| 1138557-14-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• CAS: 1138557-14-8
• 化学式: C₂₄H₂₆N₄O₃S
• 分子量: 450.561
• InChiKey: XETPYKYMWICOFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  32.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  67.15
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  、 2-氨甲基-5-甲基吡嗪 在 aluminum (III) chloride 作用下， 以 二氯甲烷 为溶剂， 生成 2-(4-ethyl-1,4-diazepan-1-yl)-N-[(5-methylpyrazin-2-yl)methyl]-5-oxo-[1,3]benzothiazolo[3,2-a][1,8]naphthyridine-6-carboxamide
  参考文献：
  名称：

  Discovery of CX-5461, the First Direct and Selective Inhibitor of RNA Polymerase I, for Cancer Therapeutics

  摘要：

  Accelerated proliferation of solid tumor and hematologic cancer cells is linked to accelerated transcription of rDNA by the RNA polymerase I (Pol I) enzyme to produce elevated levels of rRNA (rRNA). Indeed, upregulation of Pol I, frequently caused by mutational alterations among tumor suppressors and oncogenes, is required for maintenance of the cancer phenotype and forms the basis for seeking selective inhibitors of Pot I as anticancer therapeutics. 2-(4-Methyl-[1,4]diazepan-1-yl)-5-oxo-5H-7-thia-1,11b-diaza-benzo[c]fluorene-6-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide (CX-5461, 7c) has been identified as the first potent, selective, and orally bioavailable inhibitor of RNA Pot I transcription with in vivo activity in tumor growth efficacy models. The preclinical data support the development of CX-5461 as an anticancer drug with potential for activity in several types of cancer.

  DOI：

  10.1021/ml300110s
• 作为产物：
  描述：

  2,6-二氯烟酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 、 magnesium chloride 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 乙腈 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  Discovery of CX-5461, the First Direct and Selective Inhibitor of RNA Polymerase I, for Cancer Therapeutics

  摘要：

  Accelerated proliferation of solid tumor and hematologic cancer cells is linked to accelerated transcription of rDNA by the RNA polymerase I (Pol I) enzyme to produce elevated levels of rRNA (rRNA). Indeed, upregulation of Pol I, frequently caused by mutational alterations among tumor suppressors and oncogenes, is required for maintenance of the cancer phenotype and forms the basis for seeking selective inhibitors of Pot I as anticancer therapeutics. 2-(4-Methyl-[1,4]diazepan-1-yl)-5-oxo-5H-7-thia-1,11b-diaza-benzo[c]fluorene-6-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide (CX-5461, 7c) has been identified as the first potent, selective, and orally bioavailable inhibitor of RNA Pot I transcription with in vivo activity in tumor growth efficacy models. The preclinical data support the development of CX-5461 as an anticancer drug with potential for activity in several types of cancer.

  DOI：

  10.1021/ml300110s