Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 3: Identification and biological activity of indanone containing mGlu2 receptor potentiators.

Abstract

We have identified and synthesized a series of phenyl-tetrazolyl and 4-thiopyridyl indanones as allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation, as well as PK properties, led to the discovery of 28 (EC50=186 nM), which displayed activity in a rodent model for schizophrenia.

• Authors: Anthony B Pinkerton, Rowena V Cube, John H Hutchinson, Joyce K James, Michael F Gardner, Blake A Rowe, Hervé Schaffhauser, Dana E Rodriguez, Una C Campbell, Lorrie P Daggett, Jean-Michel Vernier
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 15 Issue 6 Pg. 1565-71 (Mar 15 2005) ISSN: 0960-894X [Print] England
• PMID: 15745798 (Publication Type: Journal Article)

Chemical References

• Indans
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor 2

Topics

• Allosteric Regulation
• Animals
• Brain (metabolism)
• Disease Models, Animal
• Indans (pharmacokinetics, pharmacology)
• Models, Chemical
• Molecular Structure
• Protein Binding
• Rats
• Receptors, Metabotropic Glutamate (agonists)
• Schizophrenia (drug therapy)
• Structure-Activity Relationship