1-potassio-2-nitroimidazole salt | 133733-15-0

• 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: 1-potassio-2-nitroimidazole salt
• 英文别名: 1-potassio-2-nitroimidazole；potassium;2-nitroimidazol-3-ide
• CAS: 133733-15-0
• 化学式: C₃H₂N₃O₂*K
• 分子量: 151.166
• InChiKey: DUODPFVPHCFVQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.05
• 重原子数：
  9.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.13
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-potassio-2-nitroimidazole salt 、 6-溴-1-己烯 在 18-冠醚-6 作用下， 以 乙腈 为溶剂， 以90%的产率得到1-(CHCH(CH2)4)-2-nitroimidazole
  参考文献：
  名称：

  2-硝基咪唑双功能生物还原药物：研究区域异构和侧链结构修饰对氮丙啶基和环氧乙烷基衍生物的差异细胞毒性和放射增敏作用的影响。

  摘要：

  已经制备了一系列侧链终止于或含有氮丙啶基和环氧乙烷基团的 2-硝基咪唑，并在体外评估了这些化合物作为缺氧选择性生物还原活化的细胞毒素，并测试了选定的化合物对缺氧哺乳动物细胞的放射增敏特性。化合物是具有附加甲基的强效双功能 2-硝基咪唑 α-[(1-氮丙啶基)-甲基]-2-硝基-1H-咪唑-1-乙醇 (RSU-1069, 1) 类似物的区域异构体或不同侧链长度和类型的相关环氧乙烷。环氧乙烷基衍生物几乎没有差异毒性，测试的那些作为放射增敏剂效果较差，虽然这些性质受侧链长度的影响，但差异并不大。与 1 相关但侧链长度增加的氮丙啶基化合物不稳定。1在不同区域的甲基化对放射增敏作用的影响很小，并且作为差异细胞毒药物与1相比没有明显的优势。发现 C-3 的进行性甲基化会增加毒性但会降低缺氧选择性。在 1,2-cis-2,3-trans-3-aziridin-1-yl-2-hydroxy-1-(2-nitroimidazol+

  DOI：

  10.1021/jm00097a015

文献信息

• syn-Selectivity in the epoxidation of 1-(cyclohex-2-enyl)-2-nitroimidazole mediated by hydrogen bonding
  作者：Michael D. Threadgill、Paul Webb

  DOI：10.1039/c39910000269

  日期：——

  Epoxidation of 1-(cyclohex-2-enyl)-2-nitroimidazole with 3-chloroperoxybenzoic acid occurs exclusively syn to the nitroimidazole in the absence of water; amines react only with the syn epoxide.

  1-(环己-2-烯基)-2-硝基咪唑与 3-氯过氧苯甲酸的环氧化反应，在无水的情况下，只与硝基咪唑发生同步反应；胺只与同步环氧化物发生反应。
• Aminoimidazolylmethyluracil Analogues as Potent Inhibitors of Thymidine Phosphorylase and Their Bioreductive Nitroimidazolyl Prodrugs
  作者：Philip Reigan、Philip N. Edwards、Abdul Gbaj、Christian Cole、Simon T. Barry、Ken M. Page、Susan E. Ashton、Richard W. A. Luke、Kenneth T. Douglas、Ian J. Stratford、Mohammed Jaffar、Richard A. Bryce、Sally Freeman

  DOI：10.1021/jm049494r

  日期：2005.1.1

  Thymidine phosphorylase (TP) is an important target enzyme for cancer chemotherapy because it is expressed at high levels in the hypoxic regions of many tumors and inhibitors of TP have been shown in animal model studies to inhibit angiogenesis and metastasis, and to promote tumor cell apoptosis. The 5-halo-6-[(2'-aminoimidazol-1'-yl)methyl]uracils (3, X = Cl, Br) are very potent inhibitors of E. coli and human TP with IC(50) values of similar to20 nM when the enzyme concentration is similar to40 nM. Their 4'-aminoimidazol-1'-yl analogues (4, X = Cl, Br) are >350-fold less active with IC50 values of similar to7 muM. The 5-unsubstituted analogues (3 and 4, X = H) were both less active than their 5-halo derivatives. Determination of pK(a) values and molecular modeling studies of these compounds in the active site of human TP was used to rationalize their activities. The finding that 3, X = Br has a poor pharmacokinetic (PK) profile in mice, coupled with the desire for tumor selectivity, led us to design prodrugs. The corresponding 2'-nitrolmidazol-1'-ylmethyluracils (5, X = Cl, Br) are > 1000-fold less active (IC(50) 22-24 muM) than their 2'-amino analogues and are reduced to the 2'-amino inhibitors (3, X = Cl, Br) by xanthine oxidase (XO). As XO is also highly expressed in many tumors, the 2'-nitro prodrugs have the potential to selectively deliver the potent 2'-aminoimidazol-1'-yl TP inhibitors into hypoxic solid tumors.
• Potential Tumor-Selective Nitroimidazolylmethyluracil Prodrug Derivatives:  Inhibitors of the Angiogenic Enzyme Thymidine Phosphorylase
  作者：Christian Cole、Philip Reigan、Abdul Gbaj、Philip N. Edwards、Kenneth T. Douglas、Ian J. Stratford、Sally Freeman、Mohammed Jaffar

  DOI：10.1021/jm020964w

  日期：2003.1.1

  Thymidine phosphorylase (TP) is an angiogenic growth factor and a target for anticancer drug design. Molecular modeling suggested that 2'-aminoimidazolylmethyluracils would be potent inhibitors of TP. The novel 5-halo-2-amino-imidazolylmethyluracils (4b/4c) were very potent inhibitors of E. coli TP (IC50 similar to 20 nM). Contrastingly, the corresponding 2'-nitroimidazolylmethyluracil (as bioreductively activated) prodrugs (3b/3c) were 1000-fold less active (IC50 22-24 muM). This approach may be used to selectively deliver TP inhibitors into hypoxic regions of solid tumors where TP is overexpressed.