N⁶-(benzodioxanylmethyl)adenosine | 40615-19-8

• 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: N⁶-(benzodioxanylmethyl)adenosine
• 英文别名: Adenosine, N-[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-；(2R,3R,4S,5R)-2-[6-(2,3-dihydro-1,4-benzodioxin-3-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 40615-19-8
• 化学式: C₁₉H₂₁N₅O₆
• 分子量: 415.406
• InChiKey: AEKSAIGUTNCDKX-JTXMXDKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.31
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  144.01
• 氢给体数：
  4.0
• 氢受体数：
  11.0

反应信息

• 作为产物：
  描述：

  2,3-二氢-1,4-苯并二恶-2-甲胺 、 6-氯嘌呤核苷 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以62%的产率得到N⁶-(benzodioxanylmethyl)adenosine
  参考文献：
  名称：

  Search for New Purine- and Ribose-Modified Adenosine Analogs as Selective Agonists and Antagonists at Adenosine Receptors

  摘要：

  The binding affinities at rat A(1), A(2a), and A(3) adenosine receptors of a wide range of derivatives of adenosine have been determined. Sites of modification include the purine moiety (1-, 3-, and 7-deaza; halo, alkyne, and amino substitutions at the 2- and 8-positions; and N6(-)CH(2)-ring, -hydrazino, and -hydroxylamino) and the ribose moiety (2'-, 3'-, and 5'-deoxy; 2'- and 3'-O-methyl;2'-deoxy 2'-fluoro;6'-thio;5'-uronamide;carbocyclic;4'- or 3'-methyl; and inversion of configuration. (-)- and (+)-5'-Noraristeromycin were 48- and 21-fold selective, respectively, for A(2a), vs A(1) receptors. 2-Chloro-6'-thioadenosine displayed a K-i value of 20 nM at A(2a) receptors (15-fold selective vs A(1)). 2-Chloroadenin-9-yl(beta-L-2'-deoxy-6'-thiolyxofuranoside) displayed a K-i value of 8 mu M at A(1) receptors and appeared to be an antagonist, on the basis of the absence of a GTP-induced shift in binding vs a radiolabeled antagonist (8-cyclopentyl-1,3-dipropylxanthine). 2-Chloro-2'-deoxyadenosine and 2-chloroadenin-9-yl(beta-D-6'-thioarabinoside) were putative partial agonists at A(1) receptors, with K-i values of 7.4 and 5.4 mu M, respectively. The A(2a) selective agonist 2-(1-hexynyl)-5'-(N-ethylcarbamoyl)adenosine displayed a K-i value of 26 nM at A(3) receptors. The 4'-methyl substitution of adenosine was poorly tolerated, yet when combined with other favorable modifications, potency was restored. Thus, N-6-benzyl-4'methyladenosine-5'-(N-methyluronamide) displayed a K-i value of 604 nM at A(3) receptors and was 103- and 88-fold selective vs A(1) and A(2a) receptors, respectively. This compound was a full agonist in the A(3)-mediated inhibition of adenylate cyclase in transfected CHO cells. The carbocyclic analogue of N-6-(3-iodobenzyl)adenosine-5'-(N-methyluronamide) was 2-fold selective for A(3) VS A(1) receptors and was nearly inactive at A(2a) receptors.

  DOI：

  10.1021/jm00007a014