(7-methoxy-2-phenyl-1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone

• 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: (7-methoxy-2-phenyl-1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: (7-methoxy-2-phenyl-1H-indol-3-yl)-(3,4,5-trimethoxyphenyl)methanone
• 化学式: C₂₅H₂₃NO₅
• 分子量: 417.461
• InChiKey: ACPMPJJIZOFLRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  69.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-甲氧基-6-甲基苯胺 在 aluminum (III) chloride 、 叔丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 正戊烷 为溶剂， 反应 15.03h， 生成 (7-methoxy-2-phenyl-1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  New Indole Tubulin Assembly Inhibitors Cause Stable Arrest of Mitotic Progression, Enhanced Stimulation of Natural Killer Cell Cytotoxic Activity, and Repression of Hedgehog-Dependent Cancer

  摘要：

  We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of the indole and with halogen or methoxy substituent(s) at positions 4-7. Compounds 33 and 44 strongly inhibited the growth of the P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES and Messa/Dx5. At 10 nM, 33 and 44 stimulated the cytotoxic activity of NK cells. At 20-50 nM, 33 and 44 arrested >80% of HeLa cells in the G2/M phase of the cell cycle, with stable arrest of mitotic progression. Cell cycle arrest was followed by cell death. Indoles 33, 44, and 81 showed strong inhibition of the SAG-induced Hedgehog signaling activation in NIH3T3 Shh-Light II cells with IC50 values of 19, 72, and 38 nM, respectively. Compounds of this class potently inhibited tubulin polymerization and cancer cell growth, including stimulation of natural killer cell cytotoxic activity and repression of Hedgehog-dependent cancer.

  DOI：

  10.1021/acs.jmedchem.5b00310

文献信息

• New Indole Tubulin Assembly Inhibitors Cause Stable Arrest of Mitotic Progression, Enhanced Stimulation of Natural Killer Cell Cytotoxic Activity, and Repression of Hedgehog-Dependent Cancer
  作者：Giuseppe La Regina、Ruoli Bai、Antonio Coluccia、Valeria Famiglini、Sveva Pelliccia、Sara Passacantilli、Carmela Mazzoccoli、Vitalba Ruggieri、Annalisa Verrico、Andrea Miele、Ludovica Monti、Marianna Nalli、Romina Alfonsi、Lucia Di Marcotullio、Alberto Gulino、Biancamaria Ricci、Alessandra Soriani、Angela Santoni、Michele Caraglia、Stefania Porto、Eleonora Da Pozzo、Claudia Martini、Andrea Brancale、Luciana Marinelli、Ettore Novellino、Stefania Vultaggio、Mario Varasi、Ciro Mercurio、Chiara Bigogno、Giulio Dondio、Ernest Hamel、Patrizia Lavia、Romano Silvestri

  DOI：10.1021/acs.jmedchem.5b00310

  日期：2015.8.13

  We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of the indole and with halogen or methoxy substituent(s) at positions 4-7. Compounds 33 and 44 strongly inhibited the growth of the P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES and Messa/Dx5. At 10 nM, 33 and 44 stimulated the cytotoxic activity of NK cells. At 20-50 nM, 33 and 44 arrested >80% of HeLa cells in the G2/M phase of the cell cycle, with stable arrest of mitotic progression. Cell cycle arrest was followed by cell death. Indoles 33, 44, and 81 showed strong inhibition of the SAG-induced Hedgehog signaling activation in NIH3T3 Shh-Light II cells with IC50 values of 19, 72, and 38 nM, respectively. Compounds of this class potently inhibited tubulin polymerization and cancer cell growth, including stimulation of natural killer cell cytotoxic activity and repression of Hedgehog-dependent cancer.