ethyl 7-bromo-1-cyclopropyl-8-methoxy-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylate | 846563-98-2

• 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: ethyl 7-bromo-1-cyclopropyl-8-methoxy-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 7-bromo-1-cyclopropyl-8-methoxy-2-methylsulfanyl-4-oxoquinoline-3-carboxylate
• CAS: 846563-98-2
• 化学式: C₁₇H₁₈BrNO₄S
• 分子量: 412.304
• InChiKey: DLGVJCUUTJOREL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  81.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 7-bromo-1-cyclopropyl-8-methoxy-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 sodium hydrogensulfide 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 ethyl 7-bromo-1-cyclopropyl-2-mercapto-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate
  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：

  3-氟-2-甲氧基苯胺 在 正丁基锂 、 草酰氯 、 氢溴酸 、 sodium hydride 、 N,N-二甲基甲酰胺 、 lithium diisopropyl amide 、 sodium nitrite 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 97.5h， 生成 ethyl 7-bromo-1-cyclopropyl-8-methoxy-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylate
  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

• [EN] ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS<br/>[FR] ANTI-INFECTIEUX A BASE D'ISOTHIAZOLOQUINOLONES ET DE SELS CORRESPONDANTS
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2005019228A1

  公开（公告）日：2005-03-03

  The invention provides compounds and salts of Formula (I) and Formula (II): which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula (I) and Formula (II). The variables A1, R2, R3, R5, R6, R7, A8 and R9 are defined herein. Certain compounds of Formula (I) and Formula (II) disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula (I) or Formula (II) and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula (I) or Formula (II) as the only active agent or may contain a combination of a compound of Formula (I) or Formula (II) and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  本发明提供了具有抗菌活性的公式(I)和公式(II)的化合物及盐类：本发明还提供了用于制造公式(I)和公式(II)化合物的新的合成中间体。变量A1、R2、R3、R5、R6、R7、A8和R9在此文中定义。本文披露的某些公式(I)和公式(II)化合物是细菌DNA合成和细菌复制的强效和选择性抑制剂。本发明还提供了含有一种或多种公式(I)或公式(II)化合物以及一种或多种载体、辅料或稀释剂的抗菌组合物，包括药物组合物。这样的组合物可以只含有公式(I)或公式(II)的化合物作为唯一的活性成分，也可以含有公式(I)或公式(II)的化合物与一种或多种其他活性成分的组合。本发明还提供了用于治疗动物微生物感染的方法。
• New isothiazoloquinolones and related compounds as anti-infective agents
  申请人：Bradbury James Barton

  公开号：US20060235041A1

  公开（公告）日：2006-10-19

  The invention provides certain compounds and salts of Formula I and Formula II: which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables A 1 , R 2 , R 3 , R 5 , R 6 , R 7 , A 8 and R 9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of a compound of Formula I or Formula II and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  本发明提供了公式I和公式II的某些化合物和盐：具有抗微生物活性。本发明还提供了在制备公式I和公式II的化合物中有用的新型合成中间体。本文中定义了变量A1、R2、R3、R5、R6、R7、A8和R9。本文披露的公式I和公式II的某些化合物是细菌DNA合成和细菌复制的有效和选择性抑制剂。本发明还提供了抗微生物组合物，包括制药组合物，其中包含一个或多个公式I或公式II的化合物和一个或多个载体、赋形剂或稀释剂。这样的组合物可以仅包含公式I或公式II的化合物作为唯一的活性剂，也可以包含公式I或公式II的化合物和一个或多个其他活性剂的组合物。本发明还提供了治疗动物微生物感染的方法。
• ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS
  申请人：Bradbury Barton James

  公开号：US20110223132A1

  公开（公告）日：2011-09-15

  The invention provides compounds and salts of Formula I and Formula which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables A 1 , R 2 , R 3 , R 5 , R 6 , R 7 , A 8 and R 9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of a compound of Formula I or Formula II and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  本发明提供了具有抗微生物活性的公式I和公式II的化合物和盐。本发明还提供了在制备公式I和公式II化合物中有用的新型合成中间体。变量A1、R2、R3、R5、R6、R7、A8和R9在此定义。本文所披露的某些公式I和公式II的化合物是细菌DNA合成和细菌复制的强效和选择性抑制剂。本发明还提供抗微生物组合物，包括含有一个或多个公式I或公式II化合物和一个或多个载体、赋形剂或稀释剂的药物组合物。这些组合物可以仅包含一个公式I或公式II化合物作为唯一活性剂，也可以包含一个公式I或公式II化合物和一个或多个其他活性剂的组合物。本发明还提供了治疗动物微生物感染的方法。
• Isothiazoloquinolones and related compounds as anti-infective agents
  申请人：Achillion Pharmaceuticals, Inc.

  公开号：US08114888B2

  公开（公告）日：2012-02-14

  The invention provides certain compounds and salts of Formula I and Formula II: which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables A1, R2, R3, R5, R6, R7, A8 and R9 are defined herein.

  本发明提供了某些化合物和盐的公式I和公式II：具有抗微生物活性。本发明还提供了制备公式I和公式II化合物有用的新型合成中间体。其中变量A1，R2，R3，R5，R6，R7，A8和R9在此定义。
• NEW ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS
  申请人：Bradbury Barton James

  公开号：US20120114601A1

  公开（公告）日：2012-05-10

  The invention provides certain compounds and salts of Formula I and Formula II: which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables A 1 , R 2 , R 3 , R 5 , R 6 , R 7 , A 8 and R 9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of a compound of Formula I or Formula II and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  本发明提供了公式I和公式II的某些化合物和盐：具有抗微生物活性。该发明还提供了制备公式I和公式II化合物有用的新型合成中间体。变量A1、R2、R3、R5、R6、R7、A8和R9在此有定义。本文披露的公式I和公式II的某些化合物是强效和选择性的细菌DNA合成和细菌复制抑制剂。本发明还提供了抗微生物组合物，包括含有公式I或公式II的一个或多个化合物和一个或多个载体、赋形剂或稀释剂的制药组合物。这样的组合物可以仅包含公式I或公式II的化合物作为唯一活性剂，或者可以包含公式I或公式II的化合物和一个或多个其他活性剂的组合。本发明还提供了治疗动物微生物感染的方法。