Rational Design of a Novel AMPA Receptor Modulator through a Hybridization Approach

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a family of glutamate ion channels of considerable interest in excitatory neurotransmission and associated disease processes. Here, we demonstrate how exploitation of the available X-ray crystal structure of the receptor l...

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Bibliographic Details
Published in:ACS medicinal chemistry letters 2015-04, Vol.6 (4), p.392-396
Main Authors: Caldwell, Nicola, Harms, Jonathan E, Partin, Kathryn M, Jamieson, Craig
Format: Article
Language:English
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Letter
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Summary:The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a family of glutamate ion channels of considerable interest in excitatory neurotransmission and associated disease processes. Here, we demonstrate how exploitation of the available X-ray crystal structure of the receptor ligand binding domain enabled the development of a new class of AMPA receptor positive allosteric modulators (7) through hybridization of known ligands (5 and 6), leading to a novel chemotype with promising pharmacological properties.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml5004553