benzyl [4-({[(4-(benzylamino)-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetyl]amino}methyl)phenyl](imino)methylcarbamate | 619333-03-8

• 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-({[(4-(benzylamino)-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetyl]amino}methyl)phenyl](imino)methylcarbamate
• 英文别名: benzyl N-[amino-[4-[[[2-[3-(benzylamino)-2-fluoro-6-[3-(phenylmethoxycarbonylamino)phenyl]phenyl]acetyl]amino]methyl]phenyl]methylidene]carbamate
• CAS: 619333-03-8
• 化学式: C₄₅H₄₀FN₅O₅
• 分子量: 749.842
• InChiKey: XRUXRCDVKFVGRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  56
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzyl [4-({[(4-(benzylamino)-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetyl]amino}methyl)phenyl](imino)methylcarbamate 在 氢溴酸 、 溶剂黄146 作用下， 反应 16.0h， 以52%的产率得到2-[6-(3-aminophenyl)-3-(benzylamino)-2-fluorophenyl]-N-[(4-carbamimidoylphenyl)methyl]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：

  methyl (4-amino-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetate 在 sodium hydroxide 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 0.25h， 生成 benzyl [4-({[(4-(benzylamino)-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)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