43041-67-4Relevant academic research and scientific papers
Novel Ferroptosis Inhibitors with Improved Potency and ADME Properties
Hofmans, Sam,Berghe, Tom Vanden,Devisscher, Lars,Hassannia, Behrouz,Lyssens, Sophie,Joossens, Jurgen,Van Der Veken, Pieter,Vandenabeele, Peter,Augustyns, Koen
, p. 2041 - 2053 (2016/03/22)
Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated necrosis that is critically dependent on glutathione peroxidase 4 (GPX4). It has been shown to contribute to liver and kidney ischemia reperfusion injury in mice. A chemical inhibitor discovered by high-throughput screening displayed inhibition of ferroptosis with nanomolar activity and was dubbed ferrostatin-1 (fer-1). Ferrostatins inhibit oxidative lipid damage, but suffer from inherent stability problems due to the presence of an ester moiety. This limits the application of these molecules in vivo, due to rapid hydrolysis of the ester into the inactive carboxylic acid. Previous studies highlighted the importance of the ethyl ester and suggested steric modifications of the ester for generating improved molecules. In this study, we report the synthesis of novel ferroptosis inhibitors containing amide and sulfonamide moieties with improved stability, single digit nanomolar antiferroptotic activity, and good ADME properties suitable for application in in vivo disease models.
3,4-DIAMINOBENZENESULFONAMIDE DERIVATIVES FOR INHIBITING CELL DEATH
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Page/Page column 23; 24, (2016/06/06)
The present invention relates to a novel class of compounds having the structure of formula (I) and pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof. These compounds inhibit or reduce the non-apoptotic cell death forms ferroptosis and/or oxytosis rendering them useful for the treatment of various conditions disclosed herein.
