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富马酸阿米福韦酯的合成改进
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作者 艾海马 徐明波 +4 位作者 张晓峰 李亚军 白福英 范新风 李振雷 《中国新药杂志》 CAS CSCD 北大核心 2014年第21期2495-2497,2520,共4页
目的:改进富马酸阿米福韦酯的合成工艺,提高合成收率。方法:以2-氨基-6-氯嘌呤与对甲氧基苯硫酚缩合、与2-氯乙氧基甲基膦酸二乙酯(II)缩合、水解、与氯甲基异丙基碳酸酯缩合得阿米福韦酯,再和富马酸成盐制得新型抗乙肝药物富马酸阿米... 目的:改进富马酸阿米福韦酯的合成工艺,提高合成收率。方法:以2-氨基-6-氯嘌呤与对甲氧基苯硫酚缩合、与2-氯乙氧基甲基膦酸二乙酯(II)缩合、水解、与氯甲基异丙基碳酸酯缩合得阿米福韦酯,再和富马酸成盐制得新型抗乙肝药物富马酸阿米福韦酯。结果:总收率从8.9%提高到15.6%(以2-氨基-6-氯嘌呤计)。结论:通过对富马酸阿米福韦酯的合成的改进,减少了反应步骤,提高了收率,降低了成本。产物经元素分析、1H-NMR、13C-NMR、MS结构确证。 展开更多
关键词 富马酸阿米福韦 阿米福韦 抗乙肝 碳酸酯前药 合成
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阿米福韦类似物及其前药的设计、合成与生物活性 被引量:2
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作者 王永广 何新华 仲伯华 《中国药物化学杂志》 CAS CSCD 2010年第6期484-489,共6页
目的对新型抗乙肝药物阿米福韦进行结构改造,设计合成新的前药。方法以2-氯乙醇为原料,经氯甲基化、取代、缩合、烃化、水解、缩合得到目标产物。结果合成了11个新结构化合物,并经1H-NMR、13C-NMR、MS确证结构。体外抗乙肝病毒活性测试... 目的对新型抗乙肝药物阿米福韦进行结构改造,设计合成新的前药。方法以2-氯乙醇为原料,经氯甲基化、取代、缩合、烃化、水解、缩合得到目标产物。结果合成了11个新结构化合物,并经1H-NMR、13C-NMR、MS确证结构。体外抗乙肝病毒活性测试结果显示,阿米福韦异丙基碳酸酯的抗病毒活性显著提高,为阿米福韦的100倍。结论阿米福韦碳酸酯能够更好的释放活性药物,提高抗病毒活性。 展开更多
关键词 阿米福韦 抗乙肝 碳酸酯前药 合成
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De novo combination therapy with lamivudine and adefovir dipivoxil in chronic hepatitis B patients 被引量:12
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作者 Xiao-Hong Fan Jian-Zhang Geng Li-Fen Wang Ying-Ying Zheng Hai-Ying Lu Jing Li Xiao-Yuan Xu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第43期4804-4809,共6页
AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis ... AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study.All of the patients were given 48 wk combination therapy with lamivudine(LAM) and adefovir dipivoxil(ADV) .Briefly,10 patients were given the de novo combination therapy with LAM and ADV,whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus(HBV) genetic mutation.RESULTS:Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4,12,24 and 48 wk after treatment.Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups.The serum HBV DNA level wasstill detectable in every patient in the two groups at 4 and 12 wk after combination treatment.However,in the de novo combination group,serum HBV DNA levels in 4(40%) and 9(90%) patients was decreased to below 1×10 3 copies/mL at 24 and 48 wk after the combination treatment,respectively.In parallel,serum HBV DNA levels in 2(20%) and 8(40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment,respectively.Furthermore,6(60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment,whereas only 4(20%) patients in the add-on combination group achieved seroconversion.Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment.Moreover,patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION:De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score,virus inhibition and renal function. 展开更多
关键词 Hepatitis B Chronic Cirrhosis Decompensated De novo combination Lamivudine Adefovir dipivoxil
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