cas 85721-33-1, Ciprofloxacin | Articles data

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Unrecognized role of humic acid as a reductant in accelerating fluoroquinolones oxidation by aqueous permanganate
A great concern has been raised regarding the issue of fluoroquinolones (FQs) in the environment. In this work, the transformation of FQs by commonly used oxidant permanganate (Mn(VII)) in the absence and presence of humic acid (HA), ubiquitously existing in aquatic environments, was systematically investigated. Here, the catalytic role of in-situ formed MnO2 on Mn(VII) oxidation of FQs depending on solution pH and co-existing substrates was firstly reported. It was interestingly found that HA could appreciably accelerate FQs degradation by Mn(VII) at environmentally relevant pH. HA as a reductant in accelerating FQs by Mn(VII) oxidation was distinctly elucidated for the first time, where MnO2 in situ formed from the reduction of Mn(VII) by HA served as a catalyst. Similar products were observed in the presence versus absence of HA. Considering that the accelerating role of HA was related to its reducing ability, an activation method based on Mn(VII) and reductant (i.e., Fe(II), Mn(II) and (bi)sulfite) was proposed, which exhibited considerable potential for application in the treatment of FQs contaminated water.
Zhou, Yang,Hu, Jianpeng,Gao, Yuan,Song, Yang,Pang, Su-Yan,Jiang, Jin
supporting information
p. 447 - 451
(2021/08/10)

On-Demand Continuous Manufacturing of Ciprofloxacin in Portable Plug-and-Play Factories: Development of a Highly Efficient Synthesis for Ciprofloxacin
The experimental approach taken and challenges overcome in developing a high-purity production (>100 g) scale process for the telescoped synthesis of the antibiotic ciprofloxacin is outlined. The process was first optimized for each step sequentially with regard to purity and yield, with necessary process changes identified and implemented before scaling for longer runs. These changes included implementing a continuous liquid-liquid extraction (CLLE) step and eliminating and replacing the base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) initially used in the ring-closure step due to DBU plausibly forming a decomposition side product that negatively impacted the final product purity. Process conditions were scaled 1.5-2-fold in order to enable the ultimate project goal of producing enough crude ciprofloxacin within 24 h to manufacture 1000 250 mg tablets. Working toward this goal, several production-scale runs were carried out to assess the reproducibility and robustness of the finalized process conditions, with the first three steps being run continuously up to 22 h and the last two steps being run continuously up to 10 h. The end result is a process with a throughput of ～29 g/h (～700 g/24 h) with a crude product stream profile of 94 ± 2% and 34 ± 3 mg/mL after five chemical transformations across four reactors and one continuous CLLE unit operation with each intermediate step maintaining a purity >95% by HPLC.
Armstrong, Cameron,Miyai, Yuma,Formosa, Anna,Thomas, Dale,Chen, Esther,Hart, Travis,Schultz, Victor,Desai, Bimbisar K.,Cai, Angela Y.,Almasy, Alexandra,Jensen, Klavs,Rogers, Luke,Roper, Tom
p. 1524 - 1533
(2021/07/21)

PAT Implementation on a Mobile Continuous Pharmaceutical Manufacturing System: Real-Time Process Monitoring with In-Line FTIR and Raman Spectroscopy
The strategies and experimental methods for implementation of process analytical technology (PAT) on the mobile pharmaceutical manufacturing system, Pharmacy on Demand (PoD), are discussed. With multiple processes to be monitored on the PoD end-to-end continuous manufacturing process, PAT and its real-time process monitoring capability play a significant role in ensuring final product quality. Here, we discuss PAT implementation for real-time monitoring of an intermediate and API concentrations with in-line Fourier-transformed infrared and Raman spectroscopy for the five-step continuous synthesis of ciprofloxacin on the PoD synthesis unit. Two partial least squares regression models were built and verified with flow chemistry experiments to obtain a root-mean-square error of prediction (RMSEP) of 2.2 mg/mL with a relative error of 2.8% for the step 2 FlowIR model and a RMSEP of 0.9 mg/mL with a relative error of 2.8% for the step 5 Raman model. These models were deployed during an 11 h step 1–3 and a 5 h step 4–5 continuous ciprofloxacin synthesis run performed on the PoD system. In these runs, the real-time prediction of intermediate and product concentration was achieved with an online model processing software (Solo_Predictor) and a PAT data collection and management software (synTQ).
Miyai, Yuma,Formosa, Anna,Armstrong, Cameron,Marquardt, Brian,Rogers, Luke,Roper, Thomas
p. 2707 - 2717
(2021/12/13)

