(2S,4R,5R)-(4-acetoxy-5-(2,6-dichloro-9H-purine-9-yl)tetrahydrofuran-2-yl)methyl benzoate | 1347461-82-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2S,4R,5R)-(4-acetoxy-5-(2,6-dichloro-9H-purine-9-yl)tetrahydrofuran-2-yl)methyl benzoate
• 英文别名: [(2S,4R,5R)-4-acetyloxy-5-(2,6-dichloropurin-9-yl)oxolan-2-yl]methyl benzoate
• CAS: 1347461-82-8
• 化学式: C₁₉H₁₆Cl₂N₄O₅
• 分子量: 451.266
• InChiKey: ZGMXNVIOSOJFPQ-OGHNNQOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,4R,5R)-(4-acetoxy-5-(2,6-dichloro-9H-purine-9-yl)tetrahydrofuran-2-yl)methyl benzoate 、 环戊胺 在 氨 作用下， 以 甲醇 为溶剂， 反应 21.0h， 以93%的产率得到(2R,3R,5S)-2-(2-chloro-6-(cyclopentylamino)-9H-purin-9-yl)-5-(hydroxymethyl)tetra-hydrofuran-3-ol
  参考文献：
  名称：

  Neuroprotective potential of adenosine A ₁ receptor partial agonists in experimental models of cerebral ischemia

  摘要：

  AbstractCerebral ischemia is the second most common cause of death and a major cause of disability worldwide. Available therapies are based only on anticoagulants or recombinant tissue plasminogen activator. Extracellular adenosine increases during ischemia and acts as a neuroprotective endogenous agent mainly by activating adenosine A1 receptors (A1Rs) which control calcium influx, glutamate release, membrane potential, and metabolism. Accordingly, in many experimental paradigms it has been already demonstrated that the stimulation of A1R with full agonists is able to reduce ischemia‐related structural and functional brain damage; unfortunately, cardiovascular side effects and desensitization of A1R induced by these compounds have strongly limited their exploitation in stroke therapy so far. Among the newly emerging compounds, A1R partial agonists could be almost free of side effects and equally effective. Therefore, we decided to evaluate the neuroprotective potential of two A1R partial agonists, namely 2′‐dCCPA and 3′‐dCCPA, in in vitro and ex vivo experimental models of cerebral ischemia. Within the experimental paradigm of oxygen‐glucose deprivation in vitro in human neuroblastoma (SH‐SY5Y) cells both A1R partial agonists increased cell viability. Considering the high level of expression of A1Rs in the hippocampus and the susceptibility of CA1 region to hypoxia, we performed electrophysiological experiments in this subfield. The application of 7 min of oxygen‐glucose deprivation constantly produces an irreversible synaptic failure in all the C57Bl/6 mice hippocampal slices evaluated; both tested compounds allowed a significant recovery of synaptic transmission. These findings demonstrate that A1R and its partial agonists are still of interest for cerebral ischemia therapy.Open Science BadgesThis article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. image

  DOI：

  10.1111/jnc.14660
• 作为产物：
  描述：

  2,6-二氯嘌呤 、 1,2-di-O-acetyl-5-O-benzoyl-3-deoxy-β-D-ribofuranose 在 四氯化锡 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以84%的产率得到(2S,4R,5R)-(4-acetoxy-5-(2,6-dichloro-9H-purine-9-yl)tetrahydrofuran-2-yl)methyl benzoate
  参考文献：
  名称：

  Neuroprotective potential of adenosine A ₁ receptor partial agonists in experimental models of cerebral ischemia

  摘要：

  AbstractCerebral ischemia is the second most common cause of death and a major cause of disability worldwide. Available therapies are based only on anticoagulants or recombinant tissue plasminogen activator. Extracellular adenosine increases during ischemia and acts as a neuroprotective endogenous agent mainly by activating adenosine A1 receptors (A1Rs) which control calcium influx, glutamate release, membrane potential, and metabolism. Accordingly, in many experimental paradigms it has been already demonstrated that the stimulation of A1R with full agonists is able to reduce ischemia‐related structural and functional brain damage; unfortunately, cardiovascular side effects and desensitization of A1R induced by these compounds have strongly limited their exploitation in stroke therapy so far. Among the newly emerging compounds, A1R partial agonists could be almost free of side effects and equally effective. Therefore, we decided to evaluate the neuroprotective potential of two A1R partial agonists, namely 2′‐dCCPA and 3′‐dCCPA, in in vitro and ex vivo experimental models of cerebral ischemia. Within the experimental paradigm of oxygen‐glucose deprivation in vitro in human neuroblastoma (SH‐SY5Y) cells both A1R partial agonists increased cell viability. Considering the high level of expression of A1Rs in the hippocampus and the susceptibility of CA1 region to hypoxia, we performed electrophysiological experiments in this subfield. The application of 7 min of oxygen‐glucose deprivation constantly produces an irreversible synaptic failure in all the C57Bl/6 mice hippocampal slices evaluated; both tested compounds allowed a significant recovery of synaptic transmission. These findings demonstrate that A1R and its partial agonists are still of interest for cerebral ischemia therapy.Open Science BadgesThis article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. image

  DOI：

  10.1111/jnc.14660

文献信息

• Partial and full agonists of A1 adenosine receptors
  申请人：——

  公开号：US20040198691A1

  公开（公告）日：2004-10-07

  Disclosed are novel compounds that are partial and full A 1 adenosine receptor agonists, useful for treating various disease states, in particular tachycardia and atrial flutter, angina, and myocardial infarction.

  本发明涉及一种新型化合物，它们是A1腺苷受体的部分和完全激动剂，可用于治疗各种疾病状态，特别是心动过速和心房颤动，心绞痛和心肌梗死。
• PARTIAL AND FULL AGONISTS OF A sb 1 /sb ADENOSINE RECEPTORS
  申请人：CV Therapeutics Inc.

  公开号：EP1590359A2

  公开（公告）日：2005-11-02
• US7163928B2
  申请人：——

  公开号：US7163928B2

  公开（公告）日：2007-01-16
• [EN] PARTIAL AND FULL AGONISTS OF A1 ADENOSINE RECEPTORS<br/>[FR] AGONISTES PARTIELS ET PLEINS DES RECEPTEURS A1 DE L'ADENOSINE
  申请人：CV THERAPEUTICS INC

  公开号：WO2004069185A2

  公开（公告）日：2004-08-19

  Disclosed are novel compounds that are partial and full A1 adenosine receptor agonists, useful for treating various disease states, in particular tachycardia and atrial flutter, angina, and myocardial infarction.