1H-吲哚-2-羧酸,5-甲氧基-3-(苯基硫代)-,甲基酯 | 148900-22-5

• 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
• 中文名称: 1H-吲哚-2-羧酸,5-甲氧基-3-(苯基硫代)-,甲基酯
• 英文名称: methyl 5-methoxy-3-(phenylthio)-1H-indole-2-carboxylate
• 英文别名: methyl 5-methoxy-3-phenylsulfanyl-1H-indole-2-carboxylate
• CAS: 148900-22-5
• 化学式: C₁₇H₁₅NO₃S
• 分子量: 313.377
• InChiKey: QPZZLZUIHWXQRT-UHFFFAOYSA-N

物化性质

• 熔点：
  206-210 °C(Solv: ethanol (64-17-5))
• 沸点：
  491.6±45.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  76.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1H-吲哚-2-羧酸,5-甲氧基-3-(苯基硫代)-,甲基酯 在 MCPMA 作用下， 以 氯仿 为溶剂， 反应 2.0h， 以28%的产率得到3-Benzenesulfonyl-5-methoxy-1H-indole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  New Arylthioindoles:  Potent Inhibitors of Tubulin Polymerization. 2. Structure−Activity Relationships and Molecular Modeling Studies

  摘要：

  Arylthioindoles (ATIs) that possess a 3-methoxyphenylthio or a 3,5-dimethoxyphenylthio moiety at position 2 of the indole ring were effective tubulin assembly inhibitors, but weak inhibitors of MCF-7 cell growth. ATIs bearing a 3-(3,4,5-trimethoxyphenyl)thio moiety were potent tubulin polymerization inhibitors, with IC(50)s in the 2.0 (35) to 4.5 (37) mu M range. They also inhibited MCF-7 cell growth at nanomolar concentrations. The 3,4,5-trimethoxy substituted ATIs showed potencies comparable to those of the reference compounds colchicine and combretastatin A-4 in both tubulin assembly and cell growth inhibition assays. Dynamics simulation studies correlate well with the observed experimental data. Furthermore, from careful analysis of the biological and in silico data, we can now hypothesize a basic pharmacophore for this class of compounds.

  DOI：

  10.1021/jm050809s
• 作为产物：
  描述：

  1-苯硫基-吡咯啉-2,5-二酮 、 5-甲氧基吲哚-2-羧酸甲酯 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 以24%的产率得到1H-吲哚-2-羧酸,5-甲氧基-3-(苯基硫代)-,甲基酯
  参考文献：
  名称：

  芳硫基吲哚，微管蛋白聚合的有效抑制剂。

  摘要：

  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。

  DOI：

  10.1021/jm049360d

文献信息

• [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。
• 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。
• New Arylthioindoles:  Potent Inhibitors of Tubulin Polymerization. 2. Structure−Activity Relationships and Molecular Modeling Studies
  作者：Gabriella De Martino、Michael C. Edler、Giuseppe La Regina、Antonio Coluccia、Maria Chiara Barbera、Denise Barrow、Robert I. Nicholson、Gabriela Chiosis、Andrea Brancale、Ernest Hamel、Marino Artico、Romano Silvestri

  DOI：10.1021/jm050809s

  日期：2006.2.1

  Arylthioindoles (ATIs) that possess a 3-methoxyphenylthio or a 3,5-dimethoxyphenylthio moiety at position 2 of the indole ring were effective tubulin assembly inhibitors, but weak inhibitors of MCF-7 cell growth. ATIs bearing a 3-(3,4,5-trimethoxyphenyl)thio moiety were potent tubulin polymerization inhibitors, with IC(50)s in the 2.0 (35) to 4.5 (37) mu M range. They also inhibited MCF-7 cell growth at nanomolar concentrations. The 3,4,5-trimethoxy substituted ATIs showed potencies comparable to those of the reference compounds colchicine and combretastatin A-4 in both tubulin assembly and cell growth inhibition assays. Dynamics simulation studies correlate well with the observed experimental data. Furthermore, from careful analysis of the biological and in silico data, we can now hypothesize a basic pharmacophore for this class of compounds.