9-cyclopropyl-7-(2,4-dimethoxybenzylamino)-6-fluoro-8-methoxy-9H-isothiazolo[5,4-b]quinoline-3,4-dione | 922718-52-3

• 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: 9-cyclopropyl-7-(2,4-dimethoxybenzylamino)-6-fluoro-8-methoxy-9H-isothiazolo[5,4-b]quinoline-3,4-dione
• 英文别名: 9-Cyclopropyl-7-[(2,4-dimethoxyphenyl)methylamino]-6-fluoro-8-methoxy-[1,2]thiazolo[5,4-b]quinoline-3,4-dione
• CAS: 922718-52-3
• 化学式: C₂₃H₂₂FN₃O₅S
• 分子量: 471.509
• InChiKey: PFFALSDVIBPYCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9-cyclopropyl-7-(2,4-dimethoxybenzylamino)-6-fluoro-8-methoxy-9H-isothiazolo[5,4-b]quinoline-3,4-dione 在 四(三苯基膦)钯 亚硝酸特丁酯 、 碳酸氢钠 、 copper(ll) bromide 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.5h， 生成
  参考文献：
  名称：

  Isothiazoloquinolones with Enhanced Antistaphylococcal Activities against Multidrug-Resistant Strains:  Effects of Structural Modifications at the 6-, 7-, and 8-Positions

  摘要：

  We describe the biological evaluation of isothiazoloquinolones (ITQs) having structural modifications at the 6-, 7-, and 8-positions. Addition of a methoxy substituent to C-8 effected an increase in antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and a decrease in cytotoxic activity against Hep2 cells. Removal of fluorine from C-6 or replacement of the C-8 carbon with a nitrogen compromised anti-MRSA activity. When the groups attached at C-7 were compared, the anti-MRSA activity decreased in the order 6-isoquinolinyl > 4-pyridinyl > 5-dihydroisoindolyl > 6-tetrahydroisoquinolinyl. The compound with the most desirable in vitro biological profile was 9-cyclopropyl-6-fluoro-8-methoxy-7-(2-methylpyridin-4-yl)-9H-isothiazolo[5,4-b]quinoline-3,4-dione (7g). This ITQ demonstrated (i) strong in vitro anti-MRSA activity (MIC90 = 0.5 mu g/mL), (ii) strong inhibitory activities against S. aureus DNA gyrase and topoisomerase IV, with weak activity against human topoisomerase II, (iii) weak cytotoxic activities against three cell lines, and (iv) efficacy in an in vivo murine thigh model of infection employing MRSA.

  DOI：

  10.1021/jm060844e
• 作为产物：
  描述：

  ethyl 1-cyclopropyl-6,7-difluoro-2-mercapto-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 碳酸氢钠 、 hydroxylamine-O-sulfonic acid 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 反应 24.0h， 生成 9-cyclopropyl-7-(2,4-dimethoxybenzylamino)-6-fluoro-8-methoxy-9H-isothiazolo[5,4-b]quinoline-3,4-dione
  参考文献：
  名称：

  Isothiazoloquinolones with Enhanced Antistaphylococcal Activities against Multidrug-Resistant Strains:  Effects of Structural Modifications at the 6-, 7-, and 8-Positions

  摘要：

  We describe the biological evaluation of isothiazoloquinolones (ITQs) having structural modifications at the 6-, 7-, and 8-positions. Addition of a methoxy substituent to C-8 effected an increase in antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and a decrease in cytotoxic activity against Hep2 cells. Removal of fluorine from C-6 or replacement of the C-8 carbon with a nitrogen compromised anti-MRSA activity. When the groups attached at C-7 were compared, the anti-MRSA activity decreased in the order 6-isoquinolinyl > 4-pyridinyl > 5-dihydroisoindolyl > 6-tetrahydroisoquinolinyl. The compound with the most desirable in vitro biological profile was 9-cyclopropyl-6-fluoro-8-methoxy-7-(2-methylpyridin-4-yl)-9H-isothiazolo[5,4-b]quinoline-3,4-dione (7g). This ITQ demonstrated (i) strong in vitro anti-MRSA activity (MIC90 = 0.5 mu g/mL), (ii) strong inhibitory activities against S. aureus DNA gyrase and topoisomerase IV, with weak activity against human topoisomerase II, (iii) weak cytotoxic activities against three cell lines, and (iv) efficacy in an in vivo murine thigh model of infection employing MRSA.

  DOI：

  10.1021/jm060844e

文献信息

• Isothiazoloquinolones with Enhanced Antistaphylococcal Activities against Multidrug-Resistant Strains:  Effects of Structural Modifications at the 6-, 7-, and 8-Positions
  作者：Qiuping Wang、Edlaine Lucien、Akihiro Hashimoto、Godwin C. G. Pais、David M. Nelson、Yongsheng Song、Jane A. Thanassi、Christopher W. Marlor、Christy L. Thoma、Jijun Cheng、Steven D. Podos、Yangsi Ou、Milind Deshpande、Michael J. Pucci、Douglas D. Buechter、Barton J. Bradbury、Jason A. Wiles

  DOI：10.1021/jm060844e

  日期：2007.1.1

  We describe the biological evaluation of isothiazoloquinolones (ITQs) having structural modifications at the 6-, 7-, and 8-positions. Addition of a methoxy substituent to C-8 effected an increase in antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and a decrease in cytotoxic activity against Hep2 cells. Removal of fluorine from C-6 or replacement of the C-8 carbon with a nitrogen compromised anti-MRSA activity. When the groups attached at C-7 were compared, the anti-MRSA activity decreased in the order 6-isoquinolinyl > 4-pyridinyl > 5-dihydroisoindolyl > 6-tetrahydroisoquinolinyl. The compound with the most desirable in vitro biological profile was 9-cyclopropyl-6-fluoro-8-methoxy-7-(2-methylpyridin-4-yl)-9H-isothiazolo[5,4-b]quinoline-3,4-dione (7g). This ITQ demonstrated (i) strong in vitro anti-MRSA activity (MIC90 = 0.5 mu g/mL), (ii) strong inhibitory activities against S. aureus DNA gyrase and topoisomerase IV, with weak activity against human topoisomerase II, (iii) weak cytotoxic activities against three cell lines, and (iv) efficacy in an in vivo murine thigh model of infection employing MRSA.