1-cyclopropyl-6-fluoro-4-oxo-7-(4-((4-(trifluoromethyl)phenyl)carbamothioyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid

• 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-cyclopropyl-6-fluoro-4-oxo-7-(4-((4-(trifluoromethyl)phenyl)carbamothioyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 1-cyclopropyl-6-fluoro-4-oxo-7-[4-[[4-(trifluoromethyl)phenyl]carbamothioyl]piperazin-1-yl]quinoline-3-carboxylic acid
• 化学式: C₂₅H₂₂F₄N₄O₃S
• 分子量: 534.534
• InChiKey: DMUZWIXJZNKJPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-cyclopropyl-6-fluoro-4-oxo-7-(4-((4-(trifluoromethyl)phenyl)carbamothioyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 N-(2-aminoethyl)-1-cyclopropyl-6-fluoro-4-oxo-7-(4-((4-(trifluoromethyl)phenyl)carbamothioyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxamide
  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：

  ethyl 3-(dimethylamino)-2-(2,4,5-trifluorobenzoyl)acrylate 在 potassium carbonate 作用下， 以 乙醚 、 乙醇 、 乙腈 为溶剂， 反应 59.0h， 生成 1-cyclopropyl-6-fluoro-4-oxo-7-(4-((4-(trifluoromethyl)phenyl)carbamothioyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  10.1039/d4sc00995a

  摘要：

  DOI：

  10.1039/d4sc00995a

文献信息

• ANTIBIOTIC COMPOUNDS AND COMPOSITIONS, AND METHODS FOR IDENTIFICATION THEREOF
  申请人：Fred Hutchinson Cancer Research Center

  公开号：US20150126519A1

  公开（公告）日：2015-05-07

  Disclosed herein are compounds and methods for inhibiting bacterial DNA repair enzymes, including AddAB and RecBCD helicase-nucleases. Pharmaceutical compositions and methods for treating a subject with an antibacterial agent are also disclosed herein.
• [EN] ANTIBIOTIC COMPOUNDS AND COMPOSITIONS, AND METHODS FOR IDENTIFICATION THEREOF<br/>[FR] COMPOSÉS ET COMPOSITIONS ANTIBIOTIQUES, ET PROCÉDÉS D'IDENTIFICATION ASSOCIÉS
  申请人：HUTCHINSON FRED CANCER RES

  公开号：WO2013142628A2

  公开（公告）日：2013-09-26

  Disclosed herein are compounds and methods for inhibiting bacterial DNA repair enzymes, including AddAB and RecBCD helicase-nucleases. Pharmaceutical compositions and methods for treating a subject with an antibacterial agent are also disclosed herein.
• Identification of a potent small-molecule inhibitor of bacterial DNA repair that potentiates quinolone antibiotic activity in methicillin-resistant Staphylococcus aureus
  作者：Carine S.Q. Lim、Kam Pou Ha、Rebecca S. Clarke、Leigh-Anne Gavin、Declan T. Cook、Jennie A. Hutton、Charlotte L. Sutherell、Andrew M. Edwards、Lindsay E. Evans、Edward W. Tate、Thomas Lanyon-Hogg

  DOI：10.1016/j.bmc.2019.06.025

  日期：2019.10

  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.
• 10.1039/d4sc00995a
  作者：Bradbury, Jacob D.、Hodgkinson, Thomas、Thomas, Adam M.、Tanwar, Omprakash、La Monica, Gabriele、Rogga, Vanessa V.、Mackay, Luke J.、Taylor, Emilia K.、Gilbert, Kiera、Zhu, Yihua、Sefton, Amber Y.、Edwards, Andrew M.、Gray-Hammerton, Charlotte J.、Smith, Gerald R.、Roberts, Paul M.、Walsh, Timothy R.、Lanyon-Hogg, Thomas

  DOI：10.1039/d4sc00995a

  日期：——