(7-(3-tert-butyldimethylsilanyloxyprop-1-ynyl)-6-methoxy-1H-indazol-3-yl)(3,4,5-trimethoxyphenyl)methanone | 932746-70-8

• 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-(3-tert-butyldimethylsilanyloxyprop-1-ynyl)-6-methoxy-1H-indazol-3-yl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: [7-[3-[tert-butyl(dimethyl)silyl]oxyprop-1-ynyl]-6-methoxy-2H-indazol-3-yl]-(3,4,5-trimethoxyphenyl)methanone
• CAS: 932746-70-8
• 化学式: C₂₇H₃₄N₂O₆Si
• 分子量: 510.662
• InChiKey: RQTTYHQBNNZZOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  91.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (7-(3-tert-butyldimethylsilanyloxyprop-1-ynyl)-6-methoxy-1H-indazol-3-yl)(3,4,5-trimethoxyphenyl)methanone 在 platinum(IV) oxide 、 palladium on activated charcoal 四丁基氟化铵 、 氢气 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 [7-(3-hydroxypropyl)-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
• 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-(3-tert-butyldimethylsilanyloxyprop-1-ynyl)-6-methoxy-1H-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

• 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.