4-oxo-3-(pyridin-3-yl)-2-thioxo-1,2,3,4-tetrahydroquinazoline | 119426-82-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-oxo-3-(pyridin-3-yl)-2-thioxo-1,2,3,4-tetrahydroquinazoline
• 英文别名: 3-pyridin-3-yl-2-thioxo-2,3-dihydro-1H-quinazolin-4-one；2-mercapto-3-pyridin-3-ylquinazolin-4(3H)-one；3-pyridin-3-yl-2-sulfanylidene-1H-quinazolin-4-one
• CAS: 119426-82-3
• 化学式: C₁₃H₉N₃OS
• mdl: MFCD00113288
• 分子量: 255.3
• InChiKey: RVKDBLWQYGIZDA-UHFFFAOYSA-N

物化性质

• 沸点：
  440.9±37.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)
• 溶解度：
  7.6 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-oxo-3-(pyridin-3-yl)-2-thioxo-1,2,3,4-tetrahydroquinazoline 在 sodium hydroxide 、 双氧水 作用下， 以80%的产率得到3-(pyridin-3-yl)quinazoline-2,4(1H,3H)-dione
  参考文献：
  名称：

  Graefe, I.; Kottke, K.; Kuehmstedt, H., Pharmazie, 1990, vol. 45, # 7, p. 530 - 531

  摘要：

  DOI：
• 作为产物：
  描述：

  3-氨基吡啶 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 20.0h， 生成 4-oxo-3-(pyridin-3-yl)-2-thioxo-1,2,3,4-tetrahydroquinazoline
  参考文献：
  名称：

  新型喹唑啉酮-2-硫代甲硝唑衍生物的设计、合成、体外和计算机生物学分析

  摘要：

  设计、合成了一系列新的喹唑啉酮-2-硫代甲硝唑衍生物9a-o，并测定了它们对代谢酶人类碳酸酐酶 I 和 II（hCAs I 和 II）、乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BChE）、和α-葡萄糖苷酶。结果表明，与标准抑制剂相比，所有合成的化合物对上述酶均表现出优异的抑制活性。具有代表性的是，对 CA 酶最有效的化合物 4-氟苯基衍生物9i 分别是标准抑制剂乙酰唑胺对 hCA I 和 II 的 4 倍和 7 倍；4-氟苄基衍生物9m作为对抗胆碱酯酶的最有效化合物，其对抗 AChE 和 BChE 的效力分别是标准抑制剂他克林的 11 倍和 21 倍；具有 4-甲氧基苯基部分的最活跃的 α-葡萄糖苷酶抑制剂9h 的活性是作为标准抑制剂的阿卡波糖的 5 倍。此外，为了研究相关酶活性位点中最有效化合物的相互作用模式，进行了分子建模。还预测了化合物9i、9m和9h 的药物相似性、ADME 和毒性特征。

  DOI：

  10.1016/j.molstruc.2021.130889

文献信息

• Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model
  作者：Miriam Redondo、Juan G. Zarruk、Placido Ceballos、Daniel I. Pérez、Concepción Pérez、Ana Perez-Castillo、María A. Moro、José Brea、Cristina Val、María I. Cadavid、María I. Loza、Nuria E. Campillo、Ana Martínez、Carmen Gil

  DOI：10.1016/j.ejmech.2011.10.040

  日期：2012.1

  A simple and efficient synthetic method for the preparation of quinazoline type phosphodiesterase 7 (PDE7) inhibitors, based on microwave irradiation, has been developed. The use of this methodology improved yields and reaction times, providing a scalable procedure. These compounds are pharmacologically interesting because of their in vivo efficacy both in spinal cord injury and Parkinson's disease models, as shown in previous studies from our group. Herein we describe for the first time that administration of one of the PDE7 inhibitors here optimized, 3-pheny1-2,4-dithioxo-1,2,3,4-tetrahydroquinazoline (compound 5), ameliorated brain damage and improved behavioral outcome in a permanent middle cerebral artery occlusion (pMCAO) stroke model. Furthermore, we demonstrate that these PDE7 inhibitors are potent anti-inflammatory as well as neuroprotective agents in primary cultures of neural cells. These results led us to propose PDE7 inhibitors as a new class of therapeutic agents for neuroprotection. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Development of thioquinazolinones, allosteric Chk1 kinase inhibitors
  作者：Antonella Converso、Timothy Hartingh、Robert M. Garbaccio、Edward Tasber、Keith Rickert、Mark E. Fraley、Youwei Yan、Constantine Kreatsoulas、Steve Stirdivant、Bob Drakas、Eileen S. Walsh、Kelly Hamilton、Carolyn A. Buser、Xianzhi Mao、Marc T. Abrams、Stephen C. Beck、Weikang Tao、Rob Lobell、Laura Sepp-Lorenzino、Joan Zugay-Murphy、Vinod Sardana、Sanjeev K. Munshi、Sylvie Marie Jezequel-Sur、Paul D. Zuck、George D. Hartman

  DOI：10.1016/j.bmcl.2008.12.076

  日期：2009.2

  A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at K(m) for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site approximately 13A from the ATP binding site. Preliminary data is presented for several of these compounds.
• El-Hiti, Gamal A.; Abdel-Megeed, Mohamed F.; Zied, Tarek M. M., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2002, vol. 41, # 7, p. 1519 - 1522
  作者：El-Hiti, Gamal A.、Abdel-Megeed, Mohamed F.、Zied, Tarek M. M.

  DOI：——

  日期：——
• KOTTKE, KARL;KUHMSTEDT, HANS;GRAFE, INGOLF;WEHLAN, HELMUT;KNOKE, DAGMAR
  作者：KOTTKE, KARL、KUHMSTEDT, HANS、GRAFE, INGOLF、WEHLAN, HELMUT、KNOKE, DAGMAR

  DOI：——

  日期：——
• Small Molecules for Inhibition of Protein Kinases
  申请人：Desai Renee

  公开号：US20110275645A1

  公开（公告）日：2011-11-10

  The invention provides compounds that inhibit protein kinases, prodrugs of the compounds, intermediates and methods of synthesizing the compounds and/or prodrugs, pharmaceutical compositions including the compounds and/or prodrugs and methods of using the compounds and/or prodrugs in a variety of contexts, including, for example, in the treatment and/or prevention of various diseases that are responsive to protein kinase inhibition and/or that are mediated, at least in part, by inappropriate kinase activity.