Discovery of diaryl imidazolidin-2-one derivatives, a novel class of muscarinic M3 selective antagonists (Part 2).
Synthesis and biological activity of a novel class of quaternary ammonium salt muscarinic M3 receptor antagonists, showing high selectivity versus the M2 receptor, are described. Selected compounds exhibited potent anticholinergic properties, in isolated guinea-pig trachea, and good functional selectivity for trachea over atria. In vivo, the same compounds potently inhibited acetylcholine-induced bronchoconstriction after intratracheal administration in the guinea pig.
Peretto
Ilaria
I
NiKem Research, Via Zambeletti 25, 20021 Baranzate, Milan, Italy. ilaria.peretto@nikemresearch.com
Fossati
Claudia
C
Giardina
Giuseppe A M
GA
Giardini
Alessandra
A
Guala
Matilde
M
La Porta
Elena
E
Petrillo
Paola
P
Radaelli
Stefano
S
Radice
Luigi
L
Raveglia
Luca F
LF
Santoro
Enza
E
Scudellaro
Roberta
R
Scarpitta
Francesca
F
Cerri
Alberto
A
Menegon
Sergio
S
Dondio
Giulio M
GM
Rizzi
Andrea
A
Armani
Elisabetta
E
Amari
Gabriele
G
Civelli
Maurizio
M
Villetti
Gino
G
Patacchini
Riccardo
R
Bergamaschi
Marco
M
Bassani
Franco
F
Delcanale
Maurizio
M
Imbimbo
Bruno P
BP
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006168:Guinea Pigs; D006801:Humans; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D001993:Bronchodilator Agents; D048289:Imidazolidines; D000644:Quaternary Ammonium Compounds; D043587:Receptor, Muscarinic M3