Abstract
We have identified and synthesized a series of biphenyl-carboxylic acid indanones as allosteric potentiators of the metabotropic glutamate receptor 2. Structure-activity relationship studies directed toward improving the potency and the brain to plasma ratio of the initial lead led to the discovery of 5 and 23 (EC50=111 and 5 nM, respectively).
MeSH terms
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Allosteric Regulation
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Animals
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Biphenyl Compounds / chemical synthesis*
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Biphenyl Compounds / metabolism
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Biphenyl Compounds / pharmacokinetics
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Brain Chemistry
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Humans
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Indans / chemical synthesis*
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Indans / metabolism
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Indans / pharmacokinetics
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Rats
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Receptors, Metabotropic Glutamate / agonists*
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Receptors, Metabotropic Glutamate / metabolism
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Schizophrenia / drug therapy
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Structure-Activity Relationship
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Tissue Distribution
Substances
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Biphenyl Compounds
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Indans
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor 2
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Guanosine 5'-O-(3-Thiotriphosphate)