4-(4-methyl-[1,4]diazepan-1-yl)-2-phenylquinazoline | 852466-45-6

• 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: 4-(4-methyl-[1,4]diazepan-1-yl)-2-phenylquinazoline
• 英文别名: 4-(4-Methyl-1,4-diazepan-1-yl)-2-phenylquinazoline
• CAS: 852466-45-6
• 化学式: C₂₀H₂₂N₄
• 分子量: 318.421
• InChiKey: YDIQMWNBIRADSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  32.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-甲基高哌嗪 、 4-氯-2-苯基喹唑啉 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 24.0h， 以88%的产率得到4-(4-methyl-[1,4]diazepan-1-yl)-2-phenylquinazoline
  参考文献：
  名称：

  Design and synthesis of 4-amino-2-phenylquinazolines as novel topoisomerase I inhibitors with molecular modeling

  摘要：

  4-Amino-2-phenylquinazolines 7 were designed as bioisosteres of 3-arylisoquinolinamines 6 that were energy minimized to provide stable conformers. Interestingly, the 2-phenyl ring of 4-amino-2-phenylquinazolines was parallel to the quinazoline ring and improved their DNA intercalation ability in the DNA-topo I complex. Among the synthesized 4-amino group-substituted analogs, 4-cyclohexylamino-2-phenylquinazoline 7h exhibited potent topo I inhibitory activity and strong cytotoxicity. Interestingly, consistency was observed between the cytotoxicities and topo I activities in these quinazoline analogs, suggesting that the target of 4-amino-2-phenylquinazolines is limited to topo I. Molecular docking studies were performed with the Surflex-Dock program to afford the ideal interaction mode of the compound into the binding site of the DNA-topo I complex in order to clarify the topo I activity of 7h. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.05.012

文献信息

• Design and synthesis of 4-amino-2-phenylquinazolines as novel topoisomerase I inhibitors with molecular modeling
  作者：Thanh Nguyen Le、Su Hui Yang、Daulat Bikram Khadka、Hue Thi My Van、Suk Hee Cho、Youngjoo Kwon、Eung-Seok Lee、Kyung-Tae Lee、Won-Jea Cho

  DOI：10.1016/j.bmc.2011.05.012

  日期：2011.7

  4-Amino-2-phenylquinazolines 7 were designed as bioisosteres of 3-arylisoquinolinamines 6 that were energy minimized to provide stable conformers. Interestingly, the 2-phenyl ring of 4-amino-2-phenylquinazolines was parallel to the quinazoline ring and improved their DNA intercalation ability in the DNA-topo I complex. Among the synthesized 4-amino group-substituted analogs, 4-cyclohexylamino-2-phenylquinazoline 7h exhibited potent topo I inhibitory activity and strong cytotoxicity. Interestingly, consistency was observed between the cytotoxicities and topo I activities in these quinazoline analogs, suggesting that the target of 4-amino-2-phenylquinazolines is limited to topo I. Molecular docking studies were performed with the Surflex-Dock program to afford the ideal interaction mode of the compound into the binding site of the DNA-topo I complex in order to clarify the topo I activity of 7h. (C) 2011 Elsevier Ltd. All rights reserved.