3-(3,4,5-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4'-fluorobenzylidene)indan-1-one | 1375084-28-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 3-(3,4,5-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4'-fluorobenzylidene)indan-1-one
• 英文别名: 2-[(4-fluorophenyl)methylidene]-4,5,6-trimethoxy-3-(3,4,5-trimethoxyphenyl)-3H-inden-1-one
• CAS: 1375084-28-8
• 化学式: C₂₈H₂₇FO₇
• 分子量: 494.517
• InChiKey: YZOCCKPKVYXGIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  没食子酸 在 锂硼氢 、 pyridinium chlorochromate 、 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 20.0h， 生成 3-(3,4,5-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4'-fluorobenzylidene)indan-1-one
  参考文献：
  名称：

  Fluorinated benzylidene indanone exhibits antiproliferative activity through modulation of microtubule dynamics and antiangiogenic activity

  摘要：

  The application of fluorine in drug design has been understood significantly by the medicinal chemists in recent years. Modulation of tubulin-microtubule dynamics is one of the most effective targets for cancer chemotherapeutics. A logically designed and identified lead compound, fluorinated benzylidene indanone 1 has been extensively evaluated for cancer pharmacology. It occupied colchicine binding pocket acting as microtubule destabilizer and induced a G2/M phase arrest in MCF-7 cells. Compound 1 exerted an antiangiogenic effect in MCF-7 cells by down-regulating Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-alpha (HIF-alpha). In in-vivo efficacy in C3H/Jax mice mammary carcinoma model, benzylidene indanone 1 reduced tumour volumes by 48.2%. Further in acute oral toxicity studies compound 1 was well tolerated and safe up to 1000 mg/kg dose in Swiss albino mice. The fluorinated benzylidene indanone 1, a new chemical entity (NCE) can further be optimized for better efficacy against breast adenocarcinoma.(1)

  DOI：

  10.1016/j.ejps.2020.105513

文献信息

• Synthesis and anticancer activity of 2-benzylidene indanones through inhibiting tubulin polymerization
  作者：A.P. Prakasham、A.K. Saxena、Suaib Luqman、Debabrata Chanda、Tandeep Kaur、Atul Gupta、D.K. Yadav、C.S. Chanotiya、Karuna Shanker、F. Khan、Arvind S. Negi

  DOI：10.1016/j.bmc.2012.02.057

  日期：2012.5

  In an attempt to discover a potent and selective anticancer agent, gallic acid has been modified to benzylidene indanones as tubulin polymerization inhibitors. These compounds were evaluated against several human cancer cell lines and also evaluated for inhibition of tubulin polymerase in in vitro assays. Three of the analogues exhibited strong cytotoxicity against human cancer cell lines IC50 = 10-880 nM and also showed tubulin polymerization inhibition (IC50 = 0.62-2.04 mu M). Compound 9j, the best candidate of the series was found to be non-toxic in acute oral toxicity in Swiss-albino mice up to 1000 mg/kg dose. (C) 2012 Elsevier Ltd. All rights reserved.
• Fluorinated benzylidene indanone exhibits antiproliferative activity through modulation of microtubule dynamics and antiangiogenic activity
  作者：Ankita Srivastava、Kaneez Fatima、Eram Fatima、Arjun Singh、Aastha Singh、Aparna Shukla、Suaib Luqman、Karuna Shanker、Debabrata Chanda、Feroz Khan、Arvind S. Negi

  DOI：10.1016/j.ejps.2020.105513

  日期：2020.11

  The application of fluorine in drug design has been understood significantly by the medicinal chemists in recent years. Modulation of tubulin-microtubule dynamics is one of the most effective targets for cancer chemotherapeutics. A logically designed and identified lead compound, fluorinated benzylidene indanone 1 has been extensively evaluated for cancer pharmacology. It occupied colchicine binding pocket acting as microtubule destabilizer and induced a G2/M phase arrest in MCF-7 cells. Compound 1 exerted an antiangiogenic effect in MCF-7 cells by down-regulating Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-alpha (HIF-alpha). In in-vivo efficacy in C3H/Jax mice mammary carcinoma model, benzylidene indanone 1 reduced tumour volumes by 48.2%. Further in acute oral toxicity studies compound 1 was well tolerated and safe up to 1000 mg/kg dose in Swiss albino mice. The fluorinated benzylidene indanone 1, a new chemical entity (NCE) can further be optimized for better efficacy against breast adenocarcinoma.(1)