[3-(4-Chloro-phenyl)-4-oxo-3,4-dihydro-quinazolin-2-ylsulfanyl]-acetic acid hydrazide | 133764-45-1

• 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: [3-(4-Chloro-phenyl)-4-oxo-3,4-dihydro-quinazolin-2-ylsulfanyl]-acetic acid hydrazide
• 英文别名: 2-{[3-(4-Chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]sulfanyl}acetohydrazide；2-[3-(4-chlorophenyl)-4-oxoquinazolin-2-yl]sulfanylacetohydrazide
• CAS: 133764-45-1
• 化学式: C₁₆H₁₃ClN₄O₂S
• mdl: MFCD07364328
• 分子量: 360.824
• InChiKey: HMMHPDRILXQERM-UHFFFAOYSA-N

物化性质

• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.062
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [3-(4-Chloro-phenyl)-4-oxo-3,4-dihydro-quinazolin-2-ylsulfanyl]-acetic acid hydrazide 在 盐酸 、 硫氰酸铵 作用下， 以 水 为溶剂， 反应 1.0h， 以88%的产率得到3-(4-氯苯基)-1H-喹唑啉-2,4-二酮
  参考文献：
  名称：

  几种新型喹唑啉-4(3H)-one衍生物的合成、分子结构和光谱研究；N-与S-烷基化的说明

  摘要：

  摘要 分别制备了 3-芳基-1H,3H-喹唑啉-2,4-二酮和 3-芳基-2-巯基-3H-喹唑啉-4-酮的新系列 N-和 S-烷基化产物。通过 SH 和 NH 底物与碘甲烷、溴乙酸乙酯、烯丙基溴、溴丙炔、2-溴乙醇、1,3-二溴丙烷或苯甲酰溴在 DMF 作为溶剂和无水碳酸钾中的有效亲核取代反应获得良好的产率。quinazolin-2,4-dione 有利于 N-烷基化，而 2-mercapto-3H-quinazolin-4-one 则通过 S-烷基化。DFT 反应性研究表明，前者的 N 位与 O 位相比具有更高的亲核性。相比之下，S 位点是比后者的 N 原子更亲核的中心。合成产物的结构是根据它们的熔点（m. p)、IR 和 1HNMR 数据。使用DFT B3LYP/6-311G(d,p)方法计算产物的分子结构。使用相同水平的理论计算电子和光谱特性（Uv-Vis 和 NMR 光谱）。还预测

  DOI：

  10.1016/j.molstruc.2015.12.007
• 作为产物：
  描述：

  p-chlorophenyldithiocarbamic acid triethylamine salt 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 26.0h， 生成 [3-(4-Chloro-phenyl)-4-oxo-3,4-dihydro-quinazolin-2-ylsulfanyl]-acetic acid hydrazide
  参考文献：
  名称：

  Deshmukh; Deshmukh; Shirke, Journal of the Indian Chemical Society, 1997, vol. 74, # 5, p. 422 - 423

  摘要：

  DOI：

文献信息

• Design and synthesis of novel quinazolinone-based derivatives as EGFR inhibitors with antitumor activity
  作者：Amr Sonousi、Rasha A. Hassan、Eman O. Osman、Amr M. Abdou、Soha H. Emam

  DOI：10.1080/14756366.2022.2118735

  日期：2022.12.31

  Abstract Nineteen new quinazolin-4(3H)-one derivatives 3a–g and 6a–l were designed and synthesised to inhibit EGFR. The antiproliferative activity of the synthesised compounds was tested in vitro against 60 different human cell lines. The most potent compound 6d displayed superior sub-micromolar antiproliferative activity towards NSC lung cancer cell line NCI-H460 with GI50 = 0.789 µM. It also showed

  摘要 设计并合成了19 种新的 quinazolin-4( 3H )-one 衍生物3a-g和6a-l以抑制 EGFR。合成化合物的抗增殖活性在体外针对 60 种不同的人类细胞系进行了测试。最有效的化合物6d对 NSC 肺癌细胞系 NCI-H460 具有优异的亚微摩尔抗增殖活性，GI 50 = 0.789 µM。它还对 40 种不同的癌细胞系显示出有效的细胞抑制活性（TGI 范围：2.59–9.55 µM）。与具有 IC 50的厄洛替尼相比，化合物6d有效抑制 EGFR，IC 50 = 0.069 ± 0.004 µM值为 0.045 ± 0.003 µM。化合物6d在乳腺癌 HS 578T 细胞系中显示总细胞凋亡增加 16.74 倍并导致细胞周期停滞在 G1/S 期。此外，将最有效的衍生物与 EGFR 活性位点对接以确定它们的结合模式并确认它们满足 EGFR 抑制所需的药效团特征的能力。
• 10.1039/d4ra04828h
  作者：Tawfik, Samar S.、Hamdi, Abdelrahman、Ali, Ahmed R.、Elgazar, Abdullah A.、El-Shafey, Hamed W.、El-Azab, Adel S.、Bakheit, Ahmed H.、Hefnawy, Mohamed M.、Ghabbour, Hazem A.、Abdel-Aziz, Alaa A.-M.

