Discovery of diaryl imidazolidin-2-one derivatives, a novel class of muscarinic M3 selective antagonists (Part 2).
Peretto I, Fossati C, Giardina GA, Giardini A, Guala M, La Porta E, Petrillo P, Radaelli S, Radice L, Raveglia LF, Santoro E, Scudellaro R, Scarpitta F, Cerri A, Menegon S, Dondio GM, Rizzi A, Armani E, Amari G, Civelli M, Villetti G, Patacchini R, Bergamaschi M, Bassani F, Delcanale M, Imbimbo BP.
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.