α-<<(2-bromoethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol hydrobromide | 129448-97-1

• 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-bromoethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol hydrobromide
• 英文别名: α-<<(2-bromoethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol monohydrobromide；(R,S)-α-[[(2-bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1-ethanol monohydrobromide；RB6145；1-(2-nitro-1-imidazolyl)-3-(2-bromoethylamino)-2-propanol hydrobromide；1-(2-bromoethylamino)-3-(2-nitroimidazol-1-yl)propan-2-ol;hydron;bromide
• CAS: 129448-97-1
• 化学式: BrH*C₈H₁₃BrN₄O₃
• 分子量: 374.032
• InChiKey: XPBJPGMCFKYBBV-UHFFFAOYSA-N

物化性质

• 熔点：
  167-169 °C(Solv: isopropanol (67-63-0))

计算性质

• 辛醇/水分配系数(LogP)：
  0.71
• 重原子数：
  17
• 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：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

制备方法与用途

RB-6145 是一种前药，具有口服活性，并作为缺氧细胞的放射增敏剂RSU 1069发挥作用。它既能发挥放射增敏剂和细胞毒作用，又能减少小鼠的全身毒性。

反应信息

• 作为反应物：
  描述：

  α-<<(2-bromoethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol hydrobromide 在 三乙胺 作用下， 以 various solvent(s) 为溶剂， 反应 0.5h， 生成 1-(1-氮丙啶基)-3-(2-硝基-1H-咪唑-1-基)-2-丙醇
  参考文献：
  名称：

  Dual-function radiosensitizers. .alpha.-[[(2-Bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1-ethanol and related compounds: preparation via an aziridine equivalent

  摘要：

  An improved synthesis of the dual-function radiosensitizer alpha-[[2-bromoethyl)amino]methyl]-2-nitro-H-1-imidazole-1-ethanol (2, RB 6145) has been developed. Previously, the synthetic difficulties associated with this compound limited its attractiveness as a clinical candidate, although its radiosensitizing activity in preclinical models warranted its further development. The synthesis described uses a 2-oxazolidinone as an aziridine equivalent and provides 2 in 47% yield.

  DOI：

  10.1021/jm00107a047
• 作为产物：
  描述：

  1-(1-氮丙啶基)-3-(2-硝基-1H-咪唑-1-基)-2-丙醇 在 氢溴酸 作用下， 以 丙酮 为溶剂， 以96%的产率得到α-<<(2-bromoethyl)amino>methyl>-2-nitro-1H-imidazole-1-ethanol hydrobromide
  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

• Synthesis of the enantiomers of the dual function 2-nitroimidazole radiation sensitizer RB 6145
  作者：Anthony D. Sercel、Vladimir G. Beylin、Mark E. Marlatt、Boguslawa Leja、H. D. Hollis Showalter、André Michel

  DOI：10.1002/jhet.5570430625

  日期：2006.11

  described for the synthesis of racemic 2-nitroimidazole radiation sensitizer RB-6145 (2a) and each of its corresponding (R)- and (S)-enantiomers (2b and 2c, respectively). The synthesis of each enantiomer commences with the appropriate chiral epichlorohydrin and utilizes a novel application of 3-trimethylsilyl-2-oxazolidinone (3b) as a mild, safe surrogate for highly toxic aziridine. The synthesis of the (R)-enantiomer

  描述了用于合成外消旋2-硝基咪唑辐射敏化剂RB-6145（2a）及其相应的（R）-和（S）-对映体（分别为2b和2c）的短而有效的途径。每个对映异构体的合成均始于适当的手性表氯醇，并利用3-三甲基甲硅烷基-2-恶唑烷酮（3b）的新颖应用作为温和，安全的高毒性氮丙啶的替代物。（R）-对映异构体（2b）的合成已成功扩大规模，可为早期临床前评估提供几千量的材料。
• Nitro-substituted aromatic or hetero-aromatic compounds for use in
  申请人：National Research Development Corporation

  公开号：US05098921A1

  公开（公告）日：1992-03-24

  A compound for treating a patient having a solid tumor in which it is known or suspected that hypoxic cells are present, which is a compound of formula (A): ##STR1## 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'.sub.1 to R'.sub.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 cyclization reaction; or a physiologically acceptable acid addition salt thereof.

  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。
• 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：——