Discovery of orally efficacious tetracyclic metabotropic glutamate receptor 1 (mGluR1) antagonists for the treatment of chronic pain.

Abstract

Metabotropic glutamate receptor 1 (mGluR1) plays important roles in the neurotransmission and pathogenesis of several neurological disorders, including chronic pain. Antagonists of mGlur1 are suggested to be useful for the treatment of pain. Herein, we report the discovery of a novel series of tetracyclic mGluR1 antagonists, such as 23c and 23e, with oral efficacy of ED50 of 8 and 5.1 mg/kg, respectively, in rat spinal nerve ligation neuropathic pain model.

• Authors: Wen-Lian Wu, Duane A Burnett, Martin Domalski, William J Greenlee, Cheng Li, Rosalia Bertorelli, Silva Fredduzzi, Gianluca Lozza, Alessio Veltri, Angelo Reggiani
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 23 Pg. 5550-3 (Nov 15 2007) ISSN: 0022-2623 [Print] United States
• PMID: 17929793 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Heterocyclic Compounds, 4 or More Rings
• Indazoles
• Morpholines
• Pyridines
• Pyrroles
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor type 1

Topics

• Analgesics (chemical synthesis, chemistry, pharmacology)
• Animals
• Area Under Curve
• Chronic Disease
• Heterocyclic Compounds, 4 or More Rings (chemical synthesis, chemistry, pharmacology)
• Humans
• Indazoles (chemical synthesis, chemistry, pharmacology)
• Morpholines (chemical synthesis, chemistry, pharmacology)
• Pain (drug therapy)
• Peripheral Nervous System Diseases (drug therapy)
• Pyridines (chemical synthesis, chemistry, pharmacology)
• Pyrroles (chemical synthesis, chemistry, pharmacology)
• Rats
• Receptors, Metabotropic Glutamate (antagonists & inhibitors)
• Structure-Activity Relationship