Nitric oxide reactivity accounts for N-nitroso-ciprofloxacin formation under nitrate-reducing conditions
The formation of N-nitroso-ciprofloxacin (CIP) was investigated both in wastewater treatment plants including nitrification/denitrification stages and in sludge slurry experiments under denitrifying conditions. The analysis of biological wastewater treatment plant effluents by Kendrick mass defect analysis and liquid chromatography - high resolution - mass spectrometry (LC[sbnd]HRMS) revealed the occurrence of N-nitroso-CIP and N-nitroso-hydrochlorothiazide at concentration levels of 34 ± 3 ng/L and 71 ± 6 ng/L, respectively. In laboratory experiments and dark conditions, produced N-nitroso-CIP concentrations reached a plateau during the course of biodegradation experiments. A mass balance was achieved after identification and quantification of several transformation products by LC[sbnd]HRMS. N-nitroso-CIP accounted for 14.3% of the initial CIP concentration (20 μg/L) and accumulated against time. The use of 4,5-diaminofluorescein diacetate and superoxide dismutase as scavengers for in situ production of nitric oxide and superoxide radical anion respectively, revealed that the mechanisms of formation of N-nitroso-CIP likely involved a nitrosation pathway through the formation of peroxynitrite and another one through codenitrification processes, even though the former one appeared to be prevalent. This work extended the possible sources of N-nitrosamines by including a formation pathway relying on nitric oxide reactivity with secondary amines under activated sludge treatment.
Brienza, Monica,Chiron, Serge,Manasfi, Rayana,Sauvêtre, Andrés
(2020/08/21)

Design, synthesis and antimicrobial evaluation of novel glycosylated-fluoroquinolones derivatives
Herein we report the design, synthesis and biological evaluation of structurally modified ciprofloxacin, norfloxacin and moxifloxacin standard drugs, featuring amide functional groups at C-3 of the fluoroquinolone scaffold. In vitro antimicrobial testing against various Gram-positive bacteria, Gram-negative bacteria and fungi revealed potential antibacterial and antifungal activity. Hybrid compounds 9 (MIC 0.2668 ± 0.0001 mM), 10 (MIC 0.1358 ± 00025 mM) and 13 (MIC 0.0898 ± 0.0014 mM) had potential antimicrobial activity against a fluoroquinolone-resistant Escherichia coli clinical isolate, compared to ciprofloxacin (MIC 0.5098 ± 0.0024 mM) and norfloxacin (MIC 0.2937 ± 0.0021 mM) standard drugs. Interestingly, compound 10 also exerted potential antifungal activity against Candida albicans (MIC 0.0056 ± 0.0014 mM) and Penicillium chrysogenum (MIC 0.0453 ± 0.0156 mM). Novel derivatives and standard fluoroquinolone drugs exhibited near-identical cytotoxicity levels against L6 muscle cell-line, when measured using the MTT assay.
Mohammed, Aya A. M.,Okechukwu, Patrick N.,Shehadeh, Mayadah B.,Suaifan, Ghadeer A. R. Y.
(2020/07/04)

