1-(3-Carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)pyrrolidin-3-aminium chloride | 133121-48-9

• 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: 1-(3-Carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)pyrrolidin-3-aminium chloride
• 英文别名: 7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1H-quinolin-1-ium-3-carboxylic acid;chloride
• CAS: 133121-48-9
• 化学式: C₁₇H₁₈FN₃O₃*ClH
• 分子量: 367.808
• InChiKey: JTGFVPLSVVANFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.13
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  86.9
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(3-Carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)pyrrolidin-3-aminium chloride 、 4-(三氟甲基)异硫氰酸苯酯 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以100%的产率得到1-cyclopropyl-6-fluoro-4-oxo-7-(3-(3-(4-(trifluoromethyl)phenyl)thioureido)pyrrolidin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Identification of a potent small-molecule inhibitor of bacterial DNA repair that potentiates quinolone antibiotic activity in methicillin-resistant Staphylococcus aureus

  摘要：

  The global emergence of antibiotic resistance is one of the most serious challenges facing modern medicine. There is an urgent need for validation of new drug targets and the development of small molecules with novel mechanisms of action. We therefore sought to inhibit bacterial DNA repair mediated by the AddAB/RecBCD protein complexes as a means to sensitize bacteria to DNA damage caused by the host immune system or quinolone antibiotics. A rational, hypothesis-driven compound optimization identified IMP-1700 as a cell-active, nanomolar potency compound. IMP-1700 sensitized multidrug-resistant Staphylococcus aureus to the fluoroquinolone antibiotic ciprofloxacin, where resistance results from a point mutation in the fluoroquinolone target, DNA gyrase. Cellular reporter assays indicated IMP-1700 inhibited the bacterial SOS-response to DNA damage, and compoundfunctionalized Sepharose successfully pulled-down the AddAB repair complex. This work provides validation of bacterial DNA repair as a novel therapeutic target and delivers IMP-1700 as a tool molecule and starting point for therapeutic development to address the pressing challenge of antibiotic resistance.

  DOI：

  10.1016/j.bmc.2019.06.025
• 作为产物：
  描述：

  7-<3-<(tert-butoxycarbonyl)amino>-1-pyrrolidinyl>-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以100%的产率得到1-(3-Carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)pyrrolidin-3-aminium chloride
  参考文献：
  名称：

  Identification of a potent small-molecule inhibitor of bacterial DNA repair that potentiates quinolone antibiotic activity in methicillin-resistant Staphylococcus aureus

  摘要：

  The global emergence of antibiotic resistance is one of the most serious challenges facing modern medicine. There is an urgent need for validation of new drug targets and the development of small molecules with novel mechanisms of action. We therefore sought to inhibit bacterial DNA repair mediated by the AddAB/RecBCD protein complexes as a means to sensitize bacteria to DNA damage caused by the host immune system or quinolone antibiotics. A rational, hypothesis-driven compound optimization identified IMP-1700 as a cell-active, nanomolar potency compound. IMP-1700 sensitized multidrug-resistant Staphylococcus aureus to the fluoroquinolone antibiotic ciprofloxacin, where resistance results from a point mutation in the fluoroquinolone target, DNA gyrase. Cellular reporter assays indicated IMP-1700 inhibited the bacterial SOS-response to DNA damage, and compoundfunctionalized Sepharose successfully pulled-down the AddAB repair complex. This work provides validation of bacterial DNA repair as a novel therapeutic target and delivers IMP-1700 as a tool molecule and starting point for therapeutic development to address the pressing challenge of antibiotic resistance.

  DOI：

  10.1016/j.bmc.2019.06.025

文献信息

• PETERSEN, UWE;KREBS, ANDREAS;SCHENKE, THOMAS;GROHE, KLAUS;HALLER, INGO;ME+
  作者：PETERSEN, UWE、KREBS, ANDREAS、SCHENKE, THOMAS、GROHE, KLAUS、HALLER, INGO、ME+

  DOI：——

  日期：——
• US5061712A
  申请人：——

  公开号：US5061712A

  公开（公告）日：1991-10-29
• US5648493A
  申请人：——

  公开号：US5648493A

  公开（公告）日：1997-07-15
• US5723627A
  申请人：——

  公开号：US5723627A

  公开（公告）日：1998-03-03