2-(5-硝基苯并[d]异噁唑-3-基)乙醇 | 642087-62-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 中文名称: 2-(5-硝基苯并[d]异噁唑-3-基)乙醇
• 英文名称: 2-(5-nitro-1,2-benzisoxazol-3-yl)ethanol
• 英文别名: 2-(5-Nitrobenzo[D]isoxazol-3-YL)ethanol；2-(5-nitro-1,2-benzoxazol-3-yl)ethanol
• CAS: 642087-62-5
• 化学式: C₉H₈N₂O₄
• 分子量: 208.174
• InChiKey: BVYQKAZZWPVWEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(5-硝基苯并[d]异噁唑-3-基)乙醇 在 正丁基锂 、 氨 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 6.0h， 生成 N-[amino-[2-(5-nitro-1,2-benzoxazol-3-yl)ethoxy]phosphoryl]-2-chloro-N-(2-chloroethyl)ethanamine
  参考文献：
  名称：

  1,2-Benzisoxazole Phosphorodiamidates as Novel Anticancer Prodrugs Requiring Bioreductive Activation

  摘要：

  Several 1,2-benzisoxazole phosphorodiamidates have been designed as prodrugs of phosphoramide mustard requiring bioreductive activation. Enzymatic reduction of 1,2-benziosoxazole moiety is expected to result in the formation of imine intermediate due to the cleavage of the N-O bond. The imine should then be spontaneously hydrolyzed to a ketone metabolite, thereby facilitating base-catalyzed beta-elimination of cytotoxic phosphoramide mustard. As expected, the proposed prodrugs 4, 9, and 12 were at least 3-5-fold more potent cytotoxins than control compounds 5 and 15, which lack in the phosphoramide mustard group. Upon incubation with phenobarb-induced rat liver S-9 fraction, compounds 4, 9, and 12 underwent extensive NADPH-dependent metabolism with concomitant generation of alkylating activity under both hypoxic and oxic conditions. Corresponding ketone metabolites were detected for 9 and 15. NADPH-dependent bioreduction of 15 to its ketone metabolite 16 was located in the microsomal fraction and inhibited by SKF-525A and pCMBA. Compared with phenobarb-induced rat liver microsomal fraction, incubation of 15 with rat or human P450 reductase microsomes showed moderate generation of 16. Microsomal cytochrome P450 and/or P450 reductase appear to be involved in the reductive metabolism of 1,2-benzisoxazole moiety under hypoxic as well as oxic conditions.

  DOI：

  10.1021/jm020581y
• 作为产物：
  描述：

  2-(1,2-苯异噁唑-3-基)乙酸甲酯 在 lithium aluminium tetrahydride 、 硝酸 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 生成 2-(5-硝基苯并[d]异噁唑-3-基)乙醇
  参考文献：
  名称：

  1,2-Benzisoxazole Phosphorodiamidates as Novel Anticancer Prodrugs Requiring Bioreductive Activation

  摘要：

  Several 1,2-benzisoxazole phosphorodiamidates have been designed as prodrugs of phosphoramide mustard requiring bioreductive activation. Enzymatic reduction of 1,2-benziosoxazole moiety is expected to result in the formation of imine intermediate due to the cleavage of the N-O bond. The imine should then be spontaneously hydrolyzed to a ketone metabolite, thereby facilitating base-catalyzed beta-elimination of cytotoxic phosphoramide mustard. As expected, the proposed prodrugs 4, 9, and 12 were at least 3-5-fold more potent cytotoxins than control compounds 5 and 15, which lack in the phosphoramide mustard group. Upon incubation with phenobarb-induced rat liver S-9 fraction, compounds 4, 9, and 12 underwent extensive NADPH-dependent metabolism with concomitant generation of alkylating activity under both hypoxic and oxic conditions. Corresponding ketone metabolites were detected for 9 and 15. NADPH-dependent bioreduction of 15 to its ketone metabolite 16 was located in the microsomal fraction and inhibited by SKF-525A and pCMBA. Compared with phenobarb-induced rat liver microsomal fraction, incubation of 15 with rat or human P450 reductase microsomes showed moderate generation of 16. Microsomal cytochrome P450 and/or P450 reductase appear to be involved in the reductive metabolism of 1,2-benzisoxazole moiety under hypoxic as well as oxic conditions.

  DOI：

  10.1021/jm020581y

文献信息

• 1,2-Benzisoxazole Phosphorodiamidates as Novel Anticancer Prodrugs Requiring Bioreductive Activation
  作者：Monish Jain、Chul-Hoon Kwon

  DOI：10.1021/jm020581y

  日期：2003.12.1

  Several 1,2-benzisoxazole phosphorodiamidates have been designed as prodrugs of phosphoramide mustard requiring bioreductive activation. Enzymatic reduction of 1,2-benziosoxazole moiety is expected to result in the formation of imine intermediate due to the cleavage of the N-O bond. The imine should then be spontaneously hydrolyzed to a ketone metabolite, thereby facilitating base-catalyzed beta-elimination of cytotoxic phosphoramide mustard. As expected, the proposed prodrugs 4, 9, and 12 were at least 3-5-fold more potent cytotoxins than control compounds 5 and 15, which lack in the phosphoramide mustard group. Upon incubation with phenobarb-induced rat liver S-9 fraction, compounds 4, 9, and 12 underwent extensive NADPH-dependent metabolism with concomitant generation of alkylating activity under both hypoxic and oxic conditions. Corresponding ketone metabolites were detected for 9 and 15. NADPH-dependent bioreduction of 15 to its ketone metabolite 16 was located in the microsomal fraction and inhibited by SKF-525A and pCMBA. Compared with phenobarb-induced rat liver microsomal fraction, incubation of 15 with rat or human P450 reductase microsomes showed moderate generation of 16. Microsomal cytochrome P450 and/or P450 reductase appear to be involved in the reductive metabolism of 1,2-benzisoxazole moiety under hypoxic as well as oxic conditions.