2-(2-fluoro-3-nitrobenzyl)-3-oxo-butyric acid ethyl ester | 946130-07-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2-fluoro-3-nitrobenzyl)-3-oxo-butyric acid ethyl ester
• 英文别名: 2-(2-Fluoro-3-nitrobenzyl)-3-oxobutanoic acid ethyl ester；ethyl 2-[(2-fluoro-3-nitrophenyl)methyl]-3-oxobutanoate
• CAS: 946130-07-0
• 化学式: C₁₃H₁₄FNO₅
• 分子量: 283.256
• InChiKey: DMAMRYQZBXOLTJ-UHFFFAOYSA-N

物化性质

• 沸点：
  399.2±37.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  89.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(2-fluoro-3-nitrobenzyl)-3-oxo-butyric acid ethyl ester 在 吡啶 、 甲酸 、 氯磺酰异氰酸酯 、 tin(II) chloride dihdyrate 、 硫酸 、 sodium hydride 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 32.5h， 生成 dimethylcarbamic acid 3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-yl ester
  参考文献：
  名称：

  The sulfamide moiety affords higher inhibitory activity and oral bioavailability to a series of coumarin dual selective RAF/MEK inhibitors

  摘要：

  Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50 = 8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor efficacy in the HCT116 xenograft (ED50 = 4.8 mg/kg). We confirmed the sulfamide moiety showed no negative impact on tests run on the compound to evaluate DMPK (PK profiles in three animal species, CYP inhibition and CYP induction) and the safety profile (hERG and AMES tests). Sulfamide 17 had favorable properties that warranted further preclinical assessment (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.001
• 作为产物：
  描述：

  2-氯-3-硝基苯甲酸甲酯 在 三溴化磷 、 sodium hydride 、 二异丁基氢化铝 、 cesium fluoride 作用下， 以 四氢呋喃 、 乙醚 、 二甲基亚砜 、 甲苯 为溶剂， 反应 3.67h， 生成 2-(2-fluoro-3-nitrobenzyl)-3-oxo-butyric acid ethyl ester
  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

• [EN] MEK INHIBITORS AND THERAPEUTIC USES THEREOF<br/>[FR] INHIBITEURS DE MEK ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：IMMUNEERING CORP

  公开号：WO2021142144A1

  公开（公告）日：2021-07-15

  The present disclosure provides compounds, compositions containing such compounds, and methods of designing, developing, producing and preparing compounds represented by general Formula (I), including pharmaceutically acceptable salts thereof or a synthetic intermediate thereof. The compounds act as MEK inhibitors and are capable of displaying one or more beneficial therapeutic effects, including treating cancer.

  本公开提供了化合物、含有这些化合物的组合物，以及设计、开发、生产和制备由一般式（I）表示的化合物的方法，包括其药用可接受盐或合成中间体。这些化合物作为MEK抑制剂，能够展示一种或多种有益的治疗效果，包括治疗癌症。
• 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。