1-Hydroxymethyl-5-nitro-indazol | 23301-05-5

• 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: 1-Hydroxymethyl-5-nitro-indazol
• 英文别名: (5-Nitroindazol-1-yl)methanol
• CAS: 23301-05-5
• 化学式: C₈H₇N₃O₃
• 分子量: 193.162
• InChiKey: MDTVWBQRNIFNQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-Hydroxymethyl-5-nitro-indazol 在 四氮唑 、 palladium 10% on activated carbon 、 氢气 、 双氧水 、 三乙胺 、 三苯基膦 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 90.0 ℃ 、101.33 kPa 条件下， 反应 27.5h， 生成 (5-(5-(4-chlorophenyl)oxazol-2-ylamino )-1H-indazol-1-yl)methyl 2-(di-tertbutoxyphosphoryloxy)ethylcarbamate
  参考文献：
  名称：

  Discovery of a new HIV-1 inhibitor scaffold and synthesis of potential prodrugs of indazoles

  摘要：

  A new oxazole scaffold showing great promise in HIV-1 inhibition has been discovered by cell-based screening of an in-house library and scaffold modification. Follow-up SAR study focusing on the 5-aryl substituent of the oxazole core has identified 4k (EC50 = 0.4211 mu M, TI = 50) as a potent inhibitor. However, the analogues suffered from poor aqueous solubility. To address this issue, we have developed broadly applicable potential prodrugs of indazoles. Among them, N-acyloxymethyl analogue 11b displayed promising results (i.e., increased aqueous solubility and susceptibility to enzymatic hydrolysis). Further studies are warranted to fully evaluate the analogues as the potential prodrugs with improved physiochemical and PK properties (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.075
• 作为产物：
  描述：

  聚合甲醛 、 5-硝基吲唑 在 盐酸 作用下， 以 水 为溶剂， 以96%的产率得到1-Hydroxymethyl-5-nitro-indazol
  参考文献：
  名称：

  盐酸水溶液中1H-吲唑及其4-、5-、6-和7-硝基衍生物与甲醛的加成机理研究

  摘要：

  NH-吲唑与甲醛在盐酸水溶液中的反应已经通过溶液和固态核磁共振（NMR）和晶体学进行了实验研究。确定了N 1 -CH 2 OH 衍生物的形成机理。首次通过多核 NMR 对 2-取代衍生物进行了表征。理论上，在 Becke 三参数（交换）Lee-Yang-Parr B3LYP/6-311++G(d,p) 水平上使用规范不变原子轨道 (GIAO) 的计算为实验观察提供了良好的基础。报道了四种 (1 H-吲唑-1-基) 甲醇衍生物的第一个 X 射线结构。

  DOI：

  10.1021/acs.joc.2c00154

文献信息

• WRZECIONO U.; PIETKIEWICZ K.; NIEWEGLOWSKA W.; MICHALSKA W., PHARMAZIE, 1979, 34, NO 1, 20-22
  作者：WRZECIONO U.、 PIETKIEWICZ K.、 NIEWEGLOWSKA W.、 MICHALSKA W.

  DOI：——

  日期：——
• US4554243A
  申请人：——

  公开号：US4554243A

  公开（公告）日：1985-11-19
• Discovery of a new HIV-1 inhibitor scaffold and synthesis of potential prodrugs of indazoles
  作者：Se-Ho Kim、Benjamin Markovitz、Richard Trovato、Brett R. Murphy、Harry Austin、Adam J. Willardsen、Vijay Baichwal、Scott Morham、Ashok Bajji

  DOI：10.1016/j.bmcl.2013.03.075

  日期：2013.5

  A new oxazole scaffold showing great promise in HIV-1 inhibition has been discovered by cell-based screening of an in-house library and scaffold modification. Follow-up SAR study focusing on the 5-aryl substituent of the oxazole core has identified 4k (EC50 = 0.4211 mu M, TI = 50) as a potent inhibitor. However, the analogues suffered from poor aqueous solubility. To address this issue, we have developed broadly applicable potential prodrugs of indazoles. Among them, N-acyloxymethyl analogue 11b displayed promising results (i.e., increased aqueous solubility and susceptibility to enzymatic hydrolysis). Further studies are warranted to fully evaluate the analogues as the potential prodrugs with improved physiochemical and PK properties (C) 2013 Elsevier Ltd. All rights reserved.
• Study of the Addition Mechanism of 1<i>H</i>-Indazole and Its 4-, 5-, 6-, and 7-Nitro Derivatives to Formaldehyde in Aqueous Hydrochloric Acid Solutions
  作者：Ibon Alkorta、Rosa M. Claramunt、José Elguero、Enrique Gutiérrez-Puebla、M. Ángeles Monge、Felipe Reviriego、Christian Roussel

  DOI：10.1021/acs.joc.2c00154

  日期：2022.5.6

  NH-indazoles with formaldehyde in aqueous hydrochloric acid has been experimentally studied by solution and solid-state nuclear magnetic resonance (NMR) and crystallography. The mechanism of the formation of N1-CH2OH derivatives was determined. For the first time, 2-substituted derivatives have been characterized by multinuclear NMR. Theoretically, calculations with gauge-invariant atomic orbitals (GIAOs)

  NH-吲唑与甲醛在盐酸水溶液中的反应已经通过溶液和固态核磁共振（NMR）和晶体学进行了实验研究。确定了N 1 -CH 2 OH 衍生物的形成机理。首次通过多核 NMR 对 2-取代衍生物进行了表征。理论上，在 Becke 三参数（交换）Lee-Yang-Parr B3LYP/6-311++G(d,p) 水平上使用规范不变原子轨道 (GIAO) 的计算为实验观察提供了良好的基础。报道了四种 (1 H-吲唑-1-基) 甲醇衍生物的第一个 X 射线结构。