| 1616373-91-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• CAS: 1616373-91-1
• 化学式: C₃₀H₅₇N₂O₇P
• 分子量: 588.766
• InChiKey: AAGYSSBBRURIGV-UPRLRBBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.63
• 重原子数：
  40.0
• 可旋转键数：
  19.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  112.19
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  在 三氟乙酸 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 [(3R,4R,5S)-4-acetamido-5-amino-3-pentan-3-yloxycyclohexen-1-yl]-hexoxyphosphinic acid
  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
• 作为产物：
  描述：

  (3R,4R,5S)-ethyl 4-acetamido-5-((tert-butoxycarbonyl)amino)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 trifluoroiodoethane 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 18.0h， 生成
  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