4-(2-formylthiazol-5-yl)benzonitrile

• 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-(2-formylthiazol-5-yl)benzonitrile
• 英文别名: 5-(4-cyanophenyl)thiazole-2-carbaldehyde；4-(2-formyl-1,3-thiazol-5-yl)benzonitrile
• 化学式: C₁₁H₆N₂OS
• 分子量: 214.247
• InChiKey: FWXBLPPBDBNULE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-formylthiazol-5-yl)benzonitrile 在 盐酸 、 sodium metabisulfite 、 乙醇 作用下， 以 二甲基亚砜 为溶剂， 反应 384.5h， 生成 2-(5-(4-carbamimidoylphenyl)thiazol-2-yl)-1H-benzo[d]imidazole-6-carboximidamide trihydrochloride
  参考文献：
  名称：

  Heterocyclic Diamidine DNA Ligands as HOXA9 Transcription Factor Inhibitors: Design, Molecular Evaluation, and Cellular Consequences in a HOXA9-Dependant Leukemia Cell Model

  摘要：

  Most transcription factors were for a long time considered as undruggable targets because of the absence of binding pockets for direct targeting. HOXA9, implicated in acute myeloid leukemia, is one of them. To date, only indirect targeting of HOXA9 expression or multitarget HOX/PBX protein/protein interaction inhibitors has been developed. As an attractive alternative by inhibiting the DNA binding, we selected a series of heterocyclic diamidines as efficient competitors for the HOXA9/DNA interaction through binding as minor groove DNA ligands on the HOXA9 cognate sequence. Selected DB818 and DB1055 compounds altered HOXA9-mediated transcription in luciferase assays, cell survival, and cell cycle, but increased cell death and granulocyte/monocyte differentiation, two main HOXA9 functions also highlighted using transcriptomic analysis of DB818-treated murine Hoxa9-transformed hematopoietic cells. Altogether, these data demonstrate for the first time the propensity of sequence-selective DNA ligands to inhibit HOXA9/DNA binding both in vitro and in a murine Hoxa9-dependent leukemic cell model.

  DOI：

  10.1021/acs.jmedchem.8b01448
• 作为产物：
  描述：

  5-溴噻唑-2-甲醛 、 4-氰基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 24.0h， 以51%的产率得到4-(2-formylthiazol-5-yl)benzonitrile
  参考文献：
  名称：

  Heterocyclic Diamidine DNA Ligands as HOXA9 Transcription Factor Inhibitors: Design, Molecular Evaluation, and Cellular Consequences in a HOXA9-Dependant Leukemia Cell Model

  摘要：

  Most transcription factors were for a long time considered as undruggable targets because of the absence of binding pockets for direct targeting. HOXA9, implicated in acute myeloid leukemia, is one of them. To date, only indirect targeting of HOXA9 expression or multitarget HOX/PBX protein/protein interaction inhibitors has been developed. As an attractive alternative by inhibiting the DNA binding, we selected a series of heterocyclic diamidines as efficient competitors for the HOXA9/DNA interaction through binding as minor groove DNA ligands on the HOXA9 cognate sequence. Selected DB818 and DB1055 compounds altered HOXA9-mediated transcription in luciferase assays, cell survival, and cell cycle, but increased cell death and granulocyte/monocyte differentiation, two main HOXA9 functions also highlighted using transcriptomic analysis of DB818-treated murine Hoxa9-transformed hematopoietic cells. Altogether, these data demonstrate for the first time the propensity of sequence-selective DNA ligands to inhibit HOXA9/DNA binding both in vitro and in a murine Hoxa9-dependent leukemic cell model.

  DOI：

  10.1021/acs.jmedchem.8b01448

文献信息

• Extending the σ-Hole Motif for Sequence-Specific Recognition of the DNA Minor Groove
  作者：Pu Guo、Abdelbasset A. Farahat、Ananya Paul、Arvind Kumar、David W. Boykin、W. David Wilson

  DOI：10.1021/acs.biochem.0c00090

  日期：2020.5.12

  with compounds that could selectively target DNA or RNA would greatly enhance the availability of cellular probes and therapeutic progress. We are focusing on the design of sequence-specific DNA minor groove binders that, for example, target the promoter sites of transcription factors involved in a disease. We have started with AT-specific minor groove binders that are known to enter human cells and

  当前大多数针对疾病（例如癌症）的药物可以与蛋白质中的一个或多个位点结合并抑制其活性。但是，可药用蛋白质的数量存在众所周知的限制，目前的药物与可以选择性靶向DNA或RNA的化合物互补将极大地提高细胞探针的可用性和治疗进展。我们专注于序列特异性DNA小沟结合物的设计，例如，该结合物靶向与疾病有关的转录因子的启动子位点。我们已经开始使用AT特定的小沟结合剂，这种结合剂已知会进入人体细胞并进入临床试验。为了拓宽这些化合物的序列特异性识别，已鉴定出几个具有强烈和特异性识别G·C碱基对的H键受体的模块。铅模块是基于噻吩-N-烷基-苯并咪唑σ孔的系统，该系统具有末端苯基that，对小沟中的G·C碱基对具有出色的亲和力和选择性。现在，工作重点集中在优化此模块上。在这项工作中，我们正在评估对化合物芳族体系的修饰，以提高GC的选择性和亲和力。铅化合物保留了噻吩-N-烷基-BI模块，但在末端苯基-上具有与to基