2-phenyl-3,5-dihydro-2H-pyrazolo[3,4-c]quinoline-1,4-dione | 142598-51-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-phenyl-3,5-dihydro-2H-pyrazolo[3,4-c]quinoline-1,4-dione
• 英文别名: 2-Phenyl-3,5-dihydro-2H-pyrazolo[3,4-c]chinolin-1,4-dion；3,5-dihydro-2-phenyl-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-dione；2-Phenyl-3,5-dihydro-2H-pyrazolo[3,4-c]quinoline-1,4-dione；2-phenyl-3,5-dihydropyrazolo[3,4-c]quinoline-1,4-dione
• CAS: 142598-51-4
• 化学式: C₁₆H₁₁N₃O₂
• 分子量: 277.282
• InChiKey: PAHZJYVAKCMOHL-UHFFFAOYSA-N

物化性质

• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-phenyl-3,5-dihydro-2H-pyrazolo[3,4-c]quinoline-1,4-dione 、 碘甲烷 在 sodium hydride 作用下， 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
• 作为产物：
  描述：

  羟吲哚-3-乙醛酸乙酯 在 苯肼 作用下， 以 溶剂黄146 为溶剂， 生成 2-phenyl-3,5-dihydro-2H-pyrazolo[3,4-c]quinoline-1,4-dione
  参考文献：
  名称：

  Pyrazolo-quinoline derivatives for treating cerebral ischemia

  摘要：

  一类3,5-二氢-1H-吡唑并[3,4-c]喹啉-1,4(2H)-二酮衍生物，其2-位取代为可选取代的苯基基团，是选择性非竞争性NMDA受体拮抗剂和/或AMPA受体拮抗剂，因此在治疗和/或预防需要使用NMDA和/或AMPA拮抗剂的情况下，如神经退行性疾病、惊厥或精神分裂症等方面具有实用价值。

  公开号：

  US05580877A1

文献信息

• Tricyclic Heteroaromatic Systems. Pyrazolo[3,4-c]quinolin-4-ones and Pyrazolo[3,4-c]quinoline-1,4-diones: Synthesis and Benzodiazepine Receptor Activity
  作者：Daniela Catarzi、Vittoria Colotta、Flavia Varano、Lucia Cecchi、Guido Filacchioni、Alessandro Galli、Chiara Costagli

  DOI：10.1002/ardp.19973301205

  日期：——

  and pyrazolo[3,4‐c]‐quinoline‐1,4‐diones 15–17 were prepared and biologically evaluated for their binding at the benzodiazepine receptor (BZR) in rat cortical membranes. The moderate binding activity of 1–5,7,9–10, 13 is attributable to the lack of the optional proton acceptor at position‐1, while the inactivity of the 1,4‐dione derivatives 15–17 is due to the lack of the essential proton acceptor at

  制备了一些吡唑并 [3,4 - c] 喹啉 - 4 - 1-14 和吡唑并 [3,4 - c] - 喹啉 - 1,4 - 二酮 15-17，并对其与苯二氮卓受体的结合进行了生物学评估。 BZR) 在大鼠皮层膜中。1-5,7,9-10,13 的中等结合活性归因于在 1 位缺乏可选的质子受体，而 1,4-二酮衍生物 15-17 的无活性是由于缺乏3 位必需的质子受体。这些结论证实了我们提出的药效模型的有效性。
• Graenacher; Kouniniotis, Helvetica Chimica Acta, 1928, vol. 11, p. 1243
  作者：Graenacher、Kouniniotis

  DOI：——

  日期：——
• Nagarajan, Kuppuswamy; Shah, Rashmi K., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1992, vol. 31, # 6, p. 316 - 321
  作者：Nagarajan, Kuppuswamy、Shah, Rashmi K.

  DOI：——

  日期：——
• US5580877A
  申请人：——

  公开号：US5580877A

  公开（公告）日：1996-12-03
• 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.