ARC-1012 | 1106998-46-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ARC-1012
• 英文别名: Adc-Ahx-(D-Lys)-Ahx-(D-Arg)2-NH2；(10r,20r,23r)-10-(4-Aminobutyl)-1-[(2s,3s,4r,5r)-5-(6-Amino-9h-Purin-9-Yl)-3,4-Dihydroxytetrahydrofuran-2-Yl]-20,23-Bis(3-Carbamimidamidopropyl)-1,8,11,18,21-Pentaoxo-2,9,12,19,22-Pentaazatetracosan-24-Amide；(2S,3S,4R,5R)-N-[6-[[(2R)-6-amino-1-[[6-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide
• CAS: 1106998-46-2
• 化学式: C₄₀H₇₀N₁₈O₉
• 分子量: 947.111
• InChiKey: LIYNJKNSBUCWCZ-SAPGASOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.1
• 重原子数：
  67
• 可旋转键数：
  32
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  463
• 氢给体数：
  14
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  ARC-1012 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 水 为溶剂， 反应 2.5h， 生成 ARC-1020
  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：

  在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 ARC-1012
  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