12'-thiomethylvinblastine

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 长春花生物碱
• 英文名称: 12'-thiomethylvinblastine
• 英文别名: 10'-Thiomethylvinblastine；methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-7-methylsulfanyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5(10),6,8-tetraen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate
• 化学式: C₄₇H₆₀N₄O₉S
• 分子量: 857.081
• InChiKey: JICBRHIOKVTMPJ-NEJRMLFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  61
• 可旋转键数：
  11
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  179
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  12'-thiomethylvinblastine 在 盐酸 作用下， 以 水 、 异丙醇 为溶剂， 反应 3.5h， 以87%的产率得到12'-thiomethylvinblastine dihydrochloride
  参考文献：
  名称：

  Process Development, Impurity Control, and Production of a Novel Tubulin Inhibitor

  摘要：

  Process development and production of a novel tubulin inhibitor are described. The desired API was obtained through selective iodination of the 12' position of vinblastine and subsequent thiomethylation. Most of the impurities were identified, and process parameters were adjusted to control such impurities. The optimized process was scaled up under cGMP conditions to afford 230 g of the desired API.

  DOI：

  10.1021/op3002307
• 作为产物：
  描述：

  vinblastine sulfate 在 1,1'-双(二苯基膦)二茂铁 、 硫酸 、 溶剂黄146 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 乙腈 为溶剂， 反应 10.44h， 生成 12'-thiomethylvinblastine
  参考文献：
  名称：

  Process Development, Impurity Control, and Production of a Novel Tubulin Inhibitor

  摘要：

  Process development and production of a novel tubulin inhibitor are described. The desired API was obtained through selective iodination of the 12' position of vinblastine and subsequent thiomethylation. Most of the impurities were identified, and process parameters were adjusted to control such impurities. The optimized process was scaled up under cGMP conditions to afford 230 g of the desired API.

  DOI：

  10.1021/op3002307

文献信息

• Synthesis and SAR of vinca alkaloid analogues
  作者：Matthew E. Voss、Jeffery M. Ralph、Dejian Xie、David D. Manning、Xinchao Chen、Anthony J. Frank、Andrew J. Leyhane、Lei Liu、Jason M. Stevens、Cheryl Budde、Matthew D. Surman、Thomas Friedrich、Denise Peace、Ian L. Scott、Mark Wolf、Randall Johnson

  DOI：10.1016/j.bmcl.2008.12.077

  日期：2009.2

  Versatile intermediates 12′-iodovinblastine, 12′-iodovincristine and 11′-iodovinorelbine were utilized as substrates for transition metal based chemistry which led to the preparation of novel analogues of the vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products, and the SAR based upon HeLa and MCF-7 cell toxicity assays is presented. Selected analogues

  多功能中间体12'-碘长春碱，12'-碘长春新碱和11'-碘长春碱被用作基于过渡金属的化学的底物，从而导致长春花生物碱的新类似物的制备。介绍了关键的碘代中间体的合成，它们向最终产物的转化以及基于HeLa和MCF-7细胞毒性测定的SAR。选定的类似物27和36在P388鼠白血病模型中显示出有希望的抗癌活性。
• VINCA DERIVATIVES
  申请人：SCOTT L. Ian

  公开号：US20080108644A1

  公开（公告）日：2008-05-08

  The present invention relates to derivatives of vinca alkaloids. Pharmaceutical compositions containing these compounds as well as processes of preparation and treatment of various conditions are also disclosed.

  本发明涉及长春花生物碱的衍生物。同时还揭示了含有这些化合物的药物组合物，以及制备和治疗各种疾病的过程。
• 10'-FLUORINATED VINCA ALKALOIDS PROVIDE ENHANCED BIOLOGICAL ACTIVITY AGAINST MDR CANCER CELLS
  申请人：Boger Dale L.

  公开号：US20120329822A1

  公开（公告）日：2012-12-27

  A 10′-fluoro-vinca alkaloid compound or its pharmaceutically acceptable salt is disclosed, as are methods of its preparation and use. A disclosed 10′-fluoro-vinca alkaloid compound has better cytotoxic potency against leukemia and cancer cell lines, and is about 8-times more cytotoxic to a multiple drug resistant cancer cell line than is a parental 10′-unsubstituted vinca alkaloid.

  本发明揭示了10'-氟-长春碱化合物或其药学上可接受的盐，以及其制备和使用的方法。所揭示的10'-氟-长春碱化合物对白血病和癌细胞系具有更好的细胞毒性，对多药耐药癌细胞系的细胞毒性约为亲代10'-未取代长春碱的8倍。
• 10′-fluorinated Vinca alkaloids provide enhanced biological activity against MDR cancer cells
  申请人：Boger Dale L.

  公开号：US08940754B2

  公开（公告）日：2015-01-27

  A 10′-fluoro-vinca alkaloid compound or its pharmaceutically acceptable salt is disclosed, as are methods of its preparation and use. A disclosed 10′-fluoro-vinca alkaloid compound has better cytotoxic potency against leukemia and cancer cell lines, and is about 8-times more cytotoxic to a multiple drug resistant cancer cell line than is a parental 10′-unsubstituted vinca alkaloid.

  本文披露了一种10'-氟-长春花生物碱化合物或其药学上可接受的盐，以及其制备和使用方法。披露的10'-氟-长春花生物碱化合物对白血病和癌细胞系具有更好的细胞毒性，对多重耐药癌细胞系的细胞毒性约为亲代10'-未取代长春花生物碱的8倍。
• US7238704B2
  申请人：——

  公开号：US7238704B2

  公开（公告）日：2007-07-03