Abstract
The discovery, synthesis and SAR of a novel series of 3-benzyl-1,3-oxazolidin-2-ones as positive allosteric modulators (PAMs) of mGluR2 is described. Expedient hit-to-lead work on a single HTS hit led to the identification of a ligand-efficient and structurally attractive series of mGluR2 PAMs. Human microsomal clearance and suboptimal physicochemical properties of the initial lead were improved to give potent, metabolically stable and orally available mGluR2 PAMs.
MeSH terms
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Administration, Oral
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Allosteric Regulation
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Allosteric Site
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Carbamates / chemistry*
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Chemistry, Pharmaceutical / methods
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Drug Design
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Humans
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Inhibitory Concentration 50
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Ligands
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Microsomes / metabolism
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Models, Chemical
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Molecular Structure
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Oxazolidinones / chemical synthesis*
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Oxazolidinones / chemistry
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Receptors, Metabotropic Glutamate / antagonists & inhibitors*
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Receptors, Metabotropic Glutamate / chemistry*
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Schizophrenia / drug therapy*
Substances
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Carbamates
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Ligands
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Oxazolidinones
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor 2