2-chloromethyl-3-(2-methoxyphenyl)-3H-quinazolin-4-one | 22312-81-8

• 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-methoxyphenyl)-3H-quinazolin-4-one
• 英文别名: 2-chloromethyl-3-(2-methoxy-phenyl)-3H-quinazolin-4-one；2-chloromethyl-3-(2-methoxy-phenyl)-3H-quinazolin-4-one；2-(chloromethyl)-3-(2-methoxyphenyl)quinazolin-4(3H)-one；2-(chloromethyl)-3-(2-methoxyphenyl)quinazolin-4-one
• CAS: 22312-81-8
• 化学式: C₁₆H₁₃ClN₂O₂
• mdl: MFCD00767021
• 分子量: 300.744
• InChiKey: ABOBEYWUKDBJRT-UHFFFAOYSA-N

物化性质

• 熔点：
  193-194 °C(Solv: methanol (67-56-1))
• 沸点：
  461.2±55.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloromethyl-3-(2-methoxyphenyl)-3H-quinazolin-4-one 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以94%的产率得到2-Azidomethyl-3,4-dihydro-3-(2-methoxyphenyl)-4-chinazolinon
  参考文献：
  名称：

  Chinazolinone, 2. Mitt.: Synthese und einige Reaktionen von 2-Azidomethyl-3-aryl-4-chinazolinonen

  摘要：

  DOI：

  10.1007/bf00905474
• 作为产物：
  描述：

  邻氨基苯甲酸 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 0.25h， 生成 2-chloromethyl-3-(2-methoxyphenyl)-3H-quinazolin-4-one
  参考文献：
  名称：

  Synthesis and evaluation of quinazolin-4-ones as hypoxia-inducible factor-1α inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2011.07.043

文献信息

• Design, synthesis and evaluation of novel 2-thiophen-5-yl-3H-quinazolin-4-one analogues as inhibitors of transcription factors NF-кB and AP-1 mediated transcriptional activation: Their possible utilization as anti-inflammatory and anti-cancer agents
  作者：Rajan S. Giri、Hardik M. Thaker、Tony Giordano、Jill Williams、Donna Rogers、Kamala K. Vasu、Vasudevan Sudarsanam

  DOI：10.1016/j.bmc.2010.01.007

  日期：2010.4

  inhibitors of NF-κB and AP-1 mediated transcriptional activation utilizing the concept of chemical lead based medicinal chemistry and bioisosterism a series of 2-(2,3-disubstituted-thiophen-5-yl)-3H-quinazolin-4-one analogs was designed. A facile and simple route for the synthesis of the designed molecules was developed. Synthesized molecules were evaluated for their activity as inhibitors towards NF-кB

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

  DOI：——

  日期：——
• Synthesis and screening of 2-(2-(4-substituted piperazine-1-yl)-5-phenylthiazol-4-yl)-3-aryl quinazolinone derivatives as anticancer agents
  作者：Ritesh N. Sharma、Rasik Ravani

  DOI：10.1007/s00044-012-0260-2

  日期：2013.6

  Synthesis of novel quinazolinone derivatives was performed from the reaction of N-benzoyl substituted piperazine-1-carbothioamide with 2-chloromethyl quinazolinone derivatives and screened for their in vitro cytotoxic activity by MTT assay. The cell lines used were NCI (human lung cancer cell), MCF 7 (Breast cancer cell), and HEK 293 (Normal epidermal kidney cell). Result of screening on cell line showed moderate to good anticancer activity for all the compounds. Compound 3d (IC50 = 1.1 +/- A 0.03 mu M) was found to be the most active compared to standard methotrexate (IC50 = 2.20 +/- A 0.18 mu M) and 5-florouracil (IC50 = 2.30 +/- A 0.49 mu M). Structure activity relationship of synthesized analogs suggested that the presence of NH linker with aryl moiety at the third position of quinazolinone ring was important for potent anticancer activity. Electron donating group on phenyl ring at the third position of quinazolinone ring gave better anticancer activity then unsubstituted phenyl and electron withdrawing group. Activity by substituted piperazine at 2nd position of thiazole linked with quinazolinone scaffold gave better activity in the order of H > CH3 > CO-C6H5. Our findings may impart new direction to medicinal chemists and biochemists for further investigations of quinazolinone-thiazole containing anticancer agents.
• A versatile one-pot multicomponent synthesis of novel quinazolinon-2-yl-tetrasubstituted thiophenes
  作者：Hitesh B. Jalani、Jitendra C. Kaila、Arshi B. Baraiya、Amit N. Pandya、V. Sudarsanam、Kamala K. Vasu

  DOI：10.1016/j.tetlet.2010.08.046

  日期：2010.10

  Here, we report a versatile multicomponent synthesis of novel quinazolinon-2-yl-tetrasubstituted thiophenes by a one-pot reaction using different alkyl-3-aminobutenoates, isothiocyanates and 2-halomethyl quinazolinones in good to excellent yields. The reaction probably proceeds by an intramolecular 5-exo-trig cyclisation. (C) 2010 Elsevier Ltd. All rights reserved.