Ciprofloxacin conjugated to diphenyltin(iv): A novel formulation with enhanced antimicrobial activity
The metalloantibiotic of formula Ph2Sn(CIP)2 (CIPTIN) (HCIP = ciprofloxacin) was synthesized by reacting ciprofloxacin hydrochloride (HCIP·HCl) (an antibiotic in clinical use) with diphenyltin dichloride (Ph2SnCl2DPTD). The complex was characterized in the solid state by melting point, FT-IR, X-ray Powder Diffraction (XRPD) analysis, 119Sn M?ssbauer spectroscopy, X-ray Fluorescence (XRF) spectroscopy, and Thermogravimetry/Differential Thermal Analysis (TG-DTA) and in solution by UV-Vis, 1H NMR spectroscopic techniques and Electrospray Ionisation Mass Spectrometry (ESI-MS). The crystal structure of CIPTIN and its processor HCIP was also determined by X-ray crystallography. The antibacterial activity of CIPTIN, HCIP·HCl, HCIP and DPTD was evaluated against the bacterial species Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis), by the means of Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Inhibition Zones (IZs). CIPTIN shows lower MIC values than those of HCIP·HCl (up to 4.2-fold), HCIP (up to 2.7-fold) or DPTD (>135-fold), towards the tested microbes. CIPTIN is classified into bactericidal agents according to MBC/MIC values. The developing IZs are 40.8 ± 1.5, 34.0 ± 0.8, 36.0 ± 1.1 and 42.7 ± 0.8 mm, respectively which classify the microbes P. aeruginosa, E. coli, S. aureus and S. epidermidis to susceptible ones to CIPTIN. These IZs are greater than the corresponding ones of HCIP·HCl by 1.1 to 1.5-fold against both the tested Gram negative and Gram positive bacteria. CIPTIN eradicates the biofilm of P. aeruginosa and S. aureus more efficiently than HCIP·HCl and HCIP. The in vitro toxicity and genotoxicity of CIPTIN were tested against human skin keratinocyte cells (HaCaT) (IC50 = 2.33 μM). CIPTIN exhibits 2 to 9-fold lower MIC values than its IC50 against HaCaT, while its genotoxic effect determined by micronucleus assay is equivalent to the corresponding ones of HCIP·HCl or HCIP.
Bakas, T.,Banti, C. N.,Chrysouli, M. P.,Douvalis, A.,Hadjikakou, S. K.,Hatzidimitriou, A. G.,Kourkoumelis, N.,Moushi, E. E.,Papachristodoulou, C.,Tasiopoulos, A. J.
p. 11522 - 11535
(2020/09/09)

GLYCOSYLATED 3-SUBSTITUTED FLUOROQUINOLONE DERIVATIVES, PREPARATION METHODS THEREOF, AND THEIR USE IN THE TREATMENT OF ANTIMICROBIAL INFECTIONS
The present disclosure relates to 3-substituted fluoroquinolone derivatives, and more particularly to glycosylated 3-substitutred fluoroquinolone derivatives, methods of preparation thereof, and uses thereof for treating microbial infections.
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Paragraph 038; 039

(2020/10/20)

Polymer-Based Bioorthogonal Nanocatalysts for the Treatment of Bacterial Biofilms
Bioorthogonal catalysis offers a unique strategy to modulate biological processes through the in situ generation of therapeutic agents. However, the direct application of bioorthogonal transition metal catalysts (TMCs) in complex media poses numerous challenges due to issues of limited biocompatibility, poor water solubility, and catalyst deactivation in biological environments. We report here the creation of catalytic "polyzymes", comprised of self-assembled polymer nanoparticles engineered to encapsulate lipophilic TMCs. The incorporation of catalysts into these nanoparticle scaffolds creates water-soluble constructs that provide a protective environment for the catalyst. The potential therapeutic utility of these nanozymes was demonstrated through antimicrobial studies in which a cationic nanozyme was able to penetrate into biofilms and eradicate embedded bacteria through the bioorthogonal activation of a pro-antibiotic.
He, Luke D.,Huang, Rui,Li, Cheng-Hsuan,Makabenta, Jessa Marie,Rotello, Vincent M.,Yu, Erlei,Zhang, Xianzhi,Cao-Milán, Roberto
p. 10723 - 10729
(2020/07/04)

A fluorogenic H2S-triggered prodrug based on thiolysis of the NBD amine
Based on thiolysis of the NBD amine, a H2S-triggered prodrug has been designed and synthesized for localized production of ciprofloxacin under micromolar H2S. Activation of the prodrug can be monitored through fluorescence in real-time. We envision that thiolysis of the NBD amine could be readily used for development of other H2S-triggered prodrugs in the future.
Xie, Yonghui,Huang, Haojie,Ismail, Ismail,Sun, Hongyan,Yi, Long,Xi, Zhen
(2019/08/26)

A Consolidated and Continuous Synthesis of Ciprofloxacin from a Vinylogous Cyclopropyl Amide
Ciprofloxacin is a broad-spectrum antibiotic that is recognized as one of the World Health Organization's Essential Medicines. It is particularly effective in the treatment of Gram-negative bacterial infections associated with urinary, respiratory, and gastrointestinal tract infections. A streamlined and high yielding continuous synthesis of ciprofloxacin has been developed, which employs a chemoselective C-acylation step that precludes the need for intermediate isolations, extractions, or purifications. The end-to-end process has a residence time of 4.7 min with a 15.8 g/h throughput at laboratory scale and an overall isolated yield of 83%.
Tosso, N. Perrer,Desai, Bimbisar K.,De Oliveira, Eliseu,Wen, Juekun,Tomlin, John,Gupton, B. Frank
p. 3370 - 3376
(2019/03/11)

