monohexyl (3R,4R,5S)-4-acetamido-3-(1-ethylpropoxy)-5-guanidino-1-cyclohexene-1-phosphonate | 1616376-25-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: monohexyl (3R,4R,5S)-4-acetamido-3-(1-ethylpropoxy)-5-guanidino-1-cyclohexene-1-phosphonate
• 英文别名: [(3R,4R,5S)-4-acetamido-5-(diaminomethylideneamino)-3-pentan-3-yloxycyclohexen-1-yl]-hexoxyphosphinic acid
• CAS: 1616376-25-0
• 化学式: C₂₀H₃₉N₄O₅P
• 分子量: 446.527
• InChiKey: PRKYXODIZZEVEQ-IPMKNSEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  149
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  奥司他韦 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 trifluoroiodoethane 、 碳酸氢钠 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 三氟乙酸 、 mercury dichloride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 86.0h， 生成 monohexyl (3R,4R,5S)-4-acetamido-3-(1-ethylpropoxy)-5-guanidino-1-cyclohexene-1-phosphonate
  参考文献：
  名称：

  Tamiphosphor monoesters as effective anti-influenza agents

  摘要：

  Oseltamivir is a potent neuraminidase inhibitor for influenza treatment. By replacing the carboxylate group in oseltamivir with phosphonate monoalkyl ester, a series of tamiphosphor derivatives were synthesized and shown to exhibit high inhibitory activities against influenza viruses. Our molecular modeling experiments revealed that influenza virus neuraminidase contains a 371-cavity near the S1-site to accommodate the alkyl substituents of tamiphosphor monoesters to render appreciable hydrophobic interactions for enhanced affinity. Furthermore, guanidino-tamiphosphor (TPG) monoesters are active to the oseltamivir-resistant mutant. TPG monohexyl ester 4e having a more lipophilic alkyl substituent showed better cell permeability and intestinal absorption than the corresponding monoethyl ester 4c, but both compounds showed similar bioavailability. Intranasal administration of TPG monoesters at low dose greatly improved the survival rate of mice infected with lethal dose of H1N1 influenza virus, whereas 4c provided better protection of the infected mice than oseltamivir and other phosphonate congeners by oral administration. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.082

文献信息

• Tamiphosphor monoesters as effective anti-influenza agents
  作者：Chun-Lin Chen、Tzu-Chen Lin、Shi-Yun Wang、Jiun-Jie Shie、Keng-Chang Tsai、Yih-Shyun E. Cheng、Jia-Tsrong Jan、Chun-Jung Lin、Jim-Min Fang、Chi-Huey Wong

  DOI：10.1016/j.ejmech.2014.04.082

  日期：2014.6

  Oseltamivir is a potent neuraminidase inhibitor for influenza treatment. By replacing the carboxylate group in oseltamivir with phosphonate monoalkyl ester, a series of tamiphosphor derivatives were synthesized and shown to exhibit high inhibitory activities against influenza viruses. Our molecular modeling experiments revealed that influenza virus neuraminidase contains a 371-cavity near the S1-site to accommodate the alkyl substituents of tamiphosphor monoesters to render appreciable hydrophobic interactions for enhanced affinity. Furthermore, guanidino-tamiphosphor (TPG) monoesters are active to the oseltamivir-resistant mutant. TPG monohexyl ester 4e having a more lipophilic alkyl substituent showed better cell permeability and intestinal absorption than the corresponding monoethyl ester 4c, but both compounds showed similar bioavailability. Intranasal administration of TPG monoesters at low dose greatly improved the survival rate of mice infected with lethal dose of H1N1 influenza virus, whereas 4c provided better protection of the infected mice than oseltamivir and other phosphonate congeners by oral administration. (C) 2014 Elsevier Masson SAS. All rights reserved.