Abstract
An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago-potentiator ADX-47273. This effort identified key substituents in the 3-position of oxadiazole that engendered either mGluR5 ago-potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Combinatorial Chemistry Techniques
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Molecular Structure
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Oxadiazoles / chemical synthesis*
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Oxadiazoles / chemistry
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Oxadiazoles / pharmacology*
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacology*
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate / antagonists & inhibitors*
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Receptors, Metabotropic Glutamate / metabolism
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Structure-Activity Relationship
Substances
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Oxadiazoles
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Piperidines
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate
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S-(4-fluorophenyl)-(3-(3-(4-fluorophenyl)-(1,2,4)-oxadiazol-5-yl)piperidin-1-yl)methanone