benzyl (4-{[({2,6-difluoro-3-[(2-phenylethyl)amino]phenyl}acetyl)amino]methyl}phenyl)(imino)methylcarbamate | 361336-90-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl (4-{[({2,6-difluoro-3-[(2-phenylethyl)amino]phenyl}acetyl)amino]methyl}phenyl)(imino)methylcarbamate
• 英文别名: benzyl N-[amino-[4-[[[2-[2,6-difluoro-3-(2-phenylethylamino)phenyl]acetyl]amino]methyl]phenyl]methylidene]carbamate
• CAS: 361336-90-5
• 化学式: C₃₂H₃₀F₂N₄O₃
• 分子量: 556.612
• InChiKey: AUEVNNXWWNCGAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl (4-{[({2,6-difluoro-3-[(2-phenylethyl)amino]phenyl}acetyl)amino]methyl}phenyl)(imino)methylcarbamate 在 三甲基氯硅烷 、 sodium iodide 、 甲醇 作用下， 以 乙腈 为溶剂， 以82%的产率得到N-[(4-carbamimidoylphenyl)methyl]-2-{2,6-difluoro-3-[(2-phenylethyl)amino]phenyl}acetamide
  参考文献：
  名称：

  Synthesis and Crystal Structures of Substituted Benzenes and Benzoquinones as Tissue Factor VIIa Inhibitors

  摘要：

  Several multistep syntheses of substituted benzenes are reported. The benzene analogues were 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. A variety of chemical transformations including nucleophilic additions, reductive aminations, Stille couplings, and polymer-assisted solution-phase (PASP) techniques were used to prepare key intermediates and final products. The initial analogues identified some weakly active compounds which ultimately led to a 340 nM (IC50) tissue Factor VIIa inhibitor with selectivity over other related enzymes. The structure-activity relationship of these inhibitors and the synthetic progression from the discovery of the lead compound to the development of potent analogues will be discussed. The X-ray crystal structures of fluorobenzene 50c and benzoquinone 54 inhibitors complexed with the TF/VIIa enzyme will also be described.

  DOI：

  10.1021/jm030233b
• 作为产物：
  描述：

  3-氨基-2,6-二氟苯乙酸甲酯 在 sodium hydroxide 、 PS-carbodiimide 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 benzyl (4-{[({2,6-difluoro-3-[(2-phenylethyl)amino]phenyl}acetyl)amino]methyl}phenyl)(imino)methylcarbamate
  参考文献：
  名称：

  Synthesis and Crystal Structures of Substituted Benzenes and Benzoquinones as Tissue Factor VIIa Inhibitors

  摘要：

  Several multistep syntheses of substituted benzenes are reported. The benzene analogues were 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. A variety of chemical transformations including nucleophilic additions, reductive aminations, Stille couplings, and polymer-assisted solution-phase (PASP) techniques were used to prepare key intermediates and final products. The initial analogues identified some weakly active compounds which ultimately led to a 340 nM (IC50) tissue Factor VIIa inhibitor with selectivity over other related enzymes. The structure-activity relationship of these inhibitors and the synthetic progression from the discovery of the lead compound to the development of potent analogues will be discussed. The X-ray crystal structures of fluorobenzene 50c and benzoquinone 54 inhibitors complexed with the TF/VIIa enzyme will also be described.

  DOI：

  10.1021/jm030233b

文献信息

• Synthesis and Crystal Structures of Substituted Benzenes and Benzoquinones as Tissue Factor VIIa Inhibitors
  作者：John J. Parlow、Anna M. Stevens、Roderick A. Stegeman、William C. Stallings、Ravi G. Kurumbail、Michael S. South

  DOI：10.1021/jm030233b

  日期：2003.9.1

  Several multistep syntheses of substituted benzenes are reported. The benzene analogues were 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. A variety of chemical transformations including nucleophilic additions, reductive aminations, Stille couplings, and polymer-assisted solution-phase (PASP) techniques were used to prepare key intermediates and final products. The initial analogues identified some weakly active compounds which ultimately led to a 340 nM (IC50) tissue Factor VIIa inhibitor with selectivity over other related enzymes. The structure-activity relationship of these inhibitors and the synthetic progression from the discovery of the lead compound to the development of potent analogues will be discussed. The X-ray crystal structures of fluorobenzene 50c and benzoquinone 54 inhibitors complexed with the TF/VIIa enzyme will also be described.