α-<<(2-chloro-1,2,2-trimethylpropyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol hydrochloride | 129449-02-1

• 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-chloro-1,2,2-trimethylpropyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol hydrochloride
• 英文别名: 1-(2-nitro-1-imidazolyl)-3-(2-chloro-2,3-dimethyl-3-butylamino)-2-propanol hydrochloride；(3-Chloro-2,3-dimethylbutan-2-yl)-[2-hydroxy-3-(2-nitroimidazol-1-yl)propyl]azanium;chloride
• CAS: 129449-02-1
• 化学式: C₁₂H₂₁ClN₄O₃*ClH
• 分子量: 341.238
• InChiKey: XIEQNOYBZQTJTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.96
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 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：

  1-(2,3-环氧丙基)-2-硝基咪唑 在 盐酸 作用下， 以 乙醇 、 丙酮 为溶剂， 生成 α-<<(2-chloro-1,2,2-trimethylpropyl)amino>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

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

  公开号：EP0319329A2

  公开（公告）日：1989-06-07

  A compound for treating a patient having a solid tumour in which it is known or suspected that hypoxic cells are present, which is a compound of formula (A): wherein X represents a nitro-substituted aromatic or hetero-aromatic group with a one-electron reduction potential at pH 7 of from -250 to -500 mV; each of R′₁ to R′₅ independently represents hydrogen or an alkyl, hydroxyalkyl, aryl, aralkyl or alkaryl group; m is 0 or 1; n is 1 or 2; and Z′ represents a leaving group which has the potential for expulsion via an intramolecular cyclisation reaction; or a physiologically acceptable acid addition salt thereof.

  一种用于治疗已知或怀疑存在缺氧细胞的实体瘤患者的化合物，它是式(A)化合物： 其中 X 代表硝基取代的芳香族或杂芳香族基团，在 pH 7 下的一电子还原电位为 -250 至 -500 mV；R′₁ 至 R′₅各自独立地代表氢或烷基、羟烷基、芳基、芳烷基或烷芳基；m 为 0 或 1；n 为 1 或 2；Z′代表有可能通过分子内环化反应排出的离去基团；或其生理学上可接受的酸加成盐。
• 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：——
• 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：——
• 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