4-oxo-4,5-dihydrothieno[3,2-c]quinoline-2-carboxylic acid | 950258-81-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-2-carboxylic acid
• 英文别名: 4-oxo-4,5-dihydrothiophene[3,2-c]quinoline-2-carboxylic acid；4-oxo-5H-thieno[3,2-c]quinoline-2-carboxylic acid
• CAS: 950258-81-8
• 化学式: C₁₂H₇NO₃S
• 分子量: 245.258
• InChiKey: HJIXEBZEMFGCFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  94.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-oxo-4,5-dihydrothieno[3,2-c]quinoline-2-carboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Discovery of thienoquinolone derivatives as selective and ATP non-competitive CDK5/p25 inhibitors by structure-based virtual screening

  摘要：

  Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer's disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[ 3,2-c] quinolin-4(5H)-one inhibitor (10) with ligand efficiency (LE) of 0.3 was identified as the lead molecule. Further SAR optimization led to the discovery of several low micromolar inhibitors with good selectivity. The research represents a new class of potent ATP noncompetitive CDK5/p25 inhibitors with good CDK2/E selectivity. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.09.043
• 作为产物：
  描述：

  N,N'-二(苯基)丙二酰胺 在 甲醇 、 lithium hydroxide monohydrate 、 左旋去甲麻黄碱 、 potassium carbonate 、 三氯氧磷 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.33h， 生成 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-2-carboxylic acid
  参考文献：
  名称：

  一种噻吩并喹诺酮类化合物及其制备方法和应用

  摘要：

  本发明属于医药领域，具体讲，涉及一种噻吩并喹诺酮类化合物及其制备方法和应用。本发明的噻吩并喹诺酮类化合物的结构式如式I所示。本发明获得了如式I所示的噻吩并喹诺酮类化合物，不仅对CDK5抑制活性较高，并且具有良好的水溶性。

  公开号：

  CN113429422B

文献信息

• 一种噻吩并喹诺酮类化合物及其制备方法和应用
  申请人：中国人民解放军军事科学院军事医学研究院

  公开号：CN113429422B

  公开（公告）日：2022-05-10

  本发明属于医药领域，具体讲，涉及一种噻吩并喹诺酮类化合物及其制备方法和应用。本发明的噻吩并喹诺酮类化合物的结构式如式I所示。本发明获得了如式I所示的噻吩并喹诺酮类化合物，不仅对CDK5抑制活性较高，并且具有良好的水溶性。
• Lead Discovery of Dual G-Quadruplex Stabilizers and Poly(ADP-ribose) Polymerases (PARPs) Inhibitors: A New Avenue in Anticancer Treatment
  作者：Erica Salvati、Lorenzo Botta、Jussara Amato、Francesco Saverio Di Leva、Pasquale Zizza、Antimo Gioiello、Bruno Pagano、Grazia Graziani、Madalena Tarsounas、Antonio Randazzo、Ettore Novellino、Annamaria Biroccio、Sandro Cosconati

  DOI：10.1021/acs.jmedchem.6b01563

  日期：2017.5.11

  G-quadruplex stabilizers are an established opportunity in anticancer chemotherapy. To circumvent the antiproliferative effects of G4 ligands, cancer cells recruit PARP enzymes at telomeres. Herein, starting from the structural similarity of a potent G4 ligand previously discovered by our group and a congeneric PARP inhibitor, a library of derivatives was synthesized to discover the first dual G4/PARP

  G-四链体稳定剂是抗癌化疗的既定机会。为了规避G4配体的抗增殖作用，癌细胞在端粒募集PARP酶。在本文中，从我们小组先前发现的有效G4配体和同类PARP抑制剂的结构相似性出发，合成了一个衍生物库以发现第一个双重G4 / PARP配体。我们证明适当装饰的thieno [3,2 - c ] quinolin-4（5 H）-一个稳定体外和在细胞中的G4折叠，诱导定位于端粒的DNA损伤反应，抑制细胞中的PARylation，并具有在BRCA2缺陷型肿瘤细胞中具有抗增殖作用。
• Discovery of thienoquinolone derivatives as selective and ATP non-competitive CDK5/p25 inhibitors by structure-based virtual screening
  作者：Arindam Chatterjee、Stephen J. Cutler、Robert J. Doerksen、Ikhlas A. Khan、John S. Williamson

  DOI：10.1016/j.bmc.2014.09.043

  日期：2014.11

  Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer's disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[ 3,2-c] quinolin-4(5H)-one inhibitor (10) with ligand efficiency (LE) of 0.3 was identified as the lead molecule. Further SAR optimization led to the discovery of several low micromolar inhibitors with good selectivity. The research represents a new class of potent ATP noncompetitive CDK5/p25 inhibitors with good CDK2/E selectivity. Published by Elsevier Ltd.