diethyl [(3-{[6-(3-aminophenyl)pyrimidin-4-yl]amino}phenyl)(hydroxy)methyl]phosphonate | 1606168-59-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: diethyl [(3-{[6-(3-aminophenyl)pyrimidin-4-yl]amino}phenyl)(hydroxy)methyl]phosphonate
• 英文别名: [3-[[6-(3-Aminophenyl)pyrimidin-4-yl]amino]phenyl]-diethoxyphosphoryl-methanol；[3-[[6-(3-aminophenyl)pyrimidin-4-yl]amino]phenyl]-diethoxyphosphorylmethanol
• CAS: 1606168-59-5
• 化学式: C₂₁H₂₅N₄O₄P
• 分子量: 428.428
• InChiKey: BFPCGNAMLGFTPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  alpha-羟基-3-硝基苄基膦酸二乙酯 在 盐酸 、 palladium 10% on activated carbon 、 甲酸铵 、 tin(ll) chloride 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 28.0h， 生成 diethyl [(3-{[6-(3-aminophenyl)pyrimidin-4-yl]amino}phenyl)(hydroxy)methyl]phosphonate
  参考文献：
  名称：

  Synthesis and Evaluation of Phosphorus Containing, Specific CDK9/CycT1 Inhibitors

  摘要：

  Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate, and phosphinate moieties were synthesized. Prepared compounds were evaluated in an enzymatic CDK9/CycT1 assay. The most potent molecules were tested in cell-based toxicity and HIV proliferation assays. Selectivity of shortlisted compounds against CDKs and other kinases was tested. The best compound was shown to be a highly specific, ATP-competitive inhibitor of CDK9/CycT1 with antiviral activity.

  DOI：

  10.1021/jm401742r

文献信息

• Synthesis and Evaluation of Phosphorus Containing, Specific CDK9/CycT1 Inhibitors
  作者：Gábor Németh、Zoltán Greff、Anna Sipos、Zoltán Varga、Rita Székely、Mónika Sebestyén、Zsuzsa Jászay、Szabolcs Béni、Zoltán Nemes、Jean-Luc Pirat、Jean-Noël Volle、David Virieux、Ágnes Gyuris、Katalin Kelemenics、Éva Áy、Janos Minarovits、Susan Szathmary、György Kéri、László Őrfi

  DOI：10.1021/jm401742r

  日期：2014.5.22

  Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate, and phosphinate moieties were synthesized. Prepared compounds were evaluated in an enzymatic CDK9/CycT1 assay. The most potent molecules were tested in cell-based toxicity and HIV proliferation assays. Selectivity of shortlisted compounds against CDKs and other kinases was tested. The best compound was shown to be a highly specific, ATP-competitive inhibitor of CDK9/CycT1 with antiviral activity.