Abstract
Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carboxylic Acids / chemical synthesis
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Carboxylic Acids / chemistry
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Carboxylic Acids / pharmacology*
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Cells, Cultured
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Cyclopropanes / chemical synthesis
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Cyclopropanes / chemistry
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Cyclopropanes / pharmacology*
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Dose-Response Relationship, Drug
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Drug Design*
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Glutamic Acid / chemical synthesis
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Glutamic Acid / chemistry
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Glutamic Acid / pharmacology*
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HEK293 Cells
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Humans
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Molecular Structure
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Receptors, Metabotropic Glutamate / agonists*
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Recombinant Proteins / agonists
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Carboxylic Acids
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Cyclopropanes
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Receptors, Metabotropic Glutamate
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Recombinant Proteins
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alpha-amino-beta-fluorocyclopropanecarboxylic acid
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Glutamic Acid
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metabotropic glutamate receptor 4