diethyl 2-p-toluenesulfonyloxyethoxymethanephosphonate | 116384-58-8

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: diethyl 2-p-toluenesulfonyloxyethoxymethanephosphonate
• 英文别名: 2-((Diethoxyphosphoryl)methoxy)ethyl 4-methylbenzenesulfonate；2-(diethoxyphosphorylmethoxy)ethyl 4-methylbenzenesulfonate
• CAS: 116384-58-8
• 化学式: C₁₄H₂₃O₇PS
• 分子量: 366.372
• InChiKey: WMXOFNJHPNINDL-UHFFFAOYSA-N

物化性质

• 沸点：
  487.6±35.0 °C(Predicted)
• 密度：
  1.237±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  96.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl 2-p-toluenesulfonyloxyethoxymethanephosphonate 在 四丁基氟化铵 、 氨 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 {2-[6-amino-2-(4-butyl-3-hydroxy-phenylamino)-purin-9-yl]-ethoxymethyl}-phosphonic acid diethyl ester
  参考文献：
  名称：

  Antitumor effects of guanosine-analog phosphonates identified by molecular modelling

  摘要：

  Aiming to address new drug targets, molecular modelling is gaining increasing importance although the prediction capability of the in silico method is still under debate. For an improved treatment of actinic keratosis and squamous cell carcinoma, inhibitors of human DNA polymerase alpha (pol alpha) are developed by docking nucleoside phosphonate diphosphates into the active site of pol alpha. The most promising prodrugs OxBu and OxHex were then prepared by total synthesis and tested in the squamous cancer cell line SCC25. OxBu and OxHex proved cytotoxic and antiproliferative in the nanomolar concentration range and thus exceeded activity of aphidicolin, the relevant model compound, and 5-fluorouracil, the current standard for the therapy of actinic keratosis. Interestingly, the cytotoxicity in normal human keratinocytes with OxHex was clearly less pronounced and even not detectable with OxBu. Moreover, cytotoxicity of OxBu in particular with the colorectal carcinoma cell line HT29 even surmounted cytotoxicity in SCC25, and other tumor cell lines were influenced, too, by both agents. Taken together, OxBu and OxHex may offer a new approach to cancer therapy, given the agents are sufficiently well tolerated in vivo which is to be suspected beside their chemical structure. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ijpharm.2010.06.036
• 作为产物：
  描述：

  2-((二乙氧基膦酰爪基)甲氧基)乙基醋酸盐 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 diethyl 2-p-toluenesulfonyloxyethoxymethanephosphonate
  参考文献：
  名称：

  Antitumor effects of guanosine-analog phosphonates identified by molecular modelling

  摘要：

  Aiming to address new drug targets, molecular modelling is gaining increasing importance although the prediction capability of the in silico method is still under debate. For an improved treatment of actinic keratosis and squamous cell carcinoma, inhibitors of human DNA polymerase alpha (pol alpha) are developed by docking nucleoside phosphonate diphosphates into the active site of pol alpha. The most promising prodrugs OxBu and OxHex were then prepared by total synthesis and tested in the squamous cancer cell line SCC25. OxBu and OxHex proved cytotoxic and antiproliferative in the nanomolar concentration range and thus exceeded activity of aphidicolin, the relevant model compound, and 5-fluorouracil, the current standard for the therapy of actinic keratosis. Interestingly, the cytotoxicity in normal human keratinocytes with OxHex was clearly less pronounced and even not detectable with OxBu. Moreover, cytotoxicity of OxBu in particular with the colorectal carcinoma cell line HT29 even surmounted cytotoxicity in SCC25, and other tumor cell lines were influenced, too, by both agents. Taken together, OxBu and OxHex may offer a new approach to cancer therapy, given the agents are sufficiently well tolerated in vivo which is to be suspected beside their chemical structure. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ijpharm.2010.06.036

文献信息

• Polyether bis-phosphonic acid compounds
  申请人：W. R. Grace & Co.-Conn.

  公开号：US05266722A1

  公开（公告）日：1993-11-30

  Polyether bis-phosphonic acid compounds are disclosed which have the formula (HO).sub.2 OP--R--(OR').sub.n --OR--PO(OH).sub.2 where R is selected from the group consisting of methylene and ethylene, R' is selected from the group consisting of ethylene and ethylene substituted with one or more methyl groups, and n is an integer from 1 to 4, water soluble salts thereof, and esters thereof with alkyl groups having from 1 to 6 carbon atoms. Also disclosed is a novel preparation of certain of these compounds by reacting certain hydroxyalkylphosphonic acid dialkyl ester compounds with certain 2-benzyloxyalkyl organic sulfonates; reacting the intermediate formed therefrom with hydrogen or a hydrogen source; reacting the intermediate formed therefrom with a hydrogen ion acceptor and certain sulfonyl chlorides; and reacting the intermediate formed therefrom with certain hydroxyalkyl-phosphonic acid dialkyl ester compounds to form a polyether bis-phosphonic acid compound which may be hydrolyzed to form the polyether bis-phosphonic acid. Useful intermediates are disclosed which have the formulas ##STR1## HOR'--OR--PO(OR").sub.2, HOR'--OR--PO(OH).sub.2, and X--O.sub.2 S--OR'--OR--PO(OR").sub.2, wherein the above-indicated benzene rings of said formulas are optionally substituted with selected groups, wherein R and R' are as defined above, wherein R" is an alkyl group having from 1 to 6 carbon atoms, and wherein X is selected from ##STR2## and alkyl groups having from about 1 to 6 carbon atoms.

