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.
Copyright © 2015 Elsevier Ltd. All rights reserved.
MeSH terms
-
Amides / chemical synthesis
-
Amides / chemistry*
-
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 / chemistry*
-
Muscarinic Antagonists / pharmacokinetics
-
Protein Binding
-
Protein Structure, Tertiary
-
Quaternary Ammonium Compounds / chemistry*
-
Quinuclidines / chemistry*
-
Rats
-
Receptor, Muscarinic M3 / antagonists & inhibitors*
-
Receptor, Muscarinic M3 / metabolism
-
Structure-Activity Relationship
Substances
-
Amides
-
Bronchoconstrictor Agents
-
Muscarinic Antagonists
-
Quaternary Ammonium Compounds
-
Quinuclidines
-
Receptor, Muscarinic M3