2-chloromethyl-3-(2-chlorophenyl)-3H-quinazolin-4-one | 22312-83-0

• 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: 2-chloromethyl-3-(2-chlorophenyl)-3H-quinazolin-4-one
• 英文别名: 2-chloromethyl-3-(2-chloro-phenyl)-3H-quinazolin-4-one；2-chloromethyl-3-(2-chloro-phenyl)-3H-quinazolin-4-one；2-(Chloromethyl)-3-(2-chlorophenyl)quinazolin-4(3H)-one；2-(chloromethyl)-3-(2-chlorophenyl)quinazolin-4-one
• CAS: 22312-83-0
• 化学式: C₁₅H₁₀Cl₂N₂O
• 分子量: 305.163
• InChiKey: ZFWRTNVOAGHCOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氨基-4-(4-氯苯基)噻唑 、 2-chloromethyl-3-(2-chlorophenyl)-3H-quinazolin-4-one 以 吡啶 为溶剂， 反应 4.0h， 以57.1%的产率得到3-(2-Chlorophenyl)-2-[[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]methyl]quinazolin-4-one
  参考文献：
  名称：

  Pattanaik, J. M.; Pattanaik, M.; Bhatta, D., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1998, vol. 37, # 12, p. 1304 - 1306

  摘要：

  DOI：
• 作为产物：
  描述：

  邻氯苯胺 、 2-chloroacetamidobenzoic acid 在 三氯化磷 作用下， 以 甲苯 为溶剂， 以26.4%的产率得到2-chloromethyl-3-(2-chlorophenyl)-3H-quinazolin-4-one
  参考文献：
  名称：

  设计，合成和评估新型2-噻吩-5-基-3 H-喹唑啉-4-酮类似物作为转录因子NF-кB和AP-1介导的转录激活的抑制剂：它们可能用作抗炎药和抗炎药癌症药剂

  摘要：

  为了利用基于化学铅的药物化学和生物立体异构的概念来发现新的NF-κB和AP-1介导的转录激活抑制剂，一系列2-（2,3-二取代-噻吩-5-基）-3 H设计了喹喹啉-4-酮类似物。开发了一种简单易行的合成设计分子的途径。在基于细胞系报告的分析中评估了合成分子作为针对NF-кB和AP-1介导的转录激活的抑制剂的活性。该系列为我们提供了许多抑制NF-кB和/或AP-1介导的转录激活活性的化合物。这些化合物在炎症和癌症的体内模型中还显示出抗炎和抗癌活性。发现4-吡啶基是噻吩环第三位置上最重要的抑制NF- κ的药效基团B和AP-1介导的转录激活。这些化合物在体内和体外模型中显示的活性之间的关系已通过使用FVB转基因小鼠模型建立。这些结果表明，所设计的分子框架适合作为潜在支架，用于设计对NF-κB和AP-1介导的转录激活具有抑制活性的分子，该分子也可能表现出抗炎和抗癌活性。这一系列分子值得进一步研究，

  DOI：

  10.1016/j.bmc.2010.01.007

文献信息

• Synthesis and evaluation of quinazolin-4-ones as hypoxia-inducible factor-1α inhibitors
  作者：Wenwei Huang、Ruili Huang、Matias S. Attene-Ramos、Srilatha Sakamuru、Erika E. Englund、James Inglese、Christopher P. Austin、Menghang Xia

  DOI：10.1016/j.bmcl.2011.07.043

  日期：2011.9

  Quinazolin-4-one 1 was identified as an inhibitor of the HIF-1 alpha transcriptional factor from a high-throughput screen. HIF-1 alpha up-regulation is common in many cancer cells. In this Letter, we describe an efficient one-pot sequential reaction for the synthesis of quinazolin-4-one 1 analogues. The structure-activity relationship (SAR) study led to the 5-fold more potent analogue, 16. Published by Elsevier Ltd.
• Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-κB and AP-1 mediated transcription activation and as potential anti-inflammatory agents
  作者：Rajan S. Giri、Hardik M. Thaker、Tony Giordano、Jill Williams、Donna Rogers、Vasudevan Sudersanam、Kamala K. Vasu

  DOI：10.1016/j.ejmech.2008.10.031

  日期：2009.5

  A series of 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives were designed and synthesized. Synthesized molecules were further evaluated for their inhibitory activity towards transcription factors NF-kappa B and AP-1 mediated transcriptional activation in a cell line based in vitro as well as for their anti-inflammatory activity in in vivo model of acute inflammation. This series provides us with selective and dual inhibitors of NF-kappa B and AP-1 mediated transcriptional activation which also exhibit significant efficacy in in vivo model of inflammation. Two of the compounds 9m and 9o turned out to be the most promising dual inhibitors of NF-kappa B and AP-1 mediated transcriptional activation with an IC50 of 3.3 mu M for both. 9n (IC50 = 5.5 mu M) and 9p (IC50 = 5.5 mu M) emerged as selective inhibitors of NF-kappa B mediated transcriptional activation and 9c (IC50 = 5.5 mu M) and 9d (IC50 = 5.5 mu M) were found to be more selective inhibitor of AP-1 mediated transcriptional activity. Though the relationship between the activities shown by these compounds in in vivo and in vitro model is still to be established, these results suggest the suitability of the designed molecular framework as a potential anti-inflammatory molecular framework which also exhibits the inhibitory activity towards NF-kappa B and AP-1 mediated transcriptional activation. This will be worth studying further to explore its complete potential particularly in chronic inflammatory conditions. The structure activity relationship (SAR) of this series has been discussed herein. (C) 2008 Elsevier Masson SAS. All rights reserved.
• Raghu Ram Rao; Malla Reddy, Pharmazie, 1992, vol. 47, # 10, p. 794 - 796
  作者：Raghu Ram Rao、Malla Reddy

  DOI：——

  日期：——
• KOZHEVNIKOV YU. V., NAUCH. TR. PERM. FARMATSEVT. IN-T <TRFI-AR>, 1975, HO 8, 35-37
  作者：KOZHEVNIKOV YU. V.

  DOI：——

  日期：——
• THIAZOLE AND THIOPHENE ANALOGUES, AND THEIR USE IN TREATING AUTOIMMUNE DISEASES AND CANCERS
  申请人：Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College

  公开号：EP2007393A2

  公开（公告）日：2008-12-31