(2-{2-[3-(tert-butyldiphenylsiloxy)-4-hexylphenylamino]-6-chloro-purin-9-yl}-ethoxymethyl)-phosphonic acid diethyl ester | 1252577-09-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (2-{2-[3-(tert-butyldiphenylsiloxy)-4-hexylphenylamino]-6-chloro-purin-9-yl}-ethoxymethyl)-phosphonic acid diethyl ester
• CAS: 1252577-09-5
• 化学式: C₄₀H₅₃ClN₅O₅PSi
• 分子量: 778.404
• InChiKey: VMKBYBWPAIUBCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.53
• 重原子数：
  53.0
• 可旋转键数：
  20.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  109.62
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (2-{2-[3-(tert-butyldiphenylsiloxy)-4-hexylphenylamino]-6-chloro-purin-9-yl}-ethoxymethyl)-phosphonic acid diethyl ester 在 三甲基溴硅烷 、 四丁基氟化铵 、 氨 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 33.5h， 生成 {2-[6-amino-2-(4-hexyl-3-hydroxy-phenylamino)-purin-9-yl]-ethoxymethyl}-phosphonic acid
  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：

  5-amino-2-hexylphenol 在 吡啶 、 4-二甲氨基吡啶 、 四丁基氯化铵 、 N,N-二甲基苯胺 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氯氧磷 作用下， 以 甲乙醚 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 201.25h， 生成 (2-{2-[3-(tert-butyldiphenylsiloxy)-4-hexylphenylamino]-6-chloro-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