Abstract
The known affinity of ethyl acetoacetate (ACC) toward divalent zinc prompted us to attempt its employment as a chelating moiety in the design of glyoxalase-I inhibitors. A practical synthetic route was developed to incorporate this pharmacophore into the side chain of glutamic acid, with flexibility to allow incorporation of additional functionality at the end-stage of the synthesis. Herein, the details of this synthetic approach as well as the evaluation of the resultant beta-keto ester compounds are reported.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Chelating Agents / chemistry
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Chelating Agents / pharmacology*
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Chemistry, Pharmaceutical / methods
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Crystallography, X-Ray
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Glutamic Acid / chemistry
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Hydrogen Bonding
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Kinetics
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Lactoylglutathione Lyase / antagonists & inhibitors*
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Lactoylglutathione Lyase / chemistry*
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Ligands
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Models, Chemical
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Oxygen / chemistry
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Peptides / chemistry
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Zinc / chemistry*
Substances
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Chelating Agents
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Enzyme Inhibitors
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Ligands
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Peptides
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Glutamic Acid
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Lactoylglutathione Lyase
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Zinc
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Oxygen