trans-2-[2-(4-nitrophenyl)ethenyl]-3H-quinazolin-4-one | 3440-49-1

• 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: trans-2-[2-(4-nitrophenyl)ethenyl]-3H-quinazolin-4-one
• 英文别名: 2-[(E)-2-(4-nitrophenyl)ethenyl]quinazolin-4(3H)-one；(E)-2-(4-nitrostyryl)quinazolin-4(3H)-one；2-(4-nitrostyryl)-3H-quinazolin-4-one；2-(4-Nitrophenyl)vinyl-3.4-dihydro-4-oxochinazolin；trans-2-[2-(4-nitrophenyl)vinyl]-3H-quinolin-4-one；2-(4-Nitro-styryl)-3H-chinazolin-4-on；2-(2-{4-nitrophenyl}vinyl)-4(3H)-quinazolinone；2-[(E)-2-(4-nitrophenyl)ethenyl]-3H-quinazolin-4-one
• CAS: 3440-49-1
• 化学式: C₁₆H₁₁N₃O₃
• 分子量: 293.282
• InChiKey: ZRKBGTUWFGKHKQ-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-2-[2-(4-nitrophenyl)ethenyl]-3H-quinazolin-4-one 在 4-二甲氨基吡啶 、 N,N-二甲基苯胺 、 三乙胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 22.0h， 生成 (E)-2-(4-nitrostyryl)-4-(1-piperidinylethyl)aminoquinazoline
  参考文献：
  名称：

  2-Styryl-4-aminoquinazoline derivatives as potent DNA-cleavage, p53-activation and in vivo effective anticancer agents

  摘要：

  Forty-eight analogues of CP-31398, an antitumor agent modulated the mutant p53 gene were synthesized and their cytotoxicities against four cancer cell lines with different p-53 status including bladder cell 724 (w-p53), gastric cell MGC-803 (m-p53), prostate cell DU145 (m-p53), prostate cell PC-3 (null-p53), lung cell A549 (w-p53) and normal liver cell line HL-7702 (w-p53) were examined. (E)-2-(4-Nitrostyryl)-4-(3-dimethylaminopropyl)-aminoquinazoline (10ah) was identified as the most potent compound in anti-proliferation against MGC-803 cells, with IC50 lowed to 1.73 mu M, far potency than that of CP-31398.Molecular mechanism study revealed that 10ah and CP-31398 differ greatly in mechanism to exert their antitumor properties. 10ah could intercalate into DNA and resulted in significant DNA double-strand break 10ah-treatment in MGC-803 cells increased the expression of p53, phosphorylated p53 (p-p53), CDK4, p21 to cause cell cycle arrest at G2/M phase, significantly up-regulated the levels of pro-apoptosis proteins Bak, Bax, Bim while down-regulated the anti-apoptosis proteins Bcl-2, Bcl-xL and the levels of cyclin B1, fluctuated the intracellular reactive oxygen species (ROS), Ca2+ and mitochondria! membrane potential, activated Caspase-9 and Caspase-3 to induce apoptosis. 10ah also displayed potent anticancer efficiency against MGC-803 xenograft tumors models, with tumor growth inhibition (TGI) up to 61.8% at 20 mg/kg without obvious toxicity. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111851
• 作为产物：
  描述：

  邻氨基苯甲酸 在 乙酸酐 、 溶剂黄146 、 zinc(II) chloride 作用下， 生成 trans-2-[2-(4-nitrophenyl)ethenyl]-3H-quinazolin-4-one
  参考文献：
  名称：

  Synthesis and photophysical properties of 2-styrylquinazolin-4-ones

  摘要：

  trans-2-Styryl-substituted 3H-, 3-phenyl-, and 3-naphthylquinazolin-4-ones and their 6,7-difluoro derivatives were synthesized by condensation of appropriate 2-methylquinazolin-4-ones with aromatic aldehydes or by the transformation of the heterocycle of 2-methyl-3,1-benzoxazin-4-one under the action of benzylidenephenylamines.

  DOI：

  10.1134/s1070428011050150

文献信息

• 2-对硝苯乙烯基-4-取代氨基喹唑啉衍生物及其制备方法和应用
  申请人：广西师范大学

  公开号：CN109694358B

  公开（公告）日：2022-02-08

  本发明2‑对硝苯乙烯基‑4‑取代氨基喹唑啉衍生物及其制备方法和应用，利用简便的方法合成了2‑对硝苯乙烯基‑4‑取代氨基喹唑啉衍生物，得率高，生产成本低，得到的2‑对硝苯乙烯基‑4‑取代氨基喹唑啉衍生物可直接与DNA进行作用，且通过作用于DNA而显示很强的抗肿瘤活性，在MGC‑803胃癌移植瘤模型测试中，2‑对硝苯乙烯基‑4‑取代氨基喹唑啉衍生物的体内抗肿瘤效果与目前临床上治疗胃癌的首先药物表阿霉素的抗肿瘤效果相当，而且毒性很小，对受药小鼠的体重几乎没有影响，具有很高的医学价值。
• Synthesis and properties of quinazoline derivatives containing cymantrenyl group
  作者：E. S. Kelbysheva、L. N. Telegina、E. A. Ershova、T. V. Strelkova、M. G. Ezernitskaya、E. V. Nosova、A. F. Smol´yakov、F. M. Dolgushin、N. M. Loim

