(5-isothiocyanato-1H-indazol-1-yl)methyl 2-( di-tert-butoxyphosphoryloxy)ethylcarbamate | 1432660-14-4

• 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: (5-isothiocyanato-1H-indazol-1-yl)methyl 2-( di-tert-butoxyphosphoryloxy)ethylcarbamate
• 英文别名: (5-isothiocyanatoindazol-1-yl)methyl N-[2-[bis[(2-methylpropan-2-yl)oxy]phosphoryloxy]ethyl]carbamate
• CAS: 1432660-14-4
• 化学式: C₂₀H₂₉N₄O₆PS
• 分子量: 484.513
• InChiKey: HUCADJHSEWFGNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  145
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-azido-4'-chloroacetophenone 、 (5-isothiocyanato-1H-indazol-1-yl)methyl 2-( di-tert-butoxyphosphoryloxy)ethylcarbamate 在 三苯基膦 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 以78%的产率得到(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：

  1-Hydroxymethyl-5-nitro-indazol 在 四氮唑 、 palladium 10% on activated carbon 、 氢气 、 双氧水 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 27.0h， 生成 (5-isothiocyanato-1H-indazol-1-yl)methyl 2-( di-tert-butoxyphosphoryloxy)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