Details

Autor(en) / Beteiligte

• Alagille, David
• Baldwin, Ronald M.
• Roth, Bryan L.
• Wroblewski, Jarda T.
• Grajkowska, Ewa
• Tamagnan, Gilles D.

Titel

Synthesis and receptor assay of aromatic–ethynyl–aromatic derivatives with potent mGluR5 antagonist activity

Ist Teil von

• Bioorganic & medicinal chemistry, 2005-01, Vol.13 (1), p.197-209

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• Noncompetitive antagonists of the human metabotropic glutamate receptor subtype 5 (mGluR5) have been implicated as potential therapeutics for the treatment of a variety of nervous system disorders, including pain, anxiety, and drug addiction. To discover novel noncompetitive antagonists to the mGluR5, we initiated an SAR study around the known lead compounds MPEP and M-MPEP. Our results pointed out the critical role of the para position of the two aromatic rings, which leads to inactive products and permitted the discovery of potent mGluR5 antagonists (e.g., 16, 25, 28, 34 IC 50 = 13.5, 11.9, 21, 15 nM, respectively). Noncompetitive antagonists of the human metabotropic glutamate receptor subtype 5 (mGluR5) have been implicated as potential therapeutics for the treatment of a variety of nervous system disorders, including pain, anxiety, and drug addiction. To discover novel noncompetitive antagonists to the mGluR5, we initiated an SAR study around the known lead compounds MPEP and M-MPEP. Our results pointed out the critical role of the para position of the two aromatic rings, which leads to inactive products and permitted the discovery of potent mGluR5 antagonists (e.g., 16, 25, 28, 34 IC 50 = 13.5, 11.9, 21, 15 nM, respectively).