N-(4-chlorophenyl)-2-methylquinazolin-4-amine | 677748-48-0

• 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: N-(4-chlorophenyl)-2-methylquinazolin-4-amine
• CAS: 677748-48-0
• 化学式: C₁₅H₁₂ClN₃
• 分子量: 269.733
• InChiKey: JUEGZKVCLWUDPC-UHFFFAOYSA-N

物化性质

• 熔点：
  203-205 °C
• 沸点：
  352.5±42.0 °C(Predicted)
• 密度：
  1.320±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-chlorophenyl)-2-methylquinazolin-4-amine 、 香草醛 在 sodium acetate 、 溶剂黄146 作用下， 反应 24.0h， 以58%的产率得到(E)-4-(2-(4-((4-chlorophenyl)amino)quinazolin-2-yl)vinyl)-2-methoxyphenol
  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：

  2-甲基-4(3H)-喹唑酮 在 4-二甲氨基吡啶 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 2.25h， 生成 N-(4-chlorophenyl)-2-methylquinazolin-4-amine
  参考文献：
  名称：

  A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring

  摘要：

  We report herein a new methodology for synthesizing quinazoline derivatives bearing a heteroarylamino moiety at position-4 of the quinazoline ring. As an alternative to the Buchwald-Hartwig cross-coupling reaction, which appears, until now, as the only efficient way to react 4-chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol % of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the SNAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2-substituted-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.09.024

文献信息

• Synthesis of Substituted Quinazolines: Application to the Synthesis of Verubulin
  作者：Jeffrey W. Lockman、Yevgeniya Klimova、Mark B. Anderson、J. Adam Willardsen

  DOI：10.1080/00397911.2010.529730

  日期：2012.6.15

  Through newly adapted methodology, 2-methyl-3H-quinazolin-4-one was activated using a number of methods followed by displacement to afford 4-aminoquinazolines. The most useful of these processes utilize the p-toluenesulfonate ester or I-2/PPh3 activation. Using this methodology, the anticancer vascular targeting clinical candidate verubulin (1) was synthesized in a highly efficient manner.
• HILMY, KNALID MONAMED HASSAN;MOGENSEN, JZHUSTORGEN;REDERSEN, ERIK V., ACTA CHEM. SCAND., 41,(1987) N 6, 467-468
  作者：HILMY, KNALID MONAMED HASSAN、MOGENSEN, JZHUSTORGEN、REDERSEN, ERIK V.

  DOI：——

  日期：——