3-[2-((N-methylsulfamoyl)amino)-3-fluoropyridin-4-ylmethyl]-4-methyl-7-(pyridin-2-yloxy)chromen-2-one | 946129-41-5

• 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: 3-[2-((N-methylsulfamoyl)amino)-3-fluoropyridin-4-ylmethyl]-4-methyl-7-(pyridin-2-yloxy)chromen-2-one
• 英文别名: 3-{2-(methylaminosulfonyl)amino-3-fluoropyridin-4-ylmethyl}-4-methyl-7-(pyridin-2-yloxy)-2-oxo-2H-1-benzopyran；3-[[3-Fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl]-4-methyl-7-pyridin-2-yloxychromen-2-one
• CAS: 946129-41-5
• 化学式: C₂₂H₁₉FN₄O₅S
• 分子量: 470.481
• InChiKey: GETITGUMUDFBSL-UHFFFAOYSA-N

物化性质

• 沸点：
  655.7±65.0 °C(predicted)
• 密度：
  1.461±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-氯-3-氟吡啶 在 吡啶 、 咪唑 、 sodium tetrahydroborate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 copper(l) iodide 、 甲烷磺酸 、 四丁基氟化铵 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 甲基磺酰氯 、 N,N-二甲基乙二胺 、 sodium t-butanolate 、 lithium tert-butoxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 2,2,2-三氟乙醇 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 28.67h， 生成 3-[2-((N-methylsulfamoyl)amino)-3-fluoropyridin-4-ylmethyl]-4-methyl-7-(pyridin-2-yloxy)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

• Method for Producing Coumarin Derivative
  申请人：Murakata Masatoshi

  公开号：US20140213786A1

  公开（公告）日：2014-07-31

  The present invention provides a novel method for producing a compound represented by general formula (VII) below or a pharmaceutically acceptable salt thereof or a synthetic intermediate thereof: wherein R 2 represents a hydrogen atom or a halogen atom, R c represents a C 1-6 alkyl group, X represents a group selected from a heteroaryl group etc., R 11 represents an atom or group selected from a hydrogen atom, a halogen atom, a C 1-6 alkyl group, etc., R 16 and R 17 each independently represent an atom or group selected from a hydrogen atom, a C 1-6 alkyl group, etc., and R 15 represents a hydrogen atom or a C 1-6 alkyl group.

  本发明提供了一种生产下列通式（VII）所表示的化合物或其药学上可接受的盐或其合成中间体的新方法：其中，R2代表氢原子或卤素原子，Rc代表C1-6烷基，X代表从杂环基等中选择的基团，R11代表从氢原子、卤素原子、C1-6烷基等中选择的原子或基团，R16和R17各自独立地代表从氢原子、C1-6烷基等中选择的原子或基团，而R15代表氢原子或C1-6烷基。
• 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