Design and Synthesis of Ether Analogues as Potent and Selective M2 Muscarinic Receptor Antagonists

Bioorg Med Chem Lett. 2001 Apr 9;11(7):891-4. doi: 10.1016/s0960-894x(01)00100-7.

Abstract

Novel, selective M2 muscarinic antagonists, which replace the metabolically labile styrenyl moiety of the prototypical M2 antagonist 1 with an ether linkage, were synthesized. A detailed SAR study in this class of compounds has yielded highly active compounds that showed M2 Ki values of < 1.0 nM and >100-fold selectivity against M1, M3, and M5 receptors.

MeSH terms

  • Acetylcholine / agonists*
  • Alkenes / chemical synthesis
  • Drug Design
  • Ether / analogs & derivatives*
  • Ether / pharmacology*
  • Humans
  • Muscarinic Antagonists / chemical synthesis
  • Muscarinic Antagonists / pharmacology*
  • Protein Binding
  • Receptor, Muscarinic M1
  • Receptor, Muscarinic M2
  • Receptor, Muscarinic M3
  • Receptor, Muscarinic M5
  • Receptors, Muscarinic / drug effects*
  • Structure-Activity Relationship

Substances

  • Alkenes
  • Muscarinic Antagonists
  • Receptor, Muscarinic M1
  • Receptor, Muscarinic M2
  • Receptor, Muscarinic M3
  • Receptor, Muscarinic M5
  • Receptors, Muscarinic
  • Ether
  • Acetylcholine