dimethyl carbamic acid 4-fluoromethyl-3-(3-nitro-benzyl)-2-oxo-2H-chromen-7-yl ester | 946127-36-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: dimethyl carbamic acid 4-fluoromethyl-3-(3-nitro-benzyl)-2-oxo-2H-chromen-7-yl ester
• 英文别名: dimethylcarbamic acid 4-fluoromethyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-yl ester；[4-(fluoromethyl)-3-[(3-nitrophenyl)methyl]-2-oxochromen-7-yl] N,N-dimethylcarbamate
• CAS: 946127-36-2
• 化学式: C₂₀H₁₇FN₂O₆
• 分子量: 400.363
• InChiKey: XFHMFSQNZJYGMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dimethyl carbamic acid 4-fluoromethyl-3-(3-nitro-benzyl)-2-oxo-2H-chromen-7-yl ester 在 tin(II) chloride dihdyrate 作用下， 以 乙酸乙酯 为溶剂， 反应 6.0h， 生成 dimethylcarbamic acid 3-(3-aminobenzyl)-4-fluoromethyl-2-oxo-2H-1-benzopyran-7-yl ester
  参考文献：
  名称：

  Fluorine Scanning by Nonselective Fluorination: Enhancing Raf/MEK Inhibition while Keeping Physicochemical Properties

  摘要：

  A facile methodology effective in obtaining a set of compounds monofluorinated at various positions (fluorine scan) by chemical synthesis is reported. Direct and nonselective fluorination reactions of our lead compound la and key intermediate 2a worked efficiently to afford a total of six monofluorinated derivatives. All of the derivatives kept their physicochemical properties compared with the lead la and one of them had enhanced Raf/MEK inhibitory activity. Keeping physicochemical properties could be considered a benefit of monofluorinated derivatives compared with chlorinated derivatives, iodinated derivatives, methylated derivatives, etc. This key finding led to the identification of compound 14d, which had potent tumor growth inhibition in a xenograft model, excellent PK profiles in three animal species, and no critical toxicity.

  DOI：

  10.1021/ml4002419
• 作为产物：
  描述：

  dimethyl carbamic acid 4-methyl-3-(3-nitrobenzyl)-2-oxo-2H-chromen-7-yl ester 在 lithium hexamethyldisilazane 、 N-氟代双苯磺酰胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.5h， 以53%的产率得到dimethyl carbamic acid 4-fluoromethyl-3-(3-nitro-benzyl)-2-oxo-2H-chromen-7-yl ester
  参考文献：
  名称：

  Fluorine Scanning by Nonselective Fluorination: Enhancing Raf/MEK Inhibition while Keeping Physicochemical Properties

  摘要：

  A facile methodology effective in obtaining a set of compounds monofluorinated at various positions (fluorine scan) by chemical synthesis is reported. Direct and nonselective fluorination reactions of our lead compound la and key intermediate 2a worked efficiently to afford a total of six monofluorinated derivatives. All of the derivatives kept their physicochemical properties compared with the lead la and one of them had enhanced Raf/MEK inhibitory activity. Keeping physicochemical properties could be considered a benefit of monofluorinated derivatives compared with chlorinated derivatives, iodinated derivatives, methylated derivatives, etc. This key finding led to the identification of compound 14d, which had potent tumor growth inhibition in a xenograft model, excellent PK profiles in three animal species, and no critical toxicity.

  DOI：

  10.1021/ml4002419

文献信息

• Novel Coumarin Derivative Having Antitumor Activity
  申请人：Iikura Hitoshi

  公开号：US20110092700A1

  公开（公告）日：2011-04-21

  The present invention provides a compound represented by general formula (1) below or a pharmaceutically acceptable salt thereof: wherein: X is selected from heteroaryl etc., Y 1 and Y 2 are selected from —N═ etc., Y 3 and Y 4 are selected from —CH═ etc., A is selected from sulfamide etc., R 1 is selected from hydrogen etc., and R 2 is selected from C 1-6 alkyl etc. The compound or salt has sufficiently high antitumor activity, and is useful in the treatment of cell proliferative disorders, particularly cancers. The present invention also provides a pharmaceutical composition containing the compound or salt as an active ingredient.

  本发明提供一种由下式（1）或其药学上可接受的盐所表示的化合物：其中，X选自杂环芳基等；Y1和Y2选自—N═等；Y3和Y4选自—CH═等；A选自磺酰胺等；R1选自氢等；R2选自C1-6烷基等。该化合物或盐具有足够高的抗肿瘤活性，并可用于治疗细胞增殖性疾病，特别是癌症。本发明还提供一种含有该化合物或盐作为活性成分的制药组合物。
• p27 Protein Inducer
  申请人：Sakai Toshiyuki

  公开号：US20110009398A1

  公开（公告）日：2011-01-13

  The present invention provides a p27 protein inducing agent comprising a compound represented by general formula (11) below or pharmaceutically acceptable salt thereof as an active ingredient: wherein G 1 , G 2 , G 3 and G 8 are each independently selected from —N═ etc., Ring G 6 is selected from divalent aryl etc., A is selected from amino etc., G 4 is selected from oxygen etc., G 5 is selected from oxygen etc., G 7 is selected from —CH 2 — etc., and R 2 is selected from C 1-6 alkyl etc.

  本发明提供了一种p27蛋白诱导剂，其包含以下通式（11）所表示的化合物或其药学上可接受的盐作为活性成分：其中G1，G2，G3和G8各自独立地选择自—N═等，环G6选择自双价芳基等，A选择自氨基等，G4选择自氧等，G5选择自氧等，G7选择自—CH2—等，R2选择自C1-6烷基等。
• p27 PROTEIN INDUCER
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP2172198B1

  公开（公告）日：2014-04-16
• NOVEL COUMARIN DERIVATIVE HAVING ANTITUMOR ACTIVITY
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1982982B1

  公开（公告）日：2012-09-26
• EP1982982A1
  申请人：——

  公开号：EP1982982A1

  公开（公告）日：2008-10-22