(2R,3S,4S,5R)-9-(3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-6-(5-chloro-2-methoxybenzylamino)-9H-purine-2-carbonitrile | 750644-51-0

• 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: (2R,3S,4S,5R)-9-(3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-6-(5-chloro-2-methoxybenzylamino)-9H-purine-2-carbonitrile
• 英文别名: 6-[(5-chloro-2-methoxyphenyl)methylamino]-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purine-2-carbonitrile
• CAS: 750644-51-0
• 化学式: C₁₉H₁₉ClN₆O₅
• 分子量: 446.85
• InChiKey: PZPVAHDVCKFVBP-BGIGGGFGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  159
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S,5R)-9-(3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-6-(5-chloro-2-methoxybenzylamino)-9H-purine-2-carbonitrile 在 sodium hydroxide 、 双氧水 作用下， 以 甲醇 、 乙醚 、 乙醇 、 水 为溶剂， 反应 9.0h， 生成 (2R,3S,4S,5R)-9-(3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-6-(5-chloro-2-methoxybenzylamino)-9H-purine-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Modulation of adenosine receptor affinity and intrinsic efficacy in adenine nucleosides substituted at the 2-position

  摘要：

  We studied the structural determinants of binding affinity and efficacy of adenosine receptor (AR) agonists. Substituents at the 2-position of adenosine were combined with N-6-substitutions known to enhance human A(3)AR affinity. Selectivity of binding of the analogues and their functional effects on cAMP production were studied using recombinant human A(1), A(2A), A(2B), and A(3)ARs. Mainly sterically small substituents at the 2-position modulated both the affinity and intrinsic efficacy at all subtypes. The 2-cyano group decreased hA(3)AR affinity and efficacy in the cases of N-6-(3-iodobenzyl) and N-6-(trans-2-phenyl-1-cyclopropyl), for which a full AAR agonist was converted into a selective antagonist; the 2-cyano-N-6-methyl analogue was a full A(3)AR agonist. The combination of N-6-benzyl and various 2-substitutions (chloro, trifluoromethyl, and cyano) resulted in reduced efficacy at the A(1)AR. The environment surrounding the 2-position within the putative A(3)AR binding site was explored using rhodopsin-based homology modeling and ligand docking. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.031
• 作为产物：
  描述：

  2',3',5'-三-O-乙酰-6-氯-2-碘嘌呤核苷 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 三(2-呋喃基)膦 、 N,N-二异丙基乙胺 、 1,1,3,3-四甲基脲 作用下， 反应 52.0h， 生成 (2R,3S,4S,5R)-9-(3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-6-(5-chloro-2-methoxybenzylamino)-9H-purine-2-carbonitrile
  参考文献：
  名称：

  Modulation of adenosine receptor affinity and intrinsic efficacy in adenine nucleosides substituted at the 2-position

  摘要：

  We studied the structural determinants of binding affinity and efficacy of adenosine receptor (AR) agonists. Substituents at the 2-position of adenosine were combined with N-6-substitutions known to enhance human A(3)AR affinity. Selectivity of binding of the analogues and their functional effects on cAMP production were studied using recombinant human A(1), A(2A), A(2B), and A(3)ARs. Mainly sterically small substituents at the 2-position modulated both the affinity and intrinsic efficacy at all subtypes. The 2-cyano group decreased hA(3)AR affinity and efficacy in the cases of N-6-(3-iodobenzyl) and N-6-(trans-2-phenyl-1-cyclopropyl), for which a full AAR agonist was converted into a selective antagonist; the 2-cyano-N-6-methyl analogue was a full A(3)AR agonist. The combination of N-6-benzyl and various 2-substitutions (chloro, trifluoromethyl, and cyano) resulted in reduced efficacy at the A(1)AR. The environment surrounding the 2-position within the putative A(3)AR binding site was explored using rhodopsin-based homology modeling and ligand docking. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.031

文献信息

• Modulation of adenosine receptor affinity and intrinsic efficacy in adenine nucleosides substituted at the 2-position
  作者：Michihiro Ohno、Zhan-Guo Gao、Philippe Van Rompaey、Susanna Tchilibon、Soo-Kyung Kim、Brian A Harris、Ariel S Gross、Heng T Duong、Serge Van Calenbergh、Kenneth A Jacobson

  DOI：10.1016/j.bmc.2004.03.031

  日期：2004.6

  We studied the structural determinants of binding affinity and efficacy of adenosine receptor (AR) agonists. Substituents at the 2-position of adenosine were combined with N-6-substitutions known to enhance human A(3)AR affinity. Selectivity of binding of the analogues and their functional effects on cAMP production were studied using recombinant human A(1), A(2A), A(2B), and A(3)ARs. Mainly sterically small substituents at the 2-position modulated both the affinity and intrinsic efficacy at all subtypes. The 2-cyano group decreased hA(3)AR affinity and efficacy in the cases of N-6-(3-iodobenzyl) and N-6-(trans-2-phenyl-1-cyclopropyl), for which a full AAR agonist was converted into a selective antagonist; the 2-cyano-N-6-methyl analogue was a full A(3)AR agonist. The combination of N-6-benzyl and various 2-substitutions (chloro, trifluoromethyl, and cyano) resulted in reduced efficacy at the A(1)AR. The environment surrounding the 2-position within the putative A(3)AR binding site was explored using rhodopsin-based homology modeling and ligand docking. (C) 2004 Elsevier Ltd. All rights reserved.