Discovery of Novel Quaternary Ammonium Derivatives of (3 R)-Quinuclidinol Esters as Potent and Long-Acting Muscarinic Antagonists with Potential for Minimal …

…, I Ramos, T Doménech, D Vilella, F Antón…

Index: Prat, Maria; Fernandez, Dolors; Buil, M. Antonia; Crespo, Maria I.; Casals, Gaspar; Ferrer, Manuel; Tort, Laia; Castro, Jordi; Monleon, Juan M.; Gavalda, Amadeu; Miralpeix, Montserrat; Ramos, Israel; Domenech, Teresa; Vilella, Dolors; Anton, Francisca; Huerta, Josep M.; Espinosa, Sonia; Lopez, Manuel; Sentellas, Sonia; Gonzalez, Marisa; Alberti, Joan; Segarra, Victor; Cardenas, Alvaro; Beleta, Jorge; Ryder, Hamish Journal of Medicinal Chemistry, 2009 , vol. 52, # 16 p. 5076 - 5092

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Citation Number: 43

Abstract

The objective of this work was to discover a novel, long-acting muscarinic M3 antagonist for the inhaled treatment of chronic obstructive pulmonary disease (COPD), with a potentially improved risk− benefit profile compared with current antimuscarinic agents. A series of novel quaternary ammonium derivatives of (3 R)-quinuclidinol esters were synthesized and evaluated. On the basis of its overall profile,(3 R)-3-{[hydroxy (di-2-thienyl) acetyl] oxy}-1-( ...