ARC-1021 | 1106998-56-4

• 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-1021
• 英文别名: 6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-(3-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}propyl)hexanamide；(2S,3S,4R,5R)-N-[6-[[4-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutyl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide
• CAS: 1106998-56-4
• 化学式: C₃₂H₅₄N₁₆O₈
• 分子量: 790.883
• InChiKey: VTIDEXNHCZJFTH-RHNVXQQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.3
• 重原子数：
  56
• 可旋转键数：
  24
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  408
• 氢给体数：
  12
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  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-1021
  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