α-<(ethylamino)methyl>-2-nitro-1H-imidazole-1-ethanol hydrochloride | 80479-64-7

• 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-<(ethylamino)methyl>-2-nitro-1H-imidazole-1-ethanol hydrochloride
• 英文别名: 1-(Ethylamino)-3-(2-nitroimidazol-1-yl)propan-2-ol;hydrochloride
• CAS: 80479-64-7
• 化学式: C₈H₁₄N₄O₃*ClH
• 分子量: 250.685
• InChiKey: SVMJABAIZNBHFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.18
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  乙胺 、 1-(2,3-环氧丙基)-2-硝基咪唑 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以87%的产率得到α-<(ethylamino)methyl>-2-nitro-1H-imidazole-1-ethanol hydrochloride
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00171a040

文献信息

• JENKINS, TERENCE C.;NAYLOR, MATTHEW A.;ONEILL, PETER;THREADGILL, MICHAEL +, J. MED. CHEM., 33,(1990) N, C. 2603-2610
  作者：JENKINS, TERENCE C.、NAYLOR, MATTHEW A.、ONEILL, PETER、THREADGILL, MICHAEL +

  DOI：——

  日期：——
• 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.