A norfloxacin, ciprofloxacin and enrofloxacin synthetic method
The present invention provides a norfloxacin, ciprofloxacin and enrofloxacin preparation method, which comprises the carboxylic acid and piperazine in the solvent under the catalytic action of the catalyst in the reaction step, the catalyst is AlBr3 , FeBr3 , ZnBr2 , CuBr2 Or SnBr4 , It has high yield, low cost and the advantage of energy saving and emission reduction.
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Paragraph 0007; 0028-0033; 0042; 0043

(2019/07/10)

STREAMLINED SYNTHESES OF FLUOROQUINOLONES
Methods of synthesizing fluoroquinolones such as ciprofloxacin are provided. The methods utilize affordable materials, reduce the number of synthesis steps and provide high yields.
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Page/Page column 19; 33; 36-37

(2019/01/08)

ANTIBIOTIC RESISTANCE BREAKERS
The invention relates to antibiotic compounds of formula (A1) and pharmaceutically acceptable salts, solvates, tautomers and combinations thereof, wherein X and L are optional linkers and one of RA or R1 comprises Ar1, wherein Ar1 is an antibiotic resistance breaker moiety which comprises an optionally substituted C6-10 aryl, C7-13 aralkyl, C5-10 heteroaryl, C6-13 heteroaralkyl, C5-10 heterocyclyl, C6-13 heterocyclalkyl, C3-10 carbocyclyl, C4-13 carbocyclalkyl, -C(=NR')-NR'R'' or –CH2- CH=CH2 group; wherein after administration of the compound to a bacterial infection this moiety reduces or prevents efflux. The invention also discloses pharmaceutical compositions comprising compounds of formula (A1) and the use of such compounds as medicaments, in particular, to treat bacterial infections, such as drug-resistant bacterial infections.
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Page/Page column 96; 97

(2019/01/05)

A high-efficient environment friendly preparation method of quinolone ciprofloxacin drug (by machine translation)
The invention discloses a high-efficient environmental protection quinolone ciprofloxacin preparation method of drug, is fluorobenzene formyl ethyl acetate, the original carboxylic acid triethyl amine compound as a raw material, the three raw materials into the reactor at a temperature of 90 - 150 °C reaction under 20 - 30 H prepare get quinolone basic parent ring, then adding piperazine, to aminocapronitrile as the solvent, the temperature of the reflux reaction 20 - 28 of H, continue adding 50% sodium hydroxide solution is carboxyl ester hydrolysis to obtain the target compound. The invention is simple in raw material market can buy price is cheap; multi-step reaction link together a pan operation intermediate does not need to separate operation, the reaction process is efficient labor-saving; the whole process of transformation efficiency is high, the final product does not need chromatographic treatment is simple washing can get the pure compound; safety in the course of reaction, after-treatment does not need the eluent separation only needs to ethyl acetate, petroleum ether and methanol washing and can be recycled can be pollution prevention; green reaction process, only ethanol by-product, the atom economy is high; quinolone compounds and high utility value, is important trovafloxacins antibacterial drug composition structure. (by machine translation)
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Paragraph 0026; 0028; 0029

(2019/01/04)

Nano-Fe3 O4@ZrO2-SO3 H as highly efficient recyclable catalyst for the green synthesis of fluoroquinolones
Nano-Fe3 O4 @ZrO2-SO3 H (n-FZSA), was utilized as a magnetic catalyst for the synthesis of various fluoroquinolone compounds. These compounds were prepared by the direct amination of 7-halo-6-fluoroquinolone-3-carboxylic acids with piperazine derivatives and (4aR,7aR)-octahydro-1H-pyrrolo[3,4-b] pyridine in water. The results showed that n-FZSA exhibited high catalytic activity towards the synthesis of fluoroquinolone derivatives, giving the desired products in high yields. Furthermore, the catalyst was recyclable and could be used at least seven times without any discernible loss in its catalytic activity. Overall, this new catalytic method for the synthesis of fluoroquinolone derivatives provides rapid access to the desired compounds in refluxing water following a simple work-up procedure, and avoids the use of organic solvents.
Nakhaei, Ahmad,Ramezani, Shirin,Shams-Najafi, Sayyed Jalal,Farsinejad, Sadaf
p. 739 - 746
(2018/09/26)

