ethyl 4-(4-formyl-2,6-di-tert-butylphenoxy)butanoate | 1311982-89-4

• 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: ethyl 4-(4-formyl-2,6-di-tert-butylphenoxy)butanoate
• 英文别名: ethyl 4-(2,6-di-tert-butyl-4-formylphenoxy)butanoate；Butanoic acid, 4-[2,6-bis(1,1-dimethylethyl)-4-formylphenoxy]-, ethyl ester；ethyl 4-(2,6-ditert-butyl-4-formylphenoxy)butanoate
• CAS: 1311982-89-4
• 化学式: C₂₁H₃₂O₄
• 分子量: 348.483
• InChiKey: BWRLAJCUJPGVQI-UHFFFAOYSA-N

物化性质

• 沸点：
  448.8±45.0 °C(Predicted)
• 密度：
  1.011±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-formyl-2,6-di-tert-butylphenoxy)butanoate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 硝基苯 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.5h， 生成 Targaprimir-515/885
  参考文献：
  名称：

  Defining the RNA Internal Loops Preferred by Benzimidazole Derivatives via 2D Combinatorial Screening and Computational Analysis

  摘要：

  RNA is an important therapeutic target; however, RNA targets are generally underexploited due to a lack of understanding of the small molecules that bind RNA and the RNA motifs that bind small molecules. Herein, we describe the identification of the RNA internal loops derived from a 4096 member 3 x 3 nucleotide loop library that are the most specific and highest affinity binders to a series of four designer, druglike benzimidazoles. These studies establish a potentially general protocol to define the highest affinity and most specific RNA motif targets for heterocyclic small molecules. Such information could be used to target functionally important RNAs in genomic sequence.

  DOI：

  10.1021/ja200212b
• 作为产物：
  描述：

  4-溴丁酸乙酯 、 3,5-二叔丁基-4-羟基苯甲醛 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以14%的产率得到ethyl 4-(4-formyl-2,6-di-tert-butylphenoxy)butanoate
  参考文献：
  名称：

  Defining the RNA Internal Loops Preferred by Benzimidazole Derivatives via 2D Combinatorial Screening and Computational Analysis

  摘要：

  RNA is an important therapeutic target; however, RNA targets are generally underexploited due to a lack of understanding of the small molecules that bind RNA and the RNA motifs that bind small molecules. Herein, we describe the identification of the RNA internal loops derived from a 4096 member 3 x 3 nucleotide loop library that are the most specific and highest affinity binders to a series of four designer, druglike benzimidazoles. These studies establish a potentially general protocol to define the highest affinity and most specific RNA motif targets for heterocyclic small molecules. Such information could be used to target functionally important RNAs in genomic sequence.

  DOI：

  10.1021/ja200212b

文献信息

• [EN] DEFINING RNA-SMALL MOLECULE AFFINITY LANDSCAPES ENABLES DESIGN OF A SMALL MOLECULAR INHIBITOR OF AN ONCOGENIC NON-CODING RNA<br/>[FR] DÉFINITION DE PAYSAGES D'AFFINITÉ À PETITES MOLÉCULES D'ARN PERMETTANT LA CONCEPTION D'UN PETIT INHIBITEUR MOLÉCULAIRE D'UN ARN NON CODANT ONCOGÈNE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2018151810A1

  公开（公告）日：2018-08-23

  RNA drug targets are pervasive in cells but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross Linking and isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of non-coding RNAs.

  RNA药物靶点在细胞中广泛存在，但设计针对它们的小分子的方法很少。在这里，我们报告了一种评分RNA结构-小分子相互作用亲和力和选择性的通用方法，该方法是通过筛选识别的。命名为高通量结构活性关系通过测序（HiT-STARTS），HiT-STARTS在统计性质上比较输入核酸序列与通过高通量测序结合配体的选定库成员。这种方法便于定义成千上万个RNA结构-小分子结合伙伴的适应性景观。这些结果与人类转录组中的折叠RNA相互作用，并确定了一个小分子与致癌微RNA（miR）-18a发夹前体中的Dicer核酸酶加工位点之间的强烈相互作用，该前体是miR-17-92簇的成员。将这种小分子Targapremir-18a应用于前列腺癌细胞，抑制了miR-18a从簇中的产生，解除了丝氨酸/苏氨酸蛋白激酶4蛋白（STK4）的抑制，并引发了凋亡。通过化学交联和下拉分离（Chem-CLIP）对Targapremir-18a的细胞靶标进行分析，这是一种共价小分子-RNA细胞分析方法，以及其他研究显示该化合物特异性结合到miR-18a前体，揭示了影响小分子药物对非编码RNA进行药物化的广泛适用因素。