期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

索拉非尼的合成 被引量：8

Synthesis of Sorafenib
原文传递
导出
摘要 目的合成抗肿瘤新药索拉非尼。方法以2-吡啶甲酸(2)为原料,经卤化,酰胺化,成醚制得中间体(6),再和4-氯-3-(三氟甲基)苯胺(7)成脲制得索拉非尼(1)。结果以总收率56%合成了索拉非尼,结构经核磁氢谱(1H-NMR)、质谱(MS)确证。结论本方法原料易得,操作简单,总收率较高,而且整个过程不需柱色谱纯化,适合工业化生产。 OBJECTIVE To synthesize sorafenib a new anti-tumor drug .METHODS The intermediate was obtained by halogenation, amidation and etherification with picolinic acid （2） as the starting compound. Sorafenib was obtained by ureas formation. RESULTS The total yield was 56%. The structure was verified by 1H-NMR and MS. CONCLUSION The route is effective, simple and highly productive, and there was no need to use column chromatography in all preparation steps. The process may be suitable for industrial applications.
作者 孙敏 魏红涛 蔡进 吉民
机构地区 东南大学化学化工学院制药工程系 东南大学制药工程研究所
出处 《中国药学杂志》 CAS CSCD 北大核心 2009年第5期394-396,共3页 Chinese Pharmaceutical Journal
关键词 索拉非尼 多激酶抑制剂 合成 sorafenib muti-kinase inhibitor synthesis
分类号 R914.5 [医药卫生—药物化学]
  • 相关文献

参考文献6

  • 1WILHELM S M, CARTER C, TANG L Y, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis [J]. Cancer Res, 2004, 64(19): 7099-7109.
  • 2SCOTT W, CHRISTOPHER C, MARK L, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer[J]. Nat Rev Drug Discov, 2006, 5(10): 835-844.
  • 3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
  • 4RIEDL B, DUMAS J, KHIRE U, et al. Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors: USA, 2001011135[P]. 2001-08-2.
  • 5DUMAS J, SCOTT W J, ELTING J, et al. Aryl ureas with angiogenesis inhibiting activity: USA, 2003207870[P].2003-11-6.
  • 6BANKSTON D, DUMAS J, NATERO R, et al. A scaleable synthesis of BAY 43-9006: A potent raf kinase inhibitor for the treatment of cancer[J]. Org Proc Res Dev, 2002, 6(6): 777-781.

二级参考文献13

  • 1[1]Wilhelm SM,Carter C,Tang L,et al.BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis.Cancer Res.2004 Oct 1; 64 (19):7099-109.
  • 2[2]Strumberg D,Richly H,Hilger RA,et al.Phase Ⅰ clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43 -9006in patients with advanced refractory solid tumors.J Clin Oncol,2005,23 (5):965
  • 3[3]Ratain MJ,Eisen T,Stadler WM,et al.Final findings from a phase Ⅱ,placebo-controlled,randomized discontinuatoin trial (RDT) of Sorafenib (Bay 43-9006) in patients with advanced renal cell carcinoma (RCC).J Clin Oncol,2005,23 (16S):Abstract 4544
  • 4[4]Flaherty KT,Brose M,Schuchter L,et.Phase Ⅰ/Ⅱ trial of BAY 43-9006,carboplatin (C) and paclitaxel (P)demonstrates preliminary antitumor activity in the expansion chort of patients with metastatic melanoma.Proc Am Society Clin Oncol,2004,23:Abstract 7507
  • 5[5]Richly H,Henning BF,Kupsch P,et al.Results of a Phase Ⅰ trial of sorafenib (BAY 43 -9006) in combination with doxorubicin in patients with refractory solid tumors.Ann Oncol,2006,17 (5):866
  • 6[6]Siu LL,Awada A,Takimoto CH,et al.Phase Ⅰ trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer.Clin Cancer Res,2006,12 (1):144
  • 7[7]Kupsch P,Henning BF,Passarge K,et al.Results of a phaseⅠ trial of sorafenib (BAY 43 -9006) in combination with oxaliplatin in patients with refractory solid tumors,including colorectal cancer.Clin Colorectal Cancer,2005,5 (3):188
  • 8[8]Clark JW,Eder JP,Ryan D,et al.Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor,BAY 43 -9006,in patients with advanced,refractory solid tumors.Clin Cancer Res,2005,1; 11 (15):5472
  • 9[9]Strumberg D,Awada A,Hirte H,et al.Pooled safety analysis of BAY 43 -9006 (sorafenib) monotherapy in patients with advanced solid tumors:Is rash associated with treatment outcome? Eur J Cancer,2006,42 (4):548
  • 10[10]Eisen T,Bukowski RM,Staehler M,et al.Randomized phase Ⅲ trial of Sorafenib in advanced renal cell carcinoma(RCC):Impact of crossover on survival.Proc ASCO,2006,43:Abstr 4524

共引文献56

同被引文献64

  • 1刘亚方,李小刚,李洪玉,李金岭,姜申德.索拉非尼的合成研究[J].精细化工中间体,2012,42(5):36-39. 被引量：6
  • 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
  • 3Scott W, Christopher C, Mark L, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer [J]. Nat Rev Drug Discov, 2006, 5 (10) : 835-844.
  • 4Donald B, Jacques D, Reina N, et al. A scaleable synthesis of BAY 43-9006: A potent Raf kinase inhibitor for the treatment of cancer J]. Org Process Res Dev, 2002, 6: 777-781.
  • 5Riedl B, Dumas J, Khire U, et al. Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors: US, 7235576 [P]. 2007-06-26.
  • 6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.
  • 7Buchstaller HP, Finsinger D, Stieber F, et al. Preparation of aryl semicarbazide derivatives as kinase inhibitors: WO, 2005082853 EP]. 2005-09-09.
  • 8Rossetto P, Macdonald PL, Canavesi A. Process for preparation of sorafenib and intermediates thereof: WO, 2009111061 EP]. 2009-09-11.
  • 9Muddasani PR, Nannapaneni VV. Economically and commercially viable process for the preparation of sorafenib: WO, 2009054004 [P]. 2009-04-30.
  • 10王博,罗宇.索拉非尼的合成方法:中国,101671299[P].2010.03-17.

引证文献8

二级引证文献22

中国药学杂志
2009年 第5期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部