Enrofloxacin behavior in presence of soil extracted organic matter: An electrochemical approach
In this work, a novel and simple method aimed at determining and quantifying Enrofloxacin in presence of Natural Organic Matter (NOM) is proposed. The method was based on the electrochemical oxidation of Enrofloxacin by using cyclic voltammetry as technique. It was found that this analyte presents a good electroactivity, in absence and in presence of NOM. However, this electrochemical behavior is highly pH-dependent, since the reaction is more favorable when less acid the media is. At this point, different pH values were studied in order to corroborate this phenomenon. Additionally, kinetic studies were done to determine the control of the reaction, the number of transferred electrons in the entire process and the rate determining step of the reaction by analyzing the Tafel slope. With these antecedents, a mechanism was proposed and the final product of the reaction was corroborated by using LC-MS. Finally, analytical parameters were studied with the aim of proposing this new method as an electrochemical sensor of Enrofloxacin. It was found that the method is highly linear, precise and accurate. Moreover, this method is not only sensitive but also selective to Enrofloxacin in presence of NOM, in comparison to spectrophotometric methods previously reported.
Antilén, Monica,Valencia, Camila,Peralta, Emilia,Canales, Camila,Espinosa-Bustos, Christian,Escudey, Mauricio
p. 104 - 111
(2017/05/29)

Method for preparing antibacterial and anti-inflammatory veterinary drug ciprofloxacin
The invention provides a method for preparing an antibacterial and anti-inflammatory veterinary drug ciprofloxacin. The involved method is short in reaction time, high in efficiency, relatively high in product yield and purity and mild in reaction condition, environmental pollution caused by an organic solvent is avoided, and large-scale production is facilitated. In addition, reaction is one-pot reaction, posttreatment is not required by a first reaction step, no catalyst is required to be additionally added for the reaction, and alkaline ionic liquid used for the reaction is non-corrosive to equipment, so that the equipment requirement and the investment cost are reduced, and the reaction efficiency is greatly improved.
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Paragraph 0015; 0016; 0017; 0018

(2017/08/28)

Preparation method of ciprofloxacin lactate
The invention belongs to the technical field of medicine preparation and particularly relates to a preparation method of ciprofloxacin lactate. The method comprises the steps as follows: mixing ciprofloxacin hydrochloride with a solvent, adjusting pH with alkali, and performing cooling crystallization, filtration, drying and other steps to obtain ciprofloxacin; mixing ciprofloxacin with the solvent, adding a salt forming agent for a salt forming reaction, and then performing cooling crystallization, filtration, drying and other steps to obtain a finished product of ciprofloxacin lactate. The preparation method is simple to operate, the involved reaction condition is mild and easy to control, ciprofloxacin lactate is prepared in two steps, the refining process is omitted, the production cycle is shortened, the cost is greatly reduced, and the mass yield of ciprofloxacin lactate reaches 95% or higher, and the product purity can reach 99.5%.
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Paragraph 0018; 0020; 0022

(2017/08/28)

A norfloxacin, ciprofloxacin and enrofloxacin preparation method
The invention discloses a preparation method of norfloxacin, ciprofloxacin and enrofloxacin. The preparation method comprises the following steps: directly reacting 1-ethyl-6-fluoro-7-chlo-4-oxo-1,4-dihydro-quinoline-3-carboxylate or 1-cyclopropyl-6-fluoro-7-chlo-4-oxo-1,4-dihydro-quinoline-3-carboxylate with piperazine (or N-ethyl piperazine); and then, performing after-treatment to prepare a corresponding target product norfloxacin (or ciprofloxacin or enrofloxacin). The preparation method disclosed by the invention is short in reaction step, convenient to operate, less investment and beneficial to industrial production; consumption of piperazine (or N-ethyl piperazine) can be reduced by more than half; under the catalytic action, the reaction temperature is low, the byproducts are less, the yield is high and the cost is low; heavy use of inorganic acid and inorganic alkaline is avoided, so that the pollution is reduced.
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Paragraph 0119-0120

(2017/04/25)

