5-methoxy-2-(thiophen-2-yl)-1H-indole | 153865-27-1

• 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-methoxy-2-(thiophen-2-yl)-1H-indole
• 英文别名: 2-(2-thienyl)-5-methoxyindole；5-methoxy-2-(thiophene-2-yl)-1H-indole；5-methoxy-2-thiophen-2-yl-1H-indole
• CAS: 153865-27-1
• 化学式: C₁₃H₁₁NOS
• 分子量: 229.302
• InChiKey: WAZHCCLTJCAOQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  53.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  bis(3,4,5-trimethoxyphenyl)disulfide 、 5-methoxy-2-(thiophen-2-yl)-1H-indole 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.25h， 以70%的产率得到5-methoxy-2-(thiophen-2-yl)-3-[(3,4,5-trimethoxyphenyl)thio]-1H-indole
  参考文献：
  名称：

  [EN] INDOLIC DERIVATIVES AND USE THEREOF IN MEDICAL FIELD
  [FR] DÉRIVÉS INDOLIQUES ET UTILISATION DE CELLES-CI DANS LE DOMAINE MÉDICAL

  摘要：

  本发明涉及吲哚衍生物及其在医学领域中的应用。具体而言，该发明涉及3-[(3',4',5'-三甲氧基苯基)硫基]-1 H-吲哚衍生物及其生物同位素衍生物，以及它们在肿瘤治疗中的应用。

  公开号：

  WO2011121629A1
• 作为产物：
  描述：

  3-氯-4-甲氧基苯胺 在 sodium amide 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 叔丁醇 、 苯 为溶剂， 反应 24.0h， 生成 5-methoxy-2-(thiophen-2-yl)-1H-indole
  参考文献：
  名称：

  Aggregative activation and heterocyclic chemistry I complex bases promoted arynic cyclisation of imines or enaminoketones; regiochemical synthesis of indoles

  摘要：

  The complex base NaNH2-t-BuONa allowed expeditious syntheses of indoles by arynic cyclisation of imines or enaminoketones prepared from halogeno anilines and carbonyl derivatives. Unstable imines may be used without purification, complex bases being unsensitive to impurities. It is showed that this kind of reaction may be applied to mixture of substrates suitably halogenated on the benzene ring. Formation of three components aggregates is proposed to explain a number of observations.

  DOI：

  10.1016/s0040-4020(01)89304-2

文献信息

• Pd(II)/Bu4NBr/DMSO Catalytic System for Practical Synthesis of Indoles and Pyrroles from Imines through Aerobic Dehydrogenative Cyclization
  作者：Naohiko Yoshikai、Wei Tan、Xiaoya Hou

  DOI：10.1055/s-0034-1379208

  日期：——

  scales (up to 55 mmol). N-Aryl- and N-allylimines derived typically from substituted acetophenones undergo palladium(II)-catalyzed dehydrogenative cyclization reactions in the presence of tetrabutylammonium bromide and molecular oxygen in DMSO to afford indole and pyrrole derivatives, respectively, in moderate to good yields. The reactions are operationally simple and can be readily performed on multigram

  摘要 ñ -芳基-和Ñ -allylimines通常衍生自取代的苯乙酮经历钯（II）在四丁基溴化铵和分子氧在DMSO存在下得到的吲哚并吡咯衍生物，分别催化的脱氢环化反应，在中度至良好的产率。该反应操作简单，可以容易地以克级（最高55 mmol）进行。 ñ -芳基-和Ñ -allylimines通常衍生自取代的苯乙酮经历钯（II）在四丁基溴化铵和分子氧在DMSO存在下得到的吲哚并吡咯衍生物，分别催化的脱氢环化反应，在中度至良好的产率。该反应操作简单，可以容易地以克级（最高55 mmol）进行。
• [EN] INDOLIC DERIVATIVES AND USE THEREOF IN MEDICAL FIELD<br/>[FR] DÉRIVÉS INDOLIQUES ET UTILISATION DE CELLES-CI DANS LE DOMAINE MÉDICAL
  申请人：UNI DEGLI STUDI DL ROMA LA SAPIENZA

  公开号：WO2011121629A1

  公开（公告）日：2011-10-06

  The present invention concerns indolic derivatives and use thereof in medical field. Particularly, the invention concerns 3-[(3',4',5'- trimethoxyphenyl)thio]-1 H-indole derivatives and bioisosteric derivatives thereof and their use for the treatment of tumours.

