N⁶-cyclopentyl-9-(2-C-methyl-2,3-O-isopropylidene-β-D-ribofuranosyl)adenine | 1010382-30-5

• 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: N⁶-cyclopentyl-9-(2-C-methyl-2,3-O-isopropylidene-β-D-ribofuranosyl)adenine
• CAS: 1010382-30-5
• 化学式: C₁₉H₂₇N₅O₄
• 分子量: 389.454
• InChiKey: MXMFWHZFOQWZDR-KJMSJTNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.98
• 重原子数：
  28.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  103.55
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N⁶-cyclopentyl-9-(2-C-methyl-2,3-O-isopropylidene-β-D-ribofuranosyl)adenine 在 吡啶 、 氯化亚砜 作用下， 以 乙腈 为溶剂， 以52%的产率得到N6-cyclopentyl-9H-(2-C-methyl-2,3-O-isopropylidene-5-chloro-5-deoxy-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  N 6-环烷基和N 6-双环烷基-C 5'（C 2'）修饰的腺苷衍生物对人A 1腺苷受体的高亲和力和选择性激动剂在小鼠中具有抗伤害感受性

  摘要：

  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

  DOI：

  10.1021/jm801456g
• 作为产物：
  描述：

  2,2-二甲氧基丙烷 、 N-环戊基-2’-C-甲基腺苷 在 camphorsulfonic acid 作用下， 以 丙酮 为溶剂， 生成 N⁶-cyclopentyl-9-(2-C-methyl-2,3-O-isopropylidene-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  N 6-环烷基和N 6-双环烷基-C 5'（C 2'）修饰的腺苷衍生物对人A 1腺苷受体的高亲和力和选择性激动剂在小鼠中具有抗伤害感受性

  摘要：

  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

  DOI：

  10.1021/jm801456g

文献信息

• 5′-Carbamoyl derivatives of 2′-C-methyl-purine nucleosides as selective A1 adenosine receptor agonists: Affinity, efficacy, and selectivity for A1 receptor from different species
  作者：Loredana Cappellacci、Palmarisa Franchetti、Patrizia Vita、Riccardo Petrelli、Antonio Lavecchia、Barbara Costa、Francesca Spinetti、Claudia Martini、Karl-Norbert Klotz、Mario Grifantini

  DOI：10.1016/j.bmc.2007.09.035

  日期：2008.1

  A series of 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-C-methyl analogues of the A, adenosine receptor (AIAR) full agonists N-6-cyclopentyladenosine (CPA), 2-chloro-N-6-cyclopentyladenosine (CCPA), N-6-[3-(R)-tetrahydrofuranyl]adenosine (tecadenoson), and 2-chloro analogue (2-Cl-tecadenoson) was synthesized and evaluated for their affinity for adenosine receptor subtypes from bovine, porcine, and human species. In the N-6-cyclopentylamino series, the 5'-substituted derivatives showed a reduced affinity at the bovine A(1)AR compared to the parent compounds; however, the selectivity for A(1) versus A(2A) receptor was retained or increased. The corresponding N-6-3-(R)-tetrahydrofuranylamino analogues displayed a very low affinity toward the bovine AIAR. The 5'-methylthionocarbamoyl derivative of 2'-Me-CCPA showed the best affinity at porcine AIAR with a K-i value of 13 nM. At human AR subtypes tecadenoson derivatives showed 2.3- to 5-fold lower affinity at AIAR and very low affinity at the other subtypes (A(2A), A(2B), and A(3) compared to the corresponding N-6-cyclopentyl analogues. The 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-Me-CCPA 3, 4, 7 and tecadenoson derivative 12 were found to be partial A, agonists at the porcine receptor. Docking studies explained the lower affinity of N-6-3-(R)-tetrahydrofuranyl-substituted compounds at bovine AIAR compared to that of N-6-cyclopentyl analogues, showing that the oxygen of the tetrahydrofuranyl ring establishes unfavorable electrostatic interactions with the CO oxygen of Asn254. The low binding affinity of the 2'-C-methyl-N-6-3-(R)-tetrahydrofuranyl adenosine analogues at human AIAR may be ascribed to the presence of unfavorable interactions between the hydrophilic tetrahydrofuranyl ring and the surrounding hydrophobic residues Leu250 (TM6) and Ile274 (TM7). (c) 2007 Elsevier Ltd. All rights reserved.