benzyl 3-[1-(2-tert-butoxy-2-oxoethyl)-5-(isopropylamino)-6-oxo-1,6-dihydropyridin-2-yl]-5-nitrobenzoate | 618398-49-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl 3-[1-(2-tert-butoxy-2-oxoethyl)-5-(isopropylamino)-6-oxo-1,6-dihydropyridin-2-yl]-5-nitrobenzoate
• 英文别名: benzyl 3-[1-(2-tert-butoxy-2-oxoeth-1-yl)-5-(isopropylamino)-6-oxo-1,6-dihydropyridin-2-yl]-5-nitrobenzoate；Benzyl 3-[1-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-6-oxo-5-(propan-2-ylamino)pyridin-2-yl]-5-nitrobenzoate；benzyl 3-[1-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-6-oxo-5-(propan-2-ylamino)pyridin-2-yl]-5-nitrobenzoate
• CAS: 618398-49-5
• 化学式: C₂₈H₃₁N₃O₇
• 分子量: 521.57
• InChiKey: QWSCLVUECONXON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  benzyl 3-[1-(2-tert-butoxy-2-oxoethyl)-5-(isopropylamino)-6-oxo-1,6-dihydropyridin-2-yl]-5-nitrobenzoate 在 N-甲基吗啉 、 盐酸 、 polystyrene-carbodiimide 、 1-羟基苯并三唑 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 benzyl 3-[1-(2-{[4-((E)-amino{[(benzyloxy)carbonyl]imino}methyl)benzyl]amino}-2-oxoethyl)-5-(isopropylamino)-6-oxo-1,6-dihydropyridin-2-yl]-5-nitrobenzoate
  参考文献：
  名称：

  Design, Synthesis, and Crystal Structure of Selective 2-Pyridone Tissue Factor VIIa Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm0301686
• 作为产物：
  描述：

  2,6-二溴-3-氨基吡啶 在 四(三苯基膦)钯 、 calcium hydride 、 三溴化硼 、 四氯化钛 、 sodium cyanoborohydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 115.5h， 生成 benzyl 3-[1-(2-tert-butoxy-2-oxoethyl)-5-(isopropylamino)-6-oxo-1,6-dihydropyridin-2-yl]-5-nitrobenzoate
  参考文献：
  名称：

  Design, Synthesis, and Crystal Structure of Selective 2-Pyridone Tissue Factor VIIa Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm0301686

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.
• Synthesis of 2-pyridones as tissue factor VIIa inhibitors
  作者：John J Parlow、Michael S South

  DOI：10.1016/s0040-4020(03)01239-0

  日期：2003.9

  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.