2-(3-isobutyl-4-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane | 475272-04-9

• 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: 2-(3-isobutyl-4-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane
• 英文别名: 2-(3-Isobutyl-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane；2-[4-methoxy-3-(2-methylpropyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• CAS: 475272-04-9
• 化学式: C₁₇H₂₇BO₃
• 分子量: 290.211
• InChiKey: WETMDGXVZIHSSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.19
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-isobutyl-4-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane 在 吡啶 、 盐酸 、 四(三苯基膦)钯 、 三溴化硼 、 sodium carbonate 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 125.0h， 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。
• Terphenyl-Based Bak BH3 α-Helical Proteomimetics as Low-Molecular-Weight Antagonists of Bcl-x_L
  作者：Hang Yin、Gui-in Lee、Kristine A. Sedey、Olaf Kutzki、Hyung Soon Park、Brendan P. Orner、Justin T. Ernst、Hong-Gang Wang、Said M. Sebti、Andrew D. Hamilton

  DOI：10.1021/ja050122x

  日期：2005.7.1

  a library of terphenyl derivatives to mimic the helical region of the Bak BH3 domain that binds Bcl-x(L). Fluorescence polarization assays were carried out to evaluate the ability of terphenyl derivatives to displace the Bcl-x(L)-bound Bak peptide. Terphenyl 14 exhibited good in vitro affinity with a K(i) value of 0.114 muM. These terphenyl derivatives were more selective at disrupting the Bcl-x(L)/Bak

  我们描述了一种模拟基于三联苯支架的 alpha 螺旋的一个面的一般方法，该支架以类似于两圈 alpha 螺旋的方式在空间上投射功能。合成支架降低了模拟蛋白质二级结构的灵活性和分子量。我们已将此设计应用于α-螺旋结合蛋白Bcl-x(L) 拮抗剂的开发。使用顺序合成策略，我们准备了一个三联苯衍生物库来模拟 Bak BH3 域的螺旋区域，该区域与 Bcl-x(L) 结合。进行荧光偏振测定以评估三联苯衍生物取代 Bcl-x(L) 结合 Bak 肽的能力。三联苯 14 表现出良好的体外亲和力，K(i) 值为 0.114 muM。这些三联苯衍生物在通过 HDM2/p53 相互作用破坏 Bcl-x(L)/Bak 方面更具选择性，HDM2/p53 相互作用涉及 p53 的 N 端α-螺旋与 HDM2 的结合。使用核磁共振光谱和计算机辅助对接模拟的结构研究表明，Bcl-x(L) 表面的螺旋结合区是合成配体的目标。用三联苯衍生物处理人胚胎肾
• Terphenyl‐Based Helical Mimetics That Disrupt the p53/HDM2 Interaction
  作者：Hang Yin、Gui‐in Lee、Hyung Soon Park、Gregory A. Payne、Johanna M. Rodriguez、Said M. Sebti、Andrew D. Hamilton

  DOI：10.1002/anie.200462316

  日期：2005.4.29
• Development of a Potent Bcl-x_L Antagonist Based on α-Helix Mimicry
  作者：Olaf Kutzki、Hyung Soon Park、Justin T. Ernst、Brendan P. Orner、Hang Yin、Andrew D. Hamilton

  DOI：10.1021/ja026861k

  日期：2002.10.1

  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.