取代腺嘌呤类化合物的合成及其抗病毒活性研究
摘要: 目的:修饰阿德福韦(ADV)结构,设计合成新化合物,研究其对乙肝病毒HBsAg、HBeAg的抑制活性。方法:以(ADV)为原料,经磷酰氯化、三氟乙醇酯化和氯甲酸酯缩合等反应,设计合成了未见文献报道的8个嘌呤类目标化合物1a-1h,所有化合物经1HNMR谱等确证;体外药理实验采用酶联免疫法(ELISA),阳性药物采用临床常用同类药物ADV。结果:设计合成的8个化合物,对HBsAg和HBeAg都有一定的抑制作用,其中化合物1d,1e,1g,1h对HBsAg抑制活性与ADV相当,化合物1g对HBeAg抑制活性与ADV相当。所有目标化合物对HBsAg抑制活性好于对HBeAg抑制活性。结论:在嘌呤环N6位引入较长碳链的1g活性最佳。
Synthesis and antiviral activities of substituted adenine analogues on HBV
- Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
- Received Date:
2009-03-17
Abstract: Objective :To study of design and synthesis of the new(ADV) derivatives and study their activities of inhibiting hepatitis B virus HBsAg and HBeAg. Methods :Starting with ADV,we synthesized 8 firstly reported purine compounds 1a-1h,which have been verified by NMR and MS.Enzyme-linked immunosorbent assay(ELISA) was used to assess HBsAg and HBeAg.The positive control is ADV. Results :The test results show the inhibitory rate of targeted purine compounds on HBsAg nad HBeAg is correspond with ADV. Conclusion :1g introduced long carbon chain at N6 substituted of purine shows the best activity.
吴广, 刘嘉, 牛春娟, 李科. 取代腺嘌呤类化合物的合成及其抗病毒活性研究[J]. 药学实践与服务, 2009, 27(6): 426-429.
| 引用本文: |
吴广, 刘嘉, 牛春娟, 李科. 取代腺嘌呤类化合物的合成及其抗病毒活性研究[J]. 药学实践与服务, 2009, 27(6): 426-429.
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WU Guang, LIU Jia, NIU Chun-Juan, LI Ke. Synthesis and antiviral activities of substituted adenine analogues on HBV[J]. Journal of Pharmaceutical Practice and Service, 2009, 27(6): 426-429.
| Citation: |
WU Guang, LIU Jia, NIU Chun-Juan, LI Ke. Synthesis and antiviral activities of substituted adenine analogues on HBV[J]. Journal of Pharmaceutical Practice and Service, 2009, 27(6): 426-429.
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