6-cyano-9-(tetrahydropyran-2-yl)purine | 165546-07-6

• 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-cyano-9-(tetrahydropyran-2-yl)purine
• 英文别名: 9-(Oxan-2-yl)purine-6-carbonitrile
• CAS: 165546-07-6
• 化学式: C₁₁H₁₁N₅O
• 分子量: 229.241
• InChiKey: BZMPBJZIQPODCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  76.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  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 、 二甲基亚砜 为溶剂， 反应 14.75h， 生成 (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：

  氰化钾 、 6-氯-9-(四氢-2-吡喃基)嘌呤 以 二甲基亚砜 为溶剂， 反应 6.0h， 以32%的产率得到6-cyano-9-(tetrahydropyran-2-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 of acyclic nucleotide analogues derived from N-substituted 6-(1-aminoethyl)purines via 6-acetylpurine derivatives
  作者：Michal Hocek、Milena Masojídková、Antonín Holý

  DOI：10.1016/s0040-4020(96)01130-1

  日期：1997.2

  hydrolysis gave 6-acetylpurine derivatives that after reductive amination using various primary and secondary amine hydrochlorides and sodium cyanoborohydride followed by deprotection afforded the title N-substituted 6-(1-aminoethyl)-9-(2-phosphonomethoxyethyl)purine derivatives.

  9-2- [双（2-丙氧基）膦酰基甲氧基]乙基-6-氯嘌呤与1-（乙氧基乙烯基）三丁基锡的Stille偶联得到6-（1-乙氧基乙烯基）嘌呤衍生物。它们的酸水解得到6-乙酰基嘌呤衍生物，其在使用各种伯胺和仲胺盐酸盐和氰基硼氢化钠进行还原胺化之后，脱保护，得到标题N-取代的6-（1-氨基乙基）-9-（2-膦酰基甲氧基乙基）嘌呤衍生物。
• A Facile Synthesis of 6-Cyanopurine Bases
  作者：Michal Hocek、Antonín Holý

  DOI：10.1135/cccc19951386

  日期：——

  A facile method of preparation of 6-cyanopurine bases from commercially available 6-chloropurines is reported. The 6-chloropurines were selectively protected by THP-functions and the protected derivatives reacted smoothly with tetraethylammonium cyanide and DABCO to give 6-cyanopurine derivatives that were easily deprotected to afford the title compounds.

  报道了一种从市售6-氯嘌呤制备6-氰基嘌呤碱的简便方法。将6-氯嘌呤选择性地保护为THP基团，保护衍生物与四乙基铵氰和DABCO反应，得到6-氰基嘌呤衍生物，易于脱保护得到目标化合物。
• 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.