NU6032

• 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: NU6032
• 英文别名: (5R)-5-[(2-amino-7H-purin-6-yl)oxymethyl]pyrrolidin-2-one
• 化学式: C₁₀H₁₂N₆O₂
• 分子量: 248.244
• InChiKey: UYPMMHCTXQIWDX-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2-amino-9H-purin-6-yl)-4-aza-1-azoniabicyclo[2.2.2]octane chloride 、 Sodium; ((R)-5-oxo-pyrrolidin-2-yl)-methanolate 以 二甲基亚砜 为溶剂， 以46%的产率得到NU6032
  参考文献：
  名称：

  Probing the ATP Ribose-Binding Domain of Cyclin-Dependent Kinases 1 and 2 with O⁶-Substituted Guanine Derivatives

  摘要：

  O-6-Substituted guanines are adenosine 5'-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B I and CDK2/cyclin A, the O-6 substituent occupying the kinase ribose binding site. Fifty-eight O-6-substituted guanines were prepared to probe the ribose pocket, and the structures of four representative compounds bound to monomeric CDK2 were determined by X-ray crystallography. Optimum binding occurs with a moderately sized aliphatic 06 substituent that packs tightly against the hydrophobic patch presented by the glycine loop, centered on Val18, an interaction promoted by the conformational restraints imposed in a cyclohexylmethyl or cyclohexenylmethyl ring. Structure-based design generated (R)-(2-amino-9H-purin-6-yloxymethyl)pyrrolidin-2-one (56), which reproduces the reported hydrogen bonds formed between ATP and Asp86 and Gln131 but failed to improve inhibitory potency. Thus, the parent compound O-6-cyclohexylmethylguanine (NU2058, 25) is the preferred starting point for exploring other areas of the kinase active site.

  DOI：

  10.1021/jm020056z

文献信息

• US6303618B1
  申请人：——

  公开号：US6303618B1

  公开（公告）日：2001-10-16