methyl (4-amino-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetate | 361337-10-2

• 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: methyl (4-amino-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetate
• 英文别名: Methyl 2-[3-amino-2-fluoro-6-[3-(phenylmethoxycarbonylamino)phenyl]phenyl]acetate
• CAS: 361337-10-2
• 化学式: C₂₃H₂₁FN₂O₄
• 分子量: 408.429
• InChiKey: QGYMBGWKDYDSII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  6

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	methyl (3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-4-nitro-1,1'-biphenyl-2-yl)acetate	361337-14-6	C23H19FN2O6	438.412

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	methyl [3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-4-(isopropylamino)-1,1'-biphenyl-2-yl]acetate	361337-15-7	C26H27FN2O4	450.51
  ——	[3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-4-(isopropylamino)-1,1'-biphenyl-2-yl]acetic acid	361337-16-8	C25H25FN2O4	436.483
  ——	methyl (4-(benzylamino)-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetate	361337-11-3	C30H27FN2O4	498.554
  ——	(4-(benzylamino)-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetic acid	361337-12-4	C29H25FN2O4	484.527
  ——	benzyl {4-[({[3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-4-(isopropylamino)-1,1'-biphenyl-2-yl]acetyl}amino)methyl]phenyl}(imino)methylcarbamate	361337-17-9	C41H40FN5O5	701.798
  ——	benzyl [4-({[(4-(benzylamino)-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetyl]amino}methyl)phenyl](imino)methylcarbamate	619333-03-8	C45H40FN5O5	749.842
  ——	2-[6-(3-aminophenyl)-2-fluoro-3-(propan-2-ylamino)phenyl]-N-[(4-carbamimidoylphenyl)methyl]acetamide	——	C25H28FN5O	433.529

反应信息

• 作为反应物：
  描述：

  methyl (4-amino-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetate 在 N-甲基吗啉 、 sodium hydroxide 、 polystyrene-bound carbodiimide 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 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， 生成 benzyl {4-[({[3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-4-(isopropylamino)-1,1'-biphenyl-2-yl]acetyl}amino)methyl]phenyl}(imino)methylcarbamate
  参考文献：
  名称：

  Synthesis and X-ray crystal structures of substituted fluorobenzene and benzoquinone inhibitors of the tissue factor VIIa complex

  摘要：

  Multistep syntheses of substituted benzenes and benzoquinone inhibitors of tissue Factor Vila 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 Vila (TF/VIIa) enzyme. The compounds exhibited modest potency on TF/VIIa with selectivity over Factor Xa and thrombin. The X-ray crystal structures of the targeted fluorobenzene l2a and benzoquinone 14 inhibitors bound to TF/VIIa were obtained and will be described. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.002
• 作为产物：
  描述：

  在 吡啶 、 四(三苯基膦)钯 、 potassium carbonate 、 三乙胺 、 lithium chloride 、 三甲基乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 0.25h， 生成 methyl (4-amino-3'-{[(benzyloxy)carbonyl]amino}-3-fluoro-1,1'-biphenyl-2-yl)acetate
  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.
• Synthesis and X-ray crystal structures of substituted fluorobenzene and benzoquinone inhibitors of the tissue factor VIIa complex
  作者：John J. Parlow、Ravi G. Kurumbail、Roderick A. Stegeman、Anna M. Stevens、William C. Stallings、Michael S. South

  DOI：10.1016/j.bmcl.2003.08.002

  日期：2003.11

  Multistep syntheses of substituted benzenes and benzoquinone inhibitors of tissue Factor Vila 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 Vila (TF/VIIa) enzyme. The compounds exhibited modest potency on TF/VIIa with selectivity over Factor Xa and thrombin. The X-ray crystal structures of the targeted fluorobenzene l2a and benzoquinone 14 inhibitors bound to TF/VIIa were obtained and will be described. (C) 2003 Elsevier Ltd. All rights reserved.