9-[3-Deoxy-3-(4-methylbenzamido)-β-D-xylofuranosyl]-N6-cyclopentyladenine

• 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: 9-[3-Deoxy-3-(4-methylbenzamido)-β-D-xylofuranosyl]-N6-cyclopentyladenine
• 英文别名: N-[(2S,3R,4R,5R)-5-[6-(cyclopentylamino)purin-9-yl]-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]-4-methylbenzamide
• 化学式: C₂₃H₂₈N₆O₄
• 分子量: 452.513
• InChiKey: LDARQNUFKQRDEU-PDPLOHQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N6-环戊基腺苷酸 在 palladium on activated charcoal sodium azide 、 2-乙酰氧基异丁酰溴 、 氢气 、 sodium methylate 、 1-羟基苯并三唑一水物 、 N,N'-二异丙基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、7.58 MPa 条件下， 反应 77.0h， 生成 9-[3-Deoxy-3-(4-methylbenzamido)-β-D-xylofuranosyl]-N6-cyclopentyladenine
  参考文献：
  名称：

  N⁶-Cyclopentyl-3‘-substituted-xylofuranosyladenosines:  A New Class of Non-Xanthine Adenosine A₁ Receptor Antagonists

  摘要：

  The present study explores the C-3' site of the 3-deoxy-3-xylofuranosyl ring of nucleoside analogues with an adenine or N-6-cyclopentyladenine (CPA) base moiety and evaluates the effect on adenosine receptor affinity. Two series of sugar-modified adenosines, i.e., 3'-amido-3'-deoxyadenosines and 3'-amidated 3'-deoxyxylofuranosyladenines, were synthesized and tested for their affinity at A(1) and A(2a) receptors in rat brain cortex and rat striatum, respectively. The modest affinity found in the ''xylo series'' prompted us to synthesize the corresponding N-6-cyclopentyl derivatives, which proved to be well accommodated by the A(1) receptors with potencies in the lower nanomolar range. This represents a new perspective in the purinergic field. The absence of a GTP-induced shift, i.e., the ratio between the affinities measured in the presence and absence of 1 mM GTP indicates an antagonistic behavior of this new class of CPA analogues.

  DOI：

  10.1021/jm970176k

文献信息

• Compounds derived from adenosine, use of such compound as a medicament, method for synthesizing such a compound and intermediates thereof
  申请人：K.U. LEUVEN RESEARCH & DEVELOPMENT

  公开号：EP0863148A1

  公开（公告）日：1998-09-09

  The invention relates to compounds derived from adenosine and analogs thereof, to the use of such compounds in pharmaceutical compositions as a cardiotonic, a renal protectant, a cognition enhancer and/or an antiasthmatic, to a method and to intermediates for synthesizing such a compound. The compounds according to the invention have the general formula (I): wherein R1 is a straight or branched alkyl, cycloalkyl, aralkyl or aryl group or H; R2 is a straight or branched alkyl, cycloalkyl, aralkyl, aryl group each of which is optionally substituted by at least one C1-4 alkyl, C1-4 alkoxy, nitro group or halogen; R3 is CH2R4 or CONHR5; R4 is H, OH, OR5, SR5; R5 is H, an alkyl or a cycloalkyl group; or a pharmaceutically acceptable salt thereof.

  本发明涉及由腺苷衍生的化合物及其类似物，涉及此类化合物在药物组合物中作为强心剂、肾脏保护剂、认知增强剂和/或抗哮喘剂的用途，涉及合成此类化合物的方法和中间体。 根据本发明的化合物具有通式 (I)： 其中 R1 是直链或支链烷基、环烷基、芳基或芳基或 H； R2 是直链或支链烷基、环烷基、芳烷基、芳基，其中每个基团可任选被至少一个 C1-4 烷基、C1-4 烷氧基、硝基或卤素取代； R3 是 CH2R4 或 CONHR5； R4 是 H、OH、OR5、SR5； R5 是 H、烷基或环烷基； 或其药学上可接受的盐。
• <i>N</i>⁶-Cyclopentyl-3‘-substituted-xylofuranosyladenosines:  A New Class of Non-Xanthine Adenosine A₁ Receptor Antagonists
  作者：Serge Van Calenbergh、Jacobien K. von Frijtag Drabbe Künzel、Norbert M. Blaton、Oswald M. Peeters、Jef Rozenski、Arthur Van Aerschot、Andre De Bruyn、Denis De Keukeleire、Adriaan P. IJzerman、Piet Herdewijn

  DOI：10.1021/jm970176k

  日期：1997.11.1

  The present study explores the C-3' site of the 3-deoxy-3-xylofuranosyl ring of nucleoside analogues with an adenine or N-6-cyclopentyladenine (CPA) base moiety and evaluates the effect on adenosine receptor affinity. Two series of sugar-modified adenosines, i.e., 3'-amido-3'-deoxyadenosines and 3'-amidated 3'-deoxyxylofuranosyladenines, were synthesized and tested for their affinity at A(1) and A(2a) receptors in rat brain cortex and rat striatum, respectively. The modest affinity found in the ''xylo series'' prompted us to synthesize the corresponding N-6-cyclopentyl derivatives, which proved to be well accommodated by the A(1) receptors with potencies in the lower nanomolar range. This represents a new perspective in the purinergic field. The absence of a GTP-induced shift, i.e., the ratio between the affinities measured in the presence and absence of 1 mM GTP indicates an antagonistic behavior of this new class of CPA analogues.
• 3′-Amidated 3′-Deoxyxylofuranose Analogues of <i>N</i> ⁶-⁻Cyclopentyladenosines: a New Class of Non-Xanthine Antagonists at the Adenosine A₁ Receptor.
  作者：Serge Van Calenbergh、Adriaan P. IJzerman、Piet Herdewijn

  DOI：10.1080/07328319808004688

  日期：1998.9

  Full adenosine A(1) receptor agonists like CPA and other N-6-substituted adenosine analogs have previously been shown to become partial agonists upon deletion of the 3'-hydroxyl moiety. The present study further explored the C-3' site for modification. The modest affinity at A(1) and A(2a) receptors found in the 3'-amido-3'-deoxyxylofuranosyladenine series prompted us to synthesize the corresponding N-6-cyclopentyl derivatives, which proved to exhibit potent antagonistic behaviour at the A(1) receptors. This represents a new perspective in the purinergic field.