diethyl (E)-2-{4-[(2,2-dimethylpropanoyl)amino]pyridin-3-yl}ethenephosphonate | 700862-59-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: diethyl (E)-2-{4-[(2,2-dimethylpropanoyl)amino]pyridin-3-yl}ethenephosphonate
• CAS: 700862-59-5
• 化学式: C₁₆H₂₅N₂O₄P
• 分子量: 340.359
• InChiKey: SCCJGXRVLJQIEU-PKNBQFBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  77.52
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  diethyl (E)-2-{4-[(2,2-dimethylpropanoyl)amino]pyridin-3-yl}ethenephosphonate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 diethyl 2-{4-[(2,2-dimethylpropanoyl)amino]pyridin-3-yl}ethanephosphonate
  参考文献：
  名称：

  Inhibition studies with rationally designed inhibitors of the human low molecular weight protein tyrosine phosphatase

  摘要：

  The human low molecular weight protein tyrosine phosphatase (HCPTP) is ubiquitously expressed as two isoforms in a wide range of human cells and may be involved in regulating the metastatic nature of epithelial tumors. A homology model is presented for the HCPTP-B isoform based on known X-ray crystal structures of other low molecular weight PTPs. A comparison of the two isoform structures indicates the possibility of developing isoform-specific inhibitors of HCPTP. Molecular dynamics simulations with CHARMM have been used to study the binding modes of the known adenine effector and phosphate in the active site of both isoforms. This analysis led to the design of the initial lead compound, based on an azaindole ring moiety, which was then also evaluated computationally. A comparison of these simulations indicates the need for a phosphonate group on the indole and provides insight into inhibitor binding modes. Compounds with varying degrees of structural similarity to the azaindole have been synthesized and tested for inhibition with each isoform. These molecular systems were examined with the program AutoDock, and comparisons made with the kinetics and the explicit simulations to validate AutoDock as a screening tool for potential inhibitors. Two compounds were experimentally found to have sub-millimolar inhibition, but the greater solubility of one reinforces the need for experimental testing alongside computational analysis. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.01.042
• 作为产物：
  描述：

  N-(吡啶-4-基)三甲基乙酰胺 在 sodium hydroxide 、 正丁基锂 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 0.02h， 生成 diethyl (E)-2-{4-[(2,2-dimethylpropanoyl)amino]pyridin-3-yl}ethenephosphonate
  参考文献：
  名称：

  Inhibition studies with rationally designed inhibitors of the human low molecular weight protein tyrosine phosphatase

  摘要：

  The human low molecular weight protein tyrosine phosphatase (HCPTP) is ubiquitously expressed as two isoforms in a wide range of human cells and may be involved in regulating the metastatic nature of epithelial tumors. A homology model is presented for the HCPTP-B isoform based on known X-ray crystal structures of other low molecular weight PTPs. A comparison of the two isoform structures indicates the possibility of developing isoform-specific inhibitors of HCPTP. Molecular dynamics simulations with CHARMM have been used to study the binding modes of the known adenine effector and phosphate in the active site of both isoforms. This analysis led to the design of the initial lead compound, based on an azaindole ring moiety, which was then also evaluated computationally. A comparison of these simulations indicates the need for a phosphonate group on the indole and provides insight into inhibitor binding modes. Compounds with varying degrees of structural similarity to the azaindole have been synthesized and tested for inhibition with each isoform. These molecular systems were examined with the program AutoDock, and comparisons made with the kinetics and the explicit simulations to validate AutoDock as a screening tool for potential inhibitors. Two compounds were experimentally found to have sub-millimolar inhibition, but the greater solubility of one reinforces the need for experimental testing alongside computational analysis. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.01.042