12-Oxo-N-(2-phenylethyl)-12H-5,13-diazatetracene-4-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 12-Oxo-N-(2-phenylethyl)-12H-5,13-diazatetracene-4-carboxamide
• 英文别名: 12-oxo-N-(2-phenylethyl)-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide
• 化学式: C₂₅H₁₉N₃O₂
• mdl: MFCD15093128
• 分子量: 393.4
• InChiKey: XOVGTKRHLZWGPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  3

文献信息

• COMPOUNDS WHICH INHIBIT RNA POLYMERASE, COMPOSITIONS INCLUDING SUCH COMPOUNDS, AND THEIR USE
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20170081322A1

  公开（公告）日：2017-03-23

  RNA polymerase I (Pol I) is a dedicated polymerase for the transcription of the 47S ribosomal RNA precursor subsequently processed into the mature 5.8S, 18S and 28S ribosomal RNAs and assembled into ribosomes in the nucleolus. Pol I activity is commonly deregulated in human cancers. Based on the discovery of lead molecule BMH-21, a series of pyridoquinazolinecarboxamides were synthesized as inhibitors of Pol I and activators of the destruction of RPA194, the Pol I large catalytic subunit protein. The present invention identifies a set of bioactive compounds, including purified stereoisomers, that potently cause RPA194 degradation that function in a tightly constrained chemical space. Pharmaceutical compositions comprising these compounds and their uses in cancer and other Pol I related diseases is also provided.