1-(1-氮丙啶基)-3-(2-硝基-1H-咪唑-1-基)-2-丙醇 | 88876-88-4

• 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
• 中文名称: 1-(1-氮丙啶基)-3-(2-硝基-1H-咪唑-1-基)-2-丙醇
• 英文名称: NSC 347503
• 英文别名: α-<(1-aziridinyl)methyl>-2-nitro-1H-imidazole-1-ethanol；α-(aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol；1-(aziridin-1-yl)-3-(2-nitro-1H-imidazol-1-yl)propan-2-ol；RSU-1069；1H-Imidazole-1-ethanol, alpha-(1-aziridinylmethyl)-2-nitro-；1-(aziridin-1-yl)-3-(2-nitroimidazol-1-yl)propan-2-ol
• CAS: 88876-88-4
• 化学式: C₈H₁₂N₄O₃
• 分子量: 212.208
• InChiKey: OEWYWFJWBZNJJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  86.9
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  (R,S)-3-(oxiranylmethyl)-2-oxazolidinone 在 氢溴酸 、 caesium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 various solvent(s) 为溶剂， 反应 27.13h， 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

文献信息

• Aziridino containing nitro imidazoles and pharmaceutical compositions
  申请人：National Research Development Corporation

  公开号：US04581368A1

  公开（公告）日：1986-04-08

  A compound of formula I ##STR1## in which formula: R.sub.1 represents hydrogen or an alkyl group; R.sub.2 -R.sub.5 represent hydrogen, alkyl aryl, aralkyl or alkaryl group; and n is 1.

  化合物的化学式为I ##STR1## 其中：R.sub.1代表氢或烷基；R.sub.2-R.sub.5代表氢、烷基、芳基、芳基烷基或烷基芳基基团；n为1。
• Nitro-substituted aromatic or hetero-aromatic compounds for use in
  申请人：British Technology Group Limited

  公开号：US05521203A1

  公开（公告）日：1996-05-28

  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瘤且已知或疑似存在低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下一电子还原电位为-250至-500 mV的硝基取代芳香或杂芳基；每个R'.sub.1到R'.sub.5独立地表示氢或烷基，羟基烷基，芳基，芳基烷基或烷基芳基；m为0或1；n为1或2；Z'表示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成盐。
• Use of alpha-hydroxy carbonyl compounds as reducing agents
  申请人：Morvus Technology Ltd

  公开号：US10398676B2

  公开（公告）日：2019-09-03

  There is provided the use as reducing agents of alpha-hydroxycarbonyl compounds capable of forming cyclic dimers. There is also provided corresponding methods of reducing reducible compounds, particularly reduction-activated prodrugs. Examples of the alpha-hydroxycarbonyl compounds used are dihydroxyacetone, glycolaldehyde, glyceraldehyde, erythrose, xylulose, erythrulose or 3-hydroxy-2-butanone.

  提供了能够形成环状二聚体的α-羟基羰基化合物作为还原剂的用途。还提供了相应的还原可还原化合物，特别是还原活化原药的方法。所使用的α-羟基羰基化合物的例子有二羟基丙酮、乙醛、甘油醛、赤藓糖醇、木糖、赤藓糖醇或 3-羟基-2-丁酮。
• 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：——