N6-cyclopentyl-9H-[5-deoxy-5-(2-fluorophenylthio)-β-D-ribofuranosyl]adenine | 581106-45-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: N6-cyclopentyl-9H-[5-deoxy-5-(2-fluorophenylthio)-β-D-ribofuranosyl]adenine
• 英文别名: N-Cyclopentyl-5'-S-(2-fluorophenyl)-5'-thioadenosine；(2R,3R,4S,5S)-2-[6-(cyclopentylamino)purin-9-yl]-5-[(2-fluorophenyl)sulfanylmethyl]oxolane-3,4-diol
• CAS: 581106-45-8
• 化学式: C₂₁H₂₄FN₅O₃S
• 分子量: 445.518
• InChiKey: SKEFGDREBIAUKI-HAXDFEGKSA-N

物化性质

• 沸点：
  708.1±70.0 °C(Predicted)
• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N6-环戊基腺苷酸 在 偶氮二甲酸二异丙酯 、 polystyrene bound triphenylphosphine 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 N6-cyclopentyl-9H-[5-deoxy-5-(2-fluorophenylthio)-β-D-ribofuranosyl]adenine
  参考文献：
  名称：

  Structure–affinity relationships of 5 ′ -aromatic ethers and 5 ′ -aromatic sulfides as partial A 1 adenosine agonists, potential supraventricular anti-arrhythmic agents

  摘要：

  Atrial fibrillation (AF) is the most commonly encountered sustained clinical arrhythmia with an estimated 2.3 million cases in the US (2001). A, adenosine receptor agonists can slow the electrical impulse propagation through the atrioventricular (AV) node (i.e., negative dromotropic effect) resulting in prolongation of the stimulus-to-His bundle (S-H) interval to potentially reduce ventricular rate. Compounds that are full agonists of the A, adenosine receptor can cause high grade AV block. Therefore, it is envisioned that a compound that is a partial agonist of the A, adenosine receptor could avoid this deleterious effect. 5' Phenyl sulfides (e.g., 17, EC50 = 1.26 muM) and phenyl ethers (e.g., 28, EC50 = 0.2 muM) are partial agonists with respect to their AV nodal effects in guinea pig isolated hearts. Additional affinity, GTPgammaS binding data suggesting partial activity of the A(1) adenosine receptor, and PK results for 5' modified adenosine derivatives are shown. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.096

文献信息

• <i>N</i>⁶-Cycloalkyl- and <i>N</i>⁶-Bicycloalkyl-<i>C</i>5′(<i>C</i>2′)-modified Adenosine Derivatives as High-Affinity and Selective Agonists at the Human A₁ Adenosine Receptor with Antinociceptive Effects in Mice
  作者：Palmarisa Franchetti、Loredana Cappellacci、Patrizia Vita、Riccardo Petrelli、Antonio Lavecchia、Sonja Kachler、Karl-Norbert Klotz、Ida Marabese、Livio Luongo、Sabatino Maione、Mario Grifantini

  DOI：10.1021/jm801456g

  日期：2009.4.23

  N6-(endo-norborn-2-yl)adenosine derivatives, 5′-chloro-5′-deoxy-CPA (1) and 5′-chloro-5′-deoxy-(±)-ENBA (3) displayed the highest affinity in the subnanomolar range and relevant selectivity for hA1 vs the other human receptor subtypes. The higher affinity and selectivity of 5′-chloro-5′-deoxyribonucleoside derivatives 1 and 3 for hA1 AR vs hA3 AR compared to that of the parent 5′-hydroxy compounds CPA and (±)-ENBA

  为了进一步研究新型有效和选择性的人A 1腺苷受体激动剂，我们合成了一系列5'-氯-5'-脱氧-和5'-（2-氟苯硫基）-5'-脱氧-N 6-环烷基（双环烷基）-取代的腺苷和2'- C-甲基腺苷衍生物。评价这些化合物对人A 1，A 2A，A 2B和A 3腺苷受体的亲和力和功效。在一系列N 6-环戊基和N 6-（内降冰片-2-基）腺苷衍生物中，5'-chloro-5'-deoxy-CPA（1）和5'-chloro-5'- deoxy-CPA（1） （±）-ENBA（3）显示出在亚纳摩尔范围内的最高亲和力和对hA 1的选择性相对于其他人类受体亚型。5'-chloro-5'-脱氧核糖核苷衍生物1和3对hA 1 AR与hA 3 AR的亲和力和选择性与母体5'-羟基化合物CPA和（±）-ENBA的亲和力和选择性通过分子合理化建模分析。5'-Chloro-5'-deoxy-（±）-ENBA在福尔马林试验
• Structure–affinity relationships of 5 ′ -aromatic ethers and 5 ′ -aromatic sulfides as partial A 1 adenosine agonists, potential supraventricular anti-arrhythmic agents
  作者：Christopher F. Morrison、Elfatih Elzein、Bob Jiang、Prabha N. Ibrahim、Timothy Marquart、Venkata Palle、Kevin D. Shenk、Vaibhav Varkhedkar、Tenning Maa、Lin Wu、Yuzhi Wu、Dewan Zeng、Irving Fong、David Lustig、Kwan Leung、Jeff A. Zablocki

  DOI：10.1016/j.bmcl.2004.04.096

  日期：2004.7

  Atrial fibrillation (AF) is the most commonly encountered sustained clinical arrhythmia with an estimated 2.3 million cases in the US (2001). A, adenosine receptor agonists can slow the electrical impulse propagation through the atrioventricular (AV) node (i.e., negative dromotropic effect) resulting in prolongation of the stimulus-to-His bundle (S-H) interval to potentially reduce ventricular rate. Compounds that are full agonists of the A, adenosine receptor can cause high grade AV block. Therefore, it is envisioned that a compound that is a partial agonist of the A, adenosine receptor could avoid this deleterious effect. 5' Phenyl sulfides (e.g., 17, EC50 = 1.26 muM) and phenyl ethers (e.g., 28, EC50 = 0.2 muM) are partial agonists with respect to their AV nodal effects in guinea pig isolated hearts. Additional affinity, GTPgammaS binding data suggesting partial activity of the A(1) adenosine receptor, and PK results for 5' modified adenosine derivatives are shown. (C) 2004 Elsevier Ltd. All rights reserved.