3-amino-6,7-difluoro-2-methylquinazolin-4(3H)-one

• 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-amino-6,7-difluoro-2-methylquinazolin-4(3H)-one
• 化学式: C₉H₇F₂N₃O
• 分子量: 211.171
• InChiKey: LBJWDDMPGLWBSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  60.91
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-amino-6,7-difluoro-2-methylquinazolin-4(3H)-one 、 3-甲基哌啶 以 二甲基亚砜 为溶剂， 反应 9.0h， 以79%的产率得到3-amino-6-fluoro-2-methyl-7-(3-methylpiperidin-1-yl)-3H-quinazolin-4-one
  参考文献：
  名称：

  Synthesis of 7-cycloalkylimino substituted 3-amino-6-fluoro-2-methyl-3H-quinazolin-4-ones

  摘要：

  A versatile pathway for the synthesis of 7-cycloalkylimino substituted 3-amino-6-fluoro-2-methyl-3H-quinazolin-4-ones from 4,5-difluoroanthranylic acid has been advanced. Nucleophilic amination-defluorination reaction of the 6,7-difluoro derivative of 3-amino-2-methyl-3H-quinazolin-4-one has been established to occur at position 7, as shown by X-ray crystallographic analysis. (c) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jfluchem.2012.10.003
• 作为产物：
  描述：

  6,7-difluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one 在 hydrazine hydrate 作用下， 以 乙醇 为溶剂， 以62 %的产率得到3-amino-6,7-difluoro-2-methylquinazolin-4(3H)-one
  参考文献：
  名称：

  Development of Quinazolinone Derivatives as Modulators of Virulence Factors of Pseudomonas aeruginosa Cystic Fibrosis Strains

  摘要：

  铜绿假单胞菌（Pseudomonas aeruginosa，PA）是 ESKAPE 病原体之一，是一种机会性革兰阴性菌，不仅可引起人类的院内感染，还可引起艾滋病、癌症或囊性纤维化（CF）患者的感染。由于 PA 能通过形成生物膜获得抗生素耐受性，因此治疗 CF 患者的 PA 感染是一个全球性的医疗保健问题。抗真菌化合物是一种很有前景的辅助治疗方法，它可以在不影响 PA 生长的情况下降低或消除 PA 的致病性。焦花青素是一种毒力因子，它的产生受假单胞菌喹诺酮信号（PQS）通过其受体 PqsR 的调节。多年来，人们合成了不同的 PqsR 调节剂，凸显了这一新的强大治疗策略。基于喹唑啉-4(3H)-酮的良好结构，我们开发了化合物 7a-d、8a,b、9、10 和 11a-f，这些化合物能在 50 µM 的浓度下减少导致 CF 急性和慢性感染的两种 PA 菌株的生物膜形成和毒力因子（脓蓝蛋白和焦维丁）的产生。所开发的化合物不会降低 IB3-1 支气管 CF 细胞的活力，计算研究证实了新型化合物作为潜在 Pqs 系统调节剂的潜在能力。

  DOI：

  10.3390/molecules28186535

文献信息

• Fluorine-containing heterocycles: XIX. Synthesis of fluorine-containing quinazolin-4-ones from 3,1-benzoxazin-4-ones
  作者：A. A. Laeva、E. V. Nosova、G. N. Lipunova、A. V. Golovchenko、N. Yu. Adonin、V. N. Parmon、V. N. Charushin

  DOI：10.1134/s1070428009060190

  日期：2009.6

  Reactions of fluorine-containing 3,1-benzoxazin-4-ones with ammonium acetate, hydrazine, and heteroaromatic amines gave new 3H-, 3-amino-, and 3-hetarylquinazolin-4-ones, respectively. Differences in the conditions of formation of benzoxazinones from anthranilic acids with different fluorination patterns and in the reactions of fluorinated 3,1-benzoxazinones with nitrogen-centered nucleophiles were revealed.
• Synthesis of 7-cycloalkylimino substituted 3-amino-6-fluoro-2-methyl-3H-quinazolin-4-ones
  作者：Emiliya V. Nosova、Galina N. Lipunova、Pavel A. Slepukhin、Valery N. Charushin

  DOI：10.1016/j.jfluchem.2012.10.003

  日期：2013.1

  A versatile pathway for the synthesis of 7-cycloalkylimino substituted 3-amino-6-fluoro-2-methyl-3H-quinazolin-4-ones from 4,5-difluoroanthranylic acid has been advanced. Nucleophilic amination-defluorination reaction of the 6,7-difluoro derivative of 3-amino-2-methyl-3H-quinazolin-4-one has been established to occur at position 7, as shown by X-ray crystallographic analysis. (c) 2012 Elsevier B.V. All rights reserved.
• Development of Quinazolinone Derivatives as Modulators of Virulence Factors of Pseudomonas aeruginosa Cystic Fibrosis Strains
  作者：Gabriele Carullo、Giovanni Di Bonaventura、Sara Rossi、Veronica Lupetti、Valeria Tudino、Simone Brogi、Stefania Butini、Giuseppe Campiani、Sandra Gemma、Arianna Pompilio

  DOI：10.3390/molecules28186535

  日期：——

  Pseudomonas aeruginosa (PA), one of the ESKAPE pathogens, is an opportunistic Gram-negative bacterium responsible for nosocomial infections in humans but also for infections in patients affected by AIDS, cancer, or cystic fibrosis (CF). Treatment of PA infections in CF patients is a global healthcare problem due to the ability of PA to gain antibiotic tolerance through biofilm formation. Anti-virulence compounds represent a promising approach as adjuvant therapy, which could reduce or eliminate the pathogenicity of PA without impacting its growth. Pyocyanin is one of the virulence factors whose production is modulated by the Pseudomonas quinolone signal (PQS) through its receptor PqsR. Different PqsR modulators have been synthesized over the years, highlighting this new powerful therapeutic strategy. Based on the promising structure of quinazolin-4(3H)-one, we developed compounds 7a–d, 8a,b, 9, 10, and 11a–f able to reduce biofilm formation and the production of virulence factors (pyocyanin and pyoverdine) at 50 µM in two PA strains responsible for CF acute and chronic infections. The developed compounds did not reduce the cell viability of IB3-1 bronchial CF cells, and computational studies confirmed the potential ability of novel compounds to act as potential Pqs system modulators.

  铜绿假单胞菌（Pseudomonas aeruginosa，PA）是 ESKAPE 病原体之一，是一种机会性革兰阴性菌，不仅可引起人类的院内感染，还可引起艾滋病、癌症或囊性纤维化（CF）患者的感染。由于 PA 能通过形成生物膜获得抗生素耐受性，因此治疗 CF 患者的 PA 感染是一个全球性的医疗保健问题。抗真菌化合物是一种很有前景的辅助治疗方法，它可以在不影响 PA 生长的情况下降低或消除 PA 的致病性。焦花青素是一种毒力因子，它的产生受假单胞菌喹诺酮信号（PQS）通过其受体 PqsR 的调节。多年来，人们合成了不同的 PqsR 调节剂，凸显了这一新的强大治疗策略。基于喹唑啉-4(3H)-酮的良好结构，我们开发了化合物 7a-d、8a,b、9、10 和 11a-f，这些化合物能在 50 µM 的浓度下减少导致 CF 急性和慢性感染的两种 PA 菌株的生物膜形成和毒力因子（脓蓝蛋白和焦维丁）的产生。所开发的化合物不会降低 IB3-1 支气管 CF 细胞的活力，计算研究证实了新型化合物作为潜在 Pqs 系统调节剂的潜在能力。