ethyl 5-fluoro-8-methoxy-1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate | 1443361-16-7

• 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: ethyl 5-fluoro-8-methoxy-1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: Ethyl 5-fluoro-8-methoxy-1-[(4-methoxyphenyl)methyl]-4-oxoquinoline-3-carboxylate；ethyl 5-fluoro-8-methoxy-1-[(4-methoxyphenyl)methyl]-4-oxoquinoline-3-carboxylate
• CAS: 1443361-16-7
• 化学式: C₂₁H₂₀FNO₅
• 分子量: 385.392
• InChiKey: VCDCCFVUFYWOOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 5-fluoro-8-methoxy-1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 以59%的产率得到5-fluoro-8-methoxy-1-(4-methoxybenzyl)-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
• 作为产物：
  描述：

  5-氟-2-甲氧基苯胺 在 Eaton's reagent 、 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 5-fluoro-8-methoxy-1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate
  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 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.