(1S,2R,3S,4R,5S)-ethyl (2',3'-O-isopropylidene)-4-{2-iodo-6-(4-(2-aminoethyl)benzenesulfonic acid)-9H-purin-9-yl}bicyclo-[3.1.0]hexane-1-carboxylate | 1446996-83-3

• 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: (1S,2R,3S,4R,5S)-ethyl (2',3'-O-isopropylidene)-4-{2-iodo-6-(4-(2-aminoethyl)benzenesulfonic acid)-9H-purin-9-yl}bicyclo-[3.1.0]hexane-1-carboxylate
• 英文别名: 4-[2-[[9-[(1R,2S,4S,5R,6S)-2-ethoxycarbonyl-8,8-dimethyl-7,9-dioxatricyclo[4.3.0.02,4]nonan-5-yl]-2-iodopurin-6-yl]amino]ethyl]benzenesulfonic acid
• CAS: 1446996-83-3
• 化学式: C₂₅H₂₈IN₅O₇S
• 分子量: 669.497
• InChiKey: QDCZYHQNMITFRY-DUALUDSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (1S,2R,3S,4R,5S)-ethyl (2',3'-O-isopropylidene)-4-{2-iodo-6-(4-(2-aminoethyl)benzenesulfonic acid)-9H-purin-9-yl}bicyclo-[3.1.0]hexane-1-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-[2-[[9-[(1R,2S,4S,5R,6S)-8,8-dimethyl-2-(methylcarbamoyl)-7,9-dioxatricyclo[4.3.0.02,4]nonan-5-yl]-2-(2-phenylethynyl)purin-6-yl]amino]ethyl]benzenesulfonic acid
  参考文献：
  名称：

  Rational Design of Sulfonated A₃Adenosine Receptor-Selective Nucleosides as Pharmacological Tools To Study Chronic Neuropathic Pain

  摘要：

  (N)-Methanocarba(bicyclo[3.1.0]hexane)adenosine derivatives were probed for sites of charged sulfonate substitution, which precludes diffusion across biological membranes, e.g., blood-brain barrier. Molecular modeling predicted that sulfonate groups on C2-phenylethynyl substituents would provide high affinity at both mouse (m) and human (h) A(3) adenosine receptors (ARs), while a N-6-p-sulfophenylethyl substituent would determine higher hA(3)AR vs mA(3)AR affinity. These modeling predictions, based on steric fitting of the binding cavity and crucial interactions with key residues, were confirmed by binding/efficacy studies of synthesized sulfonates. N-6-3-Chlorobenzyl-2-(3-sulfophenylethynyl) derivative 7 (MRS5841) bound selectively to h/m A(3)ARs (K-i(hA(3)AR) = 1.9 nM) as agonist, while corresponding p-sulfo isomer 6 (MRS5701) displayed mixed A(1)/A(3)AR agonism. Both nucleosides administered ip reduced mouse chronic neuropathic pain that was ascribed to either A(3)AR or A(1)/A(3)AR using A(3)AR genetic deletion. Thus, rational design methods based on A(3)AR homology models successfully predicted sites for sulfonate incorporation, for delineating adenosine's CNS vs peripheral actions.

  DOI：

  10.1021/jm4007966
• 作为产物：
  描述：

  (1'S,2'R,3'S,4'R,5'S)-4'-[6-chloro-2-iodopurin-9-yl]-2',3'-isopropylidenebicyclo[3.1.0]hexane-1'-carboxylic acid ethyl ester 、 4-(2-aminoethyl)benzenesulfonic acid 在 三乙胺 作用下， 以 甲醇 为溶剂， 以78%的产率得到(1S,2R,3S,4R,5S)-ethyl (2',3'-O-isopropylidene)-4-{2-iodo-6-(4-(2-aminoethyl)benzenesulfonic acid)-9H-purin-9-yl}bicyclo-[3.1.0]hexane-1-carboxylate
  参考文献：
  名称：

  Rational Design of Sulfonated A₃Adenosine Receptor-Selective Nucleosides as Pharmacological Tools To Study Chronic Neuropathic Pain

  摘要：

  (N)-Methanocarba(bicyclo[3.1.0]hexane)adenosine derivatives were probed for sites of charged sulfonate substitution, which precludes diffusion across biological membranes, e.g., blood-brain barrier. Molecular modeling predicted that sulfonate groups on C2-phenylethynyl substituents would provide high affinity at both mouse (m) and human (h) A(3) adenosine receptors (ARs), while a N-6-p-sulfophenylethyl substituent would determine higher hA(3)AR vs mA(3)AR affinity. These modeling predictions, based on steric fitting of the binding cavity and crucial interactions with key residues, were confirmed by binding/efficacy studies of synthesized sulfonates. N-6-3-Chlorobenzyl-2-(3-sulfophenylethynyl) derivative 7 (MRS5841) bound selectively to h/m A(3)ARs (K-i(hA(3)AR) = 1.9 nM) as agonist, while corresponding p-sulfo isomer 6 (MRS5701) displayed mixed A(1)/A(3)AR agonism. Both nucleosides administered ip reduced mouse chronic neuropathic pain that was ascribed to either A(3)AR or A(1)/A(3)AR using A(3)AR genetic deletion. Thus, rational design methods based on A(3)AR homology models successfully predicted sites for sulfonate incorporation, for delineating adenosine's CNS vs peripheral actions.

  DOI：

  10.1021/jm4007966