Synthesis and Evaluation of Calpain Inhibitors Carrying Muscle Cell Targeting Groups

Title: Synthesis and Evaluation of Calpain Inhibitors Carrying Muscle Cell Targeting Groups

Volume: 3 Issue: 3

Author(s): P. Weyermann, H. Herzner, C. Lescop, H. Siendt, R. Bolliger, M. Hennebohle, C. Rummey, A. Briguet, I. Courdier-Fruh, M. Erb, M. Foster, J.P. Magyar, A. von Sprecher and T. Meier

Affiliation:

Keywords: Calpain inhibitor, ketoamide, duchenne muscular dystrophy, lipoic acid

Abstract: Inhibition of the cysteine protease calpain is a promising strategy for the treatment of muscular dystrophies including Duchenne Muscular Dystrophy. For the treatment to be effective, uptake of the inhibitors into the muscle cells is a prerequisite. A series of α-ketoamide calpain inhibitors carrying various muscle cell targeting capping groups was synthesized. Compounds with charged or highly polar targeting groups were not able to cross the cellular membrane. Introduction of lipoic acid as end cap yielded cell permeable calpain inhibitors with nanomolar potency.

Cite this article as:

Weyermann P., Herzner H., Lescop C., Siendt H., Bolliger R., Hennebohle M., Rummey C., Briguet A., Courdier-Fruh I., Erb M., Foster M., J.P. Magyar , A. von Sprecher and T. Meier , Synthesis and Evaluation of Calpain Inhibitors Carrying Muscle Cell Targeting Groups, Letters in Drug Design & Discovery 2006; 3 (3) . https://dx.doi.org/10.2174/157018006776286916

DOI https://dx.doi.org/10.2174/157018006776286916	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X