1.
Bioorg Med Chem Lett
; 25(8): 1736-1741, 2015 Apr 15.
Article
in English
| MEDLINE
| ID: mdl-25800115
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.
Subject(s)
Amides/chemistry , Muscarinic Antagonists/chemistry , Quaternary Ammonium Compounds/chemistry , Quinuclidines/chemistry , Receptor, Muscarinic M3/antagonists & inhibitors , Amides/chemical synthesis , Amides/pharmacokinetics , Animals , Binding Sites , Bronchoconstrictor Agents/chemical synthesis , Bronchoconstrictor Agents/chemistry , Bronchoconstrictor Agents/pharmacokinetics , Drug Evaluation, Preclinical , Half-Life , Humans , Hydrogen Bonding , Molecular Docking Simulation , Muscarinic Antagonists/chemical synthesis , Muscarinic Antagonists/pharmacokinetics , Protein Binding , Protein Structure, Tertiary , Rats , Receptor, Muscarinic M3/metabolism , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 21(11): 3457-61, 2011 Jun 01.
Article
in English
| MEDLINE
| ID: mdl-21524581
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.
