9-{3,5-dideoxy-3-[(3,4-dimethylbenzoyl)amino]-β-D-xylofuranosyl}-N⁶-cyclopentyladenine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 9-{3,5-dideoxy-3-[(3,4-dimethylbenzoyl)amino]-β-D-xylofuranosyl}-N⁶-cyclopentyladenine
• 英文别名: N-[5-(6-Cyclopentylamino-purin-9-yl)-4-hydroxy-2-methyl-tetrahydro-furan-3-yl]-3,4-dimethyl-benzamide；N-[(2R,3R,4R,5R)-5-[6-(cyclopentylamino)purin-9-yl]-4-hydroxy-2-methyloxolan-3-yl]-3,4-dimethylbenzamide
• 化学式: C₂₄H₃₀N₆O₃
• 分子量: 450.541
• InChiKey: ANEWOVOUCFPRTN-XGFUBRKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-cyclopentyl-5'-deoxy-Adenosine 在 4-二甲氨基吡啶 sodium azide 、 4-sulfamylbenzoylaminomethyl polystyrene 、 2-乙酰氧基异丁酰溴 、 水 、 氢气 、 N,N-二异丙基乙胺 、 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 、 乙腈 为溶剂， 20.0~80.0 ℃ 、7.58 MPa 条件下， 反应 52.0h， 生成 9-{3,5-dideoxy-3-[(3,4-dimethylbenzoyl)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

文献信息

• 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.