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

  • Bioorg Med Chem Lett. 2011 Jun 1;21(11):3457-61. doi: 10.1016/j.bmcl.2011.03.096.
Maria Prat  1 ,  María Antonia Buil ,  Maria Dolors Fernández ,  Jordi Castro ,  Juan Manuel Monleón ,  Laia Tort ,  Gaspar Casals ,  Manuel Ferrer ,  Josep Maria Huerta ,  Sònia Espinosa ,  Manuel López ,  Victor Segarra ,  Amadeu Gavaldà ,  Montserrat Miralpeix ,  Israel Ramos ,  Dolors Vilella ,  Marisa González ,  Mònica Córdoba ,  Alvaro Cárdenas ,  Francisca Antón ,  Jorge Beleta ,  Hamish Ryder
Affiliations
  • 1. Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain. [email protected]
PMID: 21524581 DOI: 10.1016/j.bmcl.2011.03.096
Abstract

Novel quaternary ammonium derivatives of N,N-disubstituted (3R)-quinuclidinyl carbamates have been identified as potent M(3) muscarinic antagonists with long duration of action in an in vivo model of bronchoconstriction. These compounds have also presented a high level of metabolic transformation (human liver microsomes). The synthesis, structure-activity relationships and biological evaluation of these compounds are reported.