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抗肿瘤药ponatinib的合成 被引量：5

Synthesis of the antineoplastic agent ponatinib
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摘要 目的:合成Bcr-Abl激酶抑制剂ponatinib,并对工艺进行改进。方法:以6-氯-3-氨基哒嗪为起始原料通过9步反应合成Bcr-Abl激酶抑制剂ponatinib。结果与结论:目标产物结构经1H-NMR和ESI-MS确证,总收率为5.36%。此路线制备工艺反应条件温和且原料易得,适合于小规模制备的实验室研究。 Objective： To synthesize ponatinib, a small molecule Bcr-Abl kinase inhibitor, and optimize the preparing process. Methods： Using 6-chloropyridazin-3-amine as starting material, ponatinib was synthesized through 9 steps in this study. Results and Conclusion： The structure of target compound was confirmed by IH_NMR and MS, and the overall yield was 5.36%. The improved process needs mild reaction conditions, which is very suitable for lab-scale production.
作者 谢宁 李艳阳 赵砚瑾 李庶心
机构地区 军事医学科学院放射与辐射医学研究所 江西中医学院研究生部
出处 《中国新药杂志》 CAS CSCD 北大核心 2013年第22期2688-2691,共4页 Chinese Journal of New Drugs
基金 国家自然科学基金(30973016)
关键词 Bcr—Abl激酶抑制剂 PONATINIB 合成 Bcr-Abl kinase inhibitor ponatinib synthesis
分类号 R914.5 [医药卫生—药物化学]
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  • 1Stanovnik B, Tisler M. Synthesis of pyridazine derivatives -Ⅷ, imidazo [ 1,2 - b ] pyridazines and some tricyclic aza analogs [ J ]. Tetrahedron, 1967, 23: 387～395.
  • 2Kobe J, Stanovnik B, Tisler M. Synthesis of pyridazine derivatives - XV. Some electrophilic substitutions of imidazo[ 1,2 - b ] pyridazines [ J ]. Tetrahedron, 1968, 24:239 ～ 345.
  • 3Fujiwara Yoshitaka, Preparation of 6 - amino - 3 - chloropyridazine [ P]. JP :4 077 474,1992 - 03 - 11.
  • 4Soverini S, Iacobucci I, Baccarani M, et al. Targeted therapy and the T315I mutation in Philadelphia-positive leukemias[J]. Haematologic, 2007, 92(4): 437-9.
  • 5Francis JG, Jorge C, Dan J, et al. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytie leukemia with the T315I BCR-ABL mutation[J]. Blood, 2007, 109(2): 500-2.
  • 6Giovanni M, Ilaria I, Cristina P, et al. New targets for Ph+ leukaemia therapy[J]. Best Pract Res Clin Haematol, 2009,22(3): 445-54.
  • 7Sameek R, Moshe T. Managing resistance in chronic myeloid leukemia[J]. Blood Rev, 2011, 25(6): 279-90.
  • 8Van Etten RA, Chan WW, Zaleskas VM, et al. Switch pocket inhibitors of the ABL tyrosine kinase: distinct kinome inhibition profiles and in vivo ef ficacy in mouse models of CML and Blymphoblastic leukemia induced by BCR-ABL T315I [C]. ASH Annual Meeting Abstracts, 2008, 112: 576.
  • 9Artur G, Stefan B, Gunhild K, et al. Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I[J]. Blood, 2008, 111(8): 4355-64.
  • 10Emmanuele C, Marco R, Samantha Z, et al. Dual Src and Abl inhibitors target wild type Abl and the AblT315I Imatinib-resistant mutant with different mechanisms[J]. Bioorg Med Chem, 2010, 18(11): 3999-4008.

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同被引文献36

  • 1谭玉柱,黄君梅,杨国政,王道清,罗碧强,董小萍.血清药物化学应用于中药复方的研究现状[J].中药与临床,2011,2(2):53-55. 被引量：7
  • 2罗国安,梁琼麟,刘清飞,张荣利,杨辉华,李雪,王义明,贾伟,张卫东,张川,李贻奎.整合化学物质组学的整体系统生物学——中药复方配伍和作用机理研究的整体方法论[J].世界科学技术-中医药现代化,2007,9(1):10-15. 被引量：78
  • 3徐仿周,张勇慧,阮汉利,皮慧芳,陈昶,吴继洲.浙贝乙素胆汁酸盐的制备及其镇咳、祛痰和平喘活性的筛选[J].药学学报,2007,42(3):274-278. 被引量：8
  • 4Full prescribing information for Iclusig[EB/OL].[2013-12-23].http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203469s007s0081bl.pdf.
  • 5O'Hare T,Shakespeare WC,Zhu X,et al.AP24534,a panBCR-ABL inhibitor for chronic myeloid leukemia,potently inhibits the T315I mutant and overcomes mutation-based resistance[J].Cancer Cell,2009,16:401-412.
  • 6Huang W,River V,Clackson T,et al.Methods and compositions for treating cancer:WO,2011053938[P].2011-05-05.
  • 7Chinchilla R,Nájera C.The Sonogashira reaction:a booming methodology in synthetic organic chemistry[J].Chem Rev,2007,107 (3):874-922.
  • 8Huang WS,Metcalf CA,Sundaramoorthi R,et al.Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl) ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)-phenyl}benzamide (AP24534),a potent,orally active paninhibitor of breakpoint cluster region-abelson (BCR-ABL)kinase including the T315I gatekeeper mutant[J].J Med Chem,2010,53 (12):4701-4719.
  • 9O'HARE T, SHAKESPEARE W C, ZHU X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic mye- loid leukemia,potently inhibits the T315I mutant and overcomes mutation-based resistance [J]. Cancer Cell ,2009,16(5 ) :401 - 412.
  • 10HUANG W S, METCALF C A, SUNDARAMOOR- THI R,et al. Discovery of 3-[2-( imidazo[ 1,2-b] py- ridazin-3-yl ) ethynyl ] -4-methyl-N- { 4-[ ( 4-methyl- piperazin-1-y1) methyl ] -3-( trifluoromethyl ) phenyl } benzamide( AP24534 ), a potent, orally active pan-in- hibitor of breakpoint cluster region-abelson (BCR- ABL) kinase including the T315I gatekeeper mutant [J]. J Med Chem,2010,53(12) :4701 -4719.

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中国新药杂志
2013年 第22期

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