2-(chloromethyl)-3-(2-methylphenyl)-3H-quinazoline-4-one | 3166-54-9

• 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-methylphenyl)-3H-quinazoline-4-one
• 英文别名: 2-(chloromethyl)-3-(2-methylphenyl)quinazolin-4(3H)-one；2-(chloromethyl)-3-(2-methylphenyl)quinazolin-4-one
• CAS: 3166-54-9
• 化学式: C₁₆H₁₃ClN₂O
• mdl: MFCD00665343
• 分子量: 284.745
• InChiKey: GZCHSUWHNMHICW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 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-(chloromethyl)-3-(2-methylphenyl)-3H-quinazoline-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72%的产率得到2-Azidomethyl-3,4-dihydro-3-(2-methylphenyl)-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 三乙胺 、 三氯化磷 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 0.05h， 生成 2-(chloromethyl)-3-(2-methylphenyl)-3H-quinazoline-4-one
  参考文献：
  名称：

  One-pot multicomponent synthesis of medicinally important purine quinazolinone derivatives

  摘要：

  Herein, a protocol that involves microwave-assisted, multicomponent one-pot synthetic strategy for the construction of the medicinally important purine quinazolinone scaffold is reported. A series of compounds are prepared by cyclization and condensation reactions using this approach. The compounds are structural analogs of anticancer agents IC-87114 and CAL-101, which are highly isoform-selective PI3K-delta inhibitors and are presently under clinical investigation for chronic lymphocytic leukemia. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.08.137

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，
• Synthesis of Novel Thioglycoside Derivatives Containing Quinazolinone
  作者：Hui Huang、Jian-Fang Gao、Ling-Hua Cao、Duo-Zhi Wang、Jian-Bin Zhang、Shu-Bao Zhou、Yu-Qiang Zhou

  DOI：10.1002/jccs.200900062

  日期：2009.4

  A series of novel thioglycoside derivatives containing 4(3H)‐quinazolinone was designed and synthesized from 2‐chloromethyl‐quinazolin‐4(3H)‐ones and 1‐thioglycose. Several 2‐chloromethyl‐quinazolin‐4(3H)‐ones were synthesized on refluxing with 2‐(chloroacetylamino)‐benzoic acid and arylamines in acetonitrile. All of the novel compounds were characterized by IR, 1H NMR spectra and elemental analysis

  由2-氯甲基喹唑啉-4-（3 H）-酮和1-硫代糖合成了一系列含有4（3 H）-喹唑啉酮的新型硫代糖苷衍生物。与2-（氯乙酰氨基）-苯甲酸和芳胺在乙腈中回流，合成了几个2-氯甲基-喹唑啉-4-（3 H）-1 。所有新化合物均通过IR，1 H NMR光谱和元素分析进行了表征。化合物7b，8b和8c的结构已通过X射线衍射分析确定。
• Design and synthesis of 1,4-substituted 1H-1,2,3-triazolo-quinazolin-4(3H)-ones by Huisgen 1,3-dipolar cycloaddition with PI3Kγ isoform selective activity
  作者：M. Srinivas、Anup Singh Pathania、Priya Mahajan、Praveen K. Verma、Santosh S. Chobe、Fayaz A. Malik、Amit Nargotra、Ram A. Vishwakarma、Sanghapal D. Sawant

  DOI：10.1016/j.bmcl.2018.02.032

  日期：2018.4

  A strategy for construction of medicinally important 1,4-substituted 1H-1,2,3-triazolo-quinazolin-4(3H)-ones has been devised and presented here. The compounds have been synthesized using one-pot multicomponent strategy under microwave assisted conditions. Triazolyl-quinazolinone based D-ring modified analogs are designed based on IC87114 scaffold, which is first known isoform selective inhibitor of

  已经设计并提出了构建具有医学重要性的1，4-取代的1 H -1,2,3-三唑并喹唑啉-4（3 H）-ones的策略。这些化合物是在微波辅助条件下使用一锅多组分策略合成的。基于三唑基-喹唑啉酮的D环修饰类似物是基于IC87114支架设计的，该支架是第一个已知的PI3Kδ异构体选择性抑制剂。在本文中，我们基于具有PI3Kγ特异性抑制潜能的相同支架，鉴定了两种三唑基-喹唑啉酮化合物（5a和5l），对这种同工型的选择性得到了计算机模拟的充分支持结果，其中这些化合物对PI3Kγ的活性比对PI3Kδ的相互作用，亲和力和抑制活性更好。从药物化学和药物发现的角度来看，将支架从PI3Kδ转变为PI3Kγ亚型可能非常有用，可以阐明这种新支架在不同细胞途径中的分子相互作用。
• 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.
• Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters
  作者：Palle V. R. Acharyulu、P. K. Dubey、P. V. V. Prasada Reddy、Thatipally Suresh

  DOI：10.1080/00397910902735381

  日期：2009.8.20

  Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO2 in 6% H2SO4 in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K2CO3 and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.