tert-butyl (E)-3-[5-[(E)-3-[3-(4-methylpiperazin-1-yl)phenyl]-3-oxoprop-1-enyl]pyridin-2-yl]prop-2-enoate | 1204230-95-4

• 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: tert-butyl (E)-3-[5-[(E)-3-[3-(4-methylpiperazin-1-yl)phenyl]-3-oxoprop-1-enyl]pyridin-2-yl]prop-2-enoate
• CAS: 1204230-95-4
• 化学式: C₂₆H₃₁N₃O₃
• 分子量: 433.55
• InChiKey: ZSNABIHDGOQMMD-RBDPUHSXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  62.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl (E)-3-[5-[(E)-3-[3-(4-methylpiperazin-1-yl)phenyl]-3-oxoprop-1-enyl]pyridin-2-yl]prop-2-enoate 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 18.0h， 以64%的产率得到(E)-3-(5-{(E)-3-[3-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid bis-trifluoroacetate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of N-Hydroxyphenylacrylamides and N-Hydroxypyridin-2-ylacrylamides as Novel Histone Deacetylase Inhibitors

  摘要：

  The historic deacetylases (HDACs) are able to regulate gene expression, and historic deacetylase inhibitors (HDACi) emerged as a new class of agents in the treatment of cancer as well as other human disorders such as neurodegenerative diseases. In the present investigation, we report on the synthesis and biological evaluation of compounds derived from the expansion of a HDAC inhibitor scaffold having N-hydroxy-3-phenyl-2-propenamide and N-hydroxy-3-(pyridin-2-yl)-2-propenamide as core structures and containing a phenyloxopropenyl moiety, either unsubstituted or substituted by a 4-methylpiperazin-1-yl or 4-methylpiperazin-1-ylmethyl group. The compounds were evaluated for their ability to inhibit nuclear HDACs, as well as for their in vitro antiproliferative activity. Moreover, their metabolic stability in microsomes and aqueous Solubility were studied and selected compounds were further characterized by in vivo pharmacokinetic experiments. These compounds showed a remarkable stability in vivo, compared to hydroxamic acid HDAC inhibitors that have already entered clinical trials. The representative compound 30b showed in vivo antitumor activity in a human colon carcinoma xenograft model.

  DOI：

  10.1021/jm901502p
• 作为产物：
  描述：

  (E)-3-(5-formylpyridin-2-yl)acrylic acid tert-butyl ester 、 1-[3-(4-甲基-1-哌嗪)-苯基]-乙酮 在 氢氧化钾 、 乙醇 作用下， 反应 4.0h， 生成 tert-butyl (E)-3-[5-[(E)-3-[3-(4-methylpiperazin-1-yl)phenyl]-3-oxoprop-1-enyl]pyridin-2-yl]prop-2-enoate
  参考文献：
  名称：

  WO2007/113249

  摘要：

  公开号：