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

• Published in: Bioorganic & medicinal chemistry letters Vol. 15; no. 6; pp. 1565 - 1571
• Main Authors: Pinkerton, Anthony B., Cube, Rowena V., Hutchinson, John H., James, Joyce K., Gardner, Michael F., Rowe, Blake A., Schaffhauser, Hervé, Rodriguez, Dana E., Campbell, Una C., Daggett, Lorrie P., Vernier, Jean-Michel
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.03.2005; Elsevier
• Subjects: Allosteric; Allosteric Regulation; Animals; Biological and medical sciences; Brain - metabolism; Disease Models, Animal; Glutamate; Glutamatergic system (aspartate and other excitatory aminoacids); GPCRs; Indans - pharmacokinetics; Indans - pharmacology; Medical sciences; mGlu receptors; Miscellaneous; Models, Chemical; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Protein Binding; Rats; Receptors, Metabotropic Glutamate - agonists; Schizophrenia; Schizophrenia - drug therapy; Structure-Activity Relationship; Allosteric; Schizophrenia; mGlu receptors; Glutamate; GPCRs; Potentiation; Tetrazole derivatives; Indan derivatives; Rodentia; Glutamate receptor; mglu2 glutamate receptor; Encephalon; Pyridine derivatives; Psychosis; Vertebrata; Mammalia; Absorption; Structure activity relation; Metabotropic receptor; Allosteric regulation; Models; Pharmacokinetics; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.01.077

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 (EC 50 = 186 nM), which displayed activity in a rodent model for schizophrenia. 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 (EC 50 = 186 nM), which displayed activity in a rodent model for schizophrenia.