2-(4-methoxystyryl)quinazolin-4(3H)-one | 30507-21-2

• 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-(4-methoxystyryl)quinazolin-4(3H)-one
• 英文别名: 2-[2-(4-methoxyphenyl)ethenyl]-3H-quinazolin-4-one
• CAS: 30507-21-2
• 化学式: C₁₇H₁₄N₂O₂
• 分子量: 278.31
• InChiKey: LSZNCJFMLYCZKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 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：
  50.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-methoxystyryl)quinazolin-4(3H)-one 在 三氯氧磷 作用下， 反应 2.0h， 生成 4-chloro-2-[(E)-2-(4-methoxyphenyl)ethenyl]quinazoline
  参考文献：
  名称：

  Design, synthesis and molecular modeling studies of 2-styrylquinazoline derivatives as EGFR inhibitors and apoptosis inducers

  摘要：

  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).

  DOI：

  10.1016/j.bioorg.2020.104358
• 作为产物：
  描述：

  邻氨基苯甲酸 在 sodium acetate 、 溶剂黄146 作用下， 反应 22.0h， 生成 2-(4-methoxystyryl)quinazolin-4(3H)-one
  参考文献：
  名称：

  新型 4-anilino-2-vinyl-quinazolines 的设计、合成、抗肿瘤和 VEGFR-2 抑制活性：分子模型研究

  摘要：

  新合成的 4-anilino-2-vinylquinazolines 8a-r的抗肿瘤活性与作为标准药物的索拉非尼相当。评估了2-乙烯基喹唑啉8a-r的体外抗肿瘤活性。对最有效的抗肿瘤药物进行体外VEGFR-2 抑制和凋亡诱导试验。化合物8 h、8 l和8r显示出潜在的抗肿瘤活性，相对于参考药物索拉非尼，IC 50 值为 4.92–14.37 μM（IC 50值为5.47–9.18 μM）。化合物8 h具有潜在的 VEGFR-2 抑制活性 (IC 50 = 60.27 nM) 与标准药物索拉非尼 (IC 50  = 55.43 nM) 相比，而化合物8 l显示出中等抑制活性 (IC 50  = 93.50 nM)。最活跃的化合物8 h对 MCF-7 细胞的总凋亡率为 36.24%，超过了索拉非尼引起的凋亡效应 (32.46%) 和 G1/S 期停滞的细胞周期。化合物8 h是一种有效的 VEGFR-2

  DOI：

  10.1016/j.bioorg.2022.105710

文献信息

• Therapeutic reactivation of mutant p53 protein by quinazoline derivatives
  作者：Hamish S. Sutherland、In Young Hwang、Elaine S. Marshall、Brent S. Lindsay、William A. Denny、Catherine Gilchrist、Wayne R. Joseph、Debra Greenhalgh、Emma Richardson、Philip Kestell、Angela Ding、Bruce C. Baguley

  DOI：10.1007/s10637-011-9744-z

  日期：2012.10

  Purpose The human tumour suppressor protein p53 is mutated in nearly half of human tumours and most mutant proteins have single amino acid changes. Several drugs including the quinazoline derivative 1 (CP-31398) have been reported to restore p53 activity in mutant cells. The side chain of 1 contains a styryl linkage that compromises its stability and we wished to explore the activity of analogues containing more stable side chains. Methods Reactivation of p53 function was measured by flow cytometry as the ability to potentiate radiation-induced G1-phase cell cycle arrest and by western blotting to determine expression of p21WAF1. DNA binding was measured by competition with ethidium and preliminary pharmacological and xenograft studies were carried out. Results Screening of analogues for potentiation of radiation-induced G1-phase cell cycle arrest using NZOV11, an ovarian tumour cell line containing a p53R248Q mutation, demonstrated that the (2-benzofuranyl)-quinazoline derivative 5 was among the most active of the analogues. Compound 5 showed similar effects in several other p53 mutant human tumour cell lines but not in a p53 null cell line. 5 also potentiated p21WAF1 expression induced by radiation. DNA binding affinity was measured and found to correlate with p53 reactivation activity. Plasma concentrations of 5 in mice were sufficient to suggest in vivo activity and a small induced tumour growth delay (7 days) of NZM4 melanoma xenografts was observed. Conclusion Compound 5 restores p53-like function to a human tumour cells lines expressing a variety of mutant p53 proteins, thus providing a basis for the design of further new drugs.

