NU6290

• 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: NU6290
• 英文别名: 6-(cyclohexylmethoxy)-N-[4-(2-pyrrolidin-1-ylethylsulfonyl)phenyl]-7H-purin-2-amine
• 化学式: C₂₄H₃₂N₆O₃S
• 分子量: 484.622
• InChiKey: ARDJKDITQHCERY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(4-氨基苯基硫基)乙酸 在 lithium aluminium tetrahydride 、 氯化亚砜 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 2,2,2-三氟乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 110.0h， 生成 NU6290
  参考文献：
  名称：

  Searching for Cyclin-Dependent Kinase Inhibitors Using a New Variant of the Cope Elimination

  摘要：

  beta-Piperidinoethylsulfides are oxidized by m-chloroperbenzoic acid to intermediates containing both N-oxide and sulfone functions. These undergo a Cope-type elimination to a vinylsulfone that can be captured by amines to afford beta-aminoethylsulfones. When a beta-aminoethylsulfone group is linked to the 4-position of a phenyl group attached at N-2 of O6-cyclohexylmethylguanine, the resulting derivatives are inhibitors of the cyclin-dependent kinase CDK2. One of the most potent inhibitors (IC50 = 45 nM) contained a N-3-hydroxypropyl group on the aminoethylsulfonyl substituent. The crystal structure of this inhibitor bound to CDK2/cyclin A was determined and shows an unusual network of hydrogen bonds. The synthetic methodology developed can be utilized in multiple-parallel format and has numerous potential applications in medicinal chemistry.

  DOI：

  10.1021/ja060595j

文献信息

• Searching for Cyclin-Dependent Kinase Inhibitors Using a New Variant of the Cope Elimination
  作者：Roger J. Griffin、Andrew Henderson、Nicola J. Curtin、Aude Echalier、Jane A. Endicott、Ian R. Hardcastle、David R. Newell、Martin E. M. Noble、Lan-Zhen Wang、Bernard T. Golding

  DOI：10.1021/ja060595j

  日期：2006.5.1

  beta-Piperidinoethylsulfides are oxidized by m-chloroperbenzoic acid to intermediates containing both N-oxide and sulfone functions. These undergo a Cope-type elimination to a vinylsulfone that can be captured by amines to afford beta-aminoethylsulfones. When a beta-aminoethylsulfone group is linked to the 4-position of a phenyl group attached at N-2 of O6-cyclohexylmethylguanine, the resulting derivatives are inhibitors of the cyclin-dependent kinase CDK2. One of the most potent inhibitors (IC50 = 45 nM) contained a N-3-hydroxypropyl group on the aminoethylsulfonyl substituent. The crystal structure of this inhibitor bound to CDK2/cyclin A was determined and shows an unusual network of hydrogen bonds. The synthetic methodology developed can be utilized in multiple-parallel format and has numerous potential applications in medicinal chemistry.