3-acetyl-6-chloro-4-(4-chlorophenyl)quinolin-2(1H)-one | 1283108-77-9

• 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: 3-acetyl-6-chloro-4-(4-chlorophenyl)quinolin-2(1H)-one
• 英文别名: 3-acetyl-6-chloro-4-(4-chlorophenyl)-1H-quinolin-2-one
• CAS: 1283108-77-9
• 化学式: C₁₇H₁₁Cl₂NO₂
• 分子量: 332.186
• InChiKey: KHOMBBJCLYEZQF-UHFFFAOYSA-N

物化性质

• 沸点：
  546.9±50.0 °C(Predicted)
• 密度：
  1.399±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-acetyl-6-chloro-4-(4-chlorophenyl)quinolin-2(1H)-one 在 potassium hydroxide 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 1.41h， 生成 4-(3-(6-chloro-4-(4-chlorophenyl)-2-oxo-1,2-dihydroquinolin-3-yl)-5-(4-chlorophenyl)-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：

  2-氨基-5-氯-N-甲氧基-N-甲基苯甲酰胺 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.13h， 生成 3-acetyl-6-chloro-4-(4-chlorophenyl)quinolin-2(1H)-one
  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

文献信息

• Synthesis and SAR Studies of Dual AKT/NF-κB Inhibitors Against Melanoma
  作者：Elisa Barile、Surya K. De、Yongmei Feng、Vida Chen、Li Yang、Ze'ev Ronai、Maurizio Pellecchia

  DOI：10.1111/cbdd.12177

  日期：2013.11

  The protein Kinase B alpha (AKT) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathways are central regulators of cellular signaling events at the basis of tumor development and progression. Both pathways are often up‐regulated in different tumor types including melanoma. We recently reported the identification of compound 1 (BI‐69A11) as inhibitor of the AKT and the NF‐κB pathways. Here, we describe SAR studies that led to novel fluorinated derivatives with increased cellular potency, reflected in efficient inhibition of AKT and IKKs. Selected compounds demonstrated effective toxicity on melanoma, breast, and prostate cell lines. Finally, a representative derivative showed promising efficacy in an in vivo melanoma xenograft model.
• Structure–Activity Relationships and Pharmacophore Model of a Noncompetitive Pyrazoline Containing Class of GluN2C/GluN2D Selective Antagonists
  作者：Timothy M. Acker、Alpa Khatri、Katie M. Vance、Cathryn Slabber、John Bacsa、James P. Snyder、Stephen F. Traynelis、Dennis C. Liotta

  DOI：10.1021/jm400652r

  日期：2013.8.22

  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.