benzyl t-butyl (2,4-difluoro-1,3-phenylene)dicarbamate | 1380228-68-1

• 英文名称: benzyl t-butyl (2,4-difluoro-1,3-phenylene)dicarbamate
• 英文别名: benzyl N-[2,4-difluoro-3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]carbamate
• CAS: 1380228-68-1
• 化学式: C₁₉H₂₀F₂N₂O₄
• 分子量: 378.376
• InChiKey: XFMYHMSVUYPBHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl t-butyl (2,4-difluoro-1,3-phenylene)dicarbamate 在 吡啶 、 盐酸 、 palladium on activated charcoal 、 氢气 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 9.0h， 生成 N-(2,4-difluoro-3-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)-2-methylbenzenesulfonamide
  参考文献：
  名称：

  PURINYLPYRIDINYLAMINO-2,4-DIFLUOROPHENYL SULFONAMIDE DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION WITH INHIBITORY ACTIVITY AGAINST RAF KINASE, CONTAINING SAME AS ACTIVE INGREDIENT

  摘要：

  公开号：

  EP2647637B1
• 作为产物：
  描述：

  2,6-二氟-3-硝基苯甲酸 在 sodium azide 、 草酰氯 、 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 41.5h， 生成 benzyl t-butyl (2,4-difluoro-1,3-phenylene)dicarbamate
  参考文献：
  名称：

  PURINYLPYRIDINYLAMINO-2,4-DIFLUOROPHENYL SULFONAMIDE DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION WITH INHIBITORY ACTIVITY AGAINST RAF KINASE, CONTAINING SAME AS ACTIVE INGREDIENT

  摘要：

  公开号：

  EP2647637B1

文献信息

• Discovery of dual inhibitors of <scp>pan‐RAF</scp> and <scp>VEGFR2</scp>
  作者：Eun Sun Park、Jihye Choi、Sung Pyo Hong、Ho‐Seok Kwon、Jinho Kim、Soon Kil Ahn

  DOI：10.1002/bkcs.12721

  日期：2023.10

  45% of colorectal cancer patients. Early-stage BRAF-specific inhibitors have been developed to prevent aberrant activation of RAS/RAF/MEK/ERK signaling caused by K-Ras mutation, however, these BRAF-specific inhibitors lead to RAF dimer formation and paradoxical CRAF activation. Consequently, there is a need to develop pan-RAF inhibitors. In addition, it was reported that the inhibition of vascular

  结直肠癌是全球最常见和致命的恶性肿瘤之一，约 45% 的结直肠癌患者存在 K-RAs 突变。早期 BRAF 特异性抑制剂已被开发用于防止 K-RAs 突变引起的 RAS/RAF/MEK/ERK 信号传导异常激活，然而，这些 BRAF 特异性抑制剂导致 RAF 二聚体形成和矛盾的 CRAF 激活。因此，需要开发泛RAF抑制剂。此外，据报道，抑制血管内皮生长因子受体2（VEGFR2）对于结直肠癌的治疗至关重要。本研究中，我们设计并合成了94个N- (苯基)-3-(9H-嘌呤-6-基)吡啶-2-胺衍生物，并发现N- (5-(3-(9H-嘌呤) -6-基)吡啶-2-基氨基)-2-氟苯基)-3-(三氟甲基)苯甲酰胺 ( 15h )、3-(2-氰基丙烷-2-基)苯甲酰胺衍生物16h和 3,5-双(三氟甲基) ) 苯甲酰胺衍生物17ab是针对 LS513（分别为 GI 50  = 0.08、0.2 和 0
• Pyridine derivative inhibiting RAF kinase and vascular endothelial growth factor receptor, method for preparing same, pharmaceutical composition containing same, and use thereof
  申请人：SAMJIN PHARMACEUTICAL CO., LTD.

  公开号：US10844062B2

  公开（公告）日：2020-11-24

  The present invention provides a novel pyridine derivative, a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient. The pyridine derivative according to the present invention inhibits Raf kinase (B-Raf, Raf-1, or B-RafV600E) and a vascular endothelial growth factor receptor (VEGFR2) involved in angiogenesis, and thus, can be favorably used for the prevention or treatment of melanoma, colorectal cancer, prostate cancer, thyroid cancer, lung cancer, pancreatic cancer, ovarian cancer, or the like, which is induced by RAS mutation.

  本发明提供了一种新型吡啶衍生物、其药学上可接受的盐、制备方法以及含有其作为活性成分的药物组合物。 根据本发明的吡啶衍生物可抑制 RAf 激酶（B-RAf、RAf-1 或 B-RAfV600E）和参与血管生成的血管内皮生长因子受体（VEGFR2），因此可用于预防或治疗由 RAS 突变诱发的黑色素瘤、结直肠癌、前列腺癌、甲状腺癌、肺癌、胰腺癌、卵巢癌等。
• PYRIDINE DERIVATIVES INHIBITING RAF KINASE AND VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR, PHARMACEUTICAL COMPOSITION CONTAINING THEM AND USE THEREOF
  申请人：Samjin Pharmaceutical Co., Ltd.

  公开号：EP3412670B1

  公开（公告）日：2022-03-09
• Pyridine Derivative Inhibiting RAF Kinase and Vascular Endothelial Growth Factor Receptor, Method for Preparing Same, Pharmaceutical Composition Containing Same, and Use Thereof
  申请人：SAMJIN PHARMACEUTICAL CO., LTD.

  公开号：US20190300531A1

  公开（公告）日：2019-10-03

  The present invention provides a novel pyridine derivative, a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient. The pyridine derivative according to the present invention inhibits Raf kinase (B-Raf, Raf-1, or B-RafV600E) and a vascular endothelial growth factor receptor (VEGFR2) involved in angiogenesis, and thus, can be favorably used for the prevention or treatment of melanoma, colorectal cancer, prostate cancer, thyroid cancer, lung cancer, pancreatic cancer, ovarian cancer, or the like, which is induced by RAS mutation.
• [EN] PYRIDINE DERIVATIVE INHIBITING RAF KINASE AND VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR, METHOD FOR PREPARING SAME, PHARMACEUTICAL COMPOSITION CONTAINING SAME, AND USE THEREOF<br/>[FR] RAF KINASE INHIBANT UN DÉRIVÉ PYRIDINE ET RÉCEPTEUR DE FACTEUR DE CROISSANCE ENDOTHÉLIAL VASCULAIRE, PROCÉDÉ POUR LE PRÉPARER, COMPOSITION PHARMACEUTIQUE LE CONTENANT, ET SON UTILISATION<br/>[KO] 라프 키나제 및 혈관내피성장인자 수용체를 저해하는 피리딘 유도체, 이의 제조방법, 이를 포함하는 약제학적 조성물 및 이의 용도
  申请人：SAMJIN PHARM CO LTD

  公开号：WO2017135589A1

  公开（公告）日：2017-08-10

  본 발명은 신규한 피리딘 유도체, 이의 약학적으로 허용 가능한 염, 이의 제조방법, 이를 유효성분으로 함유하는 약학적 조성물을 제공한다. 본 발명에 의한 피리딘 유도체는 모든 라프 키나제(B-Raf, Raf-1, B-RafV600E)와 혈관형성에 관여하는 혈관내피성장인자 수용체(VEGFR2)를 저해함으로서, RAS 돌연변이에 의해 유도되는 흑색종, 대장암, 전립선암, 갑상선암, 폐암, 췌장암 또는 난소암 등의 예방 또는 치료에 유용하게 사용될 수 있다.