Our previous study had identified ciclopirox (CPX) as a promising lead compound for treatment of ischemic stroke. To find better neuroprotective agents, a series of -hydroxypyridone derivatives based on CPX were designed, synthesized, and evaluated in this study. Among these derivatives, compound exhibits significant neuroprotection against oxygen glucose deprivation and oxidative stress-induced injuries in neuronal cells. Moreover, compound possesses good blood-brain barrier permeability and superior antioxidant capability. In addition, a complex of compound with olamine- possesses good water solubility, negligible hERG inhibition, and superior metabolic stability. The in vivo experiment demonstrates that significantly reduces brain infarction and alleviates neurological deficits in middle cerebral artery occlusion rats. Hence, compound is identified in our research as a prospective prototype in the innovation of stroke treatment.
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