N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-2-methyl-4-(3-(3-morpholino-5-(trifluoromethyl)phenyl)ureido)-benzamide | 1292282-06-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-2-methyl-4-(3-(3-morpholino-5-(trifluoromethyl)phenyl)ureido)-benzamide
• 英文别名: N-[5-amino-1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-2-methyl-4-[[3-morpholin-4-yl-5-(trifluoromethyl)phenyl]carbamoylamino]benzamide
• CAS: 1292282-06-4
• 化学式: C₃₁H₃₂F₃N₇O₄
• 分子量: 623.635
• InChiKey: WBMUFMLEXDIGKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (4-甲氧苯基)肼盐酸盐 在 盐酸 、 tin(II) chloride dihdyrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.25h， 生成 N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-2-methyl-4-(3-(3-morpholino-5-(trifluoromethyl)phenyl)ureido)-benzamide
  参考文献：
  名称：

  Structure based design and syntheses of amino-1H-pyrazole amide derivatives as selective Raf kinase inhibitors in melanoma cells

  摘要：

  The synthesis of a novel series of N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl amide derivatives 6a-o, 7a-s and their antiproliferative activities against A375P melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-2-methylbenzamide 7c exhibited potent activities (GI(50) = 0.27 mu M). Especially, 7c was found to be a potent and selective B-Raf V600E and C-Raf inhibitor (IC50 = 0.26 mu M, IC50 = 0.11 mu M, respectively), showing a possibility as melanoma therapeutics. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.067

文献信息

• Structure based design and syntheses of amino-1H-pyrazole amide derivatives as selective Raf kinase inhibitors in melanoma cells
  作者：Mi-hyun Kim、Minjung Kim、Hana Yu、Hwan Kim、Kyung Ho Yoo、Taebo Sim、Jung-Mi Hah

  DOI：10.1016/j.bmc.2011.01.067

  日期：2011.3

  The synthesis of a novel series of N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl amide derivatives 6a-o, 7a-s and their antiproliferative activities against A375P melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-2-methylbenzamide 7c exhibited potent activities (GI(50) = 0.27 mu M). Especially, 7c was found to be a potent and selective B-Raf V600E and C-Raf inhibitor (IC50 = 0.26 mu M, IC50 = 0.11 mu M, respectively), showing a possibility as melanoma therapeutics. (C) 2011 Elsevier Ltd. All rights reserved.