9-(2,3-epoxypropyl)-6-(pyrrol-1-yl)purine | 241823-42-7

• 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: 9-(2,3-epoxypropyl)-6-(pyrrol-1-yl)purine
• 英文别名: 9-(2,3-Epoxypropyl)-6-(N-pyrrolyl)purine；9-(oxiran-2-ylmethyl)-6-pyrrol-1-ylpurine
• CAS: 241823-42-7
• 化学式: C₁₂H₁₁N₅O
• 分子量: 241.252
• InChiKey: POHYWYYRYPAVCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  61.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(1-苯基乙基)哌嗪 、 9-(2,3-epoxypropyl)-6-(pyrrol-1-yl)purine 以 乙醇 为溶剂， 反应 3.0h， 生成 1-[4-(1-Phenylethyl)piperazin-1-yl]-3-(6-pyrrol-1-ylpurin-9-yl)propan-2-ol
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of 6-Heterocyclic-Substituted Purines as Inactivation Modifiers of Cardiac Sodium Channels

  摘要：

  Purine-based analogs of SDZ 211-500 (5) were prepared and evaluated as inactivation modifiers of guinea pig or human cardiac sodium (Na) channels expressed in Xenopus oocytes. Substances which remove or slow the Na channel inactivation process in cardiac tissue are anticipated to prolong the effective refractory period and increase inotropy and thus have potential utility as antiarrhythmic agents. Heterocyclic substitution at the 6-position of the purine ring resulted in compounds with increased Na activity and potency, with 5-membered heterocycles being optimal. Only minor modifications to the benzhydrylpiperazine side chain were tolerated. Selected compounds which delayed the inactivation of Na channels were found to increase refractoriness and contractility in a rabbit Langendorff heart model, consistent with the cellular mechanism. Activity in both the oocyte and rabbit heart assays was specific to the S enantiomers. Preliminary in vivo activity has been demonstrated following intravenous infusion. The most promising compound on the basis of in vitro data is the formylpyrrole (S)-74, which is 25-fold more potent than DPI 201-106 (1) in the human heart Na channel assay.

  DOI：

  10.1021/jm00014a011
• 作为产物：
  描述：

  腺嘌呤 在 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 9-(2,3-epoxypropyl)-6-(pyrrol-1-yl)purine
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of 6-Heterocyclic-Substituted Purines as Inactivation Modifiers of Cardiac Sodium Channels

  摘要：

  Purine-based analogs of SDZ 211-500 (5) were prepared and evaluated as inactivation modifiers of guinea pig or human cardiac sodium (Na) channels expressed in Xenopus oocytes. Substances which remove or slow the Na channel inactivation process in cardiac tissue are anticipated to prolong the effective refractory period and increase inotropy and thus have potential utility as antiarrhythmic agents. Heterocyclic substitution at the 6-position of the purine ring resulted in compounds with increased Na activity and potency, with 5-membered heterocycles being optimal. Only minor modifications to the benzhydrylpiperazine side chain were tolerated. Selected compounds which delayed the inactivation of Na channels were found to increase refractoriness and contractility in a rabbit Langendorff heart model, consistent with the cellular mechanism. Activity in both the oocyte and rabbit heart assays was specific to the S enantiomers. Preliminary in vivo activity has been demonstrated following intravenous infusion. The most promising compound on the basis of in vitro data is the formylpyrrole (S)-74, which is 25-fold more potent than DPI 201-106 (1) in the human heart Na channel assay.

  DOI：

  10.1021/jm00014a011

文献信息

• Synthesis and biological evaluation of the novel purine and pyrimidine nucleoside analogues containing 2,3-epoxypropyl, 3-amino-2-hydroxypropyl or 2,3-epoxypropyl ether moieties
  作者：Silvana Raić-Malić、Mira Grdiša、Krešimir Pavelic、Mladen Mintas

  DOI：10.1016/s0223-5234(99)80090-7

  日期：1999.5

  The novel purine and pyrimidine nucleoside analogues possessing a 2,3-epoxypropyl (2a-2c and 8a-8c), 2,3-epoxypropyl ether (3), or 3-amino-2-hydroxypropyl (4a-6c and 9a-9c) moiety bonded at either N-9 of the C-6 substituted purine ring or N-1 and N-3 of the pyrimidine ring, were prepared and evaluated on their antitumour and antiviral activities. Compounds 3, 6b, 8b and sc showed marked inhibition of growth of human tumour cell lines (MiaPaCa(2) and Raji), whilst the inhibitory effect of 6b was greater against Raji cells than to the MiaPaCa2 ones. No specific activity of compounds 2a-3, 4a-6c and 9a-9c against HSV and VZV was detected. The compound 6b was slightly active against the replication of HIV 1 (IIIB), while 2a-2c and 8a-8c were inactive. (C) Elsevier, Paris.
• Synthesis and Structure-Activity Relationships of 6-Heterocyclic-Substituted Purines as Inactivation Modifiers of Cardiac Sodium Channels
  作者：Kimberly G. Estep、Kurt A. Josef、Edward R. Bacon、Philip M. Carabateas、Squire Rumney、Garry M. Pilling、Douglas S. Krafte、Walter A. Volberg、Kathleen Dillon、Nancy Dugrenier、G. Maurice Briggs、Paul C. Canniff、William P. Gorczyca、Gerald P. Stankus、Alan M. Ezrin

  DOI：10.1021/jm00014a011

  日期：1995.7

  Purine-based analogs of SDZ 211-500 (5) were prepared and evaluated as inactivation modifiers of guinea pig or human cardiac sodium (Na) channels expressed in Xenopus oocytes. Substances which remove or slow the Na channel inactivation process in cardiac tissue are anticipated to prolong the effective refractory period and increase inotropy and thus have potential utility as antiarrhythmic agents. Heterocyclic substitution at the 6-position of the purine ring resulted in compounds with increased Na activity and potency, with 5-membered heterocycles being optimal. Only minor modifications to the benzhydrylpiperazine side chain were tolerated. Selected compounds which delayed the inactivation of Na channels were found to increase refractoriness and contractility in a rabbit Langendorff heart model, consistent with the cellular mechanism. Activity in both the oocyte and rabbit heart assays was specific to the S enantiomers. Preliminary in vivo activity has been demonstrated following intravenous infusion. The most promising compound on the basis of in vitro data is the formylpyrrole (S)-74, which is 25-fold more potent than DPI 201-106 (1) in the human heart Na channel assay.