1-Hydroxy-2-pyridinone-based MMP inhibitors: synthesis and biological evaluation for the treatment of ischemic stroke.
1-Hydroxy-2-pyridinone-based MMP inhibitors: synthesis and biological evaluation for the treatment of ischemic stroke.
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DOI：
10.1016/j.bmcl.2007.10.045
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发表时间：
2008
影响因子：
2.7
通讯作者：
Yue-Mei Zhang;Xiaodong Fan;Devraj Chakaravarty;B. Xiang;R. Scannevin;Zhihong Huang;Jianya Ma;Sharon L. Burke;Prabha Karnachi;K. Rhodes;P. Jackson
中科院分区：
文献类型：
--
作者：
Yue-Mei Zhang;Xiaodong Fan;Devraj Chakaravarty;B. Xiang;R. Scannevin;Zhihong Huang;Jianya Ma;Sharon L. Burke;Prabha Karnachi;K. Rhodes;P. Jackson
基质金属蛋白酶-9 (MMP-9) 与脑缺血期间血脑屏障的破坏有关。因此，抑制 MMP-9 可能可作为中风的治疗干预措施。为此，我们合成了一系列 1-羟基-2-吡啶酮，除了抑制 MMP-2 外，它们在体外也具有优异的抑制 MMP-9 的功效。代表性化合物还在小鼠短暂性大脑中动脉闭塞（tMCAO）脑缺血模型中表现出良好的功效。
Matrix metalloproteinase-9 (MMP-9) has been implicated in the breakdown of the blood–brain barrier during cerebral ischemia. As a result, inhibition of MMP-9 may have utility as a therapeutic intervention in stroke. Towards this end, we have synthesized a series of 1-hydroxy-2-pyridinones that have excellent in vitro potency in inhibiting MMP-9 in addition to MMP-2. Representative compounds also demonstrate good efficacy in the mouse transient mid-cerebral artery occlusion (tMCAO) model of cerebral ischemia.