Design, synthesis and structure-activity relationship of N-substituted tropane muscarinic acetylcholine receptor antagonists

Bioorg Med Chem Lett. 2012 May 1;22(9):3366-9. doi: 10.1016/j.bmcl.2012.02.015. Epub 2012 Feb 15.

Abstract

A novel series of N-substituted tropane derivatives was characterized as potent muscarinic acetylcholine receptor antagonists (mAChRs). Kinetic washout studies showed that the N-endosubstituted analog 24 displayed much slower reversibility at mAChRs than the methyl-substituted parent molecule darotropium. In addition, it was shown that this characteristic appeared to translate into enhanced which duration of action in a mouse model of bronchonstriction.

MeSH terms

  • Animals
  • Bronchial Diseases / drug therapy
  • Drug Design
  • Mice
  • Muscarinic Antagonists / chemical synthesis*
  • Muscarinic Antagonists / pharmacology
  • Receptors, Muscarinic / drug effects
  • Structure-Activity Relationship
  • Tropanes / chemical synthesis*
  • Tropanes / pharmacology

Substances

  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Tropanes