4'-fluoro-3-vinylbiphenyl-4-carboxylic acid methyl ester | 873784-13-5

• 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: 4'-fluoro-3-vinylbiphenyl-4-carboxylic acid methyl ester
• 英文别名: Methyl 2-ethenyl-4-(4-fluorophenyl)benzoate
• CAS: 873784-13-5
• 化学式: C₁₆H₁₃FO₂
• 分子量: 256.276
• InChiKey: DOKAXDHOFWLTSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4'-fluoro-3-vinylbiphenyl-4-carboxylic acid methyl ester 在 lithium hydroxide 、 tris(dibenzylideneacetone)dipalladium (0) 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 15.0h， 生成 3-((E)-2-(1,1'-biphenyl)-3-ylethenyl)-4'-fluoro-(1,1'-biphenyl)-4-carboxylic acid
  参考文献：
  名称：

  Discovery of a Potent Inhibitor of the Antiapoptotic Protein Bcl-x_L from NMR and Parallel Synthesis

  摘要：

  The antiapoptotic proteins Bcl-x(L) and Bcl-2 play key roles in the maintenance of normal cellular homeostasis. However, their overexpression can lead to oncogenic transformation and is responsible for drug resistance in certain types of cancer. This makes Bcl-x(L) and Bcl-2 attractive targets for the development of potential anticancer agents. Here we describe the structure-based discovery of a potent Bcl-x(L) inhibitor directed at a hydrophobic groove on the surface of the protein. This groove represents the binding site for BH3 peptides from proapoptotic Bcl-2 family members such as Bak and Bad. Application of NMR-based screening yielded an initial biaryl acid with an affinity (K-d) of similar to 300 mu M for the protein. Following the classical "SAR by NMR" approach, a second-site ligand was identified that bound proximal to the first-site ligand in the hydrophobic groove. From NMR-based structural studies and parallel synthesis, a potent ligand was obtained, which binds to Bcl-x(L) with an inhibition constant (K-i) of 36 +/- 2 nM.

  DOI：

  10.1021/jm0507532
• 作为产物：
  描述：

  methyl 4-(4′-fluorophenyl)-2-hydroxybenzoate 在 四(三苯基膦)钯 、 三乙胺 、 cesium fluoride 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 4'-fluoro-3-vinylbiphenyl-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of a Potent Inhibitor of the Antiapoptotic Protein Bcl-x_L from NMR and Parallel Synthesis

  摘要：

  The antiapoptotic proteins Bcl-x(L) and Bcl-2 play key roles in the maintenance of normal cellular homeostasis. However, their overexpression can lead to oncogenic transformation and is responsible for drug resistance in certain types of cancer. This makes Bcl-x(L) and Bcl-2 attractive targets for the development of potential anticancer agents. Here we describe the structure-based discovery of a potent Bcl-x(L) inhibitor directed at a hydrophobic groove on the surface of the protein. This groove represents the binding site for BH3 peptides from proapoptotic Bcl-2 family members such as Bak and Bad. Application of NMR-based screening yielded an initial biaryl acid with an affinity (K-d) of similar to 300 mu M for the protein. Following the classical "SAR by NMR" approach, a second-site ligand was identified that bound proximal to the first-site ligand in the hydrophobic groove. From NMR-based structural studies and parallel synthesis, a potent ligand was obtained, which binds to Bcl-x(L) with an inhibition constant (K-i) of 36 +/- 2 nM.

  DOI：

  10.1021/jm0507532

文献信息

• Discovery of a Potent Inhibitor of the Antiapoptotic Protein Bcl-x_L from NMR and Parallel Synthesis
  作者：Andrew M. Petros、Jurgen Dinges、David J. Augeri、Steven A. Baumeister、David A. Betebenner、Mark G. Bures、Steven W. Elmore、Philip J. Hajduk、Mary K. Joseph、Shelley K. Landis、David G. Nettesheim、Saul H. Rosenberg、Wang Shen、Sheela Thomas、Xilu Wang、Irini Zanze、Haichao Zhang、Stephen W. Fesik

  DOI：10.1021/jm0507532

  日期：2006.1.1

  The antiapoptotic proteins Bcl-x(L) and Bcl-2 play key roles in the maintenance of normal cellular homeostasis. However, their overexpression can lead to oncogenic transformation and is responsible for drug resistance in certain types of cancer. This makes Bcl-x(L) and Bcl-2 attractive targets for the development of potential anticancer agents. Here we describe the structure-based discovery of a potent Bcl-x(L) inhibitor directed at a hydrophobic groove on the surface of the protein. This groove represents the binding site for BH3 peptides from proapoptotic Bcl-2 family members such as Bak and Bad. Application of NMR-based screening yielded an initial biaryl acid with an affinity (K-d) of similar to 300 mu M for the protein. Following the classical "SAR by NMR" approach, a second-site ligand was identified that bound proximal to the first-site ligand in the hydrophobic groove. From NMR-based structural studies and parallel synthesis, a potent ligand was obtained, which binds to Bcl-x(L) with an inhibition constant (K-i) of 36 +/- 2 nM.