Design, synthesis and biological evaluation of ciprofloxacin tethered bis-1,2,3-triazole conjugates as potent antibacterial agents
A series of new bis-1,2,3-triazole linked ciprofloxacin conjugates was designed, synthesized and evaluated in?vitro antibacterial activity against a panel of clinically relevant bacteria. A significant part of the compounds displayed enhanced activity against both Gram-positive and Gram-negative species of bacteria as compared to the parent drug. Additionally, negligible toxicity profile of compounds indicates that they may act a good antibiotic in future. Despite relatively small number of synthesized conjugates, it was possible to observe important dependences between their structure and activity.
Kant, Rama,Singh, Vishal,Nath, Gopal,Awasthi, Satish Kumar,Agarwal, Alka
p. 218 - 228
(2016/09/09)

Conventional and microwave-assisted synthesis of quinolone carboxylic acid derivatives
Various antibacterial fluoroquinolone compounds are synthesized by the direct amination of 7-halo-6-fluoroquinolone-3-carboxylic acids with a variety of piperazine derivatives and (4aR,7aR)-octahydro-1H-pyrrolo[3,4-b]pyridine using microwave under different reaction conditions. Solvent free high yield microwave synthesis of antibacterial fluoroquinolone compounds is convenient, rapid and environmentally friendly method.
Mirzaie,Lari,Vahedi,Hakimi
p. 2865 - 2869
(2017/03/22)

Light-controlled active release of photocaged ciprofloxacin for lipopolysaccharide-targeted drug delivery using dendrimer conjugates
We report an active delivery mechanism targeted specifically to Gram(-) bacteria based on the photochemical release of photocaged ciprofloxacin carried by a cell wall-targeted dendrimer nanoconjugate.
Wong, Pamela T.,Tang, Shengzhuang,Mukherjee, Jhindan,Tang, Kenny,Gam, Kristina,Isham, Danielle,Murat, Claire,Sun, Rachel,Baker, James R.,Choi, Seok Ki
p. 10357 - 10360
(2016/08/30)

Light-triggered release of ciprofloxacin from an in situ forming click hydrogel for antibacterial wound dressings
Light triggered release of an antibiotic from a click crosslinked hydrogel was developed by conjugating ciprofloxacin through a photo-cleavable linker to the hydrogel network structure. Upon irradiation of the hydrogel material with UV light (365 nm) at low intensity, native ciprofloxacin was released into the surrounding environment and could be detected by HPLC. The antimicrobial activity of the released compound on Staphylococcus aureus was demonstrated.
Shi, Yue,Truong, Vinh X.,Kulkarni, Ketav,Qu, Yue,Simon, George P.,Boyd, Richard L.,Perlmutter, Patrick,Lithgow, Trevor,Forsythe, John S.
p. 8771 - 8774
(2015/11/24)

REDUCTION-TRIGGERED ANTIBACTERIAL SIDEROMYCINS
A compound is provided, comprising: an Fe(III)-binding or an Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; a drug; and an Fe(III) to Fe(II) reduction triggered linker bound to the drug and the linker or, if no linker is present, then bound to the drug and the siderophore. Compositions and methods including the compound are also provided.
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Sheet 9

(2015/05/06)

New 7-[4-(4-(un)substituted)piperazine-1-carbonyl]-piperazin-1-yl] derivatives of fluoroquinolone: Synthesis and antimicrobial evaluation
Fluoroquinolones have been a class of important synthetic antimicrobial agents broadly and effectively used in clinic for infectious diseases. In this study, the synthesis of a range of fluoroquinolone derivatives with 4-(carbopiperazin-1-yl)piperazinyl moieties at the C7 position and their inhibition of bacterial pathogens commonly disseminated in hospital environment were described. The results indicated that a 7-[4-(4-(benzoyl)carbopiperazin-1- yl)]piperazinyl derivative 5h and two 7-[4-(4- (benzenesulfonyl)carbopiperazin- 1-yl)]piperazinyl derivatives 5k and 5l showed more promising growth inhibition of ciprofloxacin-resistant P. aeruginosa (CRPA) with MIC values as low as 16 μg/mL which is 16-fold more potent than ciprofloxacin, while most of other derivatives maintained potency against methicillin-resistant Staphylococcus aureus (MRSA).
Chen, Po-Ting,Lin, Wen-Po,Lee, An-Rong,Hu, Ming-Kuan
p. 7557 - 7569
(2013/08/23)

