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 M2 selective partial agonists with interesting pharmacological profiles.

Synthesis and pharmacological characterization of chiral pyrrolidinylfuran derivatives: the discovery of new functionally selective muscarinic agonists / S. Scapecchi; M. Nesi; R. Matucci; C. Bellucci; M. Buccioni; S. Dei; L. Guandalini; D. Manetti; E. Martini; G. Marucci; M.N. Romanelli; E. Teodori; R. Cirilli.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 51:(2008), pp. 3905-3912. [10.1021/jm800145d]

Synthesis and pharmacological characterization of chiral pyrrolidinylfuran derivatives: the discovery of new functionally selective muscarinic agonists

SCAPECCHI, SERENA;MATUCCI, ROSANNA;BELLUCCI, CRISTINA;DEI, SILVIA;MANETTI, DINA;ROMANELLI, MARIA NOVELLA;TEODORI, ELISABETTA;
2008

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 M2 selective partial agonists with interesting pharmacological profiles.
2008
51
3905
3912
S. Scapecchi; M. Nesi; R. Matucci; C. Bellucci; M. Buccioni; S. Dei; L. Guandalini; D. Manetti; E. Martini; G. Marucci; M.N. Romanelli; E. Teodori; R. Cirilli.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/320107
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