2,6-dichloro-9-(2,3-di-O-acetyl-5-O-methyl-β-D-ribofuranosyl)purine | 169190-87-8

• 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: 2,6-dichloro-9-(2,3-di-O-acetyl-5-O-methyl-β-D-ribofuranosyl)purine
• 英文别名: 9-(2',3'-di-O-acetyl-5'-O-methyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine；2,6-dichloro-9-(2,3-di-O-acetyl-5-O-methyl-beta-D-ribofuranosyl)-purine；[(2R,3R,4R,5R)-4-acetyloxy-5-(2,6-dichloropurin-9-yl)-2-(methoxymethyl)oxolan-3-yl] acetate
• CAS: 169190-87-8
• 化学式: C₁₅H₁₆Cl₂N₄O₆
• 分子量: 419.221
• InChiKey: QXMSOZUPQLYBJU-IDTAVKCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,6-dichloro-9-(2,3-di-O-acetyl-5-O-methyl-β-D-ribofuranosyl)purine 在 甲醇 、 氨 作用下， 反应 4.0h， 生成 2-chloro-5'-O-methyladenosine
  参考文献：
  名称：

  WO2006/81665

  摘要：

  公开号：
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 三氟甲磺酸三甲基硅酯 、 六甲基二硅氮烷 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 22.0h， 生成 2,6-dichloro-9-(2,3-di-O-acetyl-5-O-methyl-β-D-ribofuranosyl)purine
  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

• 2,5',N6-trisubstituted adenosine derivatives
  申请人：Novo Nordisk A/S

  公开号：US05589467A1

  公开（公告）日：1996-12-31

  A compound of formula (I), or a pharmaceutically acceptable salt thereof: ##STR1## wherein X is halogen, amino, perhalomethyl, cyano, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio or C.sub.1-6 -alkylamino; A is methyl, halomethyl, cyanomethyl, aminomethyl, vinyl, methylthiomethyl or methoxymethyl; R.sup.1 is selected from optionally substituted N-bonded heterocyclics. The compounds have been found useful for treating central nervous system ailments.

  公式（I）的化合物，或其药用盐：##STR1##其中X是卤素，氨基，全氟甲基，氰基，C.sub.1-6-烷氧基，C.sub.1-6-烷硫基或C.sub.1-6-烷氨基；A是甲基，卤甲基，氰基甲基，氨基甲基，乙烯基，硫甲基或甲氧基甲基；R.sup.1来自可选择替代的N-键合杂环。已发现这些化合物对治疗中枢神经系统疾病有用。
• 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。
• 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。
• BISADENOSINE COMPOUNDS AS ADENOSINE A2A RECEPTOR AGONISTS
  申请人：Novartis AG

  公开号：EP2018388B9

  公开（公告）日：2011-10-05