4-(3-(4-(4-bromophenyl)-2-oxo-1,2-dihydroquinolin-3-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid | 1449373-97-0

• 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: 4-(3-(4-(4-bromophenyl)-2-oxo-1,2-dihydroquinolin-3-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid
• 英文别名: 4-[5-[4-(4-bromophenyl)-2-oxo-1H-quinolin-3-yl]-3-phenyl-3,4-dihydropyrazol-2-yl]-4-oxobutanoic acid
• CAS: 1449373-97-0
• 化学式: C₂₈H₂₂BrN₃O₄
• 分子量: 544.404
• InChiKey: KCLGHAMKAKRLDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-acetyl-4-(4-bromophenyl)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-(4-(4-bromophenyl)-2-oxo-1,2-dihydroquinolin-3-yl)-5-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

文献信息

• Pyrazoline dihydroquinolones, pharmaceutical compositions, and uses
  申请人：Emory University

  公开号：US11117882B2

  公开（公告）日：2021-09-14

  This disclosure relates to pyrazoline dihydroquinolone derivatives, pharmaceutical compositions, and uses. In certain embodiments, the compounds are selective NMDA receptor inhibitors and are useful in therapeutic methods related thereto. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a compound of the following formula: or salts, esters, or prodrugs thereof, as provided herein.

  本公开涉及吡唑啉二氢喹啉酮衍生物、药物组合物和用途。在某些实施方案中，这些化合物是选择性 NMDA 受体抑制剂，并可用于与之相关的治疗方法。在某些实施方案中，本公开涉及包含下式化合物的药物组合物： 或其盐类、酯类或原药。
• Pyrazoline Dihydroquinolones, Pharmaceutical Compositions, and Uses
  申请人：EMORY UNIVERSITY

  公开号：US20160368897A1

  公开（公告）日：2016-12-22

  This disclosure relates to pyrazoline dihydroquinolone derivates, pharmaceutical compositions, and uses. In certain embodiments, the compounds are selective NMDA receptor inhibitors and are useful in therapeutic methods related thereto. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a compound of the following formula: Formula (I) or salts, esters, or prodrugs thereof, as provided herein.