α-<<(2-hydroxyethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol | 99464-91-2

• 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: α-<<(2-hydroxyethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol
• 英文别名: 1-(2-nitro-1-imidazolyl)-3-(2-hydroxyethylamino)-2-propanol；1-[(2-Hydroxyethyl)amino]-3-(2-nitro-1h-imidazol-1-yl)propan-2-ol；1-(2-hydroxyethylamino)-3-(2-nitroimidazol-1-yl)propan-2-ol
• CAS: 99464-91-2
• 化学式: C₈H₁₄N₄O₄
• 分子量: 230.224
• InChiKey: QTQYNIHOQCATOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  α-<<(2-hydroxyethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol 以59的产率得到α-<<(2-bromoethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol hydrobromide
  参考文献：
  名称：

  Nitro-substituted aromatic or hetero-aromatic compounds for use in

  摘要：

  一种用于治疗患有实体肿瘤且已知或怀疑存在缺氧细胞的患者的化合物，该化合物的化学式为（A）：##STR1## 其中X代表具有pH 7下从-250到-500 mV的一电子还原电位的硝基取代的芳香或杂芳基团；R'.sub.1到R'.sub.5中的每个独立地代表氢或烷基，羟基烷基，芳基，芳基烷基或烷芳基团；m为0或1；n为1或2；Z'代表具有通过分子内环化反应进行驱逐的潜力的离去基；或其生理上可接受的酸加合盐。

  公开号：

  US05098921A1
• 作为产物：
  描述：

  1-Azido-3-(2-nitroimidazol-1-yl)propan-2-ol 以96的产率得到α-<<(2-hydroxyethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol
  参考文献：
  名称：

  Nitro-substituted aromatic or hetero-aromatic compounds for use in

  摘要：

  一种用于治疗患有实体肿瘤且已知或怀疑存在缺氧细胞的患者的化合物，该化合物的化学式为（A）：##STR1## 其中X代表具有pH 7下从-250到-500 mV的一电子还原电位的硝基取代的芳香或杂芳基团；R'.sub.1到R'.sub.5中的每个独立地代表氢或烷基，羟基烷基，芳基，芳基烷基或烷芳基团；m为0或1；n为1或2；Z'代表具有通过分子内环化反应进行驱逐的潜力的离去基；或其生理上可接受的酸加合盐。

  公开号：

  US05098921A1

文献信息

• Synthesis and evaluation of .alpha.-[[(2-haloethyl)amino]methyl]-2-nitro-1H-imidazole-1-ethanols as prodrugs of .alpha.-[(1-aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanol (RSU-1069) and its analogs which are radiosensitizers and bioreductively activated cytotoxins
  作者：Terence C. Jenkins、Matthew A. Naylor、Peter O'Neill、Michael D. Threadgill、Shirley Cole、Ian J. Stratford、Gerald E. Adams、E. Martin Fielden、Mark J. Suto、Michael A. Stier

  DOI：10.1021/jm00171a040

  日期：1990.9

  alpha-[(1-Aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanols, of general formula ImCH2CH(OH)CH2NCR1R2CR3R4, where Im = 2-nitroimidazole and R1, R2, R3, R4 = H, Me, are radiosensitizers and selective bioreductively activated cytotoxins toward hypoxic tumor cells in vitro and in vivo. Treatment of the aziridines with hydrogen halide in acetone or aqueous acetone gave the corresponding 2-haloethylamines of general formula ImCH2CH(OH)CH2(+)-NH2CR1R2CR3R4X X-, where R1, R2, R3, R4 = H, Me, and X = F, Cl, Br, I. These 2-haloethylamines were evaluated as prodrugs of the parent aziridines. The rates of ring closure in aqueous solution at pH approximately 6 were found to increase with increasing methyl substitution and to depend on the nature of the leaving group (I approximately Br greater than Cl much greater than F). A competing reaction of ImCH2CH(OH)CH2+NH2CH2CH2X X- (X = Cl, Br) with aqueous HCO3- ions gives 3-[2-hyroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-2-oxazolidinone. The activities of these prodrugs as radiosensitizers or as bioreductively activated cytotoxins were consistent with the proportion converted to the parent aziridine during the course of the experiment. alpha-[[(2-Bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1- ethanol (RB 6145, 10), the prodrug of alpha-[(1-aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanol (RSU-1069, 3), is identified as the most useful compound in terms of biological activity and rate of ring closure under physiological conditions.
• ADAMS, GERAID EDWARD;FLEIDEN, EDWARD MARTIN;LIENKINS, TERENCE CHARLES;STR+
  作者：ADAMS, GERAID EDWARD、FLEIDEN, EDWARD MARTIN、LIENKINS, TERENCE CHARLES、STR+

  DOI：——

  日期：——
• Nitro-substituted aromatic or hetero-aromatic compounds for use in cancer treatment
  申请人：BRITISH TECHNOLOGY GROUP LIMITED

  公开号：EP0319329B1

  公开（公告）日：1995-11-02
• US5098921A
  申请人：——

  公开号：US5098921A

  公开（公告）日：1992-03-24
• US5521203A
  申请人：——

  公开号：US5521203A

  公开（公告）日：1996-05-28