5-{(1,4-Dioxido-1,2,4-benzotriazin-3-yl)aminopentyl}-2,2,2,-trifluoroacetamide | 1073136-50-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 5-{(1,4-Dioxido-1,2,4-benzotriazin-3-yl)aminopentyl}-2,2,2,-trifluoroacetamide
• 英文别名: TX-2240；N-[5-[(1,4-dioxido-1,2,4-benzotriazine-1,4-diium-3-yl)amino]pentyl]-2,2,2-trifluoroacetamide
• CAS: 1073136-50-1
• 化学式: C₁₄H₁₆F₃N₅O₃
• 分子量: 359.308
• InChiKey: MDHHHGKCARZJOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-{(1,4-Dioxido-1,2,4-benzotriazin-3-yl)aminopentyl}-2,2,2,-trifluoroacetamide 在 甲醇 、 氨 、 水 、 盐酸 作用下， 以 水 为溶剂， 反应 144.0h， 以100%的产率得到[5-(1,4-Dioxido-1,2,4-benzotriazine-3-yl)pentyl]-1,5-pentanediamine hydrochloride
  参考文献：
  名称：

  Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as hypoxia-targeting indoleamine 2,3-dioxygenase inhibitors

  摘要：

  We have designed and synthesized new hypoxic-neoplastic cells-targeted indoleamine 2,3-dioxygenase (IDO) inhibitors. 1-Methyl-tryptophan (1MT)-tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-dioxide) hybrid inhibitors including 1 (TX-2236), 2 (TX-2235), 3 (TX-2228), and 4 (TX-2234) were prepared. All of these compounds were uncompetitive IDO inhibitors. TPZ-monoxide hybrids 1 and 3 showed higher IDO inhibitory activities than TPZ hybrids 2 and 4. Among these hybrids, hybrid 1 was the most potent IDO inhibitor. TPZ hybrids 2 and 4 showed stronger hypoxia-selective cytotoxicity than TPZ to EMT6/KU cells. These data suggest that TPZ hybrids 2 and 4 may act through their dual biological functions: first, they function as hypoxic cytotoxins in hypoxic cells, and then are metabolized to their TPZ-monoxide (3-amino-1,2,4-benzotriazine 1-oxide) hybrids, which function as IDO inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.087
• 作为产物：
  描述：

  5-{(1-Oxido-1,2,4-benzotriazin-3-yl)aminopentyl}-2,2,2-trifluoroacetamide 在 水 、 双氧水 、 三氟乙酸酐 作用下， 反应 24.0h， 以52%的产率得到5-{(1,4-Dioxido-1,2,4-benzotriazin-3-yl)aminopentyl}-2,2,2,-trifluoroacetamide
  参考文献：
  名称：

  Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as hypoxia-targeting indoleamine 2,3-dioxygenase inhibitors

  摘要：

  We have designed and synthesized new hypoxic-neoplastic cells-targeted indoleamine 2,3-dioxygenase (IDO) inhibitors. 1-Methyl-tryptophan (1MT)-tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-dioxide) hybrid inhibitors including 1 (TX-2236), 2 (TX-2235), 3 (TX-2228), and 4 (TX-2234) were prepared. All of these compounds were uncompetitive IDO inhibitors. TPZ-monoxide hybrids 1 and 3 showed higher IDO inhibitory activities than TPZ hybrids 2 and 4. Among these hybrids, hybrid 1 was the most potent IDO inhibitor. TPZ hybrids 2 and 4 showed stronger hypoxia-selective cytotoxicity than TPZ to EMT6/KU cells. These data suggest that TPZ hybrids 2 and 4 may act through their dual biological functions: first, they function as hypoxic cytotoxins in hypoxic cells, and then are metabolized to their TPZ-monoxide (3-amino-1,2,4-benzotriazine 1-oxide) hybrids, which function as IDO inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.087

文献信息

• Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as hypoxia-targeting indoleamine 2,3-dioxygenase inhibitors
  作者：Hitomi Nakashima、Yoshihiro Uto、Eiji Nakata、Hideko Nagasawa、Kazuhiro Ikkyu、Noriko Hiraoka、Kouichiro Nakashima、Yuki Sasaki、Hiroshi Sugimoto、Yoshitsugu Shiro、Toshihiro Hashimoto、Yasuko Okamoto、Yoshinori Asakawa、Hitoshi Hori

  DOI：10.1016/j.bmc.2008.07.087

  日期：2008.9

  We have designed and synthesized new hypoxic-neoplastic cells-targeted indoleamine 2,3-dioxygenase (IDO) inhibitors. 1-Methyl-tryptophan (1MT)-tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-dioxide) hybrid inhibitors including 1 (TX-2236), 2 (TX-2235), 3 (TX-2228), and 4 (TX-2234) were prepared. All of these compounds were uncompetitive IDO inhibitors. TPZ-monoxide hybrids 1 and 3 showed higher IDO inhibitory activities than TPZ hybrids 2 and 4. Among these hybrids, hybrid 1 was the most potent IDO inhibitor. TPZ hybrids 2 and 4 showed stronger hypoxia-selective cytotoxicity than TPZ to EMT6/KU cells. These data suggest that TPZ hybrids 2 and 4 may act through their dual biological functions: first, they function as hypoxic cytotoxins in hypoxic cells, and then are metabolized to their TPZ-monoxide (3-amino-1,2,4-benzotriazine 1-oxide) hybrids, which function as IDO inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.