1-Hydroxy-2-pyridinone-based MMP inhibitors: Synthesis and biological evaluation for the treatment of ischemic stroke
作者:Yue-Mei Zhang、Xiaodong Fan、Devraj Chakaravarty、Bangping Xiang、Robert H. Scannevin、Zhihong Huang、Jianya Ma、Sharon L. Burke、Prabha Karnachi、Kenneth J. Rhodes、Paul F. Jackson
DOI:10.1016/j.bmcl.2007.10.045
日期:2008.1
Matrix metalloprotemase-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. (C) 2007 Elsevier Ltd. All rights reserved.