4-(6-nitroquinazolin-4-ylamino)benzoic acid | 51687-14-0

• 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: 4-(6-nitroquinazolin-4-ylamino)benzoic acid
• 英文别名: 4-(6-nitro-quinazolin-4-ylamino)-benzoic acid；4-[(6-Nitroquinazolin-4-yl)amino]benzoic acid
• CAS: 51687-14-0
• 化学式: C₁₅H₁₀N₄O₄
• 分子量: 310.269
• InChiKey: DHWNXEVICXEICS-UHFFFAOYSA-N

物化性质

• 沸点：
  565.1±45.0 °C(Predicted)
• 密度：
  1.548±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(6-nitroquinazolin-4-ylamino)benzoic acid 在 12 % Pd/C 、 甲酸铵 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (S)-4-((6-(2-(4-isobutylphenyl)propanamido)quinazolin-4-yl)amino)benzoic acid
  参考文献：
  名称：

  Compounds Consisting of Quinazoline, Ibuprofen, and Amino Acids with Cytotoxic and Anti‐Inflammatory Effects

  摘要：

  In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR‐TKD) and cyclooxygenase‐2 (COX‐2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A‐431, MCF‐7, MDA‐MB‐231) and epithelial non‐tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC₅₀) than gefitinib (reference drug) on three cancer cell lines (0.034 μM in A‐431, 2.67 μM in MCF‐7, and 3.64 μM in AGS) without showing activity on the non‐tumorigenic cell line (>100 μM). Furthermore, assessment of EGFR‐TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an in vivo anti‐inflammatory assay using the 12‐O‐tetradecanoylphorbol‐3‐acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR‐TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX‐2, involving S531. The RMSD graph indicated that the ligand remained stable in 50 ns.

  DOI：

  10.1002/cmdc.202300651
• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 以 N,N-二甲基乙酰胺 、 溶剂黄146 为溶剂， 反应 5.0h， 生成 4-(6-nitroquinazolin-4-ylamino)benzoic acid
  参考文献：
  名称：

  探索 4-氨基喹唑啉作为结核分枝杆菌 N-乙酰氨基葡萄糖-1-磷酸尿苷转移酶 (GlmU MTB) 抑制剂的 MDR-TB 抑制潜力

  摘要：

  耐药结核病是一项具有挑战性的任务，迫切需要开发通过新型作用方式起作用的新型抗结核药物。在这里，我们报告了 4-氨基喹唑啉作为结核分枝杆菌 N-乙酰氨基葡萄糖-1-磷酸尿苷转移酶 (GlmU MTB) 抑制剂，以克服 MDR-TB 的问题。在合成的化合物中，观察到 HMP-05 和 HMP-15 是该系列的有效化合物 [IC 50 = 6.4 µM (H37Rv)，MIC = 25 µM (MDR-TB) 和 IC 50 = 2.9 µM (H37Rv)， MIC = 6.25 µM (MDR-TB) 分别]。

  DOI：

  10.1002/cbdv.202000237

文献信息

• Exploring MDR‐TB Inhibitory Potential of 4‐Aminoquinazolines as <i>Mycobacterium tuberculosis N</i> ‐Acetylglucosamine‐1‐Phosphate Uridyltransferase (GlmU ^MTB ) Inhibitors
  作者：Harun M. Patel、Mahesh Palkar、Rajshekhar Karpoormath

  DOI：10.1002/cbdv.202000237

  日期：2020.8

  Drug resistance tuberculosis is one of the challenging tasks that dictates the desperate need for the development of new anti-tubercular agents which operate via novel modes of action. Here, we are reporting the 4-amino quinazolines as M. tuberculosis N -acetylglucosamine-1-phosphate uridyltransferase (GlmU MTB) inhibitors to overcome the problem of the MDR-TB. Amongst the synthesized compounds HMP-05

  耐药结核病是一项具有挑战性的任务，迫切需要开发通过新型作用方式起作用的新型抗结核药物。在这里，我们报告了 4-氨基喹唑啉作为结核分枝杆菌 N-乙酰氨基葡萄糖-1-磷酸尿苷转移酶 (GlmU MTB) 抑制剂，以克服 MDR-TB 的问题。在合成的化合物中，观察到 HMP-05 和 HMP-15 是该系列的有效化合物 [IC 50 = 6.4 µM (H37Rv)，MIC = 25 µM (MDR-TB) 和 IC 50 = 2.9 µM (H37Rv)， MIC = 6.25 µM (MDR-TB) 分别]。
• Compositions and methods for modulating gated ion channels
  申请人：Babinski Kazimierz

  公开号：US20070197509A1

  公开（公告）日：2007-08-23

  The present invention relates to compositions and methods to modulate the activity of gated ion channels.

  本发明涉及用于调节门控离子通道活性的组合物和方法。
• WO2007/71055
  申请人：——

  公开号：——

  公开（公告）日：——
• Compounds Consisting of Quinazoline, Ibuprofen, and Amino Acids with Cytotoxic and Anti‐Inflammatory Effects
  作者：Luis Roberto Garduño‐Villavicencio、Ulises Martínez‐Ortega、Elizabeth Ortiz‐Sánchez、José Manuel Tinajero‐Rodríguez、Francisco Hernández‐Luis

  DOI：10.1002/cmdc.202300651

  日期：——

  In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR‐TKD) and cyclooxygenase‐2 (COX‐2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A‐431, MCF‐7, MDA‐MB‐231) and epithelial non‐tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC₅₀) than gefitinib (reference drug) on three cancer cell lines (0.034 μM in A‐431, 2.67 μM in MCF‐7, and 3.64 μM in AGS) without showing activity on the non‐tumorigenic cell line (>100 μM). Furthermore, assessment of EGFR‐TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an in vivo anti‐inflammatory assay using the 12‐O‐tetradecanoylphorbol‐3‐acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR‐TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX‐2, involving S531. The RMSD graph indicated that the ligand remained stable in 50 ns.