5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 302553-01-1

• 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: 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 5,6,8-trichloro-4-oxo-1H-quinoline-3-carboxylic acid
• CAS: 302553-01-1
• 化学式: C₁₀H₄Cl₃NO₃
• mdl: MFCD01847818
• 分子量: 292.506
• InChiKey: DIMMLVONVUPWHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 5,6,8-trichloro-4-oxo-1H-quinoline-3-carboxylate 在 sodium hydroxide 作用下， 反应 1.0h， 生成 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Evaluation of 3-Carboxy-4(1H)-quinolones as Inhibitors of Human Protein Kinase CK2

  摘要：

  Due to the emerging role of protein kinase CK2 as a molecule that participates not only in the development of some cancers but also in viral infections and inflammatory failures, small organic inhibitors of CK2, besides application in scientific research, may have therapeutic significance. In this paper, we present a new class of CK2 inhibitorss3-carboxy-4(1H)-quinolones. This class of inhibitors has been selected via receptor-based virtual screening of the Otava compound library. It was revealed that the most active compounds, 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (7) (IC50 = 0.3 mu M) and 4-oxo-1,4-dihydrobenzo[h] quinoline-3-carboxylic acid (9) (IC50 = 1 AM), are ATP competitive (K-i values are 0.06 and 0.28 mu M, respectively). Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data, a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed.

  DOI：

  10.1021/jm050048t

文献信息

• Methods and pharmaceutical compositions for treating microbiome dysregulations associated with circadian clock disruption
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US11364219B2

  公开（公告）日：2022-06-21

  The present invention relates to the treatment of microbiome dysregulations. Said dysregulations may subsequently contribute to the development of several chronic diseases. Thus characterization of new post-biotic compounds inducing beneficial changes on host-microbiota interactions may be highly desirable. The inventors showed that Nlrp6 diurnally coordinates cyclical adaptation of the gut microbiota diversity to epithelial plasticity in response to a treatment with a Csnk2 inhibitor. The invention therefore relates to an inhibitor of Csnk2, for use in the treatment of microbiome dysregulations notably associated with circadian clock disruption. Said inhibitor may be selected among chemically synthesized or natural selective Csnk2 inhibitors such as flavones.

  本发明涉及微生物组失调的治疗。这些失调可能会导致多种慢性疾病的发生。因此，对能诱导宿主-微生物群相互作用发生有益变化的新生物后化合物进行表征可能是非常可取的。本发明者的研究表明，Nlrp6 在使用 Csnk2 抑制剂治疗的情况下，会周期性地协调肠道微生物群多样性对上皮可塑性的适应。因此，本发明涉及一种 Csnk2 抑制剂，用于治疗主要与昼夜节律紊乱有关的微生物组失调。所述抑制剂可选择化学合成或天然选择性 Csnk2 抑制剂，如黄酮类。
• METHODS AND PHARMACEUTICAL COMPOSITIONS FOR TREATING MICROBIOME DYSREGULATIONS ASSOCIATED WITH CIRCADIAN CLOCK DISRUPTION
  申请人：Institut National de la Santé et de la Recherche Médicale (INSERM)

  公开号：EP3458047A1

  公开（公告）日：2019-03-27
• [EN] METHODS AND PHARMACEUTICAL COMPOSITIONS FOR TREATING MICROBIOME DYSREGULATIONS ASSOCIATED WITH CIRCADIAN CLOCK DISRUPTION<br/>[FR] MÉTHODES ET COMPOSITIONS PHARMACEUTIQUES DESTINÉES À TRAITER DES DYSRÉGULATIONS DU MICROBIOME ASSOCIÉES À DES PERTURBATIONS DE L'HORLOGE BIOLOGIQUE
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECH MÉDICALE)

  公开号：WO2017198847A1

  公开（公告）日：2017-11-23

  The present invention relates to the treatment of microbiome dysregulations. Said dysregulations may subsequently contribute to the development of several chronic diseases. Thus characterization of new post-biotic compounds inducing beneficial changes on host-microbiota interactions may be highly desirable. The inventors showed that Nlrp6 diurnally coordinates cyclical adaptation of the gut microbiota diversity to epithelial plasticity in response to a treatment with a Csnk2 inhibitor. The invention therefore relates to an inhibitor of Csnk2, for use in the treatment of microbiome dysregulations notably associated with circadian clock disruption. Said inhibitor may be selected among chemically synthetized or natural selective Csnk2 inhibitors such as flavones.