trans-3-[4-(4-acetylpiperazine-1-carbonyl)cyclohexylmethyl]-6-methoxy-1-methyl-1H-quinazoline-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: trans-3-[4-(4-acetylpiperazine-1-carbonyl)cyclohexylmethyl]-6-methoxy-1-methyl-1H-quinazoline-2,4-dione
• 英文别名: 3-[[4-(4-Acetylpiperazine-1-carbonyl)cyclohexyl]methyl]-6-methoxy-1-methylquinazoline-2,4-dione
• 化学式: C₂₄H₃₂N₄O₅
• 分子量: 456.542
• InChiKey: DJNLQIFFCWEOJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  90.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-甲氧基-2-硝基苯甲酸 在 草酰氯 、 palladium on activated charcoal 、 水 、 甲酸铵 、 sodium hydride 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 99.0h， 生成 trans-3-[4-(4-acetylpiperazine-1-carbonyl)cyclohexylmethyl]-6-methoxy-1-methyl-1H-quinazoline-2,4-dione
  参考文献：
  名称：

  Structure–activity relationship and properties optimization of a series of Quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway

  摘要：

  Wnt signaling pathway plays a critical role in numerous cellular processes, including tumor initiation, proliferation, invasion/infiltration, metastasis formation and resistance to chemotherapy. In a drug discovery project aimed at the identification of inhibitors of the canonical Wnt pathway, we selected a series of quinazoline 2,4-diones as starting point for the therapeutic treatment of glioblastoma multiforme. Despite of poor physico-chemical properties of hit compound I, our medicinal chemistry effort allowed the discovery and characterization of lead compound 33 (SEN461), with improved ADME profile, good bioavailability and active in vitro and in vivo in glioblastoma, gastric and sarcoma tumors. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.055

文献信息

• Structure–activity relationship and properties optimization of a series of Quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway
  作者：Arianna Nencini、Carmela Pratelli、Joanna M. Quinn、Massimiliano Salerno、Patrizia Tunici、Alessandra De Robertis、Silvia Valensin、Federica Mennillo、Marco Rossi、Annette Bakker、Tiziana Benicchi、Federico Cappelli、Elisa Turlizzi、Martina Nibbio、Nicola P. Caradonna、Ugo Zanelli、Matteo Andreini、Matteo Magnani、Maurizio Varrone

  DOI：10.1016/j.ejmech.2015.03.055

  日期：2015.5

  Wnt signaling pathway plays a critical role in numerous cellular processes, including tumor initiation, proliferation, invasion/infiltration, metastasis formation and resistance to chemotherapy. In a drug discovery project aimed at the identification of inhibitors of the canonical Wnt pathway, we selected a series of quinazoline 2,4-diones as starting point for the therapeutic treatment of glioblastoma multiforme. Despite of poor physico-chemical properties of hit compound I, our medicinal chemistry effort allowed the discovery and characterization of lead compound 33 (SEN461), with improved ADME profile, good bioavailability and active in vitro and in vivo in glioblastoma, gastric and sarcoma tumors. (C) 2015 Elsevier Masson SAS. All rights reserved.