N-(3-叠氮丙基)-4-[3-[6-(4-甲基-1-哌嗪基)[2,6'-bi-1H-苯并咪唑]-2'-基]苯氧基]丁酰胺 | 1049722-30-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: N-(3-叠氮丙基)-4-[3-[6-(4-甲基-1-哌嗪基)[2,6'-bi-1H-苯并咪唑]-2'-基]苯氧基]丁酰胺
• 英文名称: Hoechst azide
• 英文别名: Targapremir-210；N-(3-azidopropyl)-4-[3-[6-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-benzimidazol-2-yl]phenoxy]butanamide
• CAS: 1049722-30-6
• 化学式: C₃₂H₃₆N₁₀O₂
• 分子量: 592.704
• InChiKey: PAYVJEWMAWLKAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(3-叠氮丙基)-4-[3-[6-(4-甲基-1-哌嗪基)[2,6'-bi-1H-苯并咪唑]-2'-基]苯氧基]丁酰胺 、 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Small Molecule Inhibition of microRNA-210 Reprograms an Oncogenic Hypoxic Circuit

  摘要：

  A hypoxic state is critical to the metastatic and invasive characteristics of cancer. Numerous pathways play critical roles in cancer maintenance, many of which include noncoding RNAs such as microRNA (miR)210 that regulates hypoxia inducible factors (HIFs). Herein, we describe the identification of a small molecule named Targapremir-210 that binds to the Dicer site of the miR-210 hairpin precursor. This interaction inhibits production of the mature miRNA, derepresses glycerol 3 phosphate dehydrogenase 1 like enzyme Drosha/D:cer (GPD1L), a hypoxia-associated protein negatively regulated by miR-210, decreases HIF-l alpha, and triggers apoptosis of triple negative breast cancer cells only under hypoxic conditions. Further, Targapremir-210 inhibits tumorigenesis in a mouse xenograft model of hypoxic triple negative breast cancer. Many factors govern molecular recognition of biological targets by small molecules. For protein, chemoproteomics and activity based protein profiling are invaluable tools to study small molecule target engagement and selectivity in cells. Such approaches are lacking for RNA, leaving a void in the understanding of its druggability. We applied Chemical Cross Linking and Isolation by Pull Down (Chem CLIP) to study the cellular selectivity and the on- and off targets of Targapremir-210. Targapremir-210 selectively recognizes the miR-210 precursor and can differentially recognize RNAs in cells that have the same target motif but have different expression levels, revealing this important feature for selectively drugging RNAs for the first time. These studies show that small molecules can be rapidly designed to selectively target RNAs and affect cellular responses to environmental conditions, resulting in favorable benefits against cancer. Further, they help define rules for identifying druggable targets in the transcriptome.

  DOI：

  10.1021/jacs.6b11273
• 作为产物：
  描述：

  5-(4-甲基哌嗪)-2-硝基苯胺 在 聚碳化二亚胺 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 水 、 硝基苯 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 N-(3-叠氮丙基)-4-[3-[6-(4-甲基-1-哌嗪基)[2,6'-bi-1H-苯并咪唑]-2'-基]苯氧基]丁酰胺
  参考文献：
  名称：

  二-(苯并咪唑)-1,2,3-三唑衍生物及其制备和在炎症性皮肤病中的应用

  摘要：

  本发明属于药物小分子技术领域，具体公开了一种全新的二‑(苯并咪唑)‑1,2,3‑三唑衍生物及其制备和应用。本发明研究发现，所述的全新的化合物，在炎症性皮肤病方面具有优异的药效、较低的毒副作用，在炎症性皮肤病的药物开发方面具有良好的应用前景。

  公开号：

  CN113004253B

文献信息

• [EN] TRANSCRIPTOME-WIDE DESIGN OF SELECTIVE, BIOACTIVE SMALL MOLECULES TARGETING RNA<br/>[FR] CONCEPTION DANS LE TRANSCRIPTOME DE PETITES MOLÉCULES BIOACTIVES SÉLECTIVES CIBLANT L'ARN
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2015021415A1

  公开（公告）日：2015-02-12

  Methods and computer systems are described herein for identifying small molecules that bind to selected RNA structural features (e.g., to RNA secondary structures). Also described are compounds and compositions that modulate RNA function and/or activity.

  本文描述了用于识别与选定RNA结构特征（例如RNA次级结构）结合的小分子的方法和计算机系统。还描述了调节RNA功能和/或活性的化合物和组合物。
• Covalent Small-Molecule-RNA Complex Formation Enables Cellular Profiling of Small-Molecule-RNA Interactions
  作者：Lirui Guan、Matthew D. Disney

  DOI：10.1002/anie.201301639

  日期：2013.9.16

  Won't let you go! A strategy is described to design small molecules that react with their cellular RNA targets. This approach not only improves the activity of compounds targeting RNA in cell culture by a factor of about 2500 but also enables cell‐wide profiling of its RNA targets.

  不会让你走的！描述了一种设计与其细胞 RNA 靶标反应的小分子的策略。这种方法不仅将细胞培养中靶向 RNA 的化合物的活性提高了约 2500 倍，而且还能够对其 RNA 靶标进行细胞范围的分析。
• TRANSCRIPTOME-WIDE DESIGN OF SELECTIVE, BIOACTIVE SMALL MOLECULES TARGETTING RNA
  申请人：The Scripps Research Institute

  公开号：EP3293292A1

  公开（公告）日：2018-03-14

  Methods and computer systems are described herein for identifying small molecules that bind to selected RNA structural features (e.g., to RNA secondary structures). Also described are compounds and compositions that modulate RNA function and/or activity.

  本文描述了识别与所选 RNA 结构特征（如 RNA 二级结构）结合的小分子的方法和计算机系统。还描述了调节 RNA 功能和/或活性的化合物和组合物。
• [EN] DI-(BENZIMIDAZOLE)-1, 2, 3-TRIAZOLE DERIVATIVE AND PREPARATION THEREFOR AND USE THEREOF<br/>[FR] DÉRIVÉ DE DI-(BENZIMIDAZOLE)-1, 2, 3-TRIAZOLE, SA PRÉPARATION ET SON UTILISATION<br/>[ZH] 二-(苯并咪唑)-1,2,3-三唑衍生物及其制备和应用
  申请人：2ND XIANGYA HOSPITAL CENTRAL SOUTH UNIV

  公开号：WO2022021981A1

  公开（公告）日：2022-02-03

  本发明属于药物小分子技术领域，具体公开了一种全新的二-(苯并咪唑)-1,2,3-三唑衍生物及其制备、应用以及包含该活性成分的制剂。本发明研究发现，所述的全新的化合物，在抑制miR-210表达方面具有意料不到的效果，可用于病理性miR-210过表达相关疾病的药物的开发。
• Defining the RNA Internal Loops Preferred by Benzimidazole Derivatives via 2D Combinatorial Screening and Computational Analysis
  作者：Sai Pradeep Velagapudi、Steven J. Seedhouse、Jonathan French、Matthew D. Disney

  DOI：10.1021/ja200212b

  日期：2011.7.6

  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.