4-[3-Isocyanato-5-(trifluoromethyl)phenyl]morpholine | 1236202-86-0

• 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: 4-[3-Isocyanato-5-(trifluoromethyl)phenyl]morpholine
• CAS: 1236202-86-0
• 化学式: C₁₂H₁₁F₃N₂O₂
• 分子量: 272.227
• InChiKey: PNXLSYACLFXASE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.51
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  41.9
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-[3-Isocyanato-5-(trifluoromethyl)phenyl]morpholine 、 N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-2-methyl-4-aminobenzamide 以 四氢呋喃 为溶剂， 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
• 作为产物：
  描述：

  叠氮磷酸二苯酯 、 3-吗啉-5-(三氟甲基)苯甲酸 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 4.0h， 生成 4-[3-Isocyanato-5-(trifluoromethyl)phenyl]morpholine
  参考文献：
  名称：

  WO2007/4749

  摘要：

  公开号：

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.
• Design and synthesis of new anticancer pyrimidines with multiple-kinase inhibitory effect
  作者：Ibrahim Mustafa El-Deeb、So Ha Lee

  DOI：10.1016/j.bmc.2010.04.037

  日期：2010.6.1

  A new series of N-substituted-2-aminopyrimidines based on the '4-(pyridin-3-yl)pyrimidin-2-amine' scaffold of Imatinib has been designed and synthesized. A selected group from the target compounds was tested over a panel of 60 cancer cell lines at a single dose concentration of 10 mu M, and the two most active compounds, 25b and 30, were further tested in a five-dose testing mode to determine their IC50 values over the 60 cell lines. Compound 30 has showed good potencies and high efficacies, and was accordingly tested at a single dose concentration of 10 mu M over a panel of 54 kinases. At this concentration, the compound has showed multiple inhibitions over a number of oncogenic kinases, including ABL1, AKT1, LCK, C-SRC, PIM1, FLT3, FYN, and KDR. A molecular modeling study was made by docking of the most active compound 30 and its inactive analog 29 into the kinase domain of ABL1 to investigate their possible binding interactions. (C) 2010 Elsevier Ltd. All rights reserved.
• 1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives: A novel type II Raf kinase inhibitors
  作者：Hana Yu、Yunkyung Jung、Hwan Kim、Junghun Lee、Chang-Hyun Oh、Kyung Ho Yoo、Taebo Sim、Jung-Mi Hah

  DOI：10.1016/j.bmcl.2010.04.039

  日期：2010.6

  The synthesis of a novel series of 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives 1a-b, 2a-v and their antiproliferative activities against A375P and WM3629 human melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, pyrazoloimidazole phenyl urea compounds 2a, 2d, 2g, 2i, 2t exhibited potent activities on WM3629 cell lines (IC50 = 0.56-0.86 mu M). Especially, 2t was found to be a potent and selective C-Raf inhibitor, showing a possibility as melanoma therapeutics. (C) 2010 Elsevier Ltd. All rights reserved.