3,5-dihydro-2-phenyl-3-methyl-1H-pyrazolo<3,4-c>quinoline-1,4(2H)-dione | 164364-85-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3,5-dihydro-2-phenyl-3-methyl-1H-pyrazolo<3,4-c>quinoline-1,4(2H)-dione
• 英文别名: 3-methyl-2-phenyl-3,5-dihydro-2H-pyrazolo[3,4-c]quinoline-1,4-dione；3-Methyl-2-phenyl-3,5-dihydro-2H-pyrazolo[3,4-c]chinolin-1,4-dion；3-Methyl-2-phenyl-3,5-dihydro-2H-pyrazolo[3,4-c]quinoline-1,4-dione；3-methyl-2-phenyl-5H-pyrazolo[3,4-c]quinoline-1,4-dione
• CAS: 164364-85-6
• 化学式: C₁₇H₁₃N₃O₂
• 分子量: 291.309
• InChiKey: AWRVFIQCDYWDKA-UHFFFAOYSA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  羟吲哚-3-乙醛酸乙酯 在 sodium hydride 、 溶剂黄146 作用下， 反应 2.17h， 生成 3,5-dihydro-2-phenyl-3-methyl-1H-pyrazolo<3,4-c>quinoline-1,4(2H)-dione
  参考文献：
  名称：

  Identification of 3,5-Dihydro-2-aryl-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-diones as Novel High-Affinity Glycine Site N-Methyl-D-aspartate Antagonists

  摘要：

  Almost all of the exisiting known antagonists at the glycine site of the N-methyl-D-aspartate (NMDA) receptor have a low propensity for crossing the blood-brain barrier. It has been suggested that in many cases this may be due to the presence of a carboxylic acid which is a common feature of most of the potent full antagonists at this receptor. In this study, 2-aryl-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-diones were found to have high-affinity binding at the glycine receptor. In particular, structure-activity studies identified 7-chloro-3,5-dihydro-2(4-methoxyphenyl)-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-dione as the most potent of a series of analogues with an IC50 of 3.3 nM. The measured pK(a) values in this class of compounds (typically 4.0) indicate they are of equivalent acidity to carboxylic acids. Functional antagonism was demonstrated by inhibition of NMDA-evoked responses in rat cortical slices. Anticonvulsant activity in DBA/2 mice was achieved after dosing by direct injection into the cerebral ventricles, but no activity was seen after systemic administration, suggesting low brain penetration with this class of antagonists.

  DOI：

  10.1021/jm00012a024

文献信息

• Graenacher; Kouniniotis, Helvetica Chimica Acta, 1928, vol. 11, p. 1243
  作者：Graenacher、Kouniniotis

  DOI：——

  日期：——
• Identification of 3,5-Dihydro-2-aryl-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-diones as Novel High-Affinity Glycine Site N-Methyl-D-aspartate Antagonists
  作者：Angus M. MacLeod、Sarah Grimwood、Cheryl Barton、Linda Bristow、Kay L. Saywell、George R. Marshall、Richard G. Ball

  DOI：10.1021/jm00012a024

  日期：1995.6

  Almost all of the exisiting known antagonists at the glycine site of the N-methyl-D-aspartate (NMDA) receptor have a low propensity for crossing the blood-brain barrier. It has been suggested that in many cases this may be due to the presence of a carboxylic acid which is a common feature of most of the potent full antagonists at this receptor. In this study, 2-aryl-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-diones were found to have high-affinity binding at the glycine receptor. In particular, structure-activity studies identified 7-chloro-3,5-dihydro-2(4-methoxyphenyl)-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-dione as the most potent of a series of analogues with an IC50 of 3.3 nM. The measured pK(a) values in this class of compounds (typically 4.0) indicate they are of equivalent acidity to carboxylic acids. Functional antagonism was demonstrated by inhibition of NMDA-evoked responses in rat cortical slices. Anticonvulsant activity in DBA/2 mice was achieved after dosing by direct injection into the cerebral ventricles, but no activity was seen after systemic administration, suggesting low brain penetration with this class of antagonists.