2'-deoxy-2-chloro-N⁶-cyclopentyladenosine | 215108-39-7

• 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: 2'-deoxy-2-chloro-N⁶-cyclopentyladenosine
• 英文别名: 2-chloro-2'-deoxy-N⁶-cyclopentyladenosine；2-chloro-N⁶-cyclopentyl-2'-deoxyadenosine；AAG125；2'-dCCPA；(2R,3S,5R)-5-[2-chloro-6-(cyclopentylamino)purin-9-yl]-2-(hydroxymethyl)oxolan-3-ol
• CAS: 215108-39-7
• 化学式: C₁₅H₂₀ClN₅O₃
• 分子量: 353.808
• InChiKey: POVXZSUIRZLFEN-HBNTYKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2'-deoxy-2-chloro-N⁶-cyclopentyladenosine 在 10percent Pd/C sodium hydroxide 、 氢气 作用下， 反应 8.0h， 以60%的产率得到2'-deoxyribose-N⁶-cyclopentyladenosine
  参考文献：
  名称：

  N-Cycloalkyl Derivatives of Adenosine and 1-Deazaadenosine as Agonists and Partial Agonists of the A₁ Adenosine Receptor

  摘要：

  A number of cycloalkyl substituents (from C-3 to C-8) have been int-reduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guanosine 5'-triphosphate (GTP) shift and the maximal induction of guanosine 5'-(gamma-thio)triphosphate ([S-35]GTP gamma S) binding to G proteins in rat brain membranes were used to determine the intrinsic activity of these nucleosides at the A(1) adenosine receptor. All compounds of the ribose-bearing series proved to be full agonists, the 1-deaza derivatives showing affinities for the Al receptor about 10-fold lower than the corresponding adenosines. On the other hand, all the 2'-deoxyribose derivatives bind to the A(1) receptor with affinities in the high nanomolar range, with the 2-chloro substituted compounds showing slightly higher affinities than the 2-unsubstituted counterparts. In terms of the potencies, the most potent compounds proved to be those bearing four- and five-membered rings. Both GTP shifts and [S-35]-GTP gamma S experiments showed that most of the 2'-deoxyadenosine derivatives are partial agonists, The 2'-deoxyadenosine derivatives which were identified as partial agonists consistently detected fewer Az receptors in the high-affinity state than full agonists. However, it is worthwhile noting that there was not a simple Linear relationship between receptor occupancy and activation. These results indicate that a critical density of A(1) adenosine receptors in the high-affinity state is required for G protein activation.

  DOI：

  10.1021/jm9911231
• 作为产物：
  描述：

  2,6-二氯-9-(3,5-二-O-对甲苯甲酰基-2-脱氧-beta-D-赤式-呋喃戊糖基)嘌呤 在 氨 作用下， 以 甲醇 为溶剂， 反应 80.0h， 生成 2'-deoxy-2-chloro-N⁶-cyclopentyladenosine
  参考文献：
  名称：

  N-Cycloalkyl Derivatives of Adenosine and 1-Deazaadenosine as Agonists and Partial Agonists of the A₁ Adenosine Receptor

  摘要：

  A number of cycloalkyl substituents (from C-3 to C-8) have been int-reduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guanosine 5'-triphosphate (GTP) shift and the maximal induction of guanosine 5'-(gamma-thio)triphosphate ([S-35]GTP gamma S) binding to G proteins in rat brain membranes were used to determine the intrinsic activity of these nucleosides at the A(1) adenosine receptor. All compounds of the ribose-bearing series proved to be full agonists, the 1-deaza derivatives showing affinities for the Al receptor about 10-fold lower than the corresponding adenosines. On the other hand, all the 2'-deoxyribose derivatives bind to the A(1) receptor with affinities in the high nanomolar range, with the 2-chloro substituted compounds showing slightly higher affinities than the 2-unsubstituted counterparts. In terms of the potencies, the most potent compounds proved to be those bearing four- and five-membered rings. Both GTP shifts and [S-35]-GTP gamma S experiments showed that most of the 2'-deoxyadenosine derivatives are partial agonists, The 2'-deoxyadenosine derivatives which were identified as partial agonists consistently detected fewer Az receptors in the high-affinity state than full agonists. However, it is worthwhile noting that there was not a simple Linear relationship between receptor occupancy and activation. These results indicate that a critical density of A(1) adenosine receptors in the high-affinity state is required for G protein activation.

  DOI：

  10.1021/jm9911231

文献信息

• Neuroprotective potential of adenosine A ₁ receptor partial agonists in experimental models of cerebral ischemia
  作者：Alberto Martire、Catia Lambertucci、Rita Pepponi、Antonella Ferrante、Nicholas Benati、Michela Buccioni、Diego Dal Ben、Gabriella Marucci、Karl‐Norbert Klotz、Rosaria Volpini、Patrizia Popoli

  DOI：10.1111/jnc.14660

  日期：2019.4

  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
• <i>N</i>-Cycloalkyl Derivatives of Adenosine and 1-Deazaadenosine as Agonists and Partial Agonists of the A₁ Adenosine Receptor
  作者：Sauro Vittori、Anna Lorenzen、Christina Stannek、Stefano Costanzi、Rosaria Volpini、Adriaan P. IJzerman、Jakobien K. Von Frijtag Drabbe Kunzel、Gloria Cristalli

  DOI：10.1021/jm9911231

  日期：2000.1.1

  A number of cycloalkyl substituents (from C-3 to C-8) have been int-reduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guanosine 5'-triphosphate (GTP) shift and the maximal induction of guanosine 5'-(gamma-thio)triphosphate ([S-35]GTP gamma S) binding to G proteins in rat brain membranes were used to determine the intrinsic activity of these nucleosides at the A(1) adenosine receptor. All compounds of the ribose-bearing series proved to be full agonists, the 1-deaza derivatives showing affinities for the Al receptor about 10-fold lower than the corresponding adenosines. On the other hand, all the 2'-deoxyribose derivatives bind to the A(1) receptor with affinities in the high nanomolar range, with the 2-chloro substituted compounds showing slightly higher affinities than the 2-unsubstituted counterparts. In terms of the potencies, the most potent compounds proved to be those bearing four- and five-membered rings. Both GTP shifts and [S-35]-GTP gamma S experiments showed that most of the 2'-deoxyadenosine derivatives are partial agonists, The 2'-deoxyadenosine derivatives which were identified as partial agonists consistently detected fewer Az receptors in the high-affinity state than full agonists. However, it is worthwhile noting that there was not a simple Linear relationship between receptor occupancy and activation. These results indicate that a critical density of A(1) adenosine receptors in the high-affinity state is required for G protein activation.