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瑞戈非尼的合成 被引量:7

Synthesis of Regorafenib
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摘要 3-氟-4-硝基苯酚(2)经硝基还原,与N-甲基-4-氯-2-吡啶甲酰胺(5)进行亲核取代,再与4-氯-3-三氟甲基苯异氰酸酯(8)缩合,经成盐酸盐、中和重结晶的方法得到瑞戈非尼,总收率63.8%(以2计)。 Regorafenib was synthesized from 3-fluoro-4-nitrophenol (2) via reduction nitro group, nucleophilic substitution with N-methyl-4-chloropyridine-2-carboxamide (5), condensation with 4-chloro-3-(trifluoromethyl)phenyl isocyanate (8), and then recrystallization by salt formation and neutralization with an overall yield of 63.8 % (based on 2).
出处 《中国医药工业杂志》 CAS CSCD 北大核心 2016年第5期528-530,共3页 Chinese Journal of Pharmaceuticals
关键词 瑞戈非尼 多激酶抑制剂 合成 regorafenib multikinase inhibitor synthesis
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参考文献9

  • 1US FDA. Stivarga(regorafenib) tablet label EEB/OL] [2012-09-27]. http://www.accessdata.fda.gov/drugsatfda docs/label/2012/2030851bl.pdf.
  • 2Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506) : a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potentpreclinical antitumor activity [J]. Int J Cancer, 2011, 129(1): 245-255.
  • 3Klaus M, Annette F, Simone S, et al. A phase I dose- escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors [J]. Clin Cancer Res, 2012, 18 (9) : 2658-2667.
  • 4Dirk S, Beate S. Regorafenib for cancer [J]. Expert Opin InvestigDrugs, 2012, 21 (6) : 879-889.
  • 5拜耳医药保健公司.用于治疗和预防疾病和疾病症状的氟代ω-羧芳基二苯基脲:中国,200480021091,1.[P],2013-03-06.
  • 6刘亚方,李洪玉,李金岭,姜申德.瑞格拉非尼(Regorafenib)的合成[J].精细化工中间体,2012,42(6):31-34. 被引量:7
  • 7苏鹏,袁晨欢,王德才,高瑞,赵伟.瑞戈非尼的合成工艺改进的研究[J].药学与临床研究,2015,23(4):368-369. 被引量:9
  • 8拜耳制药股份有限公司.制备4-{4_[({[4-氯-3-(三氟甲基)苯基]氨基}羰基)氨基]-3-氟苯氧基)-N-甲基吡啶-2-羧酰胺、其盐和-水合物的方法:中国,102947271A[P],2013-02-27.
  • 9/ Hammond PR. Substituent effects on the acceptor properties of 1,4-benzoquinone [J]. J Chem Soc, 1964, 471479.

二级参考文献13

  • 1刘亚方,李洪玉,李金岭,姜申德.瑞格拉非尼(Regorafenib)的合成[J].精细化工中间体,2012,42(6):31-34. 被引量:7
  • 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
  • 3Dirk S,Beate S. Regorafenib for cancer[J].Expert Opinion on Investigational Drugs,2012,(06):879-889.
  • 4Wilhelm S M,Dumas J,Adnane L. Regorafenib (BAY 73-4506):a new oral multikinase inhibitor of angiogenic,stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity[J].International Journal of Cancer,2011,(01):245-255.
  • 5Klaus M,Annette F,Simone S. A PhaseⅠ dose-escalation study of regorafenib (BAY 73-4506),an inhibitor of oncogenic,angiogenic,and stromal kinases,in patients with advanced solid tumors[J].Clinical Cancer Research,2012,(09):2658-2667.
  • 6Dumas J. Fluoro substituted omega-carboxyaryl diphenyl urea for treatment of raf,VEGFR,PDGFR,p38 and fit-3 kinasemediated diseases[P].US,2005038080 A1,2005.
  • 7Stiehl J. Process for preparation of Regorafenib[P].WO,2011128261 A1,2011.
  • 8Bankston D,Dumas J,Natero R. A scalable synthesis of BAY 43-9006:A potent Rafkinase inhibitor for the treatment of cancer[J].Organic Process Research & Development,2002,(06):777-781.
  • 9Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib(BAY 73 -4506): a new oral multikinase inhibitor ofangiogenic, stromal and oncogenic receptor tyrosine kinaseswith potent preclinical antitumor activity[J]. Int JCancer, 2011, 129(1): 245-55.
  • 10Dumas J. Bluoro substituted omegacarboxyaryldiphenylurea for treatment of raf, VEGR, PDGFR, p38 and flt-3 kinase -mediated diseases; US, 2005038080 Al [P].2005-02-17.

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