7-<3-<(tert-butoxycarbonyl)amino>-1-pyrrolidinyl>-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid | 99724-20-6

• 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: 7-<3-<(tert-butoxycarbonyl)amino>-1-pyrrolidinyl>-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
• 英文别名: 7-(3-((tert-butoxycarbonyl)amino)pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid；1-Cyclopropyl-7-[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid；1-cyclopropyl-6-fluoro-7-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]-4-oxoquinoline-3-carboxylic acid
• CAS: 99724-20-6
• 化学式: C₂₂H₂₆FN₃O₅
• 分子量: 431.464
• InChiKey: CMCJXJBMBUDOIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.2
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  1-环丙基-6,7-二氟-4-氧代-1,4-二氢喹啉-3-羧酸乙酯 在 盐酸 作用下， 以 吡啶 为溶剂， 反应 18.0h， 生成 7-<3-<(tert-butoxycarbonyl)amino>-1-pyrrolidinyl>-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
  参考文献：
  名称：

  喹诺酮类抗菌剂。8-取代的喹啉-3-羧酸和1,8-萘啶-3-羧酸的合成及构效关系。

  摘要：

  一系列7,8-二取代的1-环丙基-6-氟喹啉-3-羧酸，7-取代的1-环丙基-6-氟-1,8-萘啶-3-羧酸和10-取代的9-氟吡啶并苯并恶嗪已经制备了-6-羧酸并评估了其抗菌活性。在7-位（苯并恶嗪10-位）检测的侧链包括哌嗪基（g），3-氨基吡咯烷基（a），3-（氨基甲基）吡咯烷基（b）和烷基化的3-（氨基甲基）吡咯烷基（cf）。喹诺酮环系统C-8的变异包括氢，硝基，氨基，氟和氯。8氢喹诺酮和1,8-萘啶上侧链对革兰氏阴性生物的体外活性的相对增强比cf更大，b更大，g更大。由8个取代基赋予取代的喹诺酮核的活性的顺序为：F大于Cl大于萘啶大于H大于苯并恶嗪大于NH2大于NO2。这些趋势在体内得以保留。

  DOI：

  10.1021/jm00400a016

文献信息

• Rifamycin derivatives effective against drug-resistant microbes
  申请人：Ma Zhenkun

  公开号：US20050261262A1

  公开（公告）日：2005-11-24

  Rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms are claimed in this invention. The inventive rifamycin derivatives are uniquely designed in that they have a rifamycin moiety covalently linked to a linker group through the C-3 carbon of the rifamycin moiety and the linker is, in turn covalently linked to a therapeutic moiety or antibacterial agent/pharmacophore. The therapeutic moiety can be a quinolone, an oxazolidinone, a macrolide, an aminoglycoside, a tetracycline core or a structure/pharmacophore associated with an antibacterial agent.

  本发明涉及具有抗微生物活性的利福霉素衍生物，包括对耐药微生物的活性。本发明的利福霉素衍生物独特地设计在于，它们具有利福霉素基团通过利福霉素基团的C-3碳与连接基团共价连接，并且连接基团进一步与治疗性基团或抗菌剂/药效团共价连接。治疗性基团可以是喹诺酮、噁唑烷酮、大环内酯、氨基糖苷、四环素核心或与抗菌剂相关的结构/药效团。
• SANCHEZ, JOSEPH P.;DOMAGALA, JOHN M.;HAGEN, SUSAN E.;HEIFETZ, CARL L.;HUT+, J. MED. CHEM., 31,(1988) N 5, 983-991
  作者：SANCHEZ, JOSEPH P.、DOMAGALA, JOHN M.、HAGEN, SUSAN E.、HEIFETZ, CARL L.、HUT+

  DOI：——

  日期：——
• RIFAMYCIN DERIVATIVES EFFECTIVE AGAINST DRUG-RESISTANT MICROBES
  申请人：Cumbre Pharmaceuticals Inc.

  公开号：EP1730154A2

  公开（公告）日：2006-12-13
• US7247634B2
  申请人：——

  公开号：US7247634B2

  公开（公告）日：2007-07-24
• [EN] RIFAMYCIN DERIVATIVES EFFECTIVE AGAINST DRUG-RESISTANT MICROBES<br/>[FR] DERIVES DE RIFAMYCINE EFFICACES CONTRE DES MICROBES PHARMACORESISTANTS
  申请人：CUMBRE INC

  公开号：WO2005070940A2

  公开（公告）日：2005-08-04

  Rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms are claimed in this invention. The inventive rifamycin derivatives are uniquely designed in that they have a rifamycin moiety covalently linked to a linker group through the C-3 carbon of the rifamycin moiety and the linker is, in turn covalently linked to a therapeutic moiety or antibacterial agent/pharmacophore. The therapeutic moiety can be a quinolone, an oxazolidinone, a macrolide, an aminoglycoside, a tetracycline core or a structure/pharmacophore associated with an antibacterial agent.