(2Z,4E)-2-(1H-benzimidazolyl)-1-(4-chlorophenyl)-5-phenylpenta-2,4-dienone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: (2Z,4E)-2-(1H-benzimidazolyl)-1-(4-chlorophenyl)-5-phenylpenta-2,4-dienone
• 英文别名: (2Z,4E)-2-(benzimidazol-1-yl)-1-(4-chlorophenyl)-5-phenylpenta-2,4-dien-1-one
• 化学式: C₂₄H₁₇ClN₂O
• 分子量: 384.865
• InChiKey: OXAFVIWHLUHASQ-LMKPGGDOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2'-溴-4-氯苯乙酮 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 4.0h， 生成 (2Z,4E)-2-(1H-benzimidazolyl)-1-(4-chlorophenyl)-5-phenylpenta-2,4-dienone
  参考文献：
  名称：

  Design and synthesis of new non nucleoside inhibitors of DNMT3A

  摘要：

  DNA methylation, an epigenetic modification regulating gene expression, is a promising target in cancer. In an effort to identify new non nucleosidic inhibitors of DNA methyltransferases, the enzymes responsible for DNA methylation, we carried out a high-throughput screening of 66,000 chemical compounds based on an enzymatic assay against catalytic DNMT3A. A family of propiophenone derivatives was identified. After chemical optimization and structure activity relationship studies, a new inhibitor ( 33) was obtained with an EC50 of 2.1 mu M against DNMT3A. The mechanism of inhibition of the compound was investigated as it forms a reactive Michael acceptor group in situ. Thereby, the Michael acceptor 20 was identified. This compound was further characterized for its biological activity in cancer cells. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.066

文献信息

• Design and synthesis of new non nucleoside inhibitors of DNMT3A
  作者：Alexandre Erdmann、Yoann Menon、Christina Gros、Nicolas Molinier、Natacha Novosad、Arnaud Samson、Jean-Marc Gregoire、Christophe Long、Frédéric Ausseil、Ludovic Halby、Paola B. Arimondo

  DOI：10.1016/j.bmc.2015.06.066

  日期：2015.9

  DNA methylation, an epigenetic modification regulating gene expression, is a promising target in cancer. In an effort to identify new non nucleosidic inhibitors of DNA methyltransferases, the enzymes responsible for DNA methylation, we carried out a high-throughput screening of 66,000 chemical compounds based on an enzymatic assay against catalytic DNMT3A. A family of propiophenone derivatives was identified. After chemical optimization and structure activity relationship studies, a new inhibitor ( 33) was obtained with an EC50 of 2.1 mu M against DNMT3A. The mechanism of inhibition of the compound was investigated as it forms a reactive Michael acceptor group in situ. Thereby, the Michael acceptor 20 was identified. This compound was further characterized for its biological activity in cancer cells. (C) 2015 Elsevier Ltd. All rights reserved.