2-(thiophen-2-yl)-3-[(3',4',5'-trimethoxyphenyl)thio]-1H-indole | 1314802-67-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(thiophen-2-yl)-3-[(3',4',5'-trimethoxyphenyl)thio]-1H-indole
• 英文别名: 2-(thiophene-2-yl)-3-[(3',4',5'-trimethoxyphenyl)thio]-1H-indole；2-thiophen-2-yl-3-(3,4,5-trimethoxyphenyl)sulfanyl-1H-indole
• CAS: 1314802-67-9
• 化学式: C₂₁H₁₉NO₃S₂
• 分子量: 397.519
• InChiKey: SAEVQLMBDMPTHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  97
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-溴-1-(2-THIENYL)-1-ETHANONE 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 25.0~110.0 ℃ 、1.72 MPa 条件下， 反应 3.22h， 生成 2-(thiophen-2-yl)-3-[(3',4',5'-trimethoxyphenyl)thio]-1H-indole
  参考文献：
  名称：

  Design and Synthesis of 2-Heterocyclyl-3-arylthio-1H-indoles as Potent Tubulin Polymerization and Cell Growth Inhibitors with Improved Metabolic Stability

  摘要：

  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.

  DOI：

  10.1021/jm2012886

文献信息

• [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。
• 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.