Synthesis and muscarinic properties of (1S*,3R*,5R*)-trimethyl(1-methyl-6-oxabicyclo[3.1.0]hex-3-yl)methyl ammonium iodide.
To acquire more information about the so-called "muscarinic subsite", compound 4 was synthesized and tested. The results show that in comparison with deoxamuscarine (23) the muscarinic potency of 4 on M2 and M3 subtypes is not significantly altered by the presence of an epoxidic function, which confirms the donor-acceptor hydrogen bonding character of this receptive site. Conversely, there is a negative influence on the transduction processes. In addition, a second hydroxylic function bound on the carbon carrying the terminal methyl of the fourth substituent on the nitrogen dramatically affects the muscarinic behavior; the resulting compounds (11-14) lack any agonist or antagonist activity.
Giannella
M
M
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Piergentili
A
A
Pigini
M
M
Quaglia
W
W
Rafaiani
G
G
Tayebati
S K
SK
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010277:Parasympathomimetics / Q000138:chemical synthesis* / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010277:Parasympathomimetics; D000644:Quaternary Ammonium Compounds; D011976:Receptors, Muscarinic; C089063:trimethyl(1-methyl-6-oxabicyclo(3.1.0)hex-3-yl)methylammonium