Synthesis, NMR spectroscopy study, and antimuscarinic activity of a series of 2-(acyloxymethyl)-1,3-dioxolanes.
A series of 1,3-dioxolane-based ligands, bearing hydroxymethyl or ester functionalities, was synthesized and tested as potential muscarinic antagonists. The compounds display moderate to low affinity for the three receptor subtypes M1-M3, with some of them showing a significant selectivity for the M3 subtype. The configurational and conformational properties were studied using NOE experiments and vicinal coupling constants. The 1H and 13C NMR chemical shifts show stereochemically dependent trends. Quantitative analysis of conformer populations showed that the exocyclic CH2N CH3)3 group is prevalently in a pseudo-axial orientation in the cis isomers and in a pseudo-equatorial orientation in the trans isomers.
Malmusi
L
L
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena, Italy.
Mucci
A
A
Schenetti
L
L
Gulini
U
U
Marucci
G
G
Brasili
L
L
D000818:Animals; D004148:Dioxolanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D004148:Dioxolanes; D018727:Muscarinic Antagonists; C010962:formal glycol