Chin. J. Org. Chem. ›› 2008, Vol. 28 ›› Issue (05): 841-850. Previous Articles     Next Articles

Original Articles

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

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