methyl 5-O-cyclopropyl-2,3-O-isopropylidene-β-D-ribofuranoside

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 5-O-cyclopropyl-2,3-O-isopropylidene-β-D-ribofuranoside
• 英文别名: (3aR,4R,6R,6aR)-6-(cyclopropyloxymethyl)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole
• 化学式: C₁₂H₂₀O₅
• 分子量: 244.288
• InChiKey: MOOYXTUXFWNZIE-GWOFURMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 5-O-cyclopropyl-2,3-O-isopropylidene-β-D-ribofuranoside 在 盐酸 作用下， 反应 2.0h， 生成 5-O-cyclopropyl-α-D-ribofuranose 、 5-O-cyclopropyl-β-D-ribofuranose
  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
• 作为产物：
  描述：

  溴代环丙烷 、 甲基-2,3-O-异亚丙基-beta-D-呋喃核糖苷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以38%的产率得到methyl 5-O-cyclopropyl-2,3-O-isopropylidene-β-D-ribofuranoside
  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 pharmaceutical compositions containing them
  申请人：UNIVERSITEIT LEIDEN

  公开号：US20040127452A1

  公开（公告）日：2004-07-01

  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C2,5'-二取代和N6,C2,5'-三取代腺苷衍生物及其不同用途。这些腺苷衍生物被发现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。
• US7084127B2
  申请人：——

  公开号：US7084127B2

  公开（公告）日：2006-08-01
• US7189706B2
  申请人：——

  公开号：US7189706B2

  公开（公告）日：2007-03-13
• 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.