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Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia

Walker, James R, Fairfull-Smith, Kathryn E., Anzai, Kazunori, Lau, Shannen, White, Paul J, Scammells , Peter J., & Bottle , Steven E. (2011) Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia. MedChemComm, pp. 436-441.

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Abstract

A novel antioxidant for the potential treatment of ischaemia was designed by incorporating an isoindoline nitroxide into the framework of the free radical scavenger edaravone. 5-(3-Methyl-pyrazol-5-ol-1-yl)-1,1,3,3-tetramethylisoindolin-2-yloxyl 7 was prepared by N-arylation of 3-methyl-5-pyrazolone with 5-iodo-1,1,3,3-tetramethylisoindoline-2-yloxyl 8 in the presence of catalytic copper(I)iodide. Evaluation of 7, its methoxyamine derivative 10 and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) against edaravone 1 in ischaemic rat atrial cardiomyocytes revealed significant decreases in cell death after prolonged ischaemia for each agent; however the protective effect of the novel antioxidant 7 (showing greater than 85% reduction in cell death at 100 μM) was significantly enhanced over that of edaravone 1 alone. Furthermore, the activity for 7 was found to be equal to or greater than the potent cardioprotective agent N6-cyclopentyladenosine (CPA). The methoxyamine adduct 10 and edaravone 1 showed no difference between the extent of reduction in cell death whilst CTMIO had only a modest protective effect.

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9 citations in Web of Science®

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ID Code: 43689
Item Type: Journal Article
Keywords: cardiovascular ischaemia, Edaravone , isoindoline nitroxides
DOI: 10.1039/C1MD00041A
ISSN: 2040-2511
Divisions: Past > Schools > Chemistry
Past > QUT Faculties & Divisions > Faculty of Science and Technology
Copyright Owner: Copyright 2011 Royal Society of Chemistry
Deposited On: 27 Jul 2011 14:17
Last Modified: 28 Jul 2011 15:23

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