3-(phenylthio)-1H-indole-2-carboxylic acid | 116757-25-6

• 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-(phenylthio)-1H-indole-2-carboxylic acid
• 英文别名: 3‐(phenylthio)‐1H‐indole‐2‐carboxylic acid；3-phenylsulfanyl-1H-indole-2-carboxylic acid
• CAS: 116757-25-6
• 化学式: C₁₅H₁₁NO₂S
• mdl: MFCD15730518
• 分子量: 269.324
• InChiKey: AAPOQBAUHGNFJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  异戊醇 、 3-(phenylthio)-1H-indole-2-carboxylic acid 在 氯化亚砜 作用下， 反应 5.0h， 以21%的产率得到3-phenylthio-1H-indole-2-carboxylic acid 3-methyl-butyl 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：

  吲哚-2-羧酸甲酯 在 lithium hydroxide 、 三氟化硼乙醚 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 3-(phenylthio)-1H-indole-2-carboxylic acid
  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

• Cooperative catalysis by bovine serum albumin–iodine towards cascade oxidative coupling-C(sp²)–H sulfenylation of indoles/hydroxyaryls with thiophenols on water
  作者：Saima Saima、Danish Equbal、Aditya G. Lavekar、Arun K. Sinha

  DOI：10.1039/c6ob00930a

  日期：——

  economically reliable. Further, the gram scale synthesis of a COX-2 inhibitor (3-(pyridin-2-ylthio)-1H-indole), regioselectivity and recyclability (up to four cycles) are the additional merits of this cooperative cascade bio-chemocatalytic (BSA–I2) protocol. Moreover, HPLC and ESI-MS provide powerful insights into the mechanistic aspects of the above cascade sulfenylation reaction.

  由牛血清白蛋白（BSA） -碘允许第一时间C的性能（SP协同级联催化2）-H从容易获得的苯硫酚（-SH键）吲哚的亚磺酰化通过原位生成/二硫化物的裂解（S- S键）在空气中在水性条件下进行，而BSA或I 2分别不允许这两个步骤的顺序在同一锅中发生以形成C–S键。这种绿色的合作协议可扩展至羟基芳基的亚磺酰基化（即2-萘酚或4-羟基香豆素）与各种硫醇（芳基/杂芳基），而无需使用任何有毒的金属催化剂，碱或氧化剂，因此使该方法在环境和经济上均可靠。此外，COX-2抑制剂（3-（吡啶-2-基硫基）-1 H-吲哚）的克级合成，区域选择性和可循环性（最多四个循环）是这种协同级联生物化学催化（ BSA–I 2）协议。此外，HPLC和ESI-MS为上述级联亚磺酰化反应的机理提供了有力的见解。
• Synergistic Dual Role of [hmim]Br-ArSO₂Cl in Cascade Sulfenylation–Halogenation of Indole: Mechanistic Insight into Regioselective C–S and C–S/C–X (X = Cl and Br) Bond Formation in One Pot
  作者：Danish Equbal、Richa Singh、Saima、Aditya G. Lavekar、Arun K. Sinha

  DOI：10.1021/acs.joc.8b03097

  日期：2019.3.1

  indole at room temperature, while heating the reaction mixture at 50 °C provided an unexpected 2-halo-3-arylthio indole with construction of C–S and C–S/C–X (X = Cl and Br) bonds without addition of any external halogenating agent via cascade sulfenylation–halogenation reactions under metal-oxidant-base-free conditions. Further, insight into the reaction mechanism provides an unprecedented observation

  双功能吲哚是重要的一类具有生物活性的杂环化合物和潜在的候选药物。由于缺乏有效的合成方法，这些化合物的一锅级联合成是罕见的，并且仍然是一个挑战。为了扩展该领域，我们在此公开了一种经济且温度可调的分步策略，其中[hmim] Br-ArSO 2之间具有协同作用Cl在室温下仅通过吲哚的亚磺酰基化作用而导致生成3-芳硫基吲哚，而将反应混合物在50°C下加热可提供意想不到的2-卤-3-芳硫基吲哚，并具有C–S和C–S / C-X（X = Cl和Br）键在无金属氧化剂的条件下通过级联的磺化-卤化反应而无需添加任何外部卤化剂。此外，对反应机理的深入了解提供了前所未有的观察结果，其中[hmim] Br-ArSO 2 X在催化量的水存在下的协同相互作用会原位生成芳基磺酸酐（ArSO 2）2 ONMR，ESI-MS，DART-MS和HPLC研究表明，作为一种新的硫源，以及[hmim] PTS的形成。值得注意的是，双官能化的2-卤代（Br
• A New Synthesis of 3-Arylthioindoles
  作者：Joseph G. Atkinson、Pierre Hamel、Yves Girard

  DOI：10.1055/s-1988-27615

  日期：——

  The reaction of the anions of indoles with diaryl disulfides in dimethylformamide at room temperature gives the 3-arylthioindoles in 59-91% yield.

  在室温下，吲哚的阴离子与二芳基二硫化物在二甲基甲酰胺中反应生成 3-芳硫基吲哚，产率为 59-91%。
• Inhibitors of HIV reverse transcriptase
  申请人：Merck & Co., Inc.

  公开号：US05527819A1

  公开（公告）日：1996-06-18

  Novel indole compounds inhibit HIV reverse transcriptase, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  新型吲哚化合物抑制HIV逆转录酶，在预防或治疗HIV感染以及治疗艾滋病方面具有用途，无论是作为化合物、药学上可接受的盐、药物组成成分，还是与其他抗病毒药物、抗感染药物、免疫调节剂、抗生素或疫苗结合使用。还描述了治疗艾滋病和预防或治疗HIV感染的方法。
• HIV reverse transcriptase
  申请人：Merck & Co., Inc.

  公开号：US05124327A1

  公开（公告）日：1992-06-23

  Novel indole compounds inhibit HIV reverse transcriptase, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds or pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  新型吲哚化合物抑制HIV逆转录酶，在预防或治疗HIV感染以及治疗艾滋病方面具有用途，无论是作为化合物还是药物组成成分，无论是否与其他抗病毒药物、抗感染药物、免疫调节剂、抗生素或疫苗结合使用。还描述了治疗艾滋病的方法以及预防或治疗HIV感染的方法。