1-(4-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 1443362-34-2

• 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: 1-(4-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 1-(4-Methoxyphenyl)-4-oxoquinoline-3-carboxylic acid；1-(4-methoxyphenyl)-4-oxoquinoline-3-carboxylic acid
• CAS: 1443362-34-2
• 化学式: C₁₇H₁₃NO₄
• 分子量: 295.295
• InChiKey: PRNRJTMPDQNRPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 在 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-(4-((1H)-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-methoxyphenyl)-4-oxo-1,4-dihydroquinolin-3-carboxamide
  参考文献：
  名称：

  发现带有4-氧代喹啉部分作为潜在抗肿瘤抑制剂的新型吡咯并[2,3-b]吡啶衍生物。

  摘要：

  设计，合成了一系列带有4-氧代喹啉部分的吡咯并[2,3-b]吡啶衍生物，并评估了它们在三种癌细胞系（A549，HepG2和MCF-7）上的抗增殖作用。大多数化合物显示出中等至高的效力。测试了一些优秀的化合物对c-Met激酶的抑制活性。研究了化合物34（c-Met IC50 = 17 nM）对Flt-3，c-Kit，VEGFR-2，ALK，PDGFR-β和RON的选择性。结构-活性关系研究表明，R，R1和R2上的氢，氟原子和单电子吸取基团（单EWG，例如R2 = F）有利于靶标的抗增殖活性化合物。此外，我们还通过分子对接进一步研究了化合物34与c-Met激酶之间的结合方式。

  DOI：

  10.1016/j.bmcl.2019.126848
• 作为产物：
  描述：

  (2-氟苯甲酰)乙酸乙酯 在 lithium hydroxide monohydrate 、 二甲氧基乙烷 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 1-(4-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Pharmacological Profiling of Analogues of Benzyl Quinolone Carboxylic Acid (BQCA) as Allosteric Modulators of the M₁ Muscarinic Receptor

  摘要：

  Established therapy in Alzheimer's disease involves potentiation of the endogenous orthosteric ligand, acetylcholine, at the M, muscarinic receptors found in higher concentrations in the cortex and hippocampus. Adverse effects, due to indiscriminate activation of other muscarinic receptor subtypes, are common. M, muscarinic positive allosteric modulators/allosteric agonists such as BQCA offer an attractive solution, being exquisitely M-1-selective over other muscarinic subtypes. A common difficulty with allosteric ligands is interpreting SAR, based on composite potency values derived in the presence of fixed concentration of agonist. In reality these values encompass multiple pharmacological parameters, each potentially and differentially sensitive to structural modification of the ligand. We report novel BQCA analogues which appear to augment ligand affinity for the receptor (pK(B)), intrinsic efficacy (tau(B)), and both binding (alpha) and functional (beta) cooperativity with acetylcholine. Ultimately, development of such enriched SAR surrounding allosteric modulators will provide insight into their mode of action.

  DOI：

  10.1021/jm400540b

文献信息

• 一种多取代含氮杂环衍生物及其制备方法与应用
  申请人：湖北省生物农药工程研究中心

  公开号：CN115784988A

  公开（公告）日：2023-03-14

  本发明提供了一种多取代含氮杂环衍生物及其制备方法与应用。本发明以天然含氮杂环分子为导向开展新颖结构的设计得到多取代含氮杂环衍生物，多取代含氮杂环衍生物具备明显的杀菌活性，部分化合物对软腐菌、大肠杆菌、青枯菌等病害的杀菌活性显著，能广泛应用于农林细菌性病害的综合防控。采用本发明的多取代含氮杂环衍生物与不同助剂混合得到的杀菌剂对大肠杆菌、软腐菌、青枯菌等也具有良好的杀菌作用。
• Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety as potential antitumor inhibitor
  作者：Huimin Liu、Yongli Duan、Hehua Xiong、Jianqing Zhang、Shunmin Huang、Ting Chen、Pengwu Zheng、Qidong Tang

  DOI：10.1016/j.bmcl.2019.126848

  日期：2020.1

  A series of pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety were designed, synthesized and evaluated for the anti-proliferative on three cancer cell lines (A549, HepG2 and MCF-7) in vitro. Most of the compounds showed moderate to high potency. Some excellent compounds were tested for the inhibitory activity of c-Met kinase. Compound 34 (c-Met IC50 = 17 nM) was investigated the selectivity

  设计，合成了一系列带有4-氧代喹啉部分的吡咯并[2,3-b]吡啶衍生物，并评估了它们在三种癌细胞系（A549，HepG2和MCF-7）上的抗增殖作用。大多数化合物显示出中等至高的效力。测试了一些优秀的化合物对c-Met激酶的抑制活性。研究了化合物34（c-Met IC50 = 17 nM）对Flt-3，c-Kit，VEGFR-2，ALK，PDGFR-β和RON的选择性。结构-活性关系研究表明，R，R1和R2上的氢，氟原子和单电子吸取基团（单EWG，例如R2 = F）有利于靶标的抗增殖活性化合物。此外，我们还通过分子对接进一步研究了化合物34与c-Met激酶之间的结合方式。
• Synthesis and Pharmacological Profiling of Analogues of Benzyl Quinolone Carboxylic Acid (BQCA) as Allosteric Modulators of the M₁ Muscarinic Receptor
  作者：Shailesh N. Mistry、Celine Valant、Patrick M. Sexton、Ben Capuano、Arthur Christopoulos、Peter J. Scammells

  DOI：10.1021/jm400540b

  日期：2013.6.27

  Established therapy in Alzheimer's disease involves potentiation of the endogenous orthosteric ligand, acetylcholine, at the M, muscarinic receptors found in higher concentrations in the cortex and hippocampus. Adverse effects, due to indiscriminate activation of other muscarinic receptor subtypes, are common. M, muscarinic positive allosteric modulators/allosteric agonists such as BQCA offer an attractive solution, being exquisitely M-1-selective over other muscarinic subtypes. A common difficulty with allosteric ligands is interpreting SAR, based on composite potency values derived in the presence of fixed concentration of agonist. In reality these values encompass multiple pharmacological parameters, each potentially and differentially sensitive to structural modification of the ligand. We report novel BQCA analogues which appear to augment ligand affinity for the receptor (pK(B)), intrinsic efficacy (tau(B)), and both binding (alpha) and functional (beta) cooperativity with acetylcholine. Ultimately, development of such enriched SAR surrounding allosteric modulators will provide insight into their mode of action.