack nicotinic activity, being pure muscarinic ligands. While binding studies on the five cloned human muscarinic receptors showed no subtype selectivity, functional assays revealed that some of the mols. of the series are potent M2 selective partial agonists with interesting pharmacol. profiles.