  目的 在近一半的人类肿瘤中，人类肿瘤抑制蛋白 p53 发生突变，大多数突变蛋白只有一个氨基酸发生变化。据报道，包括喹唑啉衍生物 1（CP-31398）在内的几种药物可恢复突变细胞中 p53 的活性。1 的侧链含有苯乙烯基连接，影响了其稳定性，因此我们希望探索含有更稳定侧链的类似物的活性。方法 通过流式细胞术测量 p53 功能的重激活，即增强辐射诱导的 G1 期细胞周期停滞的能力，并通过 Western 印迹法测定 p21WAF1 的表达。通过乙啶竞争法测定 DNA 结合，并进行了初步的药理学和异种移植研究。结果 使用含有 p53R248Q 突变的卵巢肿瘤细胞系 NZOV11 对类似物进行筛选，以确定其对辐射诱导的 G1 期细胞周期停滞的增效作用，结果表明（2-苯并呋喃基）-喹唑啉衍生物 5 是活性最高的类似物之一。化合物 5 在其他几种 p53 突变的人类肿瘤细胞系中也显示出类似的作用，但在 p53 缺失的细胞系中却没有。5 还能增强辐射诱导的 p21WAF1 的表达。对 DNA 结合亲和力进行了测量，发现它与 p53 的重新激活活性相关。5 在小鼠体内的血浆浓度足以表明其体内活性，并观察到 NZM4 黑色素瘤异种移植物的肿瘤生长略有延迟（7 天）。结论 化合物 5 能使表达多种突变 p53 蛋白的人类肿瘤细胞系恢复类似 p53 的功能，从而为设计进一步的新药物提供了基础。
• A peroxo‐Mo(VI)/Mo(VI)‐mediated redox synthesis of quinazolin‐4(3 <i>H</i> )‐ones and their aggregation‐induced emission property and mechanism
  作者：Mei Chi、Wu‐Lin Xiong、Dong‐Zhao Yang、Cong‐Bin Fan、Rong‐Wei Shi、Shan‐Shan Gong、Qi Sun

  DOI：10.1002/poc.4329

  日期：2022.5

  been neglected for quinazolin-4(3H)-ones. Theoretical calculation results well rationalized their photophysical behaviors and elucidated their AIE mechanism as restriction of access to dark state (RADS). The crystallographic analysis of two representative quinazolin-4(3H)-ones not only revealed their packing mode and weak intermolecular actions but also supported the molecular conformations obtained by

  开发了一种基于过氧-Mo(VI)/Mo(VI) 氧化还原循环的高效方法，用于环境温度合成 quinazolin-4(3 H )-ones。催化磷钼酸（PMA）在反应的不同阶段表现出路易斯酸和氧化脱氢活性，真正的氧化催化物种被鉴定为过氧-Mo(VI) Keggin簇。令人惊讶的是，我们发现聚集诱导发射 (AIE) 是一种长期被 quinazolin-4(3 H )-ones 忽略的通用属性。理论计算结果很好地合理化了它们的光物理行为，并阐明了它们的AIE机制是限制进入暗态（RADS）。两种代表性喹唑啉-4( 3H )的晶体学分析)-ones不仅揭示了它们的堆积方式和弱分子间作用，而且支持了理论计算得到的分子构象。
• Merging C–H Bond Functionalization with Amide Alcoholysis: En Route to 2-Aminopyridines
  作者：Dinesh Kumar、Sandeep R. Vemula、Gregory R. Cook

  DOI：10.1021/acscatal.6b00728

  日期：2016.6.3

  A new route for the synthesis of 2-aminopyridines has been developed that merges C–H functionalization with amide alcoholysis. The key component of this method is the ability of a quinazolinone to template the chemo- and regioselective construction of a latent pyridine ring via site-selective olefinic C–H bond functionalization under Ru(II) catalysis. Thus, highly substituted 2-aminopyridines were

  已经开发了一种新的合成2-氨基吡啶的方法，该方法将CH官能团与酰胺醇解反应合并在一起。该方法的关键组成部分是喹唑啉酮能够通过Ru（II）催化下的位点选择性烯烃C–H键官能化来模板化潜在吡啶环的化学和区域选择性结构。因此，以高收率制备了高度取代的2-氨基吡啶。机理研究提供了关键的氧化C–H活化/环化过程的机理的见解。
• STYRYL QUINAZOLINE DERIVATIVES AS PHARMACEUTICALLY ACTIVE AGENTS
  申请人：VICHEM CHEMIE KUTATÓ KFT.