  DOI：10.1039/d4ra04828h

  日期：——

  potencies against all cell lines compared to sorafenib (IC50 = 5.47–7.26 μM). Dual EGFR/VEGFR-2 inhibitory activities of the most active analogues (4, 11, and 20) were investigated. Compound 4 showed comparable EGFR/VEGFR-2 inhibitory activity to the used control drugs. Flow cytometric analysis indicates that the most potent analogue 4 stopped the cell cycle at the G1 phase and induced 46.53% total apoptosis

  单分子的双重靶向已成为一种有前景的抗癌策略。在这项研究中，合成了一组新的2-thioquinazolin-4(3 H )-ones作为潜在的抗癌替代物，具有EGFR/VEGFR-2激酶双重抑制活性。针对一组四种癌细胞系评估了新合成的候选物4-27的抗肿瘤效力。准备好的候选药物4-27显示出与标准药物索拉非尼相当的活性。例如，与索拉非尼 (IC 50 = 5.47–7.26 μM) 相比，化合物4 (IC 50 = 1.50–5.86 μM) 和化合物20 (IC 50 = 4.42–6.39 μM) 对所有细胞系均表现出优异的效力。研究了最活跃的类似物（ 4、11和20 ）的双重 EGFR/VEGFR-2抑制活性。化合物4显示出与所用对照药物相当的EGFR/VEGFR-2抑制活性。流式细胞分析表明，最有效的类似物4将细胞周期终止于 G1 期，并诱导 HCT-116 细胞 46.53% 的总细胞凋亡，这比未处理的细胞（2
• Srivastava; Shukla; Prabhakar, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1991, vol. 30, # 3, p. 332 - 339
  作者：Srivastava、Shukla、Prabhakar、Saxena

  DOI：——

  日期：——
• Experimental and theoretical spectroscopic studies, HOMO–LUMO, NBO analyses and thione–thiol tautomerism of a new hybrid of 1,3,4-oxadiazole-thione with quinazolin-4-one
  作者：Saied M. Soliman、Mohamed Hagar、Farahate Ibid、El Sayed H. El Ashry

  DOI：10.1016/j.saa.2015.01.061

  日期：2015.6

  The hybrid 3-(4-chlorophenyl)-2-[(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)methylthio]quinazolin-4(3H)-one has been synthesized and characterized using elemental analysis, FTIR and NMR spectroscopy. The thione thiol tautomeric equilibria has been studied using both DFT/B3LYP and HF methods at different basis sets. The results of calculations showed predominance of the thione form. The molecular structure and vibrational spectra of the stable tautomer are predicted using the same level of theory. The complete assignments of the vibrational modes were performed on the basis of potential energy distribution (FED). The 6-311++G(d,p) gave the best results compared to the experimental data. The chemical shift values of the two tautomers are calculated using GIAO method. The NH proton of the thione tautomer have chemical shift value closer to the experimental data compared to the SH proton of the thiol one. The electronic transitions are predicted using the TD-DFT calculations at B3LYP/6-311++G(d,p) level of theory. The calculated polarizability and first hyperpolarizability showed that the studied compound has better NLO properties than urea. The molecular electrostatic potential (MEP) analysis reveals the sites for electrophilic and nudeophilic attack in the molecule. NBO analysis is carried out to investigate the stabilization energy of various intramolecular charge transfer interactions within the studied molecule. (C) 2015 Elsevier B.V. All rights reserved.
• Quinazolin-4-yl-sulfanylacetyl-hydrazone derivatives; Synthesis, molecular structure and electronic properties
  作者：Mohamed Hagar、Saied M. Soliman、Farahate Ibid、El Sayed H. El Ashry

  DOI：10.1016/j.molstruc.2013.06.005

  日期：2013.10

  Four new acetylhydrazone derivatives of quinazoline have been synthesized and characterized. The molecular structures and relative stabilities of four possible isomers for each acetylhydrazone are calculated using DFT/B3LYP/6-31G(d,p) method. The calculations results predicted higher stability of the E-isomers compared to the Z-isomers in the gas phase. The syn-E isomer is the predominant form in gaseous phase for all the studied hydrazones except for the hydrazone derived from salicylaldehyde where the anti-E is the most stable isomer. The latter is stabilized by two strong intramolecular H-bonds instead of one in the others. The electronic and spectroscopic properties of the most stable isomers were also calculated using the same level of theory. The calculated atomic polar tensor (APT) charges indicated an increase of the positive charge density at the H-sites involved in the H-bonding interactions. The HOMO and LUMO energies are negative indicating that the compounds under investigation are stable. The electronic transition from the ground state to the excited state belongs to pi-pi* transition. The calculated vibrational spectra showed strong red shifts and increase in the vibrational intensity of the N-H and O-H stretching modes due to the intramolecular H-bonding interactions. In DMSO solution, the NMR spectra of the studied hydrazones revealed that such polar solvents stabilize the syn isomers for all the studied hydrazones except for the hydrazone derived from salicylaldehyde where the anti isomer is the major. (c) 2013 Elsevier B.V. All rights reserved.