2',3'-O-isopropylideneadenosine-4'-dehydroxymethyl-4'-carboxylic acid 6-aminohexanoic acid benzyl ester conjugate | 1106998-86-0

• 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: 2',3'-O-isopropylideneadenosine-4'-dehydroxymethyl-4'-carboxylic acid 6-aminohexanoic acid benzyl ester conjugate
• CAS: 1106998-86-0
• 化学式: C₂₆H₃₂N₆O₆
• 分子量: 524.577
• InChiKey: AQUPLVNPLTVYII-FBROZUCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.25
• 重原子数：
  38.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  152.71
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylideneadenosine-4'-dehydroxymethyl-4'-carboxylic acid 6-aminohexanoic acid benzyl ester conjugate 在 三乙胺 、 三异丙基硅烷 、 三氟乙酸 作用下， 以 甲醇 、 水 为溶剂， 反应 26.0h， 生成 ARC-1010
  参考文献：
  名称：

  Structural Analysis of ARC-Type Inhibitor (ARC-1034) Binding to Protein Kinase A Catalytic Subunit and Rational Design of Bisubstrate Analogue Inhibitors of Basophilic Protein Kinases

  摘要：

  The crystal structure of a complex of the catalytic subunit (type alpha) of cAMP-dependent protein kinase (PKA C alpha) with ARC-type inhibitor (ARC-1034), the presumed lead scaffold of previously reported adenosine-oligo-arginine conjugate-based (ARC-type) inhibitors, was solved. Structural elements important for interaction with the kinase were established with specifically modified derivatives of the lead compound. On the basis of this knowledge, a new generation of inhibitors, conjugates of adenosine-4'-dehydroxymethyl-4'-carboxylic acid moiety and oligo(D-arginine), was developed with inhibitory constants well into the subnanomolar range. The structural determinants of selectivity of the new compounds were established in assays with ROCK-II and PKB gamma.

  DOI：

  10.1021/jm800797n
• 作为产物：
  描述：

  benzyl 6-aminohexanoate 、 2',3'-isopropylideneadenosine-5'-carboxylic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2',3'-O-isopropylideneadenosine-4'-dehydroxymethyl-4'-carboxylic acid 6-aminohexanoic acid benzyl ester conjugate
  参考文献：
  名称：

  Structural Analysis of ARC-Type Inhibitor (ARC-1034) Binding to Protein Kinase A Catalytic Subunit and Rational Design of Bisubstrate Analogue Inhibitors of Basophilic Protein Kinases

  摘要：

  The crystal structure of a complex of the catalytic subunit (type alpha) of cAMP-dependent protein kinase (PKA C alpha) with ARC-type inhibitor (ARC-1034), the presumed lead scaffold of previously reported adenosine-oligo-arginine conjugate-based (ARC-type) inhibitors, was solved. Structural elements important for interaction with the kinase were established with specifically modified derivatives of the lead compound. On the basis of this knowledge, a new generation of inhibitors, conjugates of adenosine-4'-dehydroxymethyl-4'-carboxylic acid moiety and oligo(D-arginine), was developed with inhibitory constants well into the subnanomolar range. The structural determinants of selectivity of the new compounds were established in assays with ROCK-II and PKB gamma.

  DOI：

  10.1021/jm800797n