2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(2,6-dimethylphenyl)acetamide | 1226760-09-3

• 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-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(2,6-dimethylphenyl)acetamide
• 英文别名: 2-[3-[(4-bromo-2-fluoro-phenyl)methyl]-4-oxo-phthalazin-1-yl]-N-(2,6-dimethylphenyl)acetamide；2-[3-[(4-bromo-2-fluorophenyl)methyl]-4-oxophthalazin-1-yl]-N-(2,6-dimethylphenyl)acetamide
• CAS: 1226760-09-3
• 化学式: C₂₅H₂₁BrFN₃O₂
• 分子量: 494.363
• InChiKey: YPWZRYOQYVTPGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  波来瑞斯 、 2,6-二甲基苯胺 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以83%的产率得到2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(2,6-dimethylphenyl)acetamide
  参考文献：
  名称：

  Synthesis and Antimycobacterial Evaluation of Novel Phthalazin-4-ylacetamides Against log- and Starved Phase Cultures

  摘要：

  Twenty four novel 2‐[3‐(4‐bromo‐2‐fluorobenzyl)‐4‐oxo‐3,4‐dihydro‐1‐phthalazinyl]acetic acid amides were synthesized from phthalic anhydride and were subjected to in vitro and in vivo evaluation against log‐ and starved phase of mycobacterial species and Mycobacterium tuberculosis isocitrate lyase enzyme inhibition studies. Among the compounds screened, 2‐(2‐(4‐bromo‐2‐fluorobenzyl)‐1,2‐dihydro‐1‐oxophthalazin‐4‐yl)‐N‐(2,6‐dimethylphenyl)acetamide (5j) inhibited all eight mycobacterial species with MIC’s ranging from 0.08 to 5.05 μm and was non‐toxic to Vero cells till 126.43 μm. Four compounds were tested against starved culture of Mycobacterium tuberculosis and they inhibited with MIC’s ranging from 3.78 to 23.2 μm. Some compounds showed 40–66% inhibition against Mycobacterium tuberculosis isocitrate lyase enzyme at 10 μm. The docking studies also confirmed the binding potential of the compounds at the isocitrate lyase active site. In the in vivo animal model, 5j reduced the mycobacterial load in lung and spleen tissues with 1.38 and 2.9‐log10 protections, respectively, at 25 mg/kg body weight dose.

  DOI：

  10.1111/j.1747-0285.2010.00947.x

文献信息

• Synthesis and Antimycobacterial Evaluation of Novel Phthalazin-4-ylacetamides Against log- and Starved Phase Cultures
  作者：Dharmarajan Sriram、Perumal Yogeeswari、Palaniappan Senthilkumar、Dewakar Sangaraju、Rohit Nelli、Debjani Banerjee、Pritesh Bhat、Thimmappa H. Manjashetty

  DOI：10.1111/j.1747-0285.2010.00947.x

  日期：2010.4

  Twenty four novel 2‐[3‐(4‐bromo‐2‐fluorobenzyl)‐4‐oxo‐3,4‐dihydro‐1‐phthalazinyl]acetic acid amides were synthesized from phthalic anhydride and were subjected to in vitro and in vivo evaluation against log‐ and starved phase of mycobacterial species and Mycobacterium tuberculosis isocitrate lyase enzyme inhibition studies. Among the compounds screened, 2‐(2‐(4‐bromo‐2‐fluorobenzyl)‐1,2‐dihydro‐1‐oxophthalazin‐4‐yl)‐N‐(2,6‐dimethylphenyl)acetamide (5j) inhibited all eight mycobacterial species with MIC’s ranging from 0.08 to 5.05 μm and was non‐toxic to Vero cells till 126.43 μm. Four compounds were tested against starved culture of Mycobacterium tuberculosis and they inhibited with MIC’s ranging from 3.78 to 23.2 μm. Some compounds showed 40–66% inhibition against Mycobacterium tuberculosis isocitrate lyase enzyme at 10 μm. The docking studies also confirmed the binding potential of the compounds at the isocitrate lyase active site. In the in vivo animal model, 5j reduced the mycobacterial load in lung and spleen tissues with 1.38 and 2.9‐log10 protections, respectively, at 25 mg/kg body weight dose.