1-Hydroxy-2-pyridinone-based MMP inhibitors: Synthesis and biological evaluation for the treatment of ischemic stroke

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.

A series of 1-hydroxy-2-pyridinone synthesized have excellent in vitro potency in inhibiting MMP-9 in addition to MMP-2 and representative compounds demonstrate good efficacy in the mouse transient mid-cerebral artery occlusion (tMCAO) model of cerebral ischemia.Figure optionsDownload as PowerPoint slide