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盐酸替沃扎尼一水合物的合成 被引量：4

Synthesis of tivozanib hydrochloride monohydrate
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摘要 目的:考察盐酸替沃扎尼一水合物(1)的合成工艺。方法:以3,4-二甲氧基苯乙酮(2)为起始原料,经过硝化、还原、环合、氯化、缩合、成脲及成盐等7步反应,制得盐酸替沃扎尼一水合物(1)。结果:中间体及目标产物1经核磁共振氢谱、电喷雾离子化质谱和(或)元素分析确证结构,总收率35%。结论:本合成工艺原料易得,反应条件温和,操作简便,收率稳定。 Objective： To investigate the synthetic process of tivozanib hydrochloride monohydrate（1）.Methods： Tivozanib hydrochloride monohydrate（1） was prepared from 3,4-dimethoxyacetophenone（2）,via nitrification,reduction,cyclization,chlorination,condensation,urea formation,and salification.Results： The structures of intermediates and target compound 1 were confirmed by 1H-NMR,ESI-MS and/or element analysis.The overall yield was 35%.Conclusion： This process boasts readily available raw materials,mild condition,simple operation and stable yield.
作者 府莹 张庆文
机构地区 中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室
出处 《中国新药杂志》 CAS CSCD 北大核心 2013年第1期26-29,共4页 Chinese Journal of New Drugs
基金 国家"重大新药创制"科技重大专项(2009ZX09301-007) 上海市基础研究重点项目(09JC1413200)
关键词 抗肿瘤药物 盐酸替沃扎尼 合成 anticancer agent tivozanib hydrochloride synthesis
分类号 R914.5 [医药卫生—药物化学]
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参考文献10

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同被引文献24

  • 1陈军,盛春泉,郑灿辉,李耀武,吕加国,张万年,周有骏,朱驹.VEGFR2活性腔性质以及与抑制剂的结合模式研究[J].化学学报,2007,65(6):547-552. 被引量：8
  • 2Yakes FM,Chen J,Tan J,et al.Cabozantinib(XL184),a novel MET and VEGFR2 inhibitor,simultaneously suppresses metastasis,angiogenesis,and tumor growth[J].Mol Cancer Ther,2011,10(12):2298-2308.
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  • 4Pinto A.Cabozantinib:a novel agent with a dual mechanism of action for castration-resistant prostate carcinoma[J].Cancer Chemoth Pharm,2014,73(2):219-222.
  • 5Brown SC,Lamb P,Gallagher WP,et al.Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl-N′-(4-fluorophenyl) cyclopropane-1-dicarboxamide,and crystalline forms therof for the treatment:WO,2010/083414[P].2010-07-22.
  • 6Wilson JA.Processes for preparing quinoline compounds and pharmaceutical compositions containing such compounds:WO,2012/109510[P].2012-08-16.
  • 7Kubo K,Shimizu T,Ohyama S,et al.A novel series of 4-phenoxyquinolines:potent and highly selective inhibitors of PDGF receptor autophosphorylation[J].Bioorg Med Chem Lett,1997,7(23):2935-2940.
  • 8Kubo K,Shimizu T,Ohyama S,et al.Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors:synthesis,structure-activity relationships,and antitumor activities of N-phenyl-N′-{4-(4-quinolyloxy) phenyl} ureas[J].JMedChem,2005,48(5):1359-1366.
  • 9Rebecca Siegel,Carol DeSantis,Katherine Virgo,Kevin Stein,Angela Mariotto,Tenbroeck Smith,Dexter Cooper,Ted Gansler,Catherine Lerro,Stacey Fedewa,Chunchieh Lin,Corinne Leach,Rachel Spillers Cannady,Hyunsoon Cho,Steve Scoppa,Mark Hachey,Rebecca Kirch,Ahmedin Jemal,Elizabeth Ward.Cancer treatment and survivorship statistics, 2012[J]. CA: A Cancer Journal for Clinicians . 2012 (4)
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中国新药杂志
2013年 第1期

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