4-chloro-2-[(E)-2-(4-methoxyphenyl)ethenyl]quinazoline | 1207435-87-7

• 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: 4-chloro-2-[(E)-2-(4-methoxyphenyl)ethenyl]quinazoline
• 英文别名: (E)-4-chloro-2-(4-methoxystyryl)quinazoline；4-chloro-2-((E)-2-(4-methoxy-phenyl)-vinyl)-quinazoline
• CAS: 1207435-87-7
• 化学式: C₁₇H₁₃ClN₂O
• 分子量: 296.756
• InChiKey: YUZLJWCISAMBTR-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-2-[(E)-2-(4-methoxyphenyl)ethenyl]quinazoline 以88%的产率得到
  参考文献：
  名称：

  BOTROS S.; SHABAN M., PHARMAZIE, 1978, 33, NO 10, 646-647

  摘要：

  DOI：
• 作为产物：
  描述：

  邻氨基苯甲酸 在 sodium acetate 、 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 以 苯 为溶剂， 反应 17.0h， 生成 4-chloro-2-[(E)-2-(4-methoxyphenyl)ethenyl]quinazoline
  参考文献：
  名称：

  作为 HDAC/EGFR 双重抑制剂的喹唑啉-查尔酮杂化物：针对多发性骨髓瘤的潜在抗癌活性的设计、合成、机理和计算机模拟研究

  摘要：

  设计了两个新系列的喹唑啉-查尔酮杂合体，将其合成为组蛋白脱乙酰酶 (HDAC)/表皮生长因子受体 (EGFR) 双重抑制剂，并针对 NCI 60 人类癌细胞系组进行体外筛选。最有效的衍生物，带有 3,4,5-三甲氧基苯基查尔酮部分的化合物5e ，对 NCI 60 人类癌细胞系表现出最有效的生长抑制值。因此，选择它进行 NCI 5 对数剂量的进一步研究。有趣的是，这种三甲氧基取代的类似物在 10 µM 浓度下可抑制 Roswell Park Memorial Institute (RPMI)-8226 细胞的增殖 96%，相对于正常血细胞，IC 50 = 9.09 ± 0.34 µM，选择性指数 = 7.19。为了确认该化合物的选择性，针对一组酪氨酸激酶对其进行了评估。从机制上讲，它成功地选择性抑制 HDAC6、HDAC8 和 EGFR，IC 50分别为 0.41 ± 0.015、0.61 ±

  DOI：

  10.1002/ardp.202300626

文献信息

• Discovery and development of extreme selective inhibitors of the ITD and D835Y mutant FLT3 kinases
  作者：Ferenc Baska、Anna Sipos、Zoltán Őrfi、Zoltán Nemes、Judit Dobos、Csaba Szántai-Kis、Eszter Szabó、Gábor Szénási、László Dézsi、Péter Hamar、Mihály T. Cserepes、József Tóvári、Rita Garamvölgyi、Marcell Krekó、László Őrfi

  DOI：10.1016/j.ejmech.2019.111710

  日期：2019.12

  tyrosine receptor kinase 3 (FLT3) is implicated in the pathogenesis of acute myeloid leukemia (AML) in 20-30% of patients. In this study we identified a highly selective (phenylethenyl)quinazoline compound family as novel potent inhibitors of the FLT3-ITD and FLT3-D835Y kinases. Their prominent effects were confirmed by biochemical and cellular proliferation assays followed by mice xenograft studies

  FMS样酪氨酸受体激酶3（FLT3）的异常激活与20-30％的患者的急性髓细胞性白血病（AML）的发病机制有关。在这项研究中，我们确定了高选择性（苯基乙烯基）喹唑啉化合物家族作为FLT3-ITD和FLT3-D835Y激酶的新型有效抑制剂。通过生化和细胞增殖测定以及随后的小鼠异种移植研究，证实了它们的显着效果。我们的建模实验和化合物的化学结构预测了共价抑制的可能性。最有效的化合物触发了FLT3-ITD AML细胞的凋亡，但在不依赖FLT3的白血病和非白血病细胞系中作用微弱或没有作用。
• Investigating Biological Activity Spectrum for Novel Styrylquinazoline Analogues
  作者：Josef Jampilek、Robert Musiol、Jacek Finster、Matus Pesko、James Carroll、Katarina Kralova、Marcela Vejsova、Jim O'Mahony、Aidan Coffey、Jiri Dohnal、Jaroslaw Polanski

  DOI：10.3390/molecules14104246

  日期：——

  In this study, series of ring-substituted 2-styrylquinazolin-4(3H)-one and 4-chloro-2-styrylquinazoline derivatives were prepared. The syntheses of the discussed compounds are presented. The compounds were analyzed by RP-HPLC to determine lipophilicity. They were tested for their inhibitory activity on photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than that of the standard isoniazid. It was found that the electronic properties of the R substituent, and not the total lipophilicity of the compound, were decisive for the photosynthesis-inhibiting activity of tested compounds.

