3-(2-溴苯基)-4-氧代-2-硫代-1,2,3,4-四氢喹唑啉 | 23921-67-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 3-(2-溴苯基)-4-氧代-2-硫代-1,2,3,4-四氢喹唑啉
• 英文名称: 3-(2-bromophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazoline
• 英文别名: 3-(o-Bromphenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydrochinazolin；3-(2-bromophenyl)-2-thio-2,4-(1H,3H)quinazolinedione；2-thioxo-3-(o-bromophenyl)quinazolin-4-one；3-(2-bromo-phenyl)-2-thioxo-2,3-dihydro-1H-quinazolin-4-one；3-(2-Brom-phenyl)-4-oxo-2-thioxo-1.2.3.4-tetrahydro-chinazolin；3-(2-bromophenyl)-2-sulfanylidene-1H-quinazolin-4-one
• CAS: 23921-67-7
• 化学式: C₁₄H₉BrN₂OS
• 分子量: 333.208
• InChiKey: FHKTYFZUNGXFGS-UHFFFAOYSA-N

物化性质

• 熔点：
  252-254 °C
• 沸点：
  456.8±47.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 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：
  2

反应信息

• 作为反应物：
  描述：

  3-(2-溴苯基)-4-氧代-2-硫代-1,2,3,4-四氢喹唑啉 在 copper(l) iodide 、 sodium hydride 作用下， 以 二乙二醇二甲醚 为溶剂， 反应 12.5h， 以75%的产率得到12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-one
  参考文献：
  名称：

  通过 Aza-Wittig 方法和 CuI 催化的杂芳基化过程的组合制备稠合四环喹唑啉酮

  摘要：

  许多与五元环稠合的线性喹唑啉酮 - 苯并咪唑 [2,1-b] 喹唑啉酮 8 和苯并噻唑并 [2,3-b] 喹唑啉酮 10 - 已从亚氨基膦 4 制备，该亚氨基正膦衍生自 N-取代的邻叠氮苯甲酰胺aza-Wittig 方法和 Cu I 催化的杂芳基化的组合。在氮杂-维蒂希反应/还原过程后，4 的 N-芳基取代基中氮官能团的存在促进了杂环化，或者穿过 2-位，得到喹唑啉[2,1-b]喹唑啉酮 11-14，或穿过4 位，以提供

  DOI：

  10.1002/ejoc.200900082
• 作为产物：
  描述：

  1-bromo-2-isothiocyanatobenzene 、 邻氨基苯甲酸甲酯 以 甲苯 为溶剂， 反应 36.0h， 以52%的产率得到3-(2-溴苯基)-4-氧代-2-硫代-1,2,3,4-四氢喹唑啉
  参考文献：
  名称：

  CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application example

  摘要：

  Phosphodiesterase (PDE) 7 is a high affinity cAMP-specific PDE whose functional role in T-cells has been the subject of some controversy. Recent findings on tissue distribution, however, support the hypothesis that PDE7 could be a good target for the treatment of airway diseases, T-cell related diseases or central nervous system (CNS) disorders. Therefore, the identification of selective inhibitors targeted against PDE7 enzyme has become an attractive area of research. We report here the first use of the descriptors generated by the CODES program for ligand-based virtual screening. This program codifies molecules from a topological point of view and the generated descriptors are related to the chemical nature of the atoms, the atomic bonds and the connectivity with the rest of the molecule. They are also able to distinguish among stereoisomers. By using this approach, 173 compounds were codified, and their similarity with the reference compound was analysed. Based on the analysis, new potential PDE7 inhibitors have been identified, synthesized and biologically evaluated confirming that CODES descriptors are valid for ligand-based virtual screening and provided new lead compounds for further optimization as potent and selective PDE7 inhibitors. (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.10.027

文献信息

• S-SUBSTITUTED QUINAZOLINES AND THEIR THERAPEUTIC APPLICATIONS FOR THE TREATMENT OF DISEASES MEDIATED BY PDE7
  申请人：Consejo Superior De lnvestigaciones Cientificas (CSIC)

  公开号：US20160340320A1

  公开（公告）日：2016-11-24

  The present invention relates to a family of S-substituted quinazoline derivatives that inhibitors of the enzyme phosphodiesterase 7 (PDE7), useful for the treatment or prevention of diseases mediated by said enzyme, especially inflammatory, neurodegenerative, neurological, psychiatric and/or autoimmune diseases.

  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。
• Energy barriers to rotation in axially chiral quinazoline-4-ones
  作者：Ari Hakgor、Sule Erol Gunal

  DOI：10.1016/j.tet.2021.132506

  日期：2021.11

  Axially chiral 2-thioxo-3-(o-aryl)-quinazolin-4-ones and 2-(benzylthio)-3-(o-aryl)-quinazolin-4-ones were synthesized and their energy barriers to rotation about the N3-Caryl bond were determined by thermal racemization of the separated enantiomers. The rotational barriers were found to range from 112.7 to 140.8 kJ/mol, depending on size of the ortho substituent and to increase linearly with the size

  合成了轴向手性 2-thioxo-3-( o - aryl)-quinazolin-4-ones 和 2-(benzylthio)-3-( o -aryl)-quinazolin-4-ones 及其绕 N 旋转的能垒3- C芳基键通过分离的对映异构体的热外消旋化确定。发现旋转势垒范围从 112.7 到 140.8 kJ/mol，这取决于邻位取代基的大小，并且随着邻位卤素取代基的范德华半径的大小线性增加。尽管具有邻位邻位的 N-C 轴向手性化合物的对映体的分离由于氟原子尺寸小，-氟取代基很少见，我们发现带有邻氟基团的喹唑啉-4-酮的旋转势垒足够高，可以分离对映体。
• A Facile Photochemical Synthesis of 12H-Benzothiazolo [2,3-b]Quinazolin-12-Ones
  作者：S. Muthusamy、V. T Ramakrishnan

  DOI：10.1080/00397919208019251

  日期：1992.2

  Abstract The photochemical synthesis of 12H-benzothiazolo [2,3-b]quinazolin-12-ones (4) by the irradiation of 2-thioquinazolinediones 1 and disulphide 5 are described.

  摘要 描述了通过 2-硫代喹唑啉二酮 1 和二硫化物 5 照射光化学合成 12H-苯并噻唑并 [2,3-b] 喹唑啉-12-酮 (4)。
• 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.
• Jira; Junghanel; Theiss, Pharmazie, 1996, vol. 51, # 5, p. 273 - 279
  作者：Jira、Junghanel、Theiss、Kottke、Besch、Schopplich、Bunke、Leuthold、Beyrich

  DOI：——

  日期：——