6-hydroxy-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid 5-methyl-1,3,4-thiadiazol-2-ylamide | 384365-95-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-hydroxy-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid 5-methyl-1,3,4-thiadiazol-2-ylamide
• 英文别名: 6-hydroxy-N-(5-methyl-1,3,4-thiadiazol-2-yl)-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide；9-hydroxy-N-(5-methyl-1,3,4-thiadiazol-2-yl)-11-oxo-1-azatricyclo[6.3.1.04,12]dodeca-4(12),5,7,9-tetraene-10-carboxamide
• CAS: 384365-95-1
• 化学式: C₁₅H₁₂N₄O₃S
• 分子量: 328.351
• InChiKey: DMQFXPNXMNWKBM-UHFFFAOYSA-N

物化性质

• 熔点：
  265-267 °C(Solv: N,N-dimethylformamide (68-12-2))
• 密度：
  1.63±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  吲哚啉 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 6-hydroxy-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid 5-methyl-1,3,4-thiadiazol-2-ylamide
  参考文献：
  名称：

  Discovery of 4-hydroxy-2-oxo-1,2-dihydroquinolines as potential inhibitors of Streptococcus pneumoniae, including drug-resistant strains

  摘要：

  New therapies for treating drug-resistant pneumococcal infections are urgently needed. The novel scaffold 6hydroxy-4-oxo-1,2-dihydro-4H-quinoline was shown to have similar efficacies against all three different serotypes of S. pneumoniae, ATCC 49617 (TM) (19F), ATCC BAA-1663 (TM) (15B), and ATCC 700904 (TM) (19A), in a resazurin-based high-throughput screen using the Korea Chemical Bank library. Further studies to identify a new lead with this scaffold, including tricyclic pyrrolo[3,2,1-ij]quinolone and pyrido[3,2,1-ij]quinolone derivatives, led to the identification of 6d, 7d and 12a. Compound 6d (IC50 = 0.92, 0.75, and 0.77 mu M), 7d (IC50 = 0.57, 0.66, and 0.38 mu M) and 12a (IC50, = 0.27, 1.03, and 0.62 mu M) showed submicromolar IC50, values against 19F, 15B, and 19A, respectively, and thus serve as a starting point for further optimization. While some of compounds in this series exhibited acceptable pharmacokinetic profiles in preliminary in vivo rat experiments, the most active compound 12a showed poor solubility and high plasma protein binding. Our current research efforts are focused on optimizing compounds to improve physicochemical properties as well as potency.

  DOI：

  10.1016/j.bmcl.2020.127071

文献信息

• 4-Hydroxy-2-quinolones. 122. 1-Hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]-quinoline-2-carboxylic acid hetarylamides as potential antitubercular agents
  作者：I. V. Ukrainets、E. V. Mospanova、L. V. Sidorenko

  DOI：10.1007/s10593-007-0137-3

  日期：2007.7
• Discovery of 4-hydroxy-2-oxo-1,2-dihydroquinolines as potential inhibitors of Streptococcus pneumoniae, including drug-resistant strains
  作者：Srigouri Huddar、Chul Min Park、Hyung Jun Kim、Soojin Jang、Sunkyung Lee

  DOI：10.1016/j.bmcl.2020.127071

  日期：2020.5

  New therapies for treating drug-resistant pneumococcal infections are urgently needed. The novel scaffold 6hydroxy-4-oxo-1,2-dihydro-4H-quinoline was shown to have similar efficacies against all three different serotypes of S. pneumoniae, ATCC 49617 (TM) (19F), ATCC BAA-1663 (TM) (15B), and ATCC 700904 (TM) (19A), in a resazurin-based high-throughput screen using the Korea Chemical Bank library. Further studies to identify a new lead with this scaffold, including tricyclic pyrrolo[3,2,1-ij]quinolone and pyrido[3,2,1-ij]quinolone derivatives, led to the identification of 6d, 7d and 12a. Compound 6d (IC50 = 0.92, 0.75, and 0.77 mu M), 7d (IC50 = 0.57, 0.66, and 0.38 mu M) and 12a (IC50, = 0.27, 1.03, and 0.62 mu M) showed submicromolar IC50, values against 19F, 15B, and 19A, respectively, and thus serve as a starting point for further optimization. While some of compounds in this series exhibited acceptable pharmacokinetic profiles in preliminary in vivo rat experiments, the most active compound 12a showed poor solubility and high plasma protein binding. Our current research efforts are focused on optimizing compounds to improve physicochemical properties as well as potency.