  公开号：US20160194291A1

  公开（公告）日：2016-07-07

  The present invention relates to styryl quinazoline derivatives of the general formula (I) and pharmaceutically acceptable solvates, hydrates, salts, regioisomeric and polymorphic forms thereof as well as pharmaceutical compositions containing at least one of the described compounds as pharmaceutically active agent. The compounds have been identified as new drug candidates for the prevention and/or treatment of diseases related to disfunction(s) of hematopoiesis and cancer or any other form of neo- or hyperplasias related to Fms-like tyrosine kinase 3 (FLT3) containing Internal Tandem Duplications (ITD), especially in the case of myeloid leukemia. The compounds have been also identified as new drug candidates as antibacterial agents (having bactericidal or bacteriostatic activity) which can be used for the prevention and/or treatment of bacterial infectious diseases.

  本发明涉及一般式（I）的苯乙烯基喹唑啉衍生物及其药学上可接受的溶剂化物、水合物、盐、区域异构体和多晶形式，以及包含所述化合物中至少一种作为药学活性剂的制药组合物。这些化合物已被确定为新药候选物，用于预防和/或治疗与造血功能障碍和癌症或与含有内部串联重复（ITD）的Fms样酪氨酸激酶3（FLT3）相关的任何形式的新生或增生有关的疾病，特别是髓系白血病的情况。这些化合物还被确定为新的抗菌剂（具有杀菌或抑菌活性），可用于预防和/或治疗细菌感染性疾病。
• 2,3-Dihydroquinazolin-4(1H)-ones and quinazolin-4(3H)-ones as broad-spectrum cytotoxic agents and their impact on tubulin polymerisation
  作者：Nicholas S. O'Brien、Jayne Gilbert、Adam McCluskey、Jennette A. Sakoff

  DOI：10.1039/d3md00600j

  日期：——

  note, 2-styrylquinazolin-4(3H)-one 51, 2-(4-hydroxystyryl)quinazolin-4(3H)-one 63, 2-(2-methoxystyryl)quinazolin-4(3H)-one 64 and 2-(3-methoxystyryl)quinazolin-4(3H)-one 65 and 2-(naphthalen-1-yl)-2,3-dihydroquinazolin-4(1H)-one 39 exhibited sub-μM potency growth inhibition values. Of these 1-naphthyl 39 has activity <50 nM against the HT29, U87, A2780, H460 and BE2-C cell lines. Molecular modelling

  微管蛋白在有丝分裂中发挥核心作用，并且是包括紫杉醇在内的多种抗癌药物的靶标。本文合成了两个独立家族的2,3-二氢喹唑啉-4(1 H )-酮和喹唑啉-4(3 H )-酮，总共包含57种化合物。针对广泛的人类癌细胞系（HT29 结肠癌、U87 和 SJ-G2 胶质母细胞瘤、MCF-7 乳腺癌、A2780 卵巢细胞、H460 肺癌、A431 皮肤细胞、Du145 前列腺细胞、BE2-C 神经母细胞瘤和 MIA 胰腺细胞）的筛选揭示了这些类似物是广谱细胞毒性化合物。特别值得注意的是，2-苯乙烯基喹唑啉-4(3 H )-一51、2- (4-羟基苯乙烯基)喹唑啉-4(3 H )-一63、2- (2-甲氧基苯乙烯基)喹唑啉-4(3 H )-一种64和 2-(3-甲氧基苯乙烯基)喹唑啉-4(3 H )-一种65和 2-(萘-1-基)-2,3-二氢喹唑啉-4(1 H )-一种39表现出亚μM效力生长抑制值。其中1-萘基39具有活性<50