3-[2-羟基-3-(2-硝基咪唑-1-基)丙基]-1,3-恶唑烷-2-酮 | 129449-06-5

• 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: 3-[2-羟基-3-(2-硝基咪唑-1-基)丙基]-1,3-恶唑烷-2-酮
• 中文别名: 3-(2-羟基-3-(2-硝基-1H-咪唑-1-基)丙基)-2-噁唑烷酮
• 英文名称: 3-<2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl>-2-oxazolidinone
• 英文别名: (R,S)-3-[2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-2-oxazolidinone；3-[2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-2-oxazolidinone；3-(2-Hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl)-2-oxazolidinone；3-[2-hydroxy-3-(2-nitroimidazol-1-yl)propyl]-1,3-oxazolidin-2-one
• CAS: 129449-06-5
• 化学式: C₉H₁₂N₄O₅
• 分子量: 256.218
• InChiKey: ATZLNNCRLCUSCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[2-羟基-3-(2-硝基咪唑-1-基)丙基]-1,3-恶唑烷-2-酮 在 氢溴酸 、 溶剂黄146 、 三乙胺 作用下， 以 various solvent(s) 为溶剂， 反应 20.8h， 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：

  2-硝基咪唑 、 (R,S)-3-(oxiranylmethyl)-2-oxazolidinone 在 caesium carbonate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以85%的产率得到3-[2-羟基-3-(2-硝基咪唑-1-基)丙基]-1,3-恶唑烷-2-酮
  参考文献：
  名称：

  双功能2-硝基咪唑辐射敏化剂RB 6145的对映异构体的合成

  摘要：

  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。

  DOI：

  10.1002/jhet.5570430625

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.
• 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：——
• SUTO, MARK J.;STIER, MICHAEL A.;WERBEL, LESLIE M., J. MED. CHEM., 34,(1991) N, C. 1207-1209
  作者：SUTO, MARK J.、STIER, MICHAEL A.、WERBEL, LESLIE M.

  DOI：——

  日期：——
• NOVEL PROCESS FOR PREPARING CHIRAL (2-BROMOETHYL)AMINO]METHYL]-2-NITRO-1$i(H)-IMIDAZOL-1-ETHANOL AND RELATED COMPOUNDS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0652870A1

  公开（公告）日：1995-05-17
• US4954515A
  申请人：——

  公开号：US4954515A

  公开（公告）日：1990-09-04