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 N-hydroxypyridone derivatives based on CPX were designed, synthesized, and evaluated in this study. Among these derivatives, compound 11 exhibits significant neuroprotection against oxygen glucose deprivation and oxidative stress-induced injuries in neuronal cells. Moreover, compound 11 possesses good blood-brain barrier permeability and superior antioxidant capability. In addition, a complex of compound 11 with olamine-11·Ola possesses good water solubility, negligible hERG inhibition, and superior metabolic stability. The in vivo experiment demonstrates that 11·Ola significantly reduces brain infarction and alleviates neurological deficits in middle cerebral artery occlusion rats. Hence, compound 11·Ola is identified in our research as a prospective prototype in the innovation of stroke treatment.

中文翻译：

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新型N-羟基吡啶酮衍生物作为潜在的抗缺血性卒中药物的开发。

我们先前的研究已确定环吡酮（CPX）是治疗缺血性中风的有前途的先导化合物。为了找到更好的神经保护剂，本研究设计，合成和评估了一系列基于CPX的N-羟基吡啶酮衍生物。在这些衍生物中，化合物11对神经元细胞中的氧葡萄糖剥夺和氧化应激诱导的损伤表现出显着的神经保护作用。此外，化合物11具有良好的血脑屏障渗透性和优异的抗氧化能力。另外，化合物11与olamine-11·Ola的复合物具有良好的水溶性，可忽略的hERG抑制作用和优异的代谢稳定性。体内实验表明，11·Ola明显减轻了大脑中动脉闭塞大鼠的脑梗塞并减轻了神经功能缺损。