1-(4-(2-((N'-((E)-3-phenylacryloyl))hydrazinecarbonyl)pyridin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 1-(4-(2-((N'-((E)-3-phenylacryloyl))hydrazinecarbonyl)pyridin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea
• 英文别名: 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[4-[2-[[[(E)-3-phenylprop-2-enoyl]amino]carbamoyl]pyridin-4-yl]oxyphenyl]urea
• 化学式: C₂₉H₂₁ClF₃N₅O₄
• 分子量: 595.965
• InChiKey: AZKKIRMAFUMKFI-AWNIVKPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.03
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  索拉非尼布杂质 在 hydrazine hydrate 、 水 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(4-(2-((N'-((E)-3-phenylacryloyl))hydrazinecarbonyl)pyridin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  Synthesis and anti-proliferative activity evaluation of sorafenib derivatives with a 3-arylacryloyl hydrazide unit

  摘要：

  A series of sorafenib derivatives with a 3-arylacryloyl hydrazide unit were designed and synthesized, and their anti-proliferative activity against human cancer cell lines (ACHN, HCT116, MDA-MB-231) were evaluated by MTT assay. Most of the synthesized compounds showed superior or similar cytotoxicity against the selected cell lines to the control sorafenib. Among these derivatives, compounds 8a, 8h, 8l, 8m, 11a and 11b showed potent anti-proliferative activity. Compounds 8h and 8m were selected for further evaluation of biological activity against more cancer cell lines. And oral administration of sorafenib analogue 8h at the same dose of sorafenib (30 mg/kg) in the pancreatic cancer Capan2 and Mia-PaCa2 xenograft models in nude mice showed tumour growth inhibition of 60.98 and 54.59 %, respectively, which is similar to the positive control sorafenib.

  DOI：

  10.1007/s00044-014-1249-9