7-hydroxy-4-methyl-3-(3-nitrobenzyl)-pyrano[2,3-b]pyridin-2-one | 946125-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃吡啶类
• 英文名称: 7-hydroxy-4-methyl-3-(3-nitrobenzyl)-pyrano[2,3-b]pyridin-2-one
• 英文别名: 7-hydroxy-4-methyl-3-(3-nitrobenzyl)pyrano[2,3-b]pyridin-2-one；4-methyl-3-[(3-nitrophenyl)methyl]-8H-pyrano[2,3-b]pyridine-2,7-dione
• CAS: 946125-89-9
• 化学式: C₁₆H₁₂N₂O₅
• 分子量: 312.282
• InChiKey: HPPIZZPGXFMCOJ-UHFFFAOYSA-N

物化性质

• 沸点：
  711.3±60.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-hydroxy-4-methyl-3-(3-nitrobenzyl)-pyrano[2,3-b]pyridin-2-one 在 tin(II) chloride dihdyrate 、 sodium hydride 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 8.75h， 生成 dimethylcarbamic acid 3-(3-(methylaminosulfonyl)aminobenzyl)-4-methyl-2-oxo-2H-pyrano[2,3-b]pyridin-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：

  2,6-二羟基吡啶 、 2-(3-nitrobenzyl)-3-oxo-butyric acid ethyl ester 在 zinc trifluoromethanesulfonate 作用下， 以 甲醇 为溶剂， 反应 30.0h， 以57%的产率得到7-hydroxy-4-methyl-3-(3-nitrobenzyl)-pyrano[2,3-b]pyridin-2-one
  参考文献：
  名称：

  ｐ27 단백질 유도제

  摘要：

  本发明提供了一种以化合物或其药学上可接受的盐所表示的有效成分作为p27蛋白诱导剂的一般式(11)。[其中，G1、G2、G3和G8分别独立地选择自-N=等，环G6选择自2个芳基等，A选择自氨基等，G4选择自氧原子等，G5选择自氧原子等，G7选择自-CH2-等，R2选择自C1-6烷基等]

  公开号：

  KR101511396B1

文献信息

• ｐ27 단백질 유도제
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA (Chugai Pharmaceutical Co., Ltd.) 추가이 세이야쿠 가부시키가이샤(520000045945)

  公开号：KR101511396B1

  公开（公告）日：2015-04-13

  본 발명은, 하기 일반식 (11) 로 나타내는 화합물 또는 그 약학상 허용할 수 있는 염을 유효 성분으로 하는 p27 단백질 유도제를 제공한다. [식 중, G1, G2, G3 및 G8은, 각각 독립적으로 -N= 등에서 선택되고, 고리 G6은 2 가의 아릴기 등에서 선택되고, A 는 아미노기 등에서 선택되고, G4 는 산소 원자 등에서 선택되고, G5 는 산소 원자 등에서 선택되고, G7 은 -CH2- 등에서 선택되고, R2 는 C1-6 알킬기 등에서 선택된다]

  本发明提供了一种以化合物或其药学上可接受的盐所表示的有效成分作为p27蛋白诱导剂的一般式(11)。[其中，G1、G2、G3和G8分别独立地选择自-N=等，环G6选择自2个芳基等，A选择自氨基等，G4选择自氧原子等，G5选择自氧原子等，G7选择自-CH2-等，R2选择自C1-6烷基等]
• Coumarin derivative having antitumor activity
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US08278465B2

  公开（公告）日：2012-10-02

  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., Y1 and Y2 are selected from —N═ etc., Y3 and Y4 are selected from —CH═ etc., A is selected from sulfamide etc., R1 is selected from hydrogen etc., and R2 is selected from C1-6 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.

  本发明提供了以下通式（1）所表示的化合物或其药学上可接受的盐： 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，可用于治疗细胞增殖性疾病，特别是癌症。本发明还提供了一种含有该化合物或盐作为活性成分的药物组合物。
• 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：US08569378B2

  公开（公告）日：2013-10-29

  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，其包括下式（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。
• 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。