aroylindazole A | 889134-60-5

• 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: aroylindazole A
• 英文别名: [6-Methoxy-7-(1-propyn-1-yl)-1H-indazol-3-yl](3,4,5-trimethoxyphenyl)methanone；(6-methoxy-7-prop-1-ynyl-2H-indazol-3-yl)-(3,4,5-trimethoxyphenyl)methanone
• CAS: 889134-60-5
• 化学式: C₂₁H₂₀N₂O₅
• 分子量: 380.4
• InChiKey: HSNDSZHCCGPCKL-UHFFFAOYSA-N

物化性质

• 沸点：
  618.8±55.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  82.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  aroylindazole A 在 potassium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 11.0h， 生成 [6-Methoxy-7-prop-1-ynyl-3-(3,4,5-trimethoxybenzoyl)indazol-1-yl]methyl-dimethyl-[(5-nitrofuran-2-yl)methyl]azanium;bromide
  参考文献：
  名称：

  WO2008/151253

  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 aroylindazole A
  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

• WO2006/57946
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.
• WO2008/151253
  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.