N-[[1-[[2-(diethylamino)ethyl]amino]-9-oxothioxanthen-4-yl]methyl]diethyl phosphoramide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫色烯
• 英文名称: N-[[1-[[2-(diethylamino)ethyl]amino]-9-oxothioxanthen-4-yl]methyl]diethyl phosphoramide
• 英文别名: 4-[(Diethoxyphosphorylamino)methyl]-1-[2-(diethylamino)ethylamino]thioxanthen-9-one
• 化学式: C₂₄H₃₄N₃O₄PS
• 分子量: 491.591
• InChiKey: OISBITGINOJOCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-[1-(2-diethylamino-ethylamino)-7-methoxy-9-oxo-9H-thioxanthen-4-ylmethyl]formamide 在 盐酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 生成 N-[[1-[[2-(diethylamino)ethyl]amino]-9-oxothioxanthen-4-yl]methyl]diethyl phosphoramide
  参考文献：
  名称：

  Synthesis and Antitumor Activity of 4-Aminomethylthioxanthenone and 5-Aminomethylbenzothiopyranoindazole Derivatives

  摘要：

  Two new series of antitumor agents, 4-aminomethylthioxanthenones (6-50) and 5-aminomethylbenzothiopyranoindazoles (51-61), are described and compared. Nearly all members of both series display excellent in vivo activity versus murine pancreatic adenocarcinoma 03 (Panc03) although there is little to distinguish the two series from each other. In both series there is no discernible relationship between structure and in vivo efficacy. Selected analogues were evaluated in vitro; all were observed to have moderate to strong DNA binding via intercalation. However, varying degrees of in vitro P388 cytotoxicity and topoisomerase II inhibition were seen. In general, those molecules which exhibited strong topoisomerase II inhibition were significantly more cytotoxic than those which did not. In both series, those derivatives (48-50, 60, and 61) having a phenolic hydroxy substitution exhibited the most potent P388 cytotoxicity and topoisomerase II inhibition.

  DOI：

  10.1021/jm9708083

文献信息

• Thioxanthenone antitumor agents
  申请人：Sanofi-Aventis

  公开号：EP1197491B1

  公开（公告）日：2004-12-29
• Synthesis and Antitumor Activity of 4-Aminomethylthioxanthenone and 5-Aminomethylbenzothiopyranoindazole Derivatives
  作者：Robert B. Perni、Mark P. Wentland、Jianhua I. Huang、Ronald G. Powles、Suzanne Aldous、Kristina M. Klingbeil、A. Danielle Peverly、Ronald G. Robinson、Thomas H. Corbett、Julie L. Jones、Kenneth C. Mattes、James B. Rake、Susan A. Coughlin

  DOI：10.1021/jm9708083

  日期：1998.9.1

  Two new series of antitumor agents, 4-aminomethylthioxanthenones (6-50) and 5-aminomethylbenzothiopyranoindazoles (51-61), are described and compared. Nearly all members of both series display excellent in vivo activity versus murine pancreatic adenocarcinoma 03 (Panc03) although there is little to distinguish the two series from each other. In both series there is no discernible relationship between structure and in vivo efficacy. Selected analogues were evaluated in vitro; all were observed to have moderate to strong DNA binding via intercalation. However, varying degrees of in vitro P388 cytotoxicity and topoisomerase II inhibition were seen. In general, those molecules which exhibited strong topoisomerase II inhibition were significantly more cytotoxic than those which did not. In both series, those derivatives (48-50, 60, and 61) having a phenolic hydroxy substitution exhibited the most potent P388 cytotoxicity and topoisomerase II inhibition.