5-[(3-乙炔苯基)氨基]-嘧啶并[4,5-c]喹啉-8-羧酸 | 1009821-06-0

• 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
• 中文名称: 5-[(3-乙炔苯基)氨基]-嘧啶并[4,5-c]喹啉-8-羧酸
• 中文别名: 5-[(3-乙炔苯基)氨基]-嘧啶并[4,5-C]喹啉-8-羧酸
• 英文名称: 5-(3-ethynylphenylamino)pyrimido[4,5-c]quinoline-8-carboxylic acid
• 英文别名: 5-((3-Ethynylphenyl)amino)pyrimido[4,5-c]quinoline-8-carboxylic acid；5-(3-ethynylanilino)pyrimido[4,5-c]quinoline-8-carboxylic acid
• CAS: 1009821-06-0
• 化学式: C₂₀H₁₂N₄O₂
• 分子量: 340.341
• InChiKey: HJGFPNFAFSFDNN-UHFFFAOYSA-N

物化性质

• 沸点：
  570.6±50.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-[(3-乙炔苯基)氨基]-嘧啶并[4,5-c]喹啉-8-羧酸 在 氯化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 以50%的产率得到5-(3-Ethynylanilino)pyrimido[4,5-c]quinoline-8-carboxamide
  参考文献：
  名称：

  Novel potent pyrimido[4,5-c]quinoline inhibitors of protein kinase CK2: SAR and preliminary assessment of their analgesic and anti-viral properties

  摘要：

  We describe the discovery of novel potent substituted pyrimido[4,5-c]quinoline ATP-competitive inhibitors of protein kinase CK2. A binding model of the inhibitors with the protein was elaborated on the basis of SAR and revealed various modes of interaction with the hinge region. Representative analog 14k (CK2 IC50 = 9 nM) showed anti-viral activity at nanomolar concentrations against HIV-1. Orally available compound 7e (CK2 IC50 = 3 nM) reduced pain in the phase II of a murine formalin model. These preliminary data confirm that properly optimized CK2 inhibitors may be used for anti-viral and pain therapy. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.091
• 作为产物：
  描述：

  5-溴-4-嘧啶甲酸甲酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 水 、 caesium carbonate 、 N,N-二异丙基乙胺 、 lithium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N-甲基吡咯烷酮 、 甲醇 、 甲苯 为溶剂， 生成 5-[(3-乙炔苯基)氨基]-嘧啶并[4,5-c]喹啉-8-羧酸
  参考文献：
  名称：

  Novel potent pyrimido[4,5-c]quinoline inhibitors of protein kinase CK2: SAR and preliminary assessment of their analgesic and anti-viral properties

  摘要：

  We describe the discovery of novel potent substituted pyrimido[4,5-c]quinoline ATP-competitive inhibitors of protein kinase CK2. A binding model of the inhibitors with the protein was elaborated on the basis of SAR and revealed various modes of interaction with the hinge region. Representative analog 14k (CK2 IC50 = 9 nM) showed anti-viral activity at nanomolar concentrations against HIV-1. Orally available compound 7e (CK2 IC50 = 3 nM) reduced pain in the phase II of a murine formalin model. These preliminary data confirm that properly optimized CK2 inhibitors may be used for anti-viral and pain therapy. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.091

文献信息

• PROTEIN KINASE MODULATORS
  申请人：CHUA Peter C.

  公开号：US20090239859A1

  公开（公告）日：2009-09-24

  The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate Pim kinase activity and/or FMS-like tyrosine kinase (Flt) activity. The invention also relates in part to methods for using such molecules.

  该发明部分涉及具有特定生物活性的分子，包括但不限于抑制细胞增殖、调节蛋白激酶活性和调节聚合酶活性。该发明的分子可以调节Pim激酶活性和/或FMS样酪氨酸激酶（Flt）活性。该发明还涉及使用这些分子的方法。
• SERINE-THREONINE PROTEIN KINASE AND PARP MODULATORS
  申请人：CHUA Peter

  公开号：US20090264423A2

  公开（公告）日：2009-10-22

  The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate casein kinase (CK) activity and/or poly(ADP-ribose)polymerase (PARP) activity. The invention also relates in part to methods for using such molecules.

  本发明涉及具有某些生物活性的分子，包括但不限于抑制细胞增殖、调节蛋白激酶活性和调节聚合酶活性。本发明的分子可以调节酪蛋白激酶（CK）活性和/或聚(ADP-核糖)聚合酶（PARP）活性。本发明还涉及使用这些分子的方法。
• METHODS OF TREATING DISORDERS ASSOCIATED WITH PROTEIN KINASE CK2 ACTIVITY
  申请人：HADDACH Mustapha

  公开号：US20100267753A1

  公开（公告）日：2010-10-21

  The invention provides methods for the treatment or amelioration of disorders associated with undesired activity of protein kinase CK2, using compounds of Formula (I) that are potent, selective inhibitors of CK2, and pharmaceutical compositions of such compounds, wherein Z 5 , R 6B , R 6D , R 8 , n, R 9 and p are defined as further described herein,

  本发明提供了使用式(I)化合物的方法，该化合物是CK2的有效、选择性抑制剂，用于治疗或改善与蛋白激酶CK2的不良活性相关的疾病，并提供了这些化合物的制药组合物。其中，Z5、R6B、R6D、R8、n、R9和p的定义如下所述。
• FUSED TRICYCLIC COMPOUNDS AS SERINE-THREONINE PROTEIN KINASE AND PARP MODULATORS
  申请人：CHUA Peter C.

  公开号：US20110263581A1

  公开（公告）日：2011-10-27

  The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate casein kinase (CK) activity and/or poly(ADP-ribose)polymerase (PARP) activity. The invention also relates in part to methods for using such molecules.

  本发明部分涉及具有某些生物活性的分子，包括但不限于抑制细胞增殖、调节蛋白激酶活性和调节聚合酶活性。本发明的分子可以调节酪氨酸激酶（CK）活性和/或聚(ADP核糖)聚合酶（PARP）活性。本发明部分还涉及使用这些分子的方法。
• 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。