Cholinergic agents structurally related to furtrethonium. 3. Synthesis and antimuscarinic activity of a series of N-(5-methyl-2-furfuryl and-tiophenyl)-dialkyl amines and of 2-dimethylamino methyl-4-(1'-substituted-acetoxy-methyl)-1,3-dioxolanes.
The introduction of an homologous series of cyclic amines at position 2 of 5-methylfurane and its isoster 5-methylthiophene induced a weak antagonist behaviour, probably depending on the steric hindrance of the substituents at the nitrogen, in the case of the cardiac tissue. Surprisingly, when evaluated on guinea-pig ileum preparatons, these compounds showed non-muscarinic effects, not-related either to nicotinic or istaminergic effects, the nature of which awaits to be explained. Substitution of the furane ring on the structure of the lead 2a, b, obtained in a previous study, with the bioisoster 1,3-dioxolane moiety gave potent but not selective analogues (17 and 18).
Manfredini
S
S
Dipartimento di Sci. Farmaceutiche, Università di Ferrara, Italy.
Guarneri
M
M
Ferroni
R
R
Simoni
D
D
Zaidi
J H
JH
Grana
E
E
Boselli
C
C
D000818:Animals; D018678:Cholinergic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D018678:Cholinergic Agents; D004148:Dioxolanes; D018727:Muscarinic Antagonists; D000644:Quaternary Ammonium Compounds; C028530:furtrethonium