3-((3,4,5-trimethoxyphenyl)thio)-1H-indole-2-carboxylic acid | 883980-08-3

• 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: 3-((3,4,5-trimethoxyphenyl)thio)-1H-indole-2-carboxylic acid
• 英文别名: 3-[(3,4,5-trimethoxyphenyl)thio]-1H-indole-2-carboxylic acid；3-(3,4,5-trimethoxyphenyl)sulfanyl-1H-indole-2-carboxylic acid
• CAS: 883980-08-3
• 化学式: C₁₈H₁₇NO₅S
• 分子量: 359.403
• InChiKey: KYXOYMUFTGDNTK-UHFFFAOYSA-N

物化性质

• 沸点：
  592.0±50.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-((3,4,5-trimethoxyphenyl)thio)-1H-indole-2-carboxylic acid 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-[3-[(3,4,5-trimethoxyphenyl)methyl]-1H-indol-2-yl]-4,5-dihydro-1,3-oxazole
  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 在 sodium hydride 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 0.25h， 生成 3-((3,4,5-trimethoxyphenyl)thio)-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  [EN] ARYLTHIOINDOLE TUBULIN POLYMERIZATION INHIBITORS AND METHODS OF TREATING OR PREVENTING CANCER USING SAME
  [FR] INHIBITEURS DE LA POLYMERISATION DE LA TUBULINE DE TYPE ARYLTHIOINDOLE, ET PROCEDES POUR TRAITER OU PREVENIR UN CANCER AU MOYEN DE CES INHIBITEURS

  摘要：

  本发明涉及芳基硫代吲哚化合物，芳基硫代吲哚化合物的药物组合物以及治疗患有癌症或炎症、心脏病或寄生虫病的患者的方法，该方法包括向患者施用本发明的一种或多种芳基硫代吲哚化合物。

  公开号：

  WO2006041961A1

文献信息

• Arylthioindoles, Potent Inhibitors of Tubulin Polymerization
  作者：Gabriella De Martino、Giuseppe La Regina、Antonio Coluccia、Michael C. Edler、Maria Chiara Barbera、Andrea Brancale、Elizabeth Wilcox、Ernest Hamel、Marino Artico、Romano Silvestri

  DOI：10.1021/jm049360d

  日期：2004.12.1

  Several arylthioindoles had excellent activity as inhibitors both of tubulin polymerization and of the growth of MCF-7 human breast carcinoma cells. Methyl 3-[(3,4,5-trimethoxyphenyl)thio]-5-methoxy-1H-indole-2-carboxylate (21), the most potent derivative, showed IC(50) = 2.0 microM, 1.6 times more active than colchicine and about as active as combretastatin A-4 (CSA4). Compound 21 inhibited the growth

  几种芳基硫代吲哚作为微管蛋白聚合和MCF-7人乳腺癌细胞生长的抑制剂均具有出色的活性。最有效的衍生物3-[（3,4,5-三甲氧基苯基）硫代] -5-甲氧基-1H-吲哚-2-羧酸甲酯（21）的IC（50）= 2.0 microM，活性是其1.6倍秋水仙碱，其活性与康维他汀A-4（CSA4）差不多。化合物21在IC（50）= 13 nM时抑制了MCF-7细胞的生长。秋水仙碱和CSA4与这些细胞分别具有13 nM和17 nM IC（50）值。
• Toward Highly Potent Cancer Agents by Modulating the C-2 Group of the Arylthioindole Class of Tubulin Polymerization Inhibitors
  作者：Giuseppe La Regina、Ruoli Bai、Whilelmina Maria Rensen、Erica Di Cesare、Antonio Coluccia、Francesco Piscitelli、Valeria Famiglini、Alessia Reggio、Marianna Nalli、Sveva Pelliccia、Eleonora Da Pozzo、Barbara Costa、Ilaria Granata、Amalia Porta、Bruno Maresca、Alessandra Soriani、Maria Luisa Iannitto、Angela Santoni、Junjie Li、Marlein Miranda Cona、Feng Chen、Yicheng Ni、Andrea Brancale、Giulio Dondio、Stefania Vultaggio、Mario Varasi、Ciro Mercurio、Claudia Martini、Ernest Hamel、Patrizia Lavia、Ettore Novellino、Romano Silvestri

  DOI：10.1021/jm3013097

  日期：2013.1.10

  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.
• [EN] ARYLTHIOINDOLE TUBULIN POLYMERIZATION INHIBITORS AND METHODS OF TREATING OR PREVENTING CANCER USING SAME<br/>[FR] INHIBITEURS DE LA POLYMERISATION DE LA TUBULINE DE TYPE ARYLTHIOINDOLE, ET PROCEDES POUR TRAITER OU PREVENIR UN CANCER AU MOYEN DE CES INHIBITEURS
  申请人：HUMAN SERVICES GOVERNMENT OF T

  公开号：WO2006041961A1

  公开（公告）日：2006-04-20

  The present invention features arylthioindole compounds, pharmaceutical compositions of arylthioindole compounds and methods of treating a patient suffering from cancer or inflammatory, cardiac, or helminthic diseases, the method comprising administering to a patient one or more arylthioindole compounds of the invention.

  本发明涉及芳基硫代吲哚化合物，芳基硫代吲哚化合物的药物组合物以及治疗患有癌症或炎症、心脏病或寄生虫病的患者的方法，该方法包括向患者施用本发明的一种或多种芳基硫代吲哚化合物。