methyl 4-[3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-5-yl]benzoate | 1449374-45-1

• 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: methyl 4-[3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-5-yl]benzoate
• CAS: 1449374-45-1
• 化学式: C₂₆H₂₀ClN₃O₃
• 分子量: 457.916
• InChiKey: MGBVCWSHGILUQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.07
• 重原子数：
  33.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  83.55
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  丁二酸酐 、 methyl 4-[3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-5-yl]benzoate 以 四氢呋喃 为溶剂， 反应 0.33h， 以13.1%的产率得到4-(3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-5-(4-(methoxycarbonyl)phenyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid
  参考文献：
  名称：

  Structure–Activity Relationships and Pharmacophore Model of a Noncompetitive Pyrazoline Containing Class of GluN2C/GluN2D Selective Antagonists

  摘要：

  Here we describe the synthesis and structure-activity relationship for a class of pyrazoline-containing dihydroquinolone negative allosteric modulators of the NMDA receptor that show strong subunit selectivity for GluN2C- and GluN2D-containing receptors over GluN2A- and GluN2B-containing receptors. Several members of this class inhibit NMDA receptor responses in the nanomolar range and are more than 50-fold selective over GluN1/GluN2A and GluN1/GluN2B NMDA receptors, as well as AMPA, kainate, GABA, glycine, nicotinic, serotonin, and purinergic receptors. Analysis of the purified enantiomers of one of the more potent and selective compounds shows that the S-enantiomer is both more potent and more selective than the R-enantiomer. The S-enantiomer had an IC50 of 0.17-0.22 mu M at GluN2D- and GluN2C-containing receptors, respectively, and showed over 70-fold selectivity over other NMDA receptor subunits. The subunit selectivity of this class of compounds should be useful in defining the role of GluN2C- and GluN2D-containing receptors in specific brain circuits in both physiological and pathophysiological conditions.

  DOI：

  10.1021/jm400652r
• 作为产物：
  描述：

  (E)-4-[3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-3-oxoprop-1-enyl]benzoic acid 在 氯化亚砜 、 肼 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 methyl 4-[3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-5-yl]benzoate
  参考文献：
  名称：

  Structure–Activity Relationships and Pharmacophore Model of a Noncompetitive Pyrazoline Containing Class of GluN2C/GluN2D Selective Antagonists

  摘要：

  Here we describe the synthesis and structure-activity relationship for a class of pyrazoline-containing dihydroquinolone negative allosteric modulators of the NMDA receptor that show strong subunit selectivity for GluN2C- and GluN2D-containing receptors over GluN2A- and GluN2B-containing receptors. Several members of this class inhibit NMDA receptor responses in the nanomolar range and are more than 50-fold selective over GluN1/GluN2A and GluN1/GluN2B NMDA receptors, as well as AMPA, kainate, GABA, glycine, nicotinic, serotonin, and purinergic receptors. Analysis of the purified enantiomers of one of the more potent and selective compounds shows that the S-enantiomer is both more potent and more selective than the R-enantiomer. The S-enantiomer had an IC50 of 0.17-0.22 mu M at GluN2D- and GluN2C-containing receptors, respectively, and showed over 70-fold selectivity over other NMDA receptor subunits. The subunit selectivity of this class of compounds should be useful in defining the role of GluN2C- and GluN2D-containing receptors in specific brain circuits in both physiological and pathophysiological conditions.

  DOI：

  10.1021/jm400652r