Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinyl amides as potent and long acting muscarinic antagonists

  • Bioorg Med Chem Lett. 2015 Apr 15;25(8):1736-1741. doi: 10.1016/j.bmcl.2015.02.065.
Maria Prat  1 ,  María Antonia Buil  2 ,  Maria Dolors Fernández  3 ,  Laia Tort  2 ,  Juan Manuel Monleón  2 ,  Gaspar Casals  2 ,  Manuel Ferrer  2 ,  Jordi Castro  2 ,  Amadeu Gavaldà  2 ,  Montserrat Miralpeix  2 ,  Israel Ramos  2 ,  Dolors Vilella  2 ,  Josep Maria Huerta  2 ,  Sònia Espinosa  2 ,  Begoña Hernández  2 ,  Victor Segarra  2 ,  Mònica Córdoba  2
Affiliations
  • 1. Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain. Electronic address: [email protected].
  • 2. Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
  • 3. Thomson Reuters, Provenza 398, 08025 Barcelona, Spain.
PMID: 25800115 DOI: 10.1016/j.bmcl.2015.02.065
Abstract

Novel quaternary ammonium derivatives of (3R)-quinuclidinyl amides have been identified as potent M3 muscarinic antagonists with a long duration of action in an in vivo model of bronchoconstriction. The synthesis, structure-activity relationships and biological evaluation of this series of compounds are reported.

Keywords
(3R)-Quinuclidinyl amides; COPD; Long acting bronchodilators; Low systemic exposure; M(3) muscarinic antagonists.
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