benzyl (1E)-amino{4-[({[6-(3-amino-5-nitrophenyl)-3-(isopropylamino)-2-oxopyridin-1(2H)-yl]acetyl}amino)methyl]phenyl}methylenecarbamate | 618398-72-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: benzyl (1E)-amino{4-[({[6-(3-amino-5-nitrophenyl)-3-(isopropylamino)-2-oxopyridin-1(2H)-yl]acetyl}amino)methyl]phenyl}methylenecarbamate
• CAS: 618398-72-4
• 化学式: C₃₂H₃₃N₇O₆
• 分子量: 611.657
• InChiKey: LYOIJQLSQZVOOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  45.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  196.97
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  benzyl (1E)-amino{4-[({[6-(3-amino-5-nitrophenyl)-3-(isopropylamino)-2-oxopyridin-1(2H)-yl]acetyl}amino)methyl]phenyl}methylenecarbamate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以39%的产率得到N-{4-[amino(imino)methyl]benzyl}-2-[6-(3-amino-5-nitrophenyl)-3-(isopropylamino)-2-oxopyridin-1(2H)-yl]acetamide
  参考文献：
  名称：

  Synthesis of 2-pyridones as tissue factor VIIa inhibitors

  摘要：

  2-Pyridones were prepared from 2,6-dibromopyridine via a multi-step synthesis. A variety of chemical transformations, including regioselective nucleophilic addition and selective nitrogen alkylation, afforded the penultimate intermediate 9. A combination of two-dimensional NMR techniques to unequivocally assign the structure of 9 is described. Compound 9 was then used in a Suzuki coupling and further derivatized to afford the targeted tissue Factor VIIa inhibitors. These compounds were tested in several serine protease enzyme assays with biological activity reported. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(03)01239-0
• 作为产物：
  描述：

  2,6-二溴-3-氨基吡啶 在 N-甲基吗啉 、 盐酸 、 四(三苯基膦)钯 、 calcium hydride 、 polystyrene-carbodiimide 、 三溴化硼 、 四氯化钛 、 sodium cyanoborohydride 、 1-羟基苯并三唑 、 caesium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 150.0h， 生成 benzyl (1E)-amino{4-[({[6-(3-amino-5-nitrophenyl)-3-(isopropylamino)-2-oxopyridin-1(2H)-yl]acetyl}amino)methyl]phenyl}methylenecarbamate
  参考文献：
  名称：

  Synthesis of 2-pyridones as tissue factor VIIa inhibitors

  摘要：

  2-Pyridones were prepared from 2,6-dibromopyridine via a multi-step synthesis. A variety of chemical transformations, including regioselective nucleophilic addition and selective nitrogen alkylation, afforded the penultimate intermediate 9. A combination of two-dimensional NMR techniques to unequivocally assign the structure of 9 is described. Compound 9 was then used in a Suzuki coupling and further derivatized to afford the targeted tissue Factor VIIa inhibitors. These compounds were tested in several serine protease enzyme assays with biological activity reported. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(03)01239-0

文献信息

• Design, Synthesis, and Crystal Structure of Selective 2-Pyridone Tissue Factor VIIa Inhibitors
  作者：John J. Parlow、Ravi G. Kurumbail、Roderick A. Stegeman、Anna M. Stevens、William C. Stallings、Michael S. South

  DOI：10.1021/jm0301686

  日期：2003.10.1

  Targeted 2-pyridones were selected as tissue Factor VIIa inhibitors and prepared from 2,6-dibromopyridine via a multistep synthesis. A variety of chemical transformations, including regioselective nucleophilic addition, selective nitrogen alkylation, and a Suzuki coupling, afforded the targeted tissue Factor VIIa inhibitors. The pyridone core was selected as a replacement for the pyrazinone core of noncovalent tissue Factor VIIa inhibitors and designed such that their substitution pattern would occupy and interact with the S-1, S-2, and S-3 pockets of the tissue Factor VIIa enzyme. These compounds were tested in several serine protease enzyme assays involved in the coagulation cascade exhibiting modest activity on tissue Factor VIIa with excellent selectivity over thrombin and Factor Xa. Finally, an X-ray crystal structure of inhibitor 14a bound to tissue Factor VIIa was obtained and will be described.