2-chloro-N-cyclopentyl-5'-O-ethyladenosine

• 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-chloro-N-cyclopentyl-5'-O-ethyladenosine
• 英文别名: N6-cyclopentyl-2-Chloro-5'-O-ethyladenosine；(2R,3R,4S,5R)-2-[2-chloro-6-(cyclopentylamino)purin-9-yl]-5-(ethoxymethyl)oxolane-3,4-diol
• 化学式: C₁₇H₂₄ClN₅O₄
• 分子量: 397.862
• InChiKey: AWTMTQOYFLGHJN-XNIJJKJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,6-二氯嘌呤 在 三氟甲磺酸三甲基硅酯 、 三乙胺 、 六甲基二硅氮烷 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 22.0h， 生成 2-chloro-N-cyclopentyl-5'-O-ethyladenosine
  参考文献：
  名称：

  5‘-O-Alkyl Ethers of N,2-Substituted Adenosine Derivatives:  Partial Agonists for the Adenosine A₁ and A₃ Receptors

  摘要：

  New N,5'-di- and N,2,5'-trisubstituted adenosine derivatives were synthesized in good overall yields. Appropriate 5-O-alkyl-substituted ribose moieties were coupled to 6-chloropurine or 2,6-dichloropurine via Vorbruggen's glycosylation method. Subsequent amination and deprotection of the intermediates yielded compounds 18-35. Binding affinities were determined for rat adenosine A(1) and A(2A) receptors and the human A(3) receptor. The ability of compounds 18-35 to inhibit forskolin-induced (10 muM) cyclic AMP (cAMP) production and their ability to stimulate guanosine 5'-O-(3-[S-35]thio)triphosphate ([S-35]GTP gammaS) binding, via either the adenosine A(1) receptor or the adenosine A(3) receptor, were assessed. N-Cyclopentyl-substituted adenosine derivatives displayed affinities in the low nanomolar range for the adenosine A(1) receptor, whereas N-(3-iodobenzyl)-substituted derivatives had high affinity for the adenosine A(3) receptor. Compound 22 had the highest affinity for the adenosine A(3) receptor (K-i value of 16 nM), and compounds 20 and 26 had the highest affinities for the adenosine A(3) receptor (K-i values of 4 and 3 nM, respectively). A chlorine substituent at the 2-position either did not affect or slightly increased the adenosine A(3) receptor affinity, whereas the A(3) receptor affinity was affected differently, depending on the N-substituent. Furthermore, the introduction of chlorine slightly increased the A(3)/A(1) selectivity ratio. At the 5 ' -position, an O-methyl substituent induced the highest adenosine A(1) receptor affinity, whereas an O-ethyl substituent did so for the A(3) receptor. All compounds showed partial agonistic effects in both the cAMP and [S-35]GTP gammaS assays, although more marked in the latter assay. In general, the 2-chloro derivatives seemed to have lower intrinsic activities compared to the 2-H-substituted compounds on both the adenosine A(1) and the adenosine A(3) receptors. The compounds with an N-(3-iodobenzyl) substituent displayed the lowest intrinsic activities. Finally, all compounds also showed partially antagonistic behavior in the [S-35]GTP gammaS assay.

  DOI：

  10.1021/jm001114o

文献信息

• C2,5'- disubstituted and N6, c2,5'- trisubstituted adenosine derivatives and their different uses
  申请人：——

  公开号：US20040132686A1

  公开（公告）日：2004-07-08

  The present invention concerns novel C2,5′-disubstituted and N 6 ′,C2,5′-trisubstituted adenosine derivatives and their different uses. These adenosine derivatives were found to be potent adenosine receptor agonists and thus are of a therapeutic value in the treatment and prophylaxis of diseases and disorders affected by adenosine receptor agonists.

  本发明涉及新型的C2,5'-二取代和N6',C2,5'-三取代腺苷衍生物及其不同的用途。发现这些腺苷衍生物是有效的腺苷受体激动剂，因此在治疗和预防受腺苷受体激动剂影响的疾病和障碍方面具有治疗价值。
• C2,5′-disubstituted and N6, C2,5′-trisubstituted adenosine derivatives and their different uses
  申请人：Universiteit Leiden

  公开号：US07084127B2

  公开（公告）日：2006-08-01

  The present invention concerns novel C2,5′-disubstituted and N6′,C2,5′-trisubstituted adenosine derivatives and their different uses. These adenosine derivatives were found to be potent adenosine receptor agonists and thus are of a therapeutic value in the treatment and prophylaxis of diseases and disorders affected by adenosine receptor agonists.

  本发明涉及新型的C2,5'-二取代和N6',C2,5'-三取代腺苷衍生物及其不同的用途。发现这些腺苷衍生物是有效的腺苷受体激动剂，因此在治疗和预防受腺苷受体激动剂影响的疾病和疾病方面具有治疗价值。
• 5‘-<i>O</i>-Alkyl Ethers of<i> N</i>,2-Substituted Adenosine Derivatives:  Partial Agonists for the Adenosine A₁ and A₃ Receptors
  作者：Erica W. van Tilburg、Pieter A. M. van der Klein、Jacobien von Frijtag Drabbe Künzel、Miriam de Groote、Christina Stannek、Anna Lorenzen、Ad P. IJzerman

  DOI：10.1021/jm001114o

  日期：2001.8.1

  New N,5'-di- and N,2,5'-trisubstituted adenosine derivatives were synthesized in good overall yields. Appropriate 5-O-alkyl-substituted ribose moieties were coupled to 6-chloropurine or 2,6-dichloropurine via Vorbruggen's glycosylation method. Subsequent amination and deprotection of the intermediates yielded compounds 18-35. Binding affinities were determined for rat adenosine A(1) and A(2A) receptors and the human A(3) receptor. The ability of compounds 18-35 to inhibit forskolin-induced (10 muM) cyclic AMP (cAMP) production and their ability to stimulate guanosine 5'-O-(3-[S-35]thio)triphosphate ([S-35]GTP gammaS) binding, via either the adenosine A(1) receptor or the adenosine A(3) receptor, were assessed. N-Cyclopentyl-substituted adenosine derivatives displayed affinities in the low nanomolar range for the adenosine A(1) receptor, whereas N-(3-iodobenzyl)-substituted derivatives had high affinity for the adenosine A(3) receptor. Compound 22 had the highest affinity for the adenosine A(3) receptor (K-i value of 16 nM), and compounds 20 and 26 had the highest affinities for the adenosine A(3) receptor (K-i values of 4 and 3 nM, respectively). A chlorine substituent at the 2-position either did not affect or slightly increased the adenosine A(3) receptor affinity, whereas the A(3) receptor affinity was affected differently, depending on the N-substituent. Furthermore, the introduction of chlorine slightly increased the A(3)/A(1) selectivity ratio. At the 5 ' -position, an O-methyl substituent induced the highest adenosine A(1) receptor affinity, whereas an O-ethyl substituent did so for the A(3) receptor. All compounds showed partial agonistic effects in both the cAMP and [S-35]GTP gammaS assays, although more marked in the latter assay. In general, the 2-chloro derivatives seemed to have lower intrinsic activities compared to the 2-H-substituted compounds on both the adenosine A(1) and the adenosine A(3) receptors. The compounds with an N-(3-iodobenzyl) substituent displayed the lowest intrinsic activities. Finally, all compounds also showed partially antagonistic behavior in the [S-35]GTP gammaS assay.