Synthesis and pharmacological characterization of chiral pyrrolidinylfuran derivatives: the discovery of new functionally selective muscarinic agonists.
Article Details
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Scapecchi S, Nesi M, Matucci R, Bellucci C, Buccioni M, Dei S, Guandalini L, Manetti D, Martini E, Marucci G, Romanelli MN, Teodori E, Cirilli R
Synthesis and pharmacological characterization of chiral pyrrolidinylfuran derivatives: the discovery of new functionally selective muscarinic agonists.
J Med Chem. 2008 Jul 10;51(13):3905-12. doi: 10.1021/jm800145d. Epub 2008 Jun 11.
- PubMed ID
- 18543900 [ View in PubMed]
- Abstract
Building on the previously and successfully applied hypothesis that stereochemical complication in the proximity of the critical cationic head of a cholinergic agonist would result in subtype selective compounds, we synthesized a series of chiral derivatives of furmethide and 5-methylfurmethide, with the aim of obtaining compounds that are useful for treating diseases derived from cholinergic receptor dysfunctions and/or useful for further characterizing subtypes of cholinergic receptors. Unlike their parent compounds, the new molecules 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 molecules of the series are potent M 2 selective partial agonists with interesting pharmacological profiles.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Carbamoylcholine Muscarinic acetylcholine receptor M1 Ki (nM) 38018.94 N/A N/A Details Carbamoylcholine Muscarinic acetylcholine receptor M2 Ki (nM) 1230.27 N/A N/A Details Carbamoylcholine Muscarinic acetylcholine receptor M3 Ki (nM) 43651.58 N/A N/A Details Carbamoylcholine Muscarinic acetylcholine receptor M4 Ki (nM) 6309.57 N/A N/A Details