Synthesis and muscarinic receptor binding profiles of antagonist benzotriazole derivatives.
A series of benzotriazole derivatives were synthesized and tested in order to determine their activities for muscarinic receptor subtypes (M1, M2 and M3). Binding affinities were measured as KI values by competition against [3H]-N-methylscopolamine in rat cortex, atria and ileum. Pharmacological in vitro tests were performed on isolated tissue preparations (rabbit vas deferens, guinea pig atria and ileum); the compounds showed antimuscarinic activity. The synthesized ligands were characterized by moderate activity; however, some of them displayed interesting selectivity profiles (M2/M1 and M2/M3); particularly, the selectivity exhibited by the benzotriazole derivative 14b was quite similar to that observed for AF-DX 116, a typical M2 specific antagonist.
Cappello
B
B
Dipartimento di Chimica Farmaceutica e Tossicologica dell'Università di Napoli, Italy.
Greco
G
G
Novellino
E
E
Perissutti
E
E
Santagada
V
V
Silipo
C
C
Vittoria
A
A
Di Carlo
R
R
Meli
R
R
Muccioli
G
G
D000818:Animals; D002855:Chromatography, Thin Layer; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018727:Muscarinic Antagonists; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014230:Triazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D014230:Triazoles; D010890:Pirenzepine; C012771:benzotriazole; C048593:otenzepad; D019832:N-Methylscopolamine