[5-(1-Oxido-1,2,4-benzotriazin-3-yl)aminopentyl]-(2S)-N-tert-butoxycarbonyl-2-amino-(1-methyl-indole-3-yl)propanamide | 1073136-27-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: [5-(1-Oxido-1,2,4-benzotriazin-3-yl)aminopentyl]-(2S)-N-tert-butoxycarbonyl-2-amino-(1-methyl-indole-3-yl)propanamide
• 英文别名: TX-2236；tert-butyl N-[(2S)-3-(1-methylindol-3-yl)-1-[5-[(1-oxido-1,2,4-benzotriazin-1-ium-3-yl)amino]pentylamino]-1-oxopropan-2-yl]carbamate
• CAS: 1073136-27-2
• 化学式: C₂₉H₃₇N₇O₄
• 分子量: 547.657
• InChiKey: NYXSHUBZGVSBBX-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  [5-(1-Oxido-1,2,4-benzotriazine-3-yl)pentyl]-1,5-pentanediamine 、 N-boc-1-甲基-L-色氨酸 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以99%的产率得到[5-(1-Oxido-1,2,4-benzotriazin-3-yl)aminopentyl]-(2S)-N-tert-butoxycarbonyl-2-amino-(1-methyl-indole-3-yl)propanamide
  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.