2-butyl-3-ethoxy-2H-indazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 2-butyl-3-ethoxy-2H-indazole
• 英文别名: 2-Butyl-3-ethoxyindazole；2-butyl-3-ethoxyindazole
• 化学式: C₁₃H₁₈N₂O
• 分子量: 218.299
• InChiKey: AGMFBUXZQLNLJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-硝基苄溴 在 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 生成 2-butyl-3-ethoxy-2H-indazole
  参考文献：
  名称：

  Inhibition of myeloperoxidase: Evaluation of 2H-indazoles and 1H-indazolones

  摘要：

  Myeloperoxidase (MPO) produces hypohalous acids as a key component of the innate immune response; however, release of these acids extracellularly results in inflammatory cell and tissue damage. The twostep, one-pot Davis-Beirut reaction was used to synthesize a library of 2H-indazoles and 1H-indazolones as putative inhibitors of MPO. A structure-activity relationship study was undertaken wherein compounds were evaluated utilizing taurine-chloramine and MPO-mediated H2O2 consumption assays. Docking studies as well as toxicophore and Lipinski analyses were performed. Fourteen compounds were found to be potent inhibitors with IC50 values < 1 mu M, suggesting these compounds could be considered as potential modulators of pro-oxidative tissue injury pertubated by the inflammatory MPO/H2O2/HOCl/HOBr system. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.09.044

文献信息

• Davis–Beirut Reaction: Alkoxide versus Hydroxide Addition to the Key <i>o</i>-Nitrosoimine Intermediate
  作者：Jie S. Zhu、Matthew R. Duong、Andrew P. Teuthorn、Julia Y. Lu、Jung-Ho Son、Makhluf J. Haddadin、Mark J. Kurth

  DOI：10.1021/acs.orglett.8b00036

  日期：2018.3.2

  Reaction options, alkoxide vs hydroxide vs amine addition to the key intermediate (o-nitrosoimine) generated in the Davis–Beirut reaction of an o-nitrobenzylamine substrate, are reported to explain the nucleophilic addition selectivity of this one-pot indazole-forming process. The hydroxide addition/deprotection pathway as well as the fate of the resulting o-nitrosobenzaldehyde were both uncovered

  据报道，在邻硝基苯甲胺底物的戴维斯-贝鲁特反应中生成的关键中间体（邻亚硝基亚胺）上的醇盐、氢氧化物和胺加成反应选项，可以解释这一一锅吲唑形成过程的亲核加成选择性。氢氧化物加成/脱保护途径以及所得邻亚硝基苯甲醛的命运均通过几种邻硝基苯甲胺底物揭示，并在新的机理见解的启发下定义了高效双戴维斯-贝鲁特反应所需的设计元素。
• N–N Bond Formation between Primary Amines and Nitrosos: Direct Synthesis of 2-Substituted Indazolones with Mechanistic Insights
  作者：Jie S. Zhu、Niklas Kraemer、Marina E. Shatskikh、Clarabella J. Li、Jung-Ho Son、Makhluf J. Haddadin、Dean J. Tantillo、Mark J. Kurth

  DOI：10.1021/acs.orglett.8b01655

  日期：2018.8.17

  A concise, one-step route to indazolones from primary alkyl amines and o-nitrobenzyl alcohols is reported. The key step in this readily scalable indazolone forming process involves base-mediated in situ o-nitrobenzyl alcohol -> o-nitrosobenzaldehyde conversion. Although this functional group interconversion is known to be useful for 2H-indazole synthesis, its reactivity was modulated for indazolone formation.
• Inhibition of myeloperoxidase: Evaluation of 2H-indazoles and 1H-indazolones
  作者：Aaron Roth、Sean Ott、Kelli M. Farber、Teresa A. Palazzo、Wayne E. Conrad、Makhluf J. Haddadin、Dean J. Tantillo、Carroll E. Cross、Jason P. Eiserich、Mark J. Kurth

  DOI：10.1016/j.bmc.2014.09.044

  日期：2014.11

  Myeloperoxidase (MPO) produces hypohalous acids as a key component of the innate immune response; however, release of these acids extracellularly results in inflammatory cell and tissue damage. The twostep, one-pot Davis-Beirut reaction was used to synthesize a library of 2H-indazoles and 1H-indazolones as putative inhibitors of MPO. A structure-activity relationship study was undertaken wherein compounds were evaluated utilizing taurine-chloramine and MPO-mediated H2O2 consumption assays. Docking studies as well as toxicophore and Lipinski analyses were performed. Fourteen compounds were found to be potent inhibitors with IC50 values < 1 mu M, suggesting these compounds could be considered as potential modulators of pro-oxidative tissue injury pertubated by the inflammatory MPO/H2O2/HOCl/HOBr system. (C) 2014 Elsevier Ltd. All rights reserved.