6-(1,2,4-oxadiazol-3-yl)-1H-purine | 165546-24-7

• 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: 6-(1,2,4-oxadiazol-3-yl)-1H-purine
• 英文别名: 3-(7H-purin-6-yl)-1,2,4-oxadiazole
• CAS: 165546-24-7
• 化学式: C₇H₄N₆O
• 分子量: 188.148
• InChiKey: UCOQIFUQSUZEDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(1,2,4-oxadiazol-3-yl)-1H-purine 、 (S)-1-(diphenylmethyl)-4-(2,3-epoxypropyl)piperazine 以 二甲基亚砜 为溶剂， 反应 12.0h， 以6%的产率得到(S)-1-(4-Benzhydryl-piperazin-1-yl)-3-(6-[1,2,4]oxadiazol-3-yl-purin-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：

  6-cyano-9-(tetrahydropyran-2-yl)purine 在 氢氧化钾 、 盐酸羟胺 、 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 反应 2.75h， 生成 6-(1,2,4-oxadiazol-3-yl)-1H-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 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.