Guanidino-Tamiphosphor Diethyl Ester | 1401808-94-3

• 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: Guanidino-Tamiphosphor Diethyl Ester
• 英文别名: N-[(1R,2R,6S)-6-(diaminomethylideneamino)-4-diethoxyphosphoryl-2-pentan-3-yloxycyclohex-3-en-1-yl]acetamide
• CAS: 1401808-94-3
• 化学式: C₁₈H₃₅N₄O₅P
• 分子量: 418.473
• InChiKey: MBMGJEBUEPROBR-GVDBMIGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  138
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Guanidino-Tamiphosphor Diethyl Ester 在 三甲基溴硅烷 作用下， 以 氯仿 为溶剂， 反应 24.0h， 以85%的产率得到(3R,4R,5S)-4-acetamido-5-guanidino-3-(1-ethylpropoxy)-1-cyclohexene-1-phosphonic acid
  参考文献：
  名称：

  Development of Oseltamivir Phosphonate Congeners as Anti-influenza Agents

  摘要：

  Oseltamivir phosphonic acid (tamiphosphor, 3a), its monoethyl ester (3c), guanidino-tamiphosphor (4a), and its monoethyl ester (4c) are potent inhibitors of influenza neuraminidases. They inhibit the replication of influenza viruses, including the oseltamivir-resistant H275Y strain, at low nanomolar to picomolar levels, and significantly protect mice from infection with lethal doses of influenza viruses when orally administered with 1 mg/kg or higher doses. These compounds are stable in simulated gastric fluid, liver microsomes, and human blood and are largely free from binding to plasma proteins. Pharmacokinetic properties of these inhibitors are thoroughly studied in dogs, rats, and mice. The absolute oral bioavailability of these compounds was lower than 12%. No conversion of monoester 4c to phosphonic acid 4a was observed in rats after intravenous administration, but partial conversion of 4c was observed with oral administration. Advanced formulation may be investigated to develop these new anti-influenza agents for better therapeutic use.

  DOI：

  10.1021/jm3008486
• 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 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 17.0h， 生成 Guanidino-Tamiphosphor Diethyl Ester
  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