329020-79-3Relevant articles and documents
COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING FERROPTOSIS AND TREATING EXCITOTOXIC DISORDERS
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, (2020/06/19)
The present disclosure provides, inter alia, a compound having the structure (1). Also provided are compositions containing a pharmaceutically acceptable carrier and one or more compounds according to the present disclosure. Further provided are methods f
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.
Design and synthesis of conformationally restricted inhibitors of active thrombin activatable fibrinolysis inhibitor (TAFIa)
Brink, Mikael,Dahlen, Anders,Olsson, Thomas,Polla, Magnus,Svensson, Tor
, p. 2261 - 2268 (2014/04/17)
A series of 4,5,6,7-tetrahydro-1H-benzimidazole-5-carboxylic acid and 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid derivatives designed as inhibitors of TAFIa has been prepared via a common hydrogenation-alkylation sequence starting from the appropriate benzimidazole and imidazopyridine system. We present a successful design strategy using a conformational restriction approach resulting in potent and selective inhibitors of TAFIa. The X-ray structure of compound 5 in complex with a H333Y/H335Q double mutant TAFI indicate that the conformational restriction is responsible for the observed potency increase.
1-Alkyl-benzotriazole-5-carboxylic acids are highly selective agonists of the human orphan G-protein-coupled receptor GPR109b
Semple, Graeme,Skinner, Philip J.,Cherrier, Martin C.,Webb, Peter J.,Sage, Carleton R.,Tamura, Susan Y.,Chen, Ruoping,Richman, Jeremy G.,Connolly, Daniel T.
, p. 1227 - 1230 (2007/10/03)
1-Substituted benzotriazole carboxylic acids have been identified as the first reported examples of selective small-molecule agonists of the human orphan G-protein-coupled receptor GPR109b (HM74), a low-affinity receptor for the HDL-raising drug niacin. N
