N-(5-(2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-3-fluorobenzenesulfonamide | 1422828-33-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(5-(2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-3-fluorobenzenesulfonamide
• CAS: 1422828-33-8
• 化学式: C₁₈H₁₂ClF₂N₃O₃S
• 分子量: 423.827
• InChiKey: VCUZKAJKJVEACE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.63
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  89.02
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-(5-(2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-3-fluorobenzenesulfonamide 在 N-溴代丁二酰亚胺(NBS) 、 氨 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 24.25h， 生成 N-{5-[5-(2-Amino-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-3-fluorobenzenesulfonamide
  参考文献：
  名称：

  Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors

  摘要：

  Hyperactive signaling of the MAP kinase pathway resulting from the constitutively active B-Raf(v600E) mutated enzyme has been observed in a number of human tumors, including melanomas. Herein we report the discovery and biological evaluation of GSK2118436, a selective inhibitor of Raf kinases with potent in vitro activity in oncogenic B-Raf-driven melanoma and colorectal carcinoma cells and robust in vivo antitumor and pharmacodynamic activity in mouse models of B-Raf(v600E) human melanoma. GSK2118436 was identified as a development candidate, and early clinical results have shown significant activity in patients with B-Raf mutant melanoma.

  DOI：

  10.1021/ml4000063
• 作为产物：
  描述：

  Methyl 4-fluoro-3-[(2-methylpropan-2-yl)oxycarbonylamino]benzoate 在 吡啶 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-(5-(2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-3-fluorobenzenesulfonamide
  参考文献：
  名称：

  Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors

  摘要：

  Hyperactive signaling of the MAP kinase pathway resulting from the constitutively active B-Raf(v600E) mutated enzyme has been observed in a number of human tumors, including melanomas. Herein we report the discovery and biological evaluation of GSK2118436, a selective inhibitor of Raf kinases with potent in vitro activity in oncogenic B-Raf-driven melanoma and colorectal carcinoma cells and robust in vivo antitumor and pharmacodynamic activity in mouse models of B-Raf(v600E) human melanoma. GSK2118436 was identified as a development candidate, and early clinical results have shown significant activity in patients with B-Raf mutant melanoma.

  DOI：

  10.1021/ml4000063