Rational design of 7-arylquinolines as non-competitive metabotropic glutamate receptor subtype 5 antagonists

Rational replacement of the alkyne linker of mGluR5 antagonist MPEP gave 7-arylquinolines. SAR optimization gave an orally active compound with high affinity for the MPEP binding site.

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 17; no. 16; pp. 4415 - 4418
Main Authors:	Milbank, Jared B.J., Knauer, Christopher S., Augelli-Szafran, Corinne E., Sakkab-Tan, Annette T., Lin, Kristin K., Yamagata, Koji, Hoffman, Jennifer K., Zhuang, Nian, Thomas, John, Galatsis, Paul, Wendt, John A., Mickelson, John W., Schwarz, Roy D., Kinsora, Jack J., Lotarski, Susan M., Stakich, Korana, Gillespie, Kristen K., Lam, Wing W., Mutlib, Abdul E.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 15-08-2007 Elsevier
Subjects:	Antagonist Biological and medical sciences Drug Design Excitatory Amino Acid Antagonists - chemistry Excitatory Amino Acid Antagonists - pharmacology Glutamatergic system (aspartate and other excitatory aminoacids) Medical sciences mGluR5 Models, Molecular Molecular Structure MPEP Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Pyridines - chemistry Pyridines - pharmacology Quinolines - chemistry Quinolines - pharmacology Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate - antagonists & inhibitors Structure-Activity Relationship mGluR5 MPEP Antagonist Group I mglu glutamate receptor Nitrile mglu5 glutamate receptor Spacer arm Oral administration Quinoline derivatives Glutamate receptor Binding site In vitro Optimization Structure activity relation Metabotropic receptor Affinity Benzonitrile derivatives Fluorine Organic compounds Chemical synthesis
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