1'-[N¹-(3-chlorobenzyl)-adenin-9-yl]-α-D-apio-L-furanose bromide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 1'-[N¹-(3-chlorobenzyl)-adenin-9-yl]-α-D-apio-L-furanose bromide
• 英文别名: (2R,3R,4S)-2-[6-amino-1-[(3-chlorophenyl)methyl]purin-1-ium-9-yl]-4-(hydroxymethyl)oxolane-3,4-diol;bromide
• 化学式: Br*C₁₇H₁₉ClN₅O₄
• 分子量: 472.726
• InChiKey: OOTLFZDLZDBOHJ-RIESPBDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.38
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 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：

  1'-[N¹-(3-chlorobenzyl)-adenin-9-yl]-α-D-apio-L-furanose bromide 在 ammonium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以56%的产率得到1′-[N⁶-(3-chlorobenzyl)-adenin-9-yl]-α-D-apio-L-furanose
  参考文献：
  名称：

  Synthesis and evaluation of N6-substituted apioadenosines as potential adenosine A3 receptor modulators

  摘要：

  Adenosine receptors (ARs) trigger signal transduction pathways inside the cell when activated by extracellular adenosine. Selective modulation of the A₃AR subtype may be beneficial in controlling diseases such as colorectal cancer and rheumatoid arthritis. Here, we report the synthesis and evaluation of β-D-apio-D-furano- and α-D-apio-L-furanoadenosines and derivatives thereof. Introduction of a 2-methoxy-5-chlorobenzyl group at N(6) of β-D-apio-D-furanoadenosine afforded an A₃AR antagonist (10c, Ki=0.98 μM), while a similar modification of an α-D-apio-L-furanoadenosine gave rise to a partial agonist (11c, Ki=3.07 μM). The structural basis for this difference was examined by docking to an A₃AR model; the antagonist lacked a crucial interaction with Thr94.

  DOI：

  10.1016/j.bmc.2014.05.036
• 作为产物：
  描述：

  1'-(adenin-9-yl)-α-D-apio-L-furanose 、 3-氯苄溴 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以44%的产率得到1'-[N¹-(3-chlorobenzyl)-adenin-9-yl]-α-D-apio-L-furanose bromide
  参考文献：
  名称：

  Synthesis and evaluation of N6-substituted apioadenosines as potential adenosine A3 receptor modulators

  摘要：

  Adenosine receptors (ARs) trigger signal transduction pathways inside the cell when activated by extracellular adenosine. Selective modulation of the A₃AR subtype may be beneficial in controlling diseases such as colorectal cancer and rheumatoid arthritis. Here, we report the synthesis and evaluation of β-D-apio-D-furano- and α-D-apio-L-furanoadenosines and derivatives thereof. Introduction of a 2-methoxy-5-chlorobenzyl group at N(6) of β-D-apio-D-furanoadenosine afforded an A₃AR antagonist (10c, Ki=0.98 μM), while a similar modification of an α-D-apio-L-furanoadenosine gave rise to a partial agonist (11c, Ki=3.07 μM). The structural basis for this difference was examined by docking to an A₃AR model; the antagonist lacked a crucial interaction with Thr94.

  DOI：

  10.1016/j.bmc.2014.05.036

文献信息

• Synthesis and evaluation of N6-substituted apioadenosines as potential adenosine A3 receptor modulators
  作者：Kiran S. Toti、Steven M. Moss、Silvia Paoletta、Zhan-Guo Gao、Kenneth A. Jacobson、Serge Van Calenbergh

  DOI：10.1016/j.bmc.2014.05.036

  日期：2014.8

  Adenosine receptors (ARs) trigger signal transduction pathways inside the cell when activated by extracellular adenosine. Selective modulation of the A₃AR subtype may be beneficial in controlling diseases such as colorectal cancer and rheumatoid arthritis. Here, we report the synthesis and evaluation of β-D-apio-D-furano- and α-D-apio-L-furanoadenosines and derivatives thereof. Introduction of a 2-methoxy-5-chlorobenzyl group at N(6) of β-D-apio-D-furanoadenosine afforded an A₃AR antagonist (10c, Ki=0.98 μM), while a similar modification of an α-D-apio-L-furanoadenosine gave rise to a partial agonist (11c, Ki=3.07 μM). The structural basis for this difference was examined by docking to an A₃AR model; the antagonist lacked a crucial interaction with Thr94.