| 1443362-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• CAS: 1443362-46-6
• 化学式: C₂₅H₂₈N₂O₃
• 分子量: 404.509
• InChiKey: ZROKQKYWGTYOSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  51.54
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 以22%的产率得到4-oxo-1-((1-(phenylcarbamoyl)piperidin-4-yl)methyl)-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：

  ethyl 4-oxo-1-(piperidin-4-ylmethyl)-1,4-dihydroquinoline-3-carboxylate hydrochloride 、 溴甲苯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以48 mg的产率得到
  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