5'-O-cyclohexanoyl-N⁶-cyclopentyladenosine

• 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: 5'-O-cyclohexanoyl-N⁶-cyclopentyladenosine
• 英文别名: [(2R,3S,4R,5R)-5-[6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl cyclohexanecarboxylate
• 化学式: C₂₂H₃₁N₅O₅
• 分子量: 445.519
• InChiKey: CXEZMYKLGTVQQF-QTQZEZTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  132
• 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 4-二甲氨基吡啶 、 三氟乙酸 、 三氯乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 75.0h， 生成 5'-O-cyclohexanoyl-N⁶-cyclopentyladenosine
  参考文献：
  名称：

  摘要：

  Purpose. A series of 5 ' -esters of N " -cyclopentyladenosine (CPA) were prepared with the aim to improve stability and bioavailability of selective A(1) agonists. Log P values, stability, affinity, and activity toward human adenosine A, receptors were evaluated.Methods. An appropriate synthetic procedure was adopted to avoid concomitant deamination at position 6. Log P values were obtained by the Mixxor system. The stability of CPA and its 5 ' -ester was evaluated in human plasma and whole blood and analyzed with highperformance liquid chromatography. The affinities to human A, receptor expressed by N-6-cyclohexyladenosine cells were obtained by binding experiments. The activities were evaluated by measurements of the inhibition of forskolin stimulated 3 ' -5 ' -cyclic adenosine monophosphate, performing competitive binding assays.Results. All prodrugs were more lipophilic than CPA, and their hydrolysis, in whole blood and in plasma, was found related, respectively, to the length and hindrance of 5 ' -substituents. Affinity and activity values indicated a very weak interaction toward adenosine A, receptor of the intact prodrugs.Conclusions. We propose 5 ' -esters of CPA, characterized by suitable lipophilicity and elevated degree of stability in physiological fluids, as possible canditates for CPA prodrugs.

  DOI：

  10.1023/a:1011018730459

文献信息

• ——
  作者：Alessandro Dalpiaz、Angelo Scatturin、Enea Menegatti、Fabrizio Bortolotti、Barbara Pavan、Carla Biondi、Elisa Durini、Stefano Manfredini

  DOI：10.1023/a:1011018730459

  日期：——

  Purpose. A series of 5 ' -esters of N " -cyclopentyladenosine (CPA) were prepared with the aim to improve stability and bioavailability of selective A(1) agonists. Log P values, stability, affinity, and activity toward human adenosine A, receptors were evaluated.Methods. An appropriate synthetic procedure was adopted to avoid concomitant deamination at position 6. Log P values were obtained by the Mixxor system. The stability of CPA and its 5 ' -ester was evaluated in human plasma and whole blood and analyzed with highperformance liquid chromatography. The affinities to human A, receptor expressed by N-6-cyclohexyladenosine cells were obtained by binding experiments. The activities were evaluated by measurements of the inhibition of forskolin stimulated 3 ' -5 ' -cyclic adenosine monophosphate, performing competitive binding assays.Results. All prodrugs were more lipophilic than CPA, and their hydrolysis, in whole blood and in plasma, was found related, respectively, to the length and hindrance of 5 ' -substituents. Affinity and activity values indicated a very weak interaction toward adenosine A, receptor of the intact prodrugs.Conclusions. We propose 5 ' -esters of CPA, characterized by suitable lipophilicity and elevated degree of stability in physiological fluids, as possible canditates for CPA prodrugs.