(E)-N-hydroxy-3-(1-methyl-1H-pyrrol-2-yl)acrylamide | 1204230-67-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (E)-N-hydroxy-3-(1-methyl-1H-pyrrol-2-yl)acrylamide
• 英文别名: (E)-N-hydroxy-3-(1-methylpyrrol-2-yl)prop-2-enamide
• CAS: 1204230-67-0
• 化学式: C₈H₁₀N₂O₂
• 分子量: 166.18
• InChiKey: GKQWZKRNDXGPEF-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  54.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 1.0h， 以86 mg的产率得到(E)-N-hydroxy-3-(1-methyl-1H-pyrrol-2-yl)acrylamide
  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

文献信息

• SELECTIVE INHIBITORS OF HISTONE DEACETYLASE
  申请人：Verner Erik

  公开号：US20110081409A1

  公开（公告）日：2011-04-07

  Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of HDAC8 activity.

  本文描述了一些化合物和含有这些化合物的药物组合物，这些化合物可以抑制组蛋白去乙酰化酶8（HDAC8）的活性。本文还描述了使用这些HDAC8抑制剂的方法，单独或与其他化合物联合使用，用于治疗需要抑制HDAC8活性的疾病或症状。
• SELECTIVE INHIBITORS OF HISTONE DEACTYLASE
  申请人：Pharmacyclics, Inc.

  公开号：US20150320758A1

  公开（公告）日：2015-11-12

  Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of HDAC8 activity.

  本文介绍了一些化合物和含有这些化合物的药物组成物，它们可以抑制组蛋白去乙酰化酶8（HDAC8）的活性。本文还介绍了使用这些HDAC8抑制剂的方法，单独或与其他化合物结合，用于治疗需要抑制HDAC8活性的疾病或病况。
• US8466193B2
  申请人：——

  公开号：US8466193B2

  公开（公告）日：2013-06-18
• US8906954B2
  申请人：——

  公开号：US8906954B2

  公开（公告）日：2014-12-09