  本发明涉及吲哚衍生物及其在医学领域中的应用。具体而言，该发明涉及3-[(3',4',5'-三甲氧基苯基)硫基]-1 H-吲哚衍生物及其生物同位素衍生物，以及它们在肿瘤治疗中的应用。
• Complex bases promoted arynic cyclisations of halogenated imines or enamines: A regiochemical synthesis of indole derivatives
  作者：Catherine Caubère、Paul Caubère、Pierre Renard、Jean-Guy Bizot-Espiart、Brigitte Jamart-Grégoire

  DOI：10.1016/s0040-4039(00)91822-7

  日期：1993.10

  The complex base NaNH2-tBuONa allows expeditious synthesis of indole derivatives by arynic cyclization of imines or enamines of chloroanilines. Unstable may be used without purification, complex bases being unsensitive to impurities.

  复杂的碱式NaNH 2 -tBuONa可以通过亚胺或氯苯胺的烯胺的芳基环化反应迅速合成吲哚衍生物。不稳定，无需纯化即可使用，复杂的碱对杂质不敏感。
• Aggregative activation and heterocyclic chemistry I complex bases promoted arynic cyclisation of imines or enaminoketones; regiochemical synthesis of indoles
  作者：Catherine Caubère、Paul Caubère、Sandra Ianelli、Mario Nardelli、Brigitte Jamart-Grégoire

  DOI：10.1016/s0040-4020(01)89304-2

  日期：1994.1

  The complex base NaNH2-t-BuONa allowed expeditious syntheses of indoles by arynic cyclisation of imines or enaminoketones prepared from halogeno anilines and carbonyl derivatives. Unstable imines may be used without purification, complex bases being unsensitive to impurities. It is showed that this kind of reaction may be applied to mixture of substrates suitably halogenated on the benzene ring. Formation of three components aggregates is proposed to explain a number of observations.
• Design and Synthesis of 2-Heterocyclyl-3-arylthio-1<i>H</i>-indoles as Potent Tubulin Polymerization and Cell Growth Inhibitors with Improved Metabolic Stability
  作者：Giuseppe La Regina、Ruoli Bai、Willeke Rensen、Antonio Coluccia、Francesco Piscitelli、Valerio Gatti、Alessio Bolognesi、Antonio Lavecchia、Ilaria Granata、Amalia Porta、Bruno Maresca、Alessandra Soriani、Maria Luisa Iannitto、Marisa Mariani、Angela Santoni、Andrea Brancale、Cristiano Ferlini、Giulio Dondio、Mario Varasi、Ciro Mercurio、Ernest Hamel、Patrizia Lavia、Ettore Novellino、Romano Silvestri

  DOI：10.1021/jm2012886

  日期：2011.12.22

  New arylthioindoles (ATIs) were obtained by replacing the 2-alkoxycarbonyl group with a bioisosteric 5-membered heterocycle nucleus. The new ATIs 5, 8, and 10 inhibited tubulin polymerization, reduced cell growth of a panel of human transformed cell lines, and showed higher metabolic stability than the reference ester 3. These compounds induced mitotic arrest and apoptosis at a similar level as combretastatin A-4 and vinblastine and triggered caspase-3 expression in a significant fraction of cells in both p53-proficient and p53-defective cell lines. Importantly, ATIs 5, 8, and 10 were more effective than vinorelbine, vinblastine, and paclitaxel as growth inhibitors of the P-glycoprotein-overexpressing cell line NCI/ADR-RES. Compound 5 was shown to have medium metabolic stability in both human and mouse liver microsomes, in contrast to the rapidly degraded reference ester 3, and a pharmacokinetic profile in the mouse characterized by a low systemic clearance and excellent oral bioavailability.