6-(1H-1,2,4-三唑-1-基)-7H-嘌呤 | 165546-19-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 6-(1H-1,2,4-三唑-1-基)-7H-嘌呤
• 英文名称: 6-(1H-1,2,4-Triazol-1-yl)-7H-purine
• 英文别名: 6-(1,2,4-triazol-1-yl)-7H-purine
• CAS: 165546-19-0
• 化学式: C₇H₅N₇
• 分子量: 187.164
• InChiKey: CDRFYYRVYMLDLE-UHFFFAOYSA-N

物化性质

• 沸点：
  619.3±58.0 °C(Predicted)
• 密度：
  1.89±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 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：
  85.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(1H-1,2,4-三唑-1-基)-7H-嘌呤 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.0h， 生成 1-(4-Benzhydryl-piperazin-1-yl)-3-(6-[1,2,4]triazol-1-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：

  1H-1,2,4-三唑 、 6-氯嘌呤 以86%的产率得到6-(1H-1,2,4-三唑-1-基)-7H-嘌呤
  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

• Methods For Selective N-9 Glycosylation of Purines
  申请人：Robins Morris J.

  公开号：US20080207891A1

  公开（公告）日：2008-08-28

  A process for providing regiospecific and highly stereoselective synthesis of 9-β anomeric purine nucleoside analogs is described. The introduction of the sugar moiety on to 6-(azolyl)-substituted purine bases is performed so that highly stereoselective formation of the β anomers of only the 9 position regioisomers of the purine nucleoside analogs (either D or L enantiomers) is obtained. This regiospecific and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs, and in particular 2′-deoxy, 3′-deoxy, 2′-deoxy-2′-halo-arabino and 2′,3′-dideoxy-2′-halo-threo purine nucleoside analogs, in high yields without formation of the 7-positional regioisomers. Processes for providing novel 6-(azolyl)purines for the regiospecific and highly stereoselective synthesis of 9-β anomeric purine nucleoside analogs are described. The compounds are drugs or intermediates to drugs.

  本文描述了一种提供9-β异构嘌呤核苷类似物的区域特异性和高度立体选择性合成的方法。将糖基引入到6-(咪唑基)-取代的嘌呤碱基上，以获得嘌呤核苷类似物的β异构体的高度立体选择性形成（D或L对映体）。这种区域特异性和立体选择性引入糖基的方法，允许高产率地合成核苷类似物，特别是2'-去氧、3'-去氧、2'-去氧-2'-卤代阿拉伯糖和2',3'-二去氧-2'-卤代-threo嘌呤核苷类似物，而不形成7位异构体。本文还描述了提供新型6-(咪唑基)嘌呤用于区域特异性和高度立体选择性合成9-β异构嘌呤核苷类似物的方法。这些化合物是药物或药物中间体。
• METHODS FOR SELECTIVE N-9 GLYCOSYLATION OF PURINES
  申请人：Brigham Young University

  公开号：EP1895841A2

  公开（公告）日：2008-03-12
• US7855285B2
  申请人：——

  公开号：US7855285B2

  公开（公告）日：2010-12-21
• [EN] METHODS FOR SELECTIVE N-9 GLYCOSYLATION OF PURINES<br/>[FR] PROCEDES DE N-9 GLYCOSYLATION SELECTIVE DE PURINES
  申请人：BRIGHAM YOUNG UNIVERSITY TRANS

  公开号：WO2006138396A2

  公开（公告）日：2006-12-28

  [EN] A process for providing regiospecific and highly stereoselective synthesis of 9-ß anomeric purine nucleoside analogs is described. The introduction of the sugar moiety on to 6-(azolyl)-substituted purine bases is performed so that highly stereoselective formation of the ß anomers of only the 9 position regioisomers of the purine nucleoside analogs (either D or L enantiomers) is obtained. This regiospecific and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs, and in particular 2'-deoxy, 3'-deoxy, 2'-deoxy-2'-halo-arabino and 2',3'-dideoxy-2'-halo-threo purine nucleoside analogs, in high yields without formation of the 7-positional regioisomers. Processes for providing novel 6-(azolyl)purines for the regiospecific and highly stereoselective synthesis of 9-ß anomeric purine nucleoside analogs are described. The compounds are drugs or intermediates to drugs.
  [FR] L'invention concerne un procédé permettant d'obtenir une synthèse régiospécifique et hautement stéréosélective d'analogues de nucléosides de purines anomériques 9-ß. L'introduction de la fraction de sucre sur des bases de purines 6-(azolyl)-substituées est effectuée de manière qu'une formation hautement stéréosélective des anomères ß d'uniquement les régiosomères en position 9 des analogues de nucléosides de purines (soit des enantiomères D ou L) soit obtenue. Cette introduction régiospécifique et stéréosélective de la fraction de sucre permet d'obtenir la synthèse des analogues de nucléosides, notamment des analogues de nucléosides de purines 2'-désoxy, 3'-désoxy, 2'-désoxy-2'-halo-arabino et 2',3'-didésoxy-2'-halo-thréo, à des rendements élevés sans formation des régiosiomères en position 7. L'invention concerne également des procédés permettant de préparer des purines 6-(azolyl) destinées à la synthèse régiospécifique et hautement stéréosélective d'analogues de nucléosides de purines anomériques 9-ß. Les composés sont des médicaments ou des intermédiaires aux médicaments.
• 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.