2,7-bis(hydroxymethyl)pyrimido[4,5-g]quinazoline-4,9-(3H,8H)-dione | 479065-46-8

• 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: 2,7-bis(hydroxymethyl)pyrimido[4,5-g]quinazoline-4,9-(3H,8H)-dione
• 英文别名: 2,7-Bis(hydroxymethyl)-3,8-dihydropyrimido[4,5-g]quinazoline-4,9-dione；2,7-bis(hydroxymethyl)-3,8-dihydropyrimido[4,5-g]quinazoline-4,9-dione
• CAS: 479065-46-8
• 化学式: C₁₂H₁₀N₄O₄
• 分子量: 274.236
• InChiKey: SMYHVNQADQJFPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,7-bis(hydroxymethyl)pyrimido[4,5-g]quinazoline-4,9-(3H,8H)-dione 在 吡啶 、 甲基磺酰氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.33h， 以52%的产率得到2,7-Bis(chloromethyl)-3,8-dihydropyrimido[4,5-g]quinazoline-4,9-dione
  参考文献：
  名称：

  Pyrimidoquinazoline-Based Antitumor Agents. Design of Topoisomerase II to DNA Cross-linkers with Activity against Protein Kinases

  摘要：

  A series of pyrimidoquinazoline analogues, possessing either 4,5-g or 5,4-g fusion, were studied with respect to cytotoxicity, topoisomerase II inhibitory activity, in vivo activity, and DNA cleavage and DNA-protein cross-linking properties. These analogues were designed as electron-deficient anthraquinones with dual alkylating centers to cross-link DNA with topoisomerase II. Our studies verified the presence of DNA-protein cross-linking in vitro as well as topoisomerase II poisoning by pyrimidoquinazoline analogues. In addition, COMPARE analysis revealed that the pyrimidoquinazolines possess inhibitory activity against both topoisomerase II and protein kinases, such as the paullones, a dual property observed in other antineoplastic agents influencing phosphoester transfer.

  DOI：

  10.1021/jm020285l
• 作为产物：
  描述：

  2-(methoxyacetamido)terephthalic acid diethyl ester 在 palladium on activated charcoal 吡啶 、 氢溴酸 、 氢气 、 硝酸 、 一水合肼 、 溶剂黄146 、 potassium nitrate 作用下， 以 甲醇 、 乙醇 、 苯 为溶剂， 反应 54.0h， 生成 2,7-bis(hydroxymethyl)pyrimido[4,5-g]quinazoline-4,9-(3H,8H)-dione
  参考文献：
  名称：

  Pyrimidoquinazoline-Based Antitumor Agents. Design of Topoisomerase II to DNA Cross-linkers with Activity against Protein Kinases

  摘要：

  A series of pyrimidoquinazoline analogues, possessing either 4,5-g or 5,4-g fusion, were studied with respect to cytotoxicity, topoisomerase II inhibitory activity, in vivo activity, and DNA cleavage and DNA-protein cross-linking properties. These analogues were designed as electron-deficient anthraquinones with dual alkylating centers to cross-link DNA with topoisomerase II. Our studies verified the presence of DNA-protein cross-linking in vitro as well as topoisomerase II poisoning by pyrimidoquinazoline analogues. In addition, COMPARE analysis revealed that the pyrimidoquinazolines possess inhibitory activity against both topoisomerase II and protein kinases, such as the paullones, a dual property observed in other antineoplastic agents influencing phosphoester transfer.

  DOI：

  10.1021/jm020285l