去乙烯基环丙沙星盐酸盐 | 528851-31-2

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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
• 中文名称: 去乙烯基环丙沙星盐酸盐
• 中文别名: 盐酸环丙沙星杂质C
• 英文名称: 7-((2-aminoethyl)amino)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 2-((3-carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)amino)ethan-1-aminium chloride；7-[(2-amino-ethyl)amino]-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-quinoline-3-carboxylic acid hydrochloride；Desethyleneciprofloxacin monohydrochloride；7-(2-aminoethylamino)-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid;hydrochloride
• CAS: 528851-31-2
• 化学式: C₁₅H₁₆FN₃O₃*ClH
• 分子量: 341.77
• InChiKey: ODOFTUIHVVTJRI-UHFFFAOYSA-N

物化性质

• 熔点：
  >240°C dec.
• 溶解度：
  DMSO（少许）、甲醇（少许）、水（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.97
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  95.7
• 氢给体数：
  4
• 氢受体数：
  7

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  去乙烯基环丙沙星盐酸盐 、 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64%的产率得到1-cyclopropyl-6-fluoro-4-oxo-7-((2-(3-(4-(trifluoromethyl)phenyl)thioureido)ethyl)amino)-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：

  1-环丙基-6,7-二氟-1,4-二氢-4-氧喹啉-3-羧酸 在 吡啶 、 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 去乙烯基环丙沙星盐酸盐
  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

• [EN] NOVEL 14 AND 15 MEMBERED-RING COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES A CYCLES A 14 ET 15 ELEMENTS
  申请人：GLAXO GROUP LTD

  公开号：WO2004101590A1

  公开（公告）日：2004-11-25

  The present invention relates to 15-membered macrolides substituted at the 4' position of formula (I) and pharmaceutically acceptable derivatives thereof, to processes for their preparation and their use in therapy or prophylaxis of systemic or topical microbial infections in a human or animal body.

  本发明涉及在式（I）的4'位置被取代的15元大环内酯及其药学上可接受的衍生物，以及它们的制备过程和在人体或动物体内治疗或预防系统性或局部微生物感染中的用途。
• Developing ciprofloxacin analogues against plant DNA gyrase: a novel herbicide mode of action
  作者：Michael D. Wallace、Nidda F. Waraich、Aleksandra W. Debowski、Maxime G. Corral、Anthony Maxwell、Joshua S. Mylne、Keith A. Stubbs

  DOI：10.1039/c7cc09518j

  日期：——

  The development of ciprofloxacin analogues against plant DNA gyrase, a novel herbicidal target, with increased herbicidal activity and diminished antibacterial activity is described.

  描述了对植物DNA旋转酶的环丙沙星类似物的开发，这是一种新的除草靶标，具有增强的除草活性和减弱的抗菌活性。
• Synthesis and activity of new macrolones: Conjugates between 6(7)-(2′-aminoethyl)-amino-1-cyclopropyl-3-carboxylic acid (2′-hydroxyethyl) amides and 4″-propenoyl-azithromycin
  作者：Samra Kapić、Andrea Fajdetić、Sanja Koštrun、Ana Čikoš、Hana Čipčić Paljetak、Roberto Antolović、David J. Holmes、Sulejman Alihodžić

  DOI：10.1016/j.bmc.2011.07.011

  日期：2011.12

  A set of novel macrolones containing the flexible C8 basic linker and quinolone 3-(2 '-hydroxyethyl)carboxamido group has been prepared and structurally characterized by NMR and IR spectroscopy, mass spectrometry and molecular modeling. The new compounds were evaluated in vitro against a panel of erythromycin-susceptible and erythromycin-resistant Gram-positive and Gram-negative bacterial strains. Compared to azithromycin, most of the compounds exhibited improved in vitro potency against the key respiratory pathogens. (C) 2011 Elsevier Ltd. All rights reserved.
• 4″-O-(ω-Quinolylamino-alkylamino)propionyl derivatives of selected macrolides with the activity against the key erythromycin resistant respiratory pathogens
  作者：A. Fajdetić、H. Čipčić Paljetak、G. Lazarevski、A. Hutinec、S. Alihodžić、M. Đerek、V. Štimac、D. Andreotti、V. Šunjić、J.M. Berge、S. Mutak、M. Dumić、S. Lociuro、D.J. Holmes、N. Maršić、V. Eraković Haber、R. Spaventi

  DOI：10.1016/j.bmc.2010.06.049

  日期：2010.9

  Four macrolides-6-O-methyl-8a-aza-8a-homoerythromycin, clarithromycin, azithromycin and azithromycin 11,12-cyclic carbonate, have been selected for the construction of a series of new quinolone derivatives. The quinolone moiety is connected to the macrolide scaffold via a diaminoaklyl 4"-O-propionyl ester chain of varying length. At the terminus the linker is attached via one of the nitrogen atoms in the linker at C(6) or C(7) of the quinolone. Many of compounds described, particularly clarithromycin derivative 37, and azithromycin derivatives 48 and 55, exhibited excellent antibacterial activity against a wide range of clinically relevant macrolide-resistant organisms, with profiles superior to that of telithromycin, an enhanced spectrum ketolide. (C) 2010 Elsevier Ltd. All rights reserved.
• 14 OR 15 MEMBERED MACROLIDES WITH ANTIBACTERIAL ACTIVITY
  申请人：GLAXO GROUP LIMITED

  公开号：EP1453846B1

  公开（公告）日：2007-05-16