methyl 3-(3,4,5-trimethoxybenzoyl)-1H-indole-2-carboxylate | 1179587-83-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 3-(3,4,5-trimethoxybenzoyl)-1H-indole-2-carboxylate
• CAS: 1179587-83-7
• 化学式: C₂₀H₁₉NO₆
• 分子量: 369.374
• InChiKey: HXVMVAUGMOCEED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  86.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-(3,4,5-trimethoxybenzoyl)-1H-indole-2-carboxylate 在 硼烷四氢呋喃络合物 、 (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 [2-(4,5-dihydro-1,3-oxazol-2-yl)-1H-indol-3-yl]-(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Toward Highly Potent Cancer Agents by Modulating the C-2 Group of the Arylthioindole Class of Tubulin Polymerization Inhibitors

  摘要：

  New arylthioindole derivatives having different cyclic substituents at position 2 of the indole were synthesized as anticancer agents. Several compounds inhibited tubulin polymerization at submicromolar concentration and inhibited cell growth at low nanomolar concentrations. Compounds 18 and 57 were superior to the previously synthesized S. Compound 18 was exceptionally potent as an inhibitor of cell growth: it showed IC50 = 1.0 nM in MCF-7 cells, and it was uniformly active in the whole panel of cancer cells and superior to colchicine and combretastatin A-4. Compounds 18, 20, 55, and 57 were notably more potent than vinorelbine, vinblastine, and paclitaxel in the NCl/ADR-RES and Messa/Dx5 cell lines, which overexpress P-glycoprotein. Compounds 18 and 57 showed initial vascular disrupting effects in a tumor model of liver rhabdomyosarcomas at 15 mg/kg intravenous dosage. Derivative 18 showed water solubility and higher metabolic stability than 5 in human liver microsomes.

  DOI：

  10.1021/jm3013097
• 作为产物：
  描述：

  吲哚-2-羧酸甲酯 、 3,4,5-三甲氧基苯甲酰氯 在 aluminum (III) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 以55%的产率得到methyl 3-(3,4,5-trimethoxybenzoyl)-1H-indole-2-carboxylate
  参考文献：
  名称：

  New Arylthioindoles and Related Bioisosteres at the Sulfur Bridging Group. 4. Synthesis, Tubulin Polymerization, Cell Growth Inhibition, and Molecular Modeling Studies

  摘要：

  New arylthioindoles along with the corresponding ketone and methylene compounds were potent tubulin assembly inhibitors. As growth inhibitors of MCF-7 cells, sulfur derivatives were superior or sometimes equivalent to the ketones, while methylene derivatives were substantially less effective. Esters 24, 27-29, 36, 39, and 41 showed similar to 50% of inhibition oil human HeLa and HCT116/chr3 cells at 0.5 mu M, and these compounds inhibited the growth of HEK, M 14, and U937 cells with IC50'S ill the 78220 nM range. While murine macrophage J744.1 cell growth was significantly less affected (20% at higher concentrations), four other nontransformed cell lines remained sensitive to these esters. The effect of drug treatment oil cell morphology was examined by time-lapse microscopy. In a protocol set up to evaluate toxicity on the Saccharomyces cerevisiae BY4741 wild type strain, compounds 24 and 54 strongly reduced cell growth, and 29, 36, and 39 also showed significant inhibition.

  DOI：

  10.1021/jm900016t