Potent anti-muscarinic activity in a novel series of quinuclidine derivatives

Bioorg Med Chem Lett. 2006 Jan 15;16(2):373-7. doi: 10.1016/j.bmcl.2005.09.079. Epub 2005 Nov 3.

Abstract

The synthesis and biological evaluation of a novel family of M(3) muscarinic antagonists are described. A systematic modification of the substituents to a novel alkyne-quinuclidine scaffold yielded original compounds displaying potent in vitro anticholinergic properties.

MeSH terms

  • Animals
  • Binding Sites
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors
  • Drug Evaluation, Preclinical
  • Guinea Pigs
  • Humans
  • In Vitro Techniques
  • Microsomes / drug effects
  • Microsomes / enzymology
  • Molecular Structure
  • Muscarinic Antagonists / chemical synthesis
  • Muscarinic Antagonists / chemistry
  • Muscarinic Antagonists / pharmacology*
  • Quinuclidines / chemical synthesis
  • Quinuclidines / chemistry
  • Quinuclidines / pharmacology*
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism
  • Structure-Activity Relationship

Substances

  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 Enzyme Inhibitors
  • Muscarinic Antagonists
  • Quinuclidines
  • Receptors, Muscarinic
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A