Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia
Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia
复制标题
含有异吲哚啉氮氧化物的依达拉奉可用于治疗心血管缺血
作者：
James R. Walker;K. Fairfull‐Smith;K. Anzai;Shannen Lau;P. White;P. Scammells;S. Bottle
通过将异吲哚氮氧化物引入自由基清除剂依达拉奉的骨架中，设计了一种新的抗氧化剂，用于治疗脑缺血。3-甲基-5-吡唑啉酮与5-(3-Methyl-pyrazol-5-ol-1-yl)-1，1，3，3-tetramethylisoindolin-2-yloxyl-8在碘化铜催化下经N-芳基化反应制得5-iodo-1，1，3，3-tetramethylisoindoline-2-yloxyl-7。7、其甲氧胺衍生物10和5-carboxy-1，1，3，3-tetramethylisoindolin-2-yloxyl(CTMIO)对缺血大鼠心房肌细胞的保护作用表明，在长时间缺血后，细胞死亡显著减少，但新型抗氧化剂7(100μM时细胞死亡减少85%以上)的保护作用明显增强。此外，7的活性被发现等于或大于有效的心脏保护剂N6-环戊基腺苷(CPA)。甲氧胺加合物10和依达拉奉1在减少细胞死亡的程度上没有差异，而CTMIO只有轻微的保护作用。
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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影响因子：
7.4
作者：
A. Samuni;W. Degraff;J. Cook;M. Krishna;A. Russo;James B. Mitchell
通讯作者：
A. Samuni;W. Degraff;J. Cook;M. Krishna;A. Russo;James B. Mitchell
影响因子：
3.5
作者：
R. Schubert;Laura R. Erker;C. Barlow;H. Yakushiji;D. Larson;A. Russo;James B. Mitchell;A. Wynshaw-Boris
通讯作者：
R. Schubert;Laura R. Erker;C. Barlow;H. Yakushiji;D. Larson;A. Russo;James B. Mitchell;A. Wynshaw-Boris
影响因子：
5.2
作者：
Yin, JJ;Buchwald, SL
通讯作者：
Buchwald, SL
影响因子：
15
作者：
Strieter, ER;Blackmond, DG;Buchwald, SL
通讯作者：
Buchwald, SL