新型氮氧自由基HPN衍生物的设计合成与抗缺氧活性研究  

Synthesis and Anti-hypoxia Activity of New Nitronyl Nitroxide Radical HPN Derivatives

作　　者：杨颖[1,2] 邵瑾[1,2] 景临林 马慧萍 贾正平[1,2] YANG Ying;SHAO Jin;JING Lin-lin;MA Hui-Ping;JIA Zheng-ping(School of Pharmacy, Lanzhou University, Lanzhou 730000, China;Department of Pharmacy, 940 Hospital of PLA Joint Logistics Support Forces, Lanzhou 730050, China)

机构地区：[1]兰州大学药学院,兰州730000 [2]中国人民解放军联勤保障部队第九四О医院药剂科,兰州730050

出　　处：《解放军医药杂志》2019年第5期1-4,共4页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金项目(81872796;81202458);甘肃省自然科学基金(18JR3RA408;1308RJYA06);中国博士后科学基金(2012M521926)

摘　　要：目的设计合成出一种可以提高氮氧自由基HPN抗缺氧活性及对脑组织具有靶向性的化合物。方法以氮氧自由基HPN和四种二溴取代烷烃为原料,通过取代反应得到四个烷基链偶联的双氮氧自由基衍生物,并通过小鼠常压密闭实验确定其抗缺氧活性。结果产物结构经电子顺磁共振、红外光谱、质谱和元素分析确认,与目标化合物一致,进一步通过常压密闭实验进行抗缺氧活性筛选,结果表明:四个衍生物均能延长缺氧小鼠的存活时间,且活性优于HPN(P<0.01)。结论采用的合成方法操作简单,条件温和、产率较高,并且这些衍生物均表现出了较好的抗缺氧活性。Objective To design and manufacture a derivative of nitronyl nitroxide radical HPN for improving anti-hypoxia activity and having targeting to brain tissues. Methods Nitronyl nitroxide radical HPN and four types of dibromo-substituted alkanes were use as starting materials, and four alkyl chain-coupled bis-nitroxyl nitroxide derivatives were obtained by substitution reaction, and then their anti-hypoxia activity were determined by normobaric hypoxia closed experiments in mice. Results Derivative structure was confirmed by electron paramagnetic resonance (EPR), infrared spectroscopy, mass spectrum and element analysis, which was consistent with target compound. Furthermore, anti-hypoxia activity screening was carried out by normobaric hypoxia closed experiments, and the results showed that all the four derivatives could prolong survival time of hypoxic mice and exhibited better activity than that of HPN ( P <0.01). Conclusion Synthetic method is easy operation, mild condition and high yield, and these derivatives showed good anti-hypoxia activities.

关 键 词：氮氧自由基 取代反应 合成 抗缺氧活性 缺氧 

分 类 号：R594.3[医药卫生—内科学] O629.9[医药卫生—临床医学]