Jacobsen E J, VanDoornik F J, Ayer D E, Belonga K L, Braughler J M, Hall E D, Houser D J
Medicinal Chemistry Research, Upjohn Company, Kalamazoo, Michigan 49001.
J Med Chem. 1992 Nov 13;35(23):4464-72. doi: 10.1021/jm00101a025.
A series of 2-(aminomethyl)chromans was developed as potent inhibitors of iron-dependent lipid peroxidation. Compounds within this class are extremely effective at inhibiting lipid peroxidation with IC50's as low as 0.2 microM. Selected members were found to enhance early neurological recovery and survival in a mouse head injury model. In this assay, improvement in the 1-h post-head-injury neurological status (grip test score) by as much as 230% of control was observed. One of the most efficacious compounds (35) was evaluated in two models of cerebral ischemia where significant neuroprotection was observed. These results provide further support for the importance of cerebroprotective antioxidants for the treatment of traumatic and ischemic injury as well as additional evidence for the role of oxygen radicals in postischemic brain damage.
开发了一系列2-(氨甲基)苯并二氢吡喃作为铁依赖性脂质过氧化的有效抑制剂。该类化合物在抑制脂质过氧化方面极其有效，IC50低至0.2微摩尔。在小鼠头部损伤模型中，发现选定的成员可促进早期神经功能恢复和提高存活率。在该试验中，观察到伤后1小时神经状态（握力测试评分）改善高达对照组的230%。其中一种最有效的化合物（35）在两种脑缺血模型中进行了评估，观察到显著的神经保护作用。这些结果进一步支持了脑保护抗氧化剂在治疗创伤性和缺血性损伤中的重要性，以及氧自由基在缺血后脑损伤中作用的更多证据。