Amination of quinolones with morpholine derivatives
The aromatic nucleophilic substitution reaction of 7-chloroquinolone carboxylic acid and its ethyl ester with cyclic amines under microwave irradiation conditions was investigated. 1H NMR spectroscopy was used to monitor the progress of the substitution reaction. The reaction proceeded in high yield with simple cyclic amines and was less efficient for sterically more demanding bimorpholine derivatives. A Pd-catalyzed amination of quinolone carboxylic acid ethyl ester with bimorpholine derivatives provided new C-7 bimorpholino-substituted quinolone derivatives.
Lippur, Kristin,Tiirik, Tonis,Kudrjashova, Marina,Jaerving, Ivar,Lopp, Margus,Kanger, Tonis
p. 9550 - 9555,6
(2020/08/20)

IMPROVED PROCESS FOR THE PREPARATION OF CIPROFLOXACIN AND ITS ACID ADDITION SALTS
An improved process for the synthesis of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (Ciprofloxacin) or and its acid addition salts preferablyhydrochloride salt with high yield and high purity, the process comprising of reacting 6-fluoro-7-chloro-1-cyclopropyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid with piperazine in presence of a catalyst in an organic solvent.
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Page/Page column 6

(2012/10/08)

Crystal structure of C17H20FN3O 3 2+ ?cuBr4 2- ?h 2O
A new compound C17H20FN3O 3 2+ ?CuBr 4 2- ?H2O is synthesized in the crystal form, where C17H18FN 3O3 (CfH, ciprofloxacin) is 4-oxo-7-(1-piperazinyl)-6- fluoro-1-cyclopropyl-1,4-dihydroquinoline-3-carboxylic acid. Crystallographic data of ciprofloxacinium tetrabromocuprate(II) monohydrate, C17H 22Br4CuFN3O4: a = 8.214(1) A, b = 10.781(2) A, c = 13.703(2) A, α = 85.144(2)°, β = 79.119(2)°, γ = 84.018(2)°, V = 1182.5(4) A3, P 1 space group, Z = 2. Supramolecular architecture of the crystal differs from that established for C17H20FN3O 3 2+ ?CuCl 4 2- ?H2O by the absence of π-π interactions of the aromatic rings of CfH 3 2+ ions and also the structural motifs formed by intermolecular hydrogen bonds.
Vasiliev,Golovnev
experimental part
p. 809 - 812
(2012/06/16)

Direct transformation of Baylis-Hillman acetates into N-substituted quinolones through an SN2′→ SNAr→(Δ3,4-Δ2,3 shift)→oxidation sequence
When subjected to tandem SN2-SNAr cyclization in the presence of alkyl or aralkyl amines, Baylis-Hillman acetates gave the corresponding 1,2-dihydroquinolines, which on simple exposure to light and oxygen afforded the corresponding 4- and 2-quinolones through sensitized oxidation or a 3,4-2,3 shift oxidation cascade. The mechanism of the oxidation step, the stabilities of the 1,2- and 1,4-dihydroquinolines in solution and in the solid state, and the synthetic elaboration of the key intermediates to known therapeutic agents are discussed. Georg Thieme Verlag Stuttgart · New York.
Napoleon, John Victor,Kannoth Manheri, Muraleedharan
supporting information; experimental part
p. 3379 - 3388
(2011/11/30)

New fluorine-containing hydrazones active against MDR-tuberculosis
Several new fluorine-containing hydrazones were synthesized and screened for their in vitro antimycobacterial activity. Nine of these derivatives have shown a remarkable activity against MDR-TB strain with MIC 0.5 μg/mL and high value of selectivity index (SI). Compound 3h with the highest SI (1268.58) was used for stability evaluation with putative metabolites (ciprofloxacin and formylciprofloxacin) detection. Compound 3h was stable at pH 7.4 of aqueous buffer and rat plasma, in acidic buffers (at pH 3 and 5) slow decomposition was observed. Interestingly, no formylciprofloxacin was detected in the solution, and only slightly increased concentration of ciprofloxacin was observed instead. Trifluoromethyl hydrazones 3f and 3g exhibited the best activity also against two strains of Mycobacterium kansasii (MIC 1-4 μmol/L). All evaluated compounds were found to be non-cytotoxic.
Vav?íková, Eva,Polanc, Slovenko,Ko?evar, Marijan,Horváti, Kata,Bsze, Szilvia,Stola?íková, Ji?ina,Vávrová, Kate?ina,Vin?ová, Jarmila
experimental part
p. 4937 - 4945
(2011/11/29)

