7-[2-Hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-7-azabicyclo[4.1.0]heptane-3-carboxylicacid, ethyl ester | 120278-01-5

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 7-[2-Hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-7-azabicyclo[4.1.0]heptane-3-carboxylicacid, ethyl ester
• 英文别名: Ethyl 7-[2-hydroxy-3-(2-nitroimidazol-1-yl)propyl]-7-azabicyclo[4.1.0]heptane-3-carboxylate
• CAS: 120278-01-5
• 化学式: C₁₅H₂₂N₄O₅
• 分子量: 338.363
• InChiKey: OVOMSZUNGGNMRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-环己烯-1-羧酸乙酯 在 sodium azide 、 间氯过氧苯甲酸 、 三苯基膦 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 89.0h， 生成 7-[2-Hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-7-azabicyclo[4.1.0]heptane-3-carboxylicacid, ethyl ester
  参考文献：
  名称：

  A new class of analog of the bifunctional radiosensitizer .alpha.-(1-aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069): the cycloalkylaziridines

  摘要：

  A series of compounds related to alpha-(1-aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069, 1) were synthesized and evaluated as selective hypoxic cell cytotoxic agents and as radiosensitizers. The aziridine moiety was replaced with a number of other potential alkylating groups including cycloalkylaziridines and azetidines. The data indicated that modification of the aziridine of 1 resulted in a substantial decrease in the ability of the compounds to selectively kill hypoxic cells. However, these modifications did not affect the compounds' in vitro radiosensitizing activity since many of the derivatives were as potent as 1. All of the compounds that were evaluated in vivo were less toxic than 1, and several members of this series had significant activity. The best compound was trans-alpha-[[(4-bromotetrahydro-2H-pyran-3-yl)amino]methyl]-2-nitro-1H-imidazole-1-ethanol (18), which, due to its activity and log P value, is a candidate for additional in vivo studies.

  DOI：

  10.1021/jm00112a026

文献信息

• A new class of analog of the bifunctional radiosensitizer .alpha.-(1-aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069): the cycloalkylaziridines
  作者：Mark J. Suto、Michael A. Stier、Leslie M. Werbel、Carla M. Arundel-Suto、Wilbur R. Leopold、William E. Elliott、Judith S. Sebolt-Leopold

  DOI：10.1021/jm00112a026

  日期：1991.8

  A series of compounds related to alpha-(1-aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069, 1) were synthesized and evaluated as selective hypoxic cell cytotoxic agents and as radiosensitizers. The aziridine moiety was replaced with a number of other potential alkylating groups including cycloalkylaziridines and azetidines. The data indicated that modification of the aziridine of 1 resulted in a substantial decrease in the ability of the compounds to selectively kill hypoxic cells. However, these modifications did not affect the compounds' in vitro radiosensitizing activity since many of the derivatives were as potent as 1. All of the compounds that were evaluated in vivo were less toxic than 1, and several members of this series had significant activity. The best compound was trans-alpha-[[(4-bromotetrahydro-2H-pyran-3-yl)amino]methyl]-2-nitro-1H-imidazole-1-ethanol (18), which, due to its activity and log P value, is a candidate for additional in vivo studies.