  DOI：10.1007/s11172-017-1735-6

  日期：2017.2

  The synthesis of new quinazoline derivatives with 2,3- and 4-positioned cymantrenyl fragment is described. Alkylation of 2-substituted quinazolin-4-ones with cymantrenylalkyl bromides on using K2CO3, potassium tert-butoxide, and sodium hydride as bases has been studied. It is established for the first time that condensation of 2-methylquinazolin-4-ones with aldehydes can cause elimination of the substituent

  描述了具有 2,3-和 4-位 cymantrenyl 片段的新喹唑啉衍生物的合成。已经研究了在使用 K2CO3、叔丁醇钾和氢化钠作为碱的情况下，2-取代的喹唑啉-4-酮与溴化氰基烷基溴化物的烷基化。首次确定了2-甲基喹唑啉-4-酮与醛的缩合可以消除3位氮原子上的取代基。新的伞花烃衍生物具有荧光特性。
• Discovery of fluorinated 2‑Styryl 4(3H)-quinazolinone as potential therapeutic hit for oral cancer
  作者：Dinesh Parshuram Satpute、Urjita Shirwadkar、Anil Kumar Tharalla、Sangita Dattatray Shinde、Gargi Nikhil Vaidya、Swarali Joshi、Priyanka Patel Vatsa、Alok Jain、Abhishek A Singh、Rachana Garg、Amit Mandoli、Dinesh Kumar

  DOI：10.1016/j.bmc.2023.117193

  日期：2023.3

  context, reported here is the identification of fluorinated 2‑styryl 4(3H)-quinazolinone as a promising hit for oral cancer. Preliminary studies indicate that the compound blocks the transition of G1 to S phase, thereby leading to arrest in the G1/S phase. Subsequent RNA-seq analysis revealed that the compound induces the activation of molecular pathways involved in apoptosis (such as TNF signalling through

  口腔鳞状细胞癌（OSCC）是最常见的恶性上皮肿瘤，影响口腔和咽喉，占口腔癌的 90%。考虑到与颈清扫术相关的发病率和现有治疗药物的局限性，最需要发现和开发用于口腔癌治疗的新抗癌药物/候选药物。在此背景下，本文报道了氟化 2-苯乙烯基 4(3 H )-喹唑啉酮作为治疗口腔癌的有希望的药物。初步研究表明，该化合物可阻断 G1 向 S 期的转变，从而导致 G1/S 期停滞。随后的 RNA-seq 分析表明，该化合物可诱导参与细胞凋亡（例如通过 NF-κB、p53 途径的 TNF 信号传导）和细胞分化的分子途径的激活，并抑制细胞生长和发育的途径（例如 KRAS 信号传导）。 CAL-27 癌细胞。值得注意的是，根据计算分析，所识别的命中符合 ADME 属性的有利范围。
• Bogert; Beal, Journal of the American Chemical Society, 1912, vol. 34, p. 522
  作者：Bogert、Beal

  DOI：——

  日期：——
• The p53 stabilizing agent CP-31398 and multi-kinase inhibitors. Designing, synthesizing and screening of styrylquinazoline series
  作者：Jacek Mularski、Katarzyna Malarz、Marcin Pacholczyk、Robert Musiol

  DOI：10.1016/j.ejmech.2018.12.012

  日期：2019.2

  Quinazoline derivatives constitute a large family of small-molecule inhibitors of tyrosine kinases. In the current study, the p53 protein reactivator CP-31398 was tested against a panel of kinases on the assumption that it was structurally similar to other active inhibitors. Although it was found to be active in the enzyme-based assay, this compound did not block the proliferation of cancer cells at a feasible concentration level. The styrylquinazoline was used to design new structures that might be potential multitarget inhibitors. Subsequently, a series of compounds was obtained and characterized. Their inhibitory activity in a panel of tyrosine kinases had an antiproliferative effect against several cancer cell lines that have different expression levels of those proteins. The mode of protein interaction was tested for the most active compound in docking experiments. (C) 2018 Elsevier Masson SAS. All rights reserved.