NOVEL METHOD OF SYNTHESIS OF FLUOROQUINOLONES
The invention relates to a method of preparation of fluoroquinolones of formula (I) from compounds of formula (II): in which R1, R2, R3, R4, R5, R6, R7, and X are as defined in Claim 1.
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Page/Page column 6; 10

(2009/04/24)

PROCESS FOR PREPARING PURIFIED CIPROFLOXACIN
A process for purifying of ciprofloxacin is described wherein a solution of ciprofloxacin is contacted with a solid phase.
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Page/Page column 12-14; 18-19

(2008/06/13)

Regioselective synthesis of quinolone antibacterials via borate complex of quinolone carboxylic acid
1-substituted 7-chloro-6-fluoro-4-oxo-1,2-dihydroquinoline-3-carboxylic acids were converted to borate complexes. These compounds were treated with piperazine in presence of triethylamine to afford ciprofloxacin and norfloxacin in high yields.
Heravi, Majid M.,Jaddi, Zeinab S.,Oskooie, Hossein A.,Khaleghi, Shahnaz,Ghassemzadeh, Mitra
p. 578 - 579
(2007/10/03)

Convenient one pot synthesis of some fluoroquinolones in aqueous media
A one pot synthetic strategy for the preparation of fluoroquinolones from 1 is introduced. Product 3 was condensed with piperazine in an aqueous media to produce pharmaceutical grade ciprofloxacin in 86% yield. The method was extended to the synthesis of some other fluoroquinolones with pharmaceutical grade quality.
Abaee, M. Saeed,Sharifi, Ruhollah,Borhani, Shahin,Heravi, Majid M.,Motahari, Hossein
p. 415 - 418
(2007/10/03)

Process for the preparation of quinolone derivatives
This invention relates to an improved process for the preparation of quinolone drugs of the formula (I), wherein R=C1-C6 alkyl, C3-C6 cycloalklyl, aryl, substituted aryl, NR1R2=diarylamino, arylalkylamino, C1-C6-dialkylamino, piprazinyl, N or C alkyl (C1-C6) substituted piperazinyl, morpholino, pyrrolidinyl, substituted pyrrolidinyl, aralkyl, substituted aralkyl etc. Some of the compounds falling within the formula (I) are ciprofloxacin, enrofloxin, pefloxacin, etc. These compounds are useful as antibacterial drugs. The process of the present invention for preparation of compound of formula (I) comprises in enhancing the reactivity of the displaceable halogen (X) in the compound of the formula (II) towards various amines of formula (III) wherein R=as defined for compound of formula (I), R3=COOR6 (R6=C1-C6 alkyl, aryl, aralkyl), nitrile a carboxamide (—CONR7R8, R7 and R8=C1-C6 alkyl, C3-C6 cycloalkyl, aralkyl), X=Cl, Br, F; NR1R2=as defined above by introducing a nitro group ortho to the displaceable halo group and subsequently removing the nitro group in a conventional manner. The process of the present invention enhances the yield of the compound of the formula (I) and also improves the quality of the prepared compound.
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(2008/06/13)

Microreaction technology as a novel approach to drug design, process development and reliability
This paper focuses on the application of microreaction technology in the life science industry. Certain features of microreaction technology, for example, mixing, heat transfer, and residence time distribution, are discussed. Important advantages such as high operational safety and the possibility to transfer the experimental results directly from laboratory to the production of pilot-plant scales are mentioned. Potential application fields in the drug discovery and development processes, from research to production, by including chemical synthesis of different targets in the case of the quinoline acid derivative (ciprofloxacin) and the Paal - Knorr pyrrole synthesis are presented.
Taghavi-Moghadam, Shahriyar,Kleemann, Axel,Golbig, Klaus Georg
p. 652 - 658
(2013/09/07)

Microwave assisted amination of quinolone carboxylic acids: An expeditious synthesis of fluoroquinolone antibacterials
A facile amination of quinolone carboxylic acids to fluoroquinolone antibacterials under microwave irradiation is described.
Reddy,Baskaran
p. 6775 - 6777
(2007/10/03)

Methods for the manufacture of quinolone carboxylic acids derivatives and intermediates thereof
Novel process for the preