2-(4-bromophenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one | 142354-82-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 2-(4-bromophenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
• 英文别名: 2-(4-bromophenyl)-5,6,7,8-tetrahydro-3H-[1]benzothiolo[2,3-d]pyrimidin-4-one
• CAS: 142354-82-3
• 化学式: C₁₆H₁₃BrN₂OS
• 分子量: 361.262
• InChiKey: OMNNWJBLBAMJEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  环己酮 在 sulfur 作用下， 以 乙醇 为溶剂， 反应 11.0h， 生成 2-(4-bromophenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
  参考文献：
  名称：

  ZnO-CeO2纳米复合材料：制备噻吩并[2,3-d]嘧啶-4(3H)-one衍生物的高效催化剂

  摘要：

  摘要 采用共沉淀法制备氧化锌-氧化铈(ZnO-CeO2)纳米复合材料，并通过X射线衍射(XRD)、场发射扫描电子显微镜(FE-SEM)和粒度分布分析对其进行表征。XRD图显示氧化铈的立方相作为主要相。FE-SEM 图像显示了样品中氧化锌和氧化铈的均匀性分布。通过动态光散射技术测定的纳米复合材料的平均粒径为 58 nm。ZnO-CeO2 纳米复合材料的催化活性在噻吩并[2,3-d]嘧啶-4(3H)-one 衍生物的合成中进行了检测。在所有情况下，产品都以良好到极好的收率获得。

  DOI：

  10.1515/mgmc-2017-0038

文献信息

• Three possible products from the reactions of gewald's amide with aromatic aldehydes
  作者：Sergey G. Dzhavakhishvili、Nikolay Yu. Gorobets、Vladimir I. Musatov、Sergey M. Desenko、Boris V. Paponov

  DOI：10.1002/jhet.5570450243

  日期：2008.3

  Transformations of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (Gewald's amide) in the reactions with aromatic aldehydes were studied. Efficient methods for synthesis of three possible types of products: 2-aryl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one, 2-(1-arylmethylidene-amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide and 2-aryl-2,3,5,6,7,8-hexahydro[1]benzo-thieno[2

  研究了2-氨基-4,5,6,7-四氢苯并[ b ]噻吩-3-羧酰胺（Gewald's amide）在与芳族醛的反应中的转化。合成三种可能类型产物的有效方法：2-芳基-5,6,7,8-四氢[1]苯并噻吩并[2,3 - d ]嘧啶-4（3 H）-one，2-（1-芳基亚甲基-氨基）-4,5,6,7-四氢苯并[ b ]噻吩-3-羧酰胺和2-芳基-2,3,5,6,7,8-六氢[1]苯并噻吩并[2,3 - d ]嘧啶-4（1 ħ） -酮衍生物被开发出来。通过过滤可以容易地分离所有产物，具有非常好的总产率。还研究了这些化合物的相互转化。
• Discovery of a Small-Molecule Bromodomain-Containing Protein 4 (BRD4) Inhibitor That Induces AMP-Activated Protein Kinase-Modulated Autophagy-Associated Cell Death in Breast Cancer
  作者：Liang Ouyang、Lan Zhang、Jie Liu、Leilei Fu、Dahong Yao、Yuqian Zhao、Shouyue Zhang、Guan Wang、Gu He、Bo Liu

  DOI：10.1021/acs.jmedchem.7b00275

  日期：2017.12.28

  Upon the basis of The Cancer Genome Atlas (TCGA) data set, we identified that several autophagy-related proteins such as AMP-activated protein kinase (AMPK) were remarkably downregulated in breast cancer. Combined with coimmunoprecipitation assay, we demonstrated that BRD4 might interact with AMPK. After analyses of the pharmacophore and WPF interaction optimization, we designed a small-molecule inhibitor of BRD4, 9f (FL-411) which was validated by cocrystal structure with BD1 of BRD4. Subsequently, 9f was discovered to induce ATG5-dependent autophagy-associated cell death (ACD) by blocking BRD4-AMPK interaction and thus activating AMPK-mTOR-ULK1-modulated autophagic pathway in breast cancer cells. Interestingly, the iTRAQ-based proteomics analyses revealed that 9f induced ACD pathways involved in HMGB1, VDAC1/2, and eEF2. Moreover, 9f displayed a therapeutic potential on both breast cancer xenograft mouse and zebrafish models. Together, these results demonstrate that a novel small-molecule inhibitor of BRD4 induces BRD4-AMPK-modulated ACD in breast cancer, which may provide a candidate drug for future cancer therapy.