  本研究制备了一系列环取代的 2-苯乙烯基喹唑啉-4(3H)-酮和 4-氯-2-苯乙烯基喹唑啉衍生物。文中介绍了所讨论化合物的合成方法。化合物通过 RP-HPLC 进行分析，以确定其亲油性。测试了这些化合物对菠菜叶绿体光合电子传递（PET）的抑制活性。此外，还针对四种分枝杆菌菌株和八种真菌菌株对合成的化合物进行了体外初筛。一些化合物显示出与标准异烟肼相当或更高的生物活性。研究发现，R 取代基的电子特性，而不是化合物的总亲油性，对测试化合物的光合作用抑制活性起着决定性作用。
• Design, synthesis and molecular modeling studies of 2-styrylquinazoline derivatives as EGFR inhibitors and apoptosis inducers
  作者：Noha H. Amin、Mohammed T. Elsaadi、Shimaa S. Zaki、Hamdy M. Abdel-Rahman

  DOI：10.1016/j.bioorg.2020.104358

  日期：2020.12

  Herein, we report the synthesis of novel 2-substituted styrylquinazolines conjugated with aniline or sulfonamide moieties, anticipated to act as potent anticancer therapeutic agents through preferential EGFR inhibition. In doing so, all the synthesized compounds were screened for their in vitro anticancer activities (nine subpanels) at the National Cancer Institute (NCI), USA. The resulting two most active anticancer compounds (7b and 8c) were then chemically manipulated to investigate feasible derivatives (12a-e and 15a-d). MTT cytotoxicity, in vitro cell free EGFR and anti-proliferative activity against EGFR/ A549 cell line evaluation for the most active broadly spectrum candidates (7a/b, 8c/e, 12b and 15d) was conducted. Promising results were obtained for the styrylquinazoline-benzenesulfonamide derivative 8c (IC₅₀ = 8.62 µM, 0.190 µM and = 79.25%), if compared to lapatanib (IC₅₀ = 11.98 µM, 0.190 µM, and 79.25%), respectively. Moreover, its apoptotic induction potential was studied through cell cycle analysis, Annexin-V and caspase-3 activation assays. Results showed a clear cell arrest at G2/M phase, a late apoptotic increase (76 folds) and a fruitful caspase-3 expression change (8 folds), compared to the control. Finally, molecular docking studies of compounds 7a/b, 8c/e, 12b and 15d revealed proper fitting into the active site of EGFR with a low binding energy score for compound 8c (-13.19 Kcal/mole), compared to lapatanib (-14.54 Kcal/mole).
• Investigating the anti-proliferative activity of styrylazanaphthalenes and azanaphthalenediones
  作者：Anna Mrozek-Wilczkiewicz、Danuta S. Kalinowski、Robert Musiol、Jacek Finster、Agnieszka Szurko、Katarzyna Serafin、Magdalena Knas、Sishir K. Kamalapuram、Zaklina Kovacevic、Josef Jampilek、Alicja Ratuszna、Joanna Rzeszowska-Wolny、Des R. Richardson、Jaroslaw Polanski

  DOI：10.1016/j.bmc.2010.02.025

  日期：2010.4

  A group of styrylazanaphthalenes and azanaphthalenediones were synthesized and tested for their anti-proliferative activity. Most of the compounds were obtained with the use of microwave-assisted synthesis. The lipophilicity of the compounds was measured by RP-HPLC and their anti-proliferative activity was assayed against the human SK-N-MC neuroepithelioma and HCT116 human colon carcinoma cell lines. Active compounds were also tested in clonogenity and comet assays. Several quinazolinone and styrylquinazoline analogues were found to have markedly greater anti-proliferative activity than desferoxamine and cis-platin. (C) 2010 Elsevier Ltd. All rights reserved.
• BOTROS S.; SHABAN M., PHARMAZIE, 1978, 33, NO 10, 646-647
  作者：BOTROS S.、 SHABAN M.

  DOI：——

  日期：——