5,6-dimethoxy-3-phenylsulfanyl-1H-indole-2-carboxylic acid ethyl ester | 808137-34-0

• 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: 5,6-dimethoxy-3-phenylsulfanyl-1H-indole-2-carboxylic acid ethyl ester
• 英文别名: ethyl 5,6-dimethoxy-3-phenylsulfanyl-1H-indole-2-carboxylate
• CAS: 808137-34-0
• 化学式: C₁₉H₁₉NO₄S
• 分子量: 357.43
• InChiKey: WYSDVQNBXSRGCA-UHFFFAOYSA-N

物化性质

• 熔点：
  137-139 °C(Solv: ethanol (64-17-5))
• 沸点：
  518.4±50.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  85.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,6-dimethoxy-3-phenylsulfanyl-1H-indole-2-carboxylic acid ethyl ester 在 MCPMA 作用下， 以 氯仿 为溶剂， 反应 2.0h， 以47%的产率得到ethyl 3-(benzenesulfonyl)-5,6-dimethoxy-1H-indole-2-carboxylate
  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 、 5,6-二甲氧基吲哚-2-甲酸乙酯 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以35%的产率得到5,6-dimethoxy-3-phenylsulfanyl-1H-indole-2-carboxylic acid ethyl 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

文献信息

• [EN] 3-SUBSTITUTED INDOLES AND DERIVATIVES THEREOF AS THERAPEUTIC AGENTS<br/>[FR] INDOLES 3-SUBSTITUES ET LEURS DERIVES UTILISES COMME AGENTS THERAPEUTIQUES
  申请人：WARNER LAMBERT CO

  公开号：WO2004108708A1

  公开（公告）日：2004-12-16

  The present invention provides indoles of Formula I: wherein R1 and R2 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cardiovascular diseases, and cancers. Also provided are pharmaceutical compositions comprising one or more compounds of Formula I.

  本发明提供了公式I的吲哚化合物：其中R1和R2具有规范中定义的任何值，以及其药学上可接受的盐，这些化合物在治疗疾病和病状，包括炎症性疾病、心血管疾病和癌症方面有用。还提供了包含一个或多个公式I化合物的药物组合物。
• 3-Substituted indoles and derivatives thereof as therapeutic agents
  申请人：Para Suzanne Kimberly

  公开号：US20050004195A1

  公开（公告）日：2005-01-06

  The present invention provides indoles of Formula I: wherein R 1 and R 2 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cardiovascular diseases, and cancers. Also provided are pharmaceutical compositions comprising one or more compounds of Formula I.

  本发明提供了式I的吲哚化合物：其中R1和R2具有规范中定义的任何值，以及其药学上可接受的盐，作为治疗疾病和病症的药物，包括炎症性疾病、心血管疾病和癌症。还提供了包含一种或多种式I化合物的制药组合物。
• 3-SUBSTITUTED INDOLES AND DERIVATIVES THEREOF AS THERAPEUTIC AGENTS
  申请人：Warner-Lambert Company LLC

  公开号：EP1644360A1

  公开（公告）日：2006-04-12
• US7074814B2
  申请人：——

  公开号：US7074814B2

  公开（公告）日：2006-07-11
• 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.