Identification and Characterization of m4 Selective Muscarinic Antagonists

Bioorg Med Chem Lett. 1998 Aug 4;8(15):1991-6. doi: 10.1016/s0960-894x(98)00351-5.


Our interest in the area of m4 muscarinic antagonists had led us to study a series of benzoxazine isoquinolines. One of the most potent and selective compounds of this series is example 1 with an IC50 value of 90.7 nM at m4 receptors, and 72-fold (m1), 38-fold (m2), 10-fold (m3), and 82-fold (m5) more selective compared to the other receptors. The synthesis and receptor binding affinity of analogs of 1 are reported.

MeSH terms

  • Isoquinolines / chemistry*
  • Isoquinolines / metabolism
  • Isoquinolines / pharmacology
  • Muscarinic Antagonists / chemistry*
  • Muscarinic Antagonists / metabolism
  • Muscarinic Antagonists / pharmacology
  • Protein Binding
  • Receptor, Muscarinic M4
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism


  • Isoquinolines
  • Muscarinic Antagonists
  • Receptor, Muscarinic M4
  • Receptors, Muscarinic