8-氯-5-甲氧基-4-氧代-1H-喹啉-3-羧酸乙酯 | 1226760-34-4

• 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: 8-氯-5-甲氧基-4-氧代-1H-喹啉-3-羧酸乙酯
• 中文别名: 8-氯-5-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酸乙酯；8-氯-4-羟基-5-甲氧基喹啉-3-羧酸乙酯
• 英文名称: ethyl 8-chloro-5-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 8-chloro-5-methoxy-4-oxo-1H-quinoline-3-carboxylate
• CAS: 1226760-34-4；63010-41-3
• 化学式: C₁₃H₁₂ClNO₄
• mdl: MFCD26150356
• 分子量: 281.696
• InChiKey: WRFBSLBCCKYENH-UHFFFAOYSA-N

物化性质

• 熔点：
  142 °C(Solv: methanol (67-56-1))
• 沸点：
  403.2±40.0 °C(Predicted)
• 密度：
  1.370±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-氯-5-甲氧基-4-氧代-1H-喹啉-3-羧酸乙酯 以89%的产率得到
  参考文献：
  名称：

  RENAULT S.; RENAULT J.; CAVIER R., EUR. J. MED. CHEM., 1976, 11, NO 6, 561-565

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氯-5-甲氧基苯胺盐酸盐 在 Eaton's reagent 、 三乙胺 作用下， 反应 1.0h， 生成 8-氯-5-甲氧基-4-氧代-1H-喹啉-3-羧酸乙酯
  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

• Synthesis and structure–activity relationships of antimalarial 4-oxo-3-carboxyl quinolones
  作者：Yiqun Zhang、W. Armand Guiguemde、Martina Sigal、Fangyi Zhu、Michele C. Connelly、Solomon Nwaka、R. Kiplin Guy

  DOI：10.1016/j.bmc.2010.02.013

  日期：2010.4

  while carrying out rationally directed low-throughput screening of potential antimalarial agents as part of an effort directed by the World Health Organization. Here we report the design, synthesis, and preliminary pharmacologic characterization of a series of analogues of 4-oxo-3-carboxyl quinolones. These studies indicate that the series has good potential for preclinical development.

  疟疾是非洲，亚洲和美洲的热带和亚热带地区的地方病。耐多药性恶性疟原虫的流行日益增加，因此不断需要开发新的抗疟药。鉴于此，特别感兴趣的是未暴露寄生虫的新型支架。最近，瑞士热带研究所的工作人员发现了两种新型的对恶性疟原虫的红细胞内阶段有活性的4-氧代-3-羧基喹诺酮类药物。同时根据世界卫生组织的指导，对潜在的抗疟药进行合理的定向低通量筛选。在这里，我们报告一系列4-氧代-3-羧基喹诺酮类似物的设计，合成和初步药理学表征。这些研究表明该系列药物在临床前开发方面具有良好的潜力。
• 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.
• RENAULT S.; RENAULT J.; CAVIER R., EUR. J. MED. CHEM., 1976, 11, NO 6, 561-565
  作者：RENAULT S.、 RENAULT J.、 CAVIER R.

  DOI：——

  日期：——