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 β-keto ester compounds are reported.
Bibliographical noteFunding Information:
This work was supported by the funding from the Center for Drug Design, Academic Health Center, University of Minnesota.
Copyright 2008 Elsevier B.V., All rights reserved.
- Ethyl acetoacetate
- Transition-state inhibitor
- β-Keto ester