1. Discovery of 1,5-disubstituted pyridones: a new class of positive allosteric modulators of the metabotropic glutamate 2 receptor.
- Author
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Cid JM, Duvey G, Cluzeau P, Nhem V, Macary K, Raux A, Poirier N, Muller J, Boléa C, Finn T, Poli S, Epping-Jordan M, Chamelot E, Derouet F, Girard F, Macdonald GJ, Vega JA, de Lucas AI, Matesanz E, Lavreysen H, Linares ML, Oehlrich D, Oyarzábal J, Tresadern G, Trabanco AA, Andrés JI, Le Poul E, Imogai H, Lutjens R, and Rocher JP
- Subjects
- Allosteric Regulation, Amino Acids chemistry, Animals, Bridged Bicyclo Compounds chemistry, Drug Evaluation, Preclinical, Drug Stability, Excitatory Amino Acid Agonists chemistry, Excitatory Amino Acid Agonists classification, Humans, Hydrophobic and Hydrophilic Interactions, Mice, Molecular Structure, Motor Activity drug effects, Pyridines chemistry, Pyridones chemistry, Pyridones classification, Pyridones isolation & purification, Recombinant Proteins drug effects, Structure-Activity Relationship, Sulfonamides chemistry, Amino Acids pharmacology, Bridged Bicyclo Compounds pharmacology, Excitatory Amino Acid Agonists pharmacology, Pyridines pharmacology, Pyridones pharmacology, Receptors, Metabotropic Glutamate agonists, Sulfonamides pharmacology
- Abstract
A series of 1,5-disubstituted pyridones was identified as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2) via high throughput screening (HTS). Subsequent SAR exploration led to the identification of several compounds with improved in vitro activity. Lead compound 8 was further profiled and found to attenuate the increase in PCP induced locomotor activity in mice.
- Published
- 2010
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