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索拉非尼的合成研究 被引量：6

Study on the Synthesis of Sorafenib
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摘要 索拉非尼是新型多激酶抑制剂,主要用于晚期肾细胞癌和不能切除的肝细胞癌的治疗。笔者以2-吡啶甲酸为原料,经氯化、醇解、酰胺化、与对氨基苯酚发生亲核取代反应得到中间体4-(4-氨基苯氧基)-2-(甲基氨甲酰基)吡啶,再与4-氯-3-三氟甲基苯异氰酸酯缩合得到索拉非尼。索拉非尼的总收率为55%(以2-吡啶甲酸计)。 Sorafenib is a new multi-kinase inhibitor approved for the treatment of advanced renal cell carcinoma and unresectable hepatocellular carcinoma.Sorafenib was synthesized from 4-chloro-3-(trifluoromethy1)phenyl isocyanate and 4-(4-aminophenoxy)-2-(methylcarbamoy1)pyridine,the later being obtained from 2-picolinic acid via chlorination,alcoholysis,amidation,nucleophilic substitution with 4-aminophenol.The overall yield of the title compound was 55% from 2-picolinic acid.
作者 刘亚方 李小刚 李洪玉 李金岭 姜申德
机构地区 天津大学药物科学与技术学院 河北康泰药业有限公司
出处 《精细化工中间体》 CAS 2012年第5期36-39,47,共5页 Fine Chemical Intermediates
关键词 抗癌药物 多激酶抑制剂 索拉非尼 合成 anti-cancer drug multikinase inhibitor Sorafenib synthesis
分类号 R979.1 [医药卫生—药品]
  • 相关文献

参考文献10

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  • 3王芳,符立梧.多靶点抗肿瘤新药索拉非尼的研究进展[J].中国药理学通报,2008,24(8):1117-1120. 被引量：24
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  • 7赵乘有,陈林捷,许煦,罗晓燕,冀亚飞.对甲苯磺酸索拉非尼的合成[J].中国医药工业杂志,2007,38(9):614-616. 被引量：15
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二级参考文献41

  • 1王绪根,谭心舜.异氰酸酯的反应动力学研究[J].青岛科技大学学报（自然科学版）,2005,26(5):382-385. 被引量：6
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共引文献38

同被引文献44

  • 1周爱萍,孙燕.多靶点抗肿瘤新药索拉非尼的研究进展[J].癌症进展,2006,4(6):529-533. 被引量：57
  • 2赵乘有,陈林捷,许煦,罗晓燕,冀亚飞.对甲苯磺酸索拉非尼的合成[J].中国医药工业杂志,2007,38(9):614-616. 被引量：15
  • 3刘新科.一种环境友好的索拉非尼中间体制备方法:中国,101302193[P].2008.11-12.
  • 4王博,罗宇.索拉非尼的合成方法:中国,101671299[P].2010.03-17.
  • 5Yao J, Chen J, He Z, et al. Design,synthesis and biological activities of thiourea containing sorafenib analogs as antitumor agents[J]. Bioorg Med Chem Lett, 2012, 20(9): 2 923-2 929.
  • 6Berwe M. Process for the preparation of 4-{4-[({{4 chloro-3- (trifluoromethyl) phenyl] amino] carbonyl) amino] phenoxy}-N- methylpyridine-2-carboxamide: US, 8124782[P]. 2012-02-28.
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  • 10Anchoori R K, Kortenhorst M S Q, Hidalgo M, et al. Novel microtubule-interacting phenoxy pyridine and phenyl sulfanyl pyridine analogues for cancer therapy[J]. J Med Chem, 2008, 51 (19): 5 953-5 957.

引证文献6

二级引证文献12

精细化工中间体
2012年 第5期

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