  聚醚双膦酸化合物的化学式为(HO).sub.2 OP--R--(OR').sub.n --OR--PO(OH).sub.2，其中R从亚甲基和乙烯组成的群体中选择，R'从乙烯和乙烯上取代一个或多个甲基的群体中选择，n为1到4的整数，以及其水溶性盐和具有1到6个碳原子的烷基基团的酯。还披露了通过将某些羟基磷酸二烷基酯化合物与某些2-苄氧基烷基有机磺酸盐反应；将形成的中间体与氢或氢源反应；将形成的中间体与氢离子受体和某些磺酰氯反应；将形成的中间体与某些羟基磷酸二烷基酯化合物反应以形成聚醚双膦酸化合物的新制备方法，该聚醚双膦酸化合物可以水解形成聚醚双膦酸。披露了具有以下化学式的有用中间体##STR1## HOR'--OR--PO(OR").sub.2，HOR'--OR--PO(OH).sub.2，和X--O.sub.2 S--OR'--OR--PO(OR").sub.2，其中上述化学式的苯环可选择地取代有选定的基团，其中R和R'如上所定义，R"是具有1到6个碳原子的烷基基团，X从##STR2## 和具有大约1到6个碳原子的烷基基团中选择。
• Synthesis of a novel ring-expanded (“fat”) nucleotide analogue of phosphonomethoxyethylguanine (PMEG) containing the imidazo[4,5-<i>e</i>][1,3]diazepine ring system
  作者：Huan-Ming Chen、Ramachandra S. Hosmane

  DOI：10.1002/jhet.5570380611

  日期：2001.11

  The synthesis of 6-amino-4,5-dihydro-8H-1-(2-phosphonylmethoxyethyl)imidazo[4,5-e][1,3]diazepine-4,8-dione (7), a novel ring-expanded (“fat”) acyclic nucleotide analogue of phosphonomethoxyethylguanine (PMEG), has been reported. It was prepared in 4 steps in 51% overall yield starting from dimethyl imida-zole-4,5-dicarboxylate.

  6-氨基-4,5-二氢-8 H -1-（2-膦酰基甲氧基乙基）咪唑并[4,5- e ] [1,3]二氮杂-4,8-​​二酮（7）的合成已经报道了膦酰基甲氧基乙基鸟嘌呤（PMEG）的-扩展的（“脂肪”）无环核苷酸类似物。它由4个步骤制备，总产率为51％，从亚甲基咪唑-4,5-二羧酸二甲酯开始。
• ACYCLIC NUCLEOSIDE/NUCLEOTIDE ANALOGUES WITH AN IMIDAZOLE RING SKELETON
  作者：Huan-Ming Chen、Ramachandra S. Hosmane

  DOI：10.1081/ncn-100105250

  日期：2001.7.31

  potential prodrugs of the above compounds, including the acetyl derivatives 5 and 6 (of 1 and 4, respectively), and the diethyl phosphonate ester 9 (of 10). In addition, the corresponding benzyl-protected precursors 11 and 12 (of 1 and 4, respectively), along with their common hydrolysis product, 1-(2-benzyloxy-ethoxymethyl)-4,5-imidazoledicarboxylic acid (3), are reported. Another potential prodrug included

  已经报道了一些含有咪唑环的无环核苷和无环核苷膦酸酯类似物的合成。这些类似物包括1-（2-羟基乙氧基甲基）咪唑-4甲基，5-二苯甲酸酯（1），4,5-二氨基甲酰基-1-（2-羟基乙氧基甲基）咪唑（2），4,5-二氰基-1- （2-羟基乙氧基甲基）咪唑（4），1-（2-溴乙氧基甲基）咪唑-4,5-二羧酸酯（7），4,5-二氰基-（2-溴乙氧基甲基）咪唑（8）和甲基1-（ 2-膦酰基甲氧基乙基）咪唑（10）。还报道了上述化合物的一些潜在前药，包括乙酰基衍生物5和6（分别为1和4）和二乙基膦酸酯9（为10）。此外，相应的苄基保护的前体11和12（分别为1和4）以及它们常见的水解产物1-（2-苄氧基-乙氧基甲基）-4，报道了5-咪唑二羧酸（3）。列表中包括的另一种潜在前药是1-（2-乙酰氧基乙基）-4,5-二氰基咪唑（15）。筛选化合物对多种疱疹和呼吸道病毒的体外抗病毒活性。最具活性的化合物是膦酸酯
• 8-Aza-analogues of PMEA and PMEG: Synthesis and<i>In Vitro</i>Anti-HIV Activity
  作者：P. Franchetti、G. Abu Sheikha、L. Cappellacci、L. Messini、M. Grifantini、A. G. Loi、A. De Montis、M. G. Spiga、P. La Colla

  DOI：10.1080/15257779408009475

  日期：1994.9

  8-Aza-analogues of the potent antiviral nucleotide analogues 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG) were prepared and evaluated for activity against human immunodeficiency viruses. When compared to the parent compounds, 8-aza-PMEA (1) and -PMEG (2) were less cytotoxic for MT-4 cells, but also less potent against HIV-1 and HIV-2. A new synthesis of PMEG starting from guanine is also reported.
• Holy, Antonin; Rosenberg, Ivan; Dvorakova, Hana, Collection of Czechoslovak Chemical Communications, 1989, vol. 54, # 8, p. 2190 - 2210
  作者：Holy, Antonin、Rosenberg, Ivan、Dvorakova, Hana

  DOI：——

  日期：——