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有机化学
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有机化学 ›› 2008, Vol. 28 ›› Issue (05): 841-850. 上一篇    下一篇

研究论文

氢化可的松与有机硝酸酯及呋咱氮氧化合物偶联物的合成、抗炎活性及安全性研究

房雷a，黄张建a，张奕华*,a，季晖b，丁大永b   

  1. (a中国药科大学新药研究中心 南京 210009)
    (b中国药科大学药理学教研室 南京 210009)
  • 收稿日期:2007-04-14 修回日期:2007-11-07 发布日期:2008-05-20
  • 通讯作者: 张奕华

Synthesis, Anti-inflammatory Activity and Safety of Hydrocortisone Derivatives Coupled with Furoxans and Nitrates

FANG Leia,HUANG Zhang-Jiana,ZHANG Yi-Hua*,a,JI Huib,DING Da-Yongb   

  1. (a Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009)
    (b Department of Pharmacology, China Pharmaceutical University, Nanjing 210009)
  • Received:2007-04-14 Revised:2007-11-07 Published:2008-05-20
  • Contact: ZHANG Yi-Hua

PDF

1101

被引次数

3

以氢化可的松为先导物, 通过不同长度及柔度的连接基团, 分别与有机硝酸酯及呋咱氮氧化合物两类NO供体偶联, 合成了两个系列的衍生物I1～I7及II1～II8, 以期寻找到药效更强、安全性更高的新型抗炎药物. 衍生物的化学结构经MS, IR, 1H NMR和元素分析确证. 初步抗炎活性筛选显示, 化合物I3, II3, II5具有良好的抗炎活性; 进一步抗炎活性及安全性试验表明, II5在急性、亚急性及免疫等多种炎症动物模型中活性与阳性对照物氢化可的松相当, 同时, II5能够有效地防止骨丢失, 避免诱发高血压, 因而较之氢化可的松具有更好的安全性.

关键词: 安全性, 氢化可的松, 呋咱氮氧化物, 抗炎活性, 硝酸酯, NO供体

In order to search for novel anti-inflammatory agents with high potency and safety, hydrocortisone was used as a leading compound and coupled with two groups of NO donors furoxans and nitrates through linkers with different length and flexibility. Compounds I1～I7 and II1～II8 were obtained and their structures were confirmed by MS, IR, 1H NMR spectra and elemental analysis. Compounds I3, II3 and II5 showed a good anti-inflammatory activity in the primary pharmacological screening. Furthermore II5 also exhibited a potent anti-inflammatory activity in acute, sub-acute and immune inflammatory models. Compared with hydrocortisone II5 could effectively prevent bone loss and avoid inducing hypertension in the safety screenings, indicating that it should have a better safety.

Key words: furoxan, safety, nitrate, anti-inflammatory activity, NO donor, hydrocortisone