7-hydroxy-4,6-dimethyl-3-(3-nitrobenzyl)chromen-2-one | 946125-82-2

• 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: 7-hydroxy-4,6-dimethyl-3-(3-nitrobenzyl)chromen-2-one
• 英文别名: 3-(3-nitrobenzyl)-7-hydroxy-4-methyl-6-methyl-2-oxo-2H-1-benzopyran；7-hydroxy-4,6-dimethyl-3-[(3-nitrophenyl)methyl]chromen-2-one
• CAS: 946125-82-2
• 化学式: C₁₈H₁₅NO₅
• 分子量: 325.321
• InChiKey: SYMHQPAMPJFKQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-hydroxy-4,6-dimethyl-3-(3-nitrobenzyl)chromen-2-one 在 tin(II) chloride dihdyrate 、 sodium hydride 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.25h， 生成 dimethyl-carbamic acid 3-(3-aminobenzyl)-4,6-dimethyl-2-oxo-2H-chromen-7-yl ester
  参考文献：
  名称：

  Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning

  摘要：

  Substituting a carbon atom with a nitrogen atom (nitrogen substitution) on an aromatic ring in our leads 1 la and 13g by applying nitrogen scanning afforded a set of compounds that improved not only the solubility but also the metabolic stability. The impact after nitrogen substitution on interactions between a derivative and its on- and off-target proteins (Raf/MEK, CYPs, and hERG channel) was also detected, most of them contributing to weaker interactions. After identifying the positions that kept inhibitory activity on HCT116 cell growth and Raf/MEK, compound I (CH5126766/RO5126766) was selected as a clinical compound. A phase I clinical trial is ongoing for solid cancers.

  DOI：

  10.1021/ml400379x
• 作为产物：
  描述：

  4-甲基间苯二酚 、 2-(3-nitrobenzyl)-3-oxo-butyric acid ethyl ester 在 硫酸 作用下， 以 水 为溶剂， 反应 18.0h， 以45%的产率得到7-hydroxy-4,6-dimethyl-3-(3-nitrobenzyl)chromen-2-one
  参考文献：
  名称：

  Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning

  摘要：

  Substituting a carbon atom with a nitrogen atom (nitrogen substitution) on an aromatic ring in our leads 1 la and 13g by applying nitrogen scanning afforded a set of compounds that improved not only the solubility but also the metabolic stability. The impact after nitrogen substitution on interactions between a derivative and its on- and off-target proteins (Raf/MEK, CYPs, and hERG channel) was also detected, most of them contributing to weaker interactions. After identifying the positions that kept inhibitory activity on HCT116 cell growth and Raf/MEK, compound I (CH5126766/RO5126766) was selected as a clinical compound. A phase I clinical trial is ongoing for solid cancers.

  DOI：

  10.1021/ml400379x

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：EP2172198A1

  公开（公告）日：2010-04-07

  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 G1, G2, G3 and G8 are each independently selected from -N= etc., Ring G6 is selected from divalent aryl etc., A is selected from amino etc., G4 is selected from oxygen etc., G5 is selected from oxygen etc., G7 is selected from -CH2- etc., and R2 is selected from C1-6 alkyl etc.

  本发明提供了一种 p27 蛋白诱导剂，其活性成分包括下式（11）所代表的化合物或其药学上可接受的盐： 其中G1、G2、G3和G8各自独立地选自-N＝等，环G6选自二价芳基等，A选自氨基等，G4选自氧等，G5选自氧等，G7选自-CH2-等，R2选自C1-6烷基等。
• 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