4-Amino-2-(6-cyclopentylamino-purin-9-yl)-5-hydroxymethyl-tetrahydro-furan-3-ol | 197796-87-5

• 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: 4-Amino-2-(6-cyclopentylamino-purin-9-yl)-5-hydroxymethyl-tetrahydro-furan-3-ol
• 英文别名: (2R,3R,4R,5S)-4-amino-2-[6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolan-3-ol
• CAS: 197796-87-5
• 化学式: C₁₅H₂₂N₆O₃
• 分子量: 334.378
• InChiKey: VDLILMGMLIFWHR-KVQFHVITSA-N

物化性质

• 沸点：
  662.4±65.0 °C(Predicted)
• 密度：
  1.78±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  131
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-异丙基苯甲酸 、 4-Amino-2-(6-cyclopentylamino-purin-9-yl)-5-hydroxymethyl-tetrahydro-furan-3-ol 在 4-二甲氨基吡啶 4-sulfamylbenzoylaminomethyl polystyrene 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 、 N-甲基吡咯烷酮 、 溴乙腈 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 9-{3-deoxy-3-[(4-isopropylbenzoyl)amino]-β-D-xylofuranosyl}-N⁶-cyclopentyladenine
  参考文献：
  名称：

  5‘-Deoxy Congeners of 9-(3-Amido-3-deoxy-β-d-xylofuranosyl)-N⁶-cyclopentyladenine:  New Adenosine A₁ Receptor Antagonists and Inverse Agonists

  摘要：

  The synthesis and structure-activity relationship of AT6-cyclopentyl-3'-substituted-xylofuranosyladenosine analogues with respect to various adenosine receptors were explored in order to identify selective and potent antagonists and inverse agonists for the adenosine A(1) receptor. In particular, the effects of removal of the 5'-OH group and introduction of selected substituents at the 3'-NH2 position of 9-(3-amino-3-deoxy-beta-D-xylofuranosyl)-N-6-cyclopentyladenine were probed. A solid phase-assisted synthetic approach was used to optimize the 3'-amide functionality. In view of the general concern of the presence of a 5'-OH moiety with regard to cellular toxicity, the present study describes 5'-deoxy compounds with reasonable affinity for the human adenosine A, receptor. Interestingly, this study shows that optimization of the 3'-"up" amide sustituent can substantially compensate for the drop in affinity for the adenosine A, receptor, which is generally observed upon removal of the 5'-OH group. The fact that for several 3'-amido-substituted (5'-deoxy)-N-6-cyclopentyladenosine derivatives, guanosine 5'-triphosphate-induced shifts in K-i values were significantly lower than 1 implies that these analogues behave as inverse agonists. This is further supported by their 1,3-dipropyl-8-cyclopentylxanthine-like capacity to increase forskolin-induced adenosine cyclic 3',5'-phosphate production.

  DOI：

  10.1021/jm0110439
• 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 、 水 、 氢气 、 sodium methylate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-Amino-2-(6-cyclopentylamino-purin-9-yl)-5-hydroxymethyl-tetrahydro-furan-3-ol
  参考文献：
  名称：

  3′-Amidated 3′-Deoxyxylofuranose Analogues of N ⁶-⁻Cyclopentyladenosines: a New Class of Non-Xanthine Antagonists at the Adenosine A₁ Receptor.

  摘要：

  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.

  DOI：

  10.1080/07328319808004688

文献信息

• <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.
• 5‘-Deoxy Congeners of 9-(3-Amido-3-deoxy-<i>β</i>-<scp>d</scp>-xylofuranosyl)-<i>N</i>⁶-cyclopentyladenine:  New Adenosine A₁ Receptor Antagonists and Inverse Agonists
  作者：Serge Van Calenbergh、Andreas Link、Shelly Fujikawa、Rianne A. F. de Ligt、Veerle Vanheusden、Abolfasl Golisade、Norbert M. Blaton、Jef Rozenski、Adriaan P. IJzerman、Piet Herdewijn

  DOI：10.1021/jm0110439

  日期：2002.4.1

  The synthesis and structure-activity relationship of AT6-cyclopentyl-3'-substituted-xylofuranosyladenosine analogues with respect to various adenosine receptors were explored in order to identify selective and potent antagonists and inverse agonists for the adenosine A(1) receptor. In particular, the effects of removal of the 5'-OH group and introduction of selected substituents at the 3'-NH2 position of 9-(3-amino-3-deoxy-beta-D-xylofuranosyl)-N-6-cyclopentyladenine were probed. A solid phase-assisted synthetic approach was used to optimize the 3'-amide functionality. In view of the general concern of the presence of a 5'-OH moiety with regard to cellular toxicity, the present study describes 5'-deoxy compounds with reasonable affinity for the human adenosine A, receptor. Interestingly, this study shows that optimization of the 3'-"up" amide sustituent can substantially compensate for the drop in affinity for the adenosine A, receptor, which is generally observed upon removal of the 5'-OH group. The fact that for several 3'-amido-substituted (5'-deoxy)-N-6-cyclopentyladenosine derivatives, guanosine 5'-triphosphate-induced shifts in K-i values were significantly lower than 1 implies that these analogues behave as inverse agonists. This is further supported by their 1,3-dipropyl-8-cyclopentylxanthine-like capacity to increase forskolin-induced adenosine cyclic 3',5'-phosphate production.
• 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.