N-(4-acetylphenyl)-4-(2-((4-thiomorpholinophenyl)amino)pyrimidin-4-yl)piperazine-1-carboxamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(4-acetylphenyl)-4-(2-((4-thiomorpholinophenyl)amino)pyrimidin-4-yl)piperazine-1-carboxamide
• 英文别名: N-(4-acetylphenyl)-4-(2-{[4-(4-thiomorpholinyl)phenyl]amino}pyrimidin-4-yl)piperazine-1-carboxamide；N-(4-acetylphenyl)-4-[2-(4-thiomorpholin-4-ylanilino)pyrimidin-4-yl]piperazine-1-carboxamide
• 化学式: C₂₇H₃₁N₇O₂S
• 分子量: 517.655
• InChiKey: AREIPKJSJWXHTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氯-4-(4-BOC-1-哌嗪基)嘧啶 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 13.0h， 生成 N-(4-acetylphenyl)-4-(2-((4-thiomorpholinophenyl)amino)pyrimidin-4-yl)piperazine-1-carboxamide
  参考文献：
  名称：

  Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3

  摘要：

  Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives. All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the "A" phenyl ring and "B" phenyl ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G(1)/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111590