foscarnet

• 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: foscarnet
• 英文别名: Foscarnet sodium；phosphonoformate sodium salt；trisodium phosphonoformate；forscanet；foscavir；sodium;phosphonatoformate
• 化学式: CO₅P*3Na
• 分子量: 191.951
• InChiKey: BWGBIGLMQJPOEE-UHFFFAOYSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -5.75
• 重原子数：
  8.0
• 可旋转键数：
  1.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  103.32
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-ethyl-N-(2,3-dihydro-1,4-phthalazinedion-6-yl)-{4-[1,5-bis(4-N,N-dimethylaminophenyl)-5-(4-N-ethyl-N-(2,3-dihydro-1,4-phthalazinedion-6-yl)aminophenyl)-2,4-pentadienylidene]-2,5-cyclohexadien-1-ylidene}ammonium perchlorate 、 foscarnet 以 二甲基亚砜 为溶剂， 生成 6a-Foscarnet
  参考文献：
  名称：

  Preparation of prodrugs for selective drug delivery

  摘要：

  合成具有A-B-C化学式的化合物，可用于药物传递等应用，其中A是化学发光基团，B是光致变色基团，C是生物活性基团，其中A-B-C可作为前药。本发明的新型合成方法用于形成前药，包括以下步骤：(1)形成苯酮，(2)形成二芳基乙烯，(3)将邻苯二甲酰亚胺基团连接到乙烯的至少一个芳基上，形成邻苯二甲酰亚胺-乙烯共轭物，(4)缩合两个乙烯-邻苯二甲酰亚胺共轭物，形成邻苯二甲酰亚胺-戊二烯共轭物，(5)通过与肼反应将邻苯二甲酰亚胺转化为邻苯二酰肼，形成本发明的载体化合物，(6)将载体化合物与药物的亲核基团反应，形成相应的前药。另外，可以通过使用卤代二芳基乙烯制备相应的阳离子类似的类似类似染料化合物。然后，通过与亲核试剂反应保护阳离子类似化合物，并通过钯催化的胺化与氨基邻苯二甲酰亚胺偶联，形成保护的邻苯二甲酰亚胺-戊二烯共轭物。后者与肼回流，将其邻苯二甲酰亚胺转化为邻苯二酰肼，并酸化以得到载体。本发明的另一个方面涉及将这些化合物用作抗病毒剂，用于治疗病毒感染，如HIV，以及用作抗癌剂，用于治疗结肠癌、肺癌和乳腺癌等癌症。

  公开号：

  US20050080260A1
• 作为产物：
  描述：

  4-Ethyl-4-methyl-3-oxo-1-aminohexan-1,1-diphosphonsaeure 在 sodium hydroxide 作用下， 反应 48.0h， 以0.056 mol的产率得到foscarnet
  参考文献：
  名称：

  Blum, Helmut, Zeitschrift fur Naturforschung, B: Chemical Sciences, 1988, vol. 43, # 1, p. 75 - 81

  摘要：

  DOI：

文献信息

• Acyloxymethyl and 4-acyloxybenzyl diester prodrugs of phosphonoformate
  作者：Andrew D. Briggs、Michel Camplo、Sally Freeman、Jan Lundström、Brian G. Pring

  DOI：10.1016/0040-4020(96)00906-4

  日期：1996.11

  (pivaloyloxymethoxycarbonyl)phosphonate 4, sodium 4-acyloxybenzyl phenoxycarbonylphosphonates 14a-c and sodium 4-acyloxybenzyl benzyloxycarbonylphosphonates 15a,b have been prepared as bioreversible prodrugs of the antiviral phosphonoformate 1. Their hydrolyses, in vivo systemic bioavailability and antiviral activity are reported. Of the compounds evaluated 4 was the best prodrug.

  新戊酰氧基钠（新戊酰氧基）膦4，钠4-酰氧基phenoxycarbonylphosphonates 14A-C和钠4-酰氧基benzyloxycarbonylphosphonates 15A，B已经制备作为抗病毒的磷酰前药生物可逆1。报告了它们的水解，体内全身生物利用度和抗病毒活性。在所评估的化合物中，有4种是最好的前药。
• Protection of Phosphonate Function by Means of Ethoxycarbonyl Group. A New Method for Generation of Reactive Silyl Phosphite Intermediates
  作者：Mitsuo Sekine、Hiroyuki Mori、Tsujiaki Hata

  DOI：10.1246/bcsj.55.239

  日期：1982.1

  to highly reactive bis(trimethylsilyl) nucleoside phosphite intermediates which were allowed in situ to react with water, diphenyl disulfide, 2,2′-dipyridyl disulfide, and aldehydes to afford the corresponding nucleoside phosphonates, nucleoside S-phenyl phosphorothioates, nucleoside phosphates, and nucleoside α-hydroxy phosphonates in good yields, respectively. The nucleoside phosphonates were further

  核苷乙氧羰基膦酸酯通过适当保护的核苷与乙氧羰基膦酸缩合制备。它们很容易通过用 1 M NaOH 处理然后三甲基甲硅烷基化转化为高反应性的双（三甲基甲硅烷基）核苷亚磷酸酯中间体，然后原位与水、二苯基二硫化物、2,2'-二吡啶基二硫化物和醛反应，得到相应的核苷膦酸酯、核苷 S-苯基硫代磷酸酯、核苷磷酸酯和核苷 α-羟基膦酸酯分别具有良好的产率。在温和的酸性条件下，核苷膦酸酯进一步转化为核苷。因此，乙氧羰基被证明是一种多功能的保护基团，不仅可以保护 H-P(O)，还可以保护 HO-P(O) 和糖的羟基。
• The preparation and crystal structures of new platinum/phosphonate complexes
  作者：Robert. Bau、Sharon K. S. Huang、Jin An. Feng、Charles E. McKenna

  DOI：10.1021/ja00230a050

  日期：1988.10

  Preparation et structure cristalline et moleculaire de [cis-Pt(NH 3 ) 2 (PFA)] − , [Pt(trans-l-dach)(PFA)] − et [Pt 2 (cis-dach) 2 (MDP)]

  [cis-Pt(NH 3 ) 2 (PFA)] - , [Pt(trans-l-dach)(PFA)] - et [Pt 2 (cis-dach) 2 (MDP)]
• <i>In vitro</i> and <i>in vivo</i> evaluation of benzathine foscarnet microcrystals as a potential intravitreal drug depot
  作者：Jiaxing Wang、Yong Tao、Jing Feng、Yidong Niu、Jichao Liu、Yanbin Huang

  DOI：10.1039/c9ra03070k

  日期：——

  Benzathine foscarnet microcrystals as a potential intravitreal drug depot.

  苯扎嗪福司卡那微晶体作为潜在的眼内药物沉积物。
• Synthesis of esters of phosphonoformic acid and their antiherpes activity
  作者：Jan O. Noren、Erik Helgstrand、Nils G. Johansson、Alfons Misiorny、Goeran Stening

  DOI：10.1021/jm00356a028

  日期：1983.2

  Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic acid (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and were hydrolyzed to di- and monoesters. The compounds were tested for antiviral activity on isolated herpes simplex virus type 1 (HSV-1) DNA polymerase, in a HSV-1 plaque reduction assay, and on a cutaneous HSV-1 infection in guinea pigs. None of the esters inhibited the activity of isolated HSV-1 polymerases. Monoesters with a free carboxylic group and diesters with an aromatic carboxylic ester function were active against the cutaneous herpes infection. Mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with aliphatic carboxylic ester groups were inactive in all test systems. The results show that all three acidic groups of phosphonoformic acid must be free in order to get antiviral activity at the enzyme level. However, certain esters of this acid may be biotransformed to the acid itself to give antiherpes activity.