8-chloro-3-(2,6-difluorophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazoline | 1357082-28-0

• 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: 8-chloro-3-(2,6-difluorophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazoline
• 英文别名: 8-chloro-3-(2,6-difluorophenyl)-2-sulfanylidene-1H-quinazolin-4-one
• CAS: 1357082-28-0
• 化学式: C₁₄H₇ClF₂N₂OS
• 分子量: 324.738
• InChiKey: WXCWPGAPWZSWMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 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：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  硫酸二乙酯 、 8-chloro-3-(2,6-difluorophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazoline 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以33%的产率得到8-chloro-2-ethylthio-3-(2,6-difluorophenyl)-4-oxo-3,4-dihydroquinazoline
  参考文献：
  名称：

  S-SUBSTITUTED QUINAZOLINES AND THEIR THERAPEUTIC APPLICATIONS FOR THE TREATMENT OF DISEASES MEDIATED BY PDE7

  摘要：

  本发明涉及一类S-取代喹唑啉衍生物家族，它们是磷酸二酯酶7（PDE7）的抑制剂，用于治疗或预防由该酶介导的疾病，特别是炎症性、神经退行性、神经系统、精神和/或自身免疫性疾病。

  公开号：

  US20160340320A1
• 作为产物：
  描述：

  2-氨基-3-氯苯甲酸 、 2,6-二氟异硫氰酸苯酯 以 水 、 二甲基亚砜 为溶剂， 反应 0.67h， 以63%的产率得到8-chloro-3-(2,6-difluorophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazoline
  参考文献：
  名称：

  Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2011.10.040

文献信息

• Unraveling phosphodiesterase surfaces. Identification of phosphodiesterase 7 allosteric modulation cavities
  作者：Miriam Redondo、Ignacio Soteras、José Brea、Alejandro González-García、María Isabel Cadavid、María Isabel Loza、Ana Martinez、Carmen Gil、Nuria E. Campillo

  DOI：10.1016/j.ejmech.2013.10.035

  日期：2013.12

  The last findings of our group by using chemical genetic approaches have shown that PDE7 is an interesting target in neurodegenerative diseases. The following step in this travel to unravel PDE7 is the design of more selective inhibitors. In this sense we have proposed to perform an analysis of PDE7 surface to identify possible allosteric sites following by a docking study of different PDE7 inhibitors synthesized by our group. Thanks to these studies we have proved the existence of allosteric sites in PDE7 and we have been able to explain the binding modes of the employed PDE7 inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.
• US9796687B2
  申请人：——

  公开号：US9796687B2

  公开（公告）日：2017-10-24