[7-(4-hydroxybut-1-ynyl)-6-methoxy-2H-indazol-3-yl]-(3,4,5-trimethoxyphenyl)methanone | 932746-65-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [7-(4-hydroxybut-1-ynyl)-6-methoxy-2H-indazol-3-yl]-(3,4,5-trimethoxyphenyl)methanone
• CAS: 932746-65-1
• 化学式: C₂₂H₂₂N₂O₆
• 分子量: 410.426
• InChiKey: NHHLTLNXNVGNSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [7-(4-hydroxybut-1-ynyl)-6-methoxy-2H-indazol-3-yl]-(3,4,5-trimethoxyphenyl)methanone 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 为溶剂， 生成 [7-(4-hydroxybutyl)-6-methoxy-2H-indazol-3-yl]-(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  WO2006/57946

  摘要：

  公开号：
• 作为产物：
  描述：

  4-碘基-3-硝基苯甲醚 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 盐酸 、 N-碘代丁二酰亚胺 、 铁粉 、 溶剂黄146 、 三乙胺 、 sodium nitrite 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 7.5h， 生成 [7-(4-hydroxybut-1-ynyl)-6-methoxy-2H-indazol-3-yl]-(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Potent Antitubulin Tumor Cell Cytotoxins Based on 3-Aroyl Indazoles

  摘要：

  A series of 3-aroyl indazoles was synthesized. Modification of the C-7 position resulted in a significant structure-activity relationship (SAR) with acetylene modifications conferring unusual potency in a tumor cell cytotoxicity assay. The most potent compounds exceeded the activity of combretastatin A4 (CA-4), showing single digit nM IC50 values against all cell lines tested including those with known efflux resistance pumps. The inhibition of in vitro tubulin polymerization was comparable to CA-4, consistent with tubulin being the target for these compounds. Competition binding experiments employing [H-3]colchicine and purified tubulins demonstrated that the compound specifically binds to the colchicine site.

  DOI：

  10.1021/jm061348t

文献信息

• Tubulin Binding Anti Cancer Agents And Prodrugs Thereof
  申请人：Matteucci Mark

  公开号：US20090042820A1

  公开（公告）日：2009-02-12

  Novel tubulin binding compounds and hypoxia activated prodrugs of novel and known tubulin binding compounds useful for treating cancer and other hyperproliferative diseases are disclosed.
• [EN] TUBULIN BINDING ANTI CANCER COMPOUNDS AND PRODRUGS THEREOF<br/>[FR] COMPOSÉS ANTI-CANCÉREUX DE LIAISON À LA TUBULINE ET PROMÉDICAMENTS À BASE DE TELS COMPOSÉS
  申请人：THRESHOLD PHARMACEUTICALS INC

  公开号：WO2007137196A2

  公开（公告）日：2007-11-29

  [EN] Novel tublin binding compuunds and hypoxia activated prodrugs of novel and known tubulin binding compounds are useful for treating cancer and other hyperproliferative diseases.
  [FR] La présente invention concerne de nouveaux composés de liaison à la tubuline et de promédicaments activés par l'hypoxie de composés à base de nouveaux et connus de liaison à la tubuline utiles pour traiter le cancer et d'autres maladies hyperproliférantes.
• WO2006/57946
  申请人：——

  公开号：——

  公开（公告）日：——
• Potent Antitubulin Tumor Cell Cytotoxins Based on 3-Aroyl Indazoles
  作者：Jian-Xin Duan、Xiaohong Cai、Fanying Meng、Leslie Lan、Charles Hart、Mark Matteucci

  DOI：10.1021/jm061348t

  日期：2007.3.1

  A series of 3-aroyl indazoles was synthesized. Modification of the C-7 position resulted in a significant structure-activity relationship (SAR) with acetylene modifications conferring unusual potency in a tumor cell cytotoxicity assay. The most potent compounds exceeded the activity of combretastatin A4 (CA-4), showing single digit nM IC50 values against all cell lines tested including those with known efflux resistance pumps. The inhibition of in vitro tubulin polymerization was comparable to CA-4, consistent with tubulin being the target for these compounds. Competition binding experiments employing [H-3]colchicine and purified tubulins demonstrated that the compound specifically binds to the colchicine site.