Zhang Yue-Mei, Fan Xiaodong, Chakaravarty Devraj, Xiang Bangping, Scannevin Robert H, Huang Zhihong, Ma Jianya, Burke Sharon L, Karnachi Prabha, Rhodes Kenneth J, Jackson Paul F
East Coast Research and Early Development, Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Bioorg Med Chem Lett. 2008 Jan 1;18(1):409-13. doi: 10.1016/j.bmcl.2007.10.045. Epub 2007 Oct 18.
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.
基质金属蛋白酶-9（MMP-9）被认为与脑缺血期间血脑屏障的破坏有关。因此，抑制MMP-9可能作为中风的一种治疗干预手段。为此，我们合成了一系列1-羟基-2-吡啶酮，它们除了对MMP-2有抑制作用外，在体外对MMP-9也有优异的抑制效力。代表性化合物在小鼠大脑中动脉短暂闭塞（tMCAO）脑缺血模型中也显示出良好的疗效。
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