3-(2',2''-diisobutyl-4-methoxycarbonylmethoxy-3-naphthalen-1-ylmethyl-[1,1':4',1'']-terphenyl-4''-yl)propionic acid methyl ester | 475272-53-8

• 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: 3-(2',2''-diisobutyl-4-methoxycarbonylmethoxy-3-naphthalen-1-ylmethyl-[1,1':4',1'']-terphenyl-4''-yl)propionic acid methyl ester
• 英文别名: Methyl 3-[4-[4-[4-(2-methoxy-2-oxoethoxy)-3-(naphthalen-1-ylmethyl)phenyl]-3-(2-methylpropyl)phenyl]-3-(2-methylpropyl)phenyl]propanoate
• CAS: 475272-53-8
• 化学式: C₄₄H₄₈O₅
• 分子量: 656.862
• InChiKey: RIBVSGMWSSGOLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.5
• 重原子数：
  49
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2',2''-diisobutyl-4-methoxycarbonylmethoxy-3-naphthalen-1-ylmethyl-[1,1':4',1'']-terphenyl-4''-yl)propionic acid methyl ester 在 sodium hydroxide 、 四丁基氢氧化铵 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 以100%的产率得到Terphenyl scaffold, 19
  参考文献：
  名称：

  Development of a Potent Bcl-x_L Antagonist Based on α-Helix Mimicry

  摘要：

  The rational design of low-molecular weight ligands that disrupt protein-protein interactions is still a challenging goal in medicinal chemistry. Our approach to this problem involves the design of molecular scaffolds that mimic the surface functionality projected along one face of an alpha-helix. Using a terphenyl scaffold, which in a staggered conformation closely reproduces the projection of functionality on the surface of an alpha-helix, we designed mimics of the pro-apoptotic alpha-helical Bak-peptide as inhibitors of the Bak/Bcl-xL interaction. This led to the development of a potent Bcl-xL antagonist (KD = 114 nM), whose binding affinity for Bcl-xL was assessed by a fluorescence polarization assay. To determine the binding site of the developed inhibitor we used docking studies and an HSQC-NMR experiment with 15N-labeled Bcl-xL protein. These studies suggest that the inhibitor is binding in the same hydrophobic cleft as the Bak- and Bad-peptides.

  DOI：

  10.1021/ja026861k
• 作为产物：
  描述：

  3-(4-hydroxy-2',2''-diisobutyl-3-naphthalen-1-ylmethyl-[1,1':4',1'']-terphenyl-4''-yl)propionitrile 在 盐酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 41.0h， 生成 3-(2',2''-diisobutyl-4-methoxycarbonylmethoxy-3-naphthalen-1-ylmethyl-[1,1':4',1'']-terphenyl-4''-yl)propionic acid methyl ester
  参考文献：
  名称：

  Development of a Potent Bcl-x_L Antagonist Based on α-Helix Mimicry

  摘要：

  The rational design of low-molecular weight ligands that disrupt protein-protein interactions is still a challenging goal in medicinal chemistry. Our approach to this problem involves the design of molecular scaffolds that mimic the surface functionality projected along one face of an alpha-helix. Using a terphenyl scaffold, which in a staggered conformation closely reproduces the projection of functionality on the surface of an alpha-helix, we designed mimics of the pro-apoptotic alpha-helical Bak-peptide as inhibitors of the Bak/Bcl-xL interaction. This led to the development of a potent Bcl-xL antagonist (KD = 114 nM), whose binding affinity for Bcl-xL was assessed by a fluorescence polarization assay. To determine the binding site of the developed inhibitor we used docking studies and an HSQC-NMR experiment with 15N-labeled Bcl-xL protein. These studies suggest that the inhibitor is binding in the same hydrophobic cleft as the Bak- and Bad-peptides.

  DOI：

  10.1021/ja026861k

文献信息

• Proteomimetic compounds and methods
  申请人：——

  公开号：US20030008882A1

  公开（公告）日：2003-01-09

  The present invention relates to compounds and pharmaceutical compositions which are proteomimetic and to methods for inhibiting the interaction of an alpha-helical protein with another protein or binding site. Methods for treating diseases or conditions which are modulated through interactions between alpha helical proteins and their binding sites are other aspects of the invention.

  本发明涉及具有蛋白质拟态作用的化合物和药物组合物，以及抑制α-螺旋蛋白与另一蛋白或结合位点相互作用的方法。治疗通过α-螺旋蛋白与其结合位点之间相互作用调节的疾病或病况的方法是本发明的其他方面。
• PROTEOMIMETIC COMPOUNDS AND METHODS
  申请人：Yale University

  公开号：EP1408986B1

  公开（公告）日：2008-09-24
• US6858600B2
  申请人：——

  公开号：US6858600B2

  公开（公告）日：2005-02-22
• US7312246B2
  申请人：——

  公开号：US7312246B2

  公开（公告）日：2007-12-25