1,5-Benzodioxepin Derivatives as a Novel Class of Muscarinic M3 Receptor Antagonists

Bioorg Med Chem Lett. 2007 Feb 15;17(4):925-31. doi: 10.1016/j.bmcl.2006.11.058. Epub 2006 Nov 22.

Abstract

The structure-activity relationships of novel 1,5-benzodioxepin derivatives as muscarinic M(1)-M(3) receptor antagonists are reported. Some of these compounds were found to possess high binding affinity for the muscarinic M(3) receptor and potent effect on rhythmic increase in bladder pressure in unanesthetized rats following oral administration. These compounds displayed selectivity for the bladder over the salivary gland.

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Cell Line
  • Humans
  • Indicators and Reagents
  • Insecta
  • Mandelic Acids / pharmacology
  • Muscarinic Antagonists / chemical synthesis*
  • Muscarinic Antagonists / metabolism
  • Muscarinic Antagonists / pharmacology*
  • Oxepins / chemical synthesis*
  • Oxepins / metabolism
  • Oxepins / pharmacology*
  • Rats
  • Receptor, Muscarinic M3 / antagonists & inhibitors*
  • Salivary Glands / drug effects
  • Scopolamine / metabolism
  • Structure-Activity Relationship
  • Urinary Bladder, Neurogenic / drug therapy

Substances

  • Indicators and Reagents
  • Mandelic Acids
  • Muscarinic Antagonists
  • Oxepins
  • Receptor, Muscarinic M3
  • Scopolamine
  • oxybutynin