2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((7-(hydroxyamino)-7-oxoheptyl)amino)-3-nitrophenyl)sulfonyl)benzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((7-(hydroxyamino)-7-oxoheptyl)amino)-3-nitrophenyl)sulfonyl)benzamide
• 英文别名: 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[7-(hydroxyamino)-7-oxoheptyl]amino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
• 化学式: C₄₆H₅₃ClN₈O₈S
• 分子量: 913.495
• InChiKey: FQNRJUPFEMJKDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  64
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  223
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  7-氨基庚酸乙酯(或盐酸盐) 在 4-二甲氨基吡啶 、 盐酸羟胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 35.03h， 生成 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((7-(hydroxyamino)-7-oxoheptyl)amino)-3-nitrophenyl)sulfonyl)benzamide
  参考文献：
  名称：

  Design, synthesis, and bioactivity evaluation of novel Bcl-2/HDAC dual-target inhibitors for the treatment of multiple myeloma

  摘要：

  Multiple myeloma (MM) is the second most common haematological malignancy. Almost all patients with MM eventually relapse, and most recommended treatment protocols for the patients with relapsed refractory MM comprise a combination of drugs with different mechanisms of action. Therefore novel drugs are in urgent need in clinic. Bcl-2 inhibitors and HDAC inhibitors were proved their anti-MM effect in clinic or under clinical trials, and they were further discovered to have synergistic interactions. In this study, a series of Bcl-2/HDAC dual-target inhibitors were designed and synthesized. Among them, compounds 7e-7g showed good inhibitory activities against HDAC6 and high binding affinities to Bcl-2 protein simultaneously. They also displayed good growth inhibitory activities against human MM cell line RPMI-8226, which proved their potential value for the treatment of multiple myeloma.

  DOI：

  10.1016/j.bmcl.2018.12.052