1-(3-(1-(4-methoxybenzyl)-7-oxo-1,6,7,8-tetrahydropyrazolo[3,4-b][1,4]diazepin-5-yl)phenyl)-3-(3-morpholino-5-(trifluoromethyl)phenyl)urea | 1346441-20-0

• 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: 1-(3-(1-(4-methoxybenzyl)-7-oxo-1,6,7,8-tetrahydropyrazolo[3,4-b][1,4]diazepin-5-yl)phenyl)-3-(3-morpholino-5-(trifluoromethyl)phenyl)urea
• 英文别名: 1-[3-[1-[(4-Methoxyphenyl)methyl]-7-oxo-6,8-dihydropyrazolo[3,4-b][1,4]diazepin-5-yl]phenyl]-3-[3-morpholin-4-yl-5-(trifluoromethyl)phenyl]urea；1-[3-[1-[(4-methoxyphenyl)methyl]-7-oxo-6,8-dihydropyrazolo[3,4-b][1,4]diazepin-5-yl]phenyl]-3-[3-morpholin-4-yl-5-(trifluoromethyl)phenyl]urea
• CAS: 1346441-20-0
• 化学式: C₃₂H₃₀F₃N₇O₄
• 分子量: 633.63
• InChiKey: APHJYVNGEUCYPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  46
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-硝基苯甲酰乙酸乙酯 在 铁粉 、 氯化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 28.5h， 生成 1-(3-(1-(4-methoxybenzyl)-7-oxo-1,6,7,8-tetrahydropyrazolo[3,4-b][1,4]diazepin-5-yl)phenyl)-3-(3-morpholino-5-(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  Syntheses of phenylpyrazolodiazepin-7-ones as conformationally rigid analogs of aminopyrazole amide scaffold and their antiproliferative effects on cancer cells

  摘要：

  Recently, we have reported the syntheses and antiproliferative activities of N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl amide derivatives on melanoma cells. As a continuous work for antiproliferative agents in melanoma, here we report the synthesis of conformationally rigid analogs, phenyl-6,8-dihydropyrazolo[3,4-b][1,4] diazepin-7(1H)-one derivatives7a-g, 8a-o and their antiproliferative activities against A375P melanoma cell line and U937 hematopoietic cell line. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(3-(1-benzyl-7-oxo-1,6, 7,8-tetrahydropyrazolo[3,4-b][1,4]diazepin-5-yl)phenyl)-4-chloro-3-(trifluoro methyl)benzamide-amino1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-(3-(4-chloro-3-(trifluoromethyl) phenyl) ureido)-2-methylbenzamide (7b) exhibited potent activities (GI(50) = 0.43 mu M and 0.06 mu M) on both cell lines. It has been further confirmed to be a potent and selective Raf kinases inhibitor and also mild inhibitor of PI3K alpha. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.042

文献信息

• Syntheses of phenylpyrazolodiazepin-7-ones as conformationally rigid analogs of aminopyrazole amide scaffold and their antiproliferative effects on cancer cells
  作者：Hyangmi Kim、Minjung Kim、Junghun Lee、Hana Yu、Jung-Mi Hah

  DOI：10.1016/j.bmc.2011.09.042

  日期：2011.11

  Recently, we have reported the syntheses and antiproliferative activities of N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl amide derivatives on melanoma cells. As a continuous work for antiproliferative agents in melanoma, here we report the synthesis of conformationally rigid analogs, phenyl-6,8-dihydropyrazolo[3,4-b][1,4] diazepin-7(1H)-one derivatives7a-g, 8a-o and their antiproliferative activities against A375P melanoma cell line and U937 hematopoietic cell line. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(3-(1-benzyl-7-oxo-1,6, 7,8-tetrahydropyrazolo[3,4-b][1,4]diazepin-5-yl)phenyl)-4-chloro-3-(trifluoro methyl)benzamide-amino1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-(3-(4-chloro-3-(trifluoromethyl) phenyl) ureido)-2-methylbenzamide (7b) exhibited potent activities (GI(50) = 0.43 mu M and 0.06 mu M) on both cell lines. It has been further confirmed to be a potent and selective Raf kinases inhibitor and also mild inhibitor of PI3K alpha. (C) 2011 Elsevier Ltd. All rights reserved.