{2-[6-amino-2-(4-hexyl-3-hydroxy-phenylamino)-purin-9-yl]-ethoxymethyl}-phosphonic acid | 1077883-92-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: {2-[6-amino-2-(4-hexyl-3-hydroxy-phenylamino)-purin-9-yl]-ethoxymethyl}-phosphonic acid
• 英文别名: 2-[6-Amino-2-(4-hexyl-3-hydroxyanilino)purin-9-yl]ethoxymethylphosphonic acid
• CAS: 1077883-92-1
• 化学式: C₂₀H₂₉N₆O₅P
• 分子量: 464.461
• InChiKey: UIAHQGJCAHFSEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  169
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-溴次黄嘌呤 在 三甲基溴硅烷 、 四丁基氯化铵 、 氨 、 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 甲醇 、 甲乙醚 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 88.25h， 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

文献信息

• Polymerase-Hemmer und ihre Verwendung zur Behandlung von Tumoren
  申请人：Freie Universität Berlin

  公开号：EP1990054A1

  公开（公告）日：2008-11-12

  Die Erfindung betrifft Polymerase-Hemmer, insbesondere Polymerase alpha-Hemmer und ihre Verwendung bei Zellwachstumsstörungen, insbesondere Tumorerkrankungen, bevorzugt Basaliome und/oder spinozelluläre Karzinome.

  本发明涉及聚合酶抑制剂，特别是聚合酶α抑制剂，以及它们在细胞生长障碍，特别是肿瘤疾病，最好是基底细胞癌和/或棘细胞癌中的应用。
• POLYMERASE INHIBITORS AND THE USE THEREOF FOR THE TREATMENT OF TUMORS
  申请人：Schaefer-Korting Monika

  公开号：US20110182973A1

  公开（公告）日：2011-07-28

  The invention relates to polymerase inhibitors, particularly polymerase alpha inhibitors, and the use thereof in the treatment of cell growth disorders, particularly tumor disorders, preferably actinic keratoses, basal cell carcinomas, and/or spinocellular carcinomas.
• [DE] POLYMERASE-HEMMER UND IHRE VERWENDUNG ZUR BEHANDLUNG VON TUMOREN<br/>[EN] POLYMERASE INHIBITORS AND THE USE THEREOF FOR THE TREATMENT OF TUMORS<br/>[FR] INHIBITEURS DE POLYMÉRASE ET LEUR UTILISATION POUR LE TRAITEMENT DE TUMEURS
  申请人：UNIV BERLIN FREIE

  公开号：WO2008138327A9

  公开（公告）日：2009-12-30

  [EN] The invention relates to polymerase inhibitors, particularly polymerase alpha inhibitors, and the use thereof in the treatment of cell growth disorders, particularly tumor disorders, preferably actinic keratoses, basal cell carcinomas, and/or spinocellular carcinomas.
  [FR] L'invention concerne des inhibiteurs de polymérase, notamment des inhibiteurs de polymérase alpha, et leur utilisation lors de dysfonctionnements cellulaires, notamment de maladies tumorales, de préférence pour des kératoses actiniques, des basaliomes et/ou des carcinomes spinocellulaires.
  [DE] Die Erfindung betrifft Polymerase-Hemmer, insbesondere Polymerase alpha-Hemmer und ihre Verwendung bei Zellwachstumsstörungen, insbesondere Tumorerkrankungen, bevorzugt aktinische Keratosen, Basaliome und/oder spinozelluläre Karzinome.
• Antitumor effects of guanosine-analog phosphonates identified by molecular modelling
  作者：Anja Schwanke、Caterina Murruzzu、Barbara Zdrazil、Ralf Zuhse、Maja Natek、Monika Höltje、Hans Christian Korting、Hans-Ulrich Reissig、Hans-Dieter Höltje、Monika Schäfer-Korting

  DOI：10.1016/j.ijpharm.2010.06.036

  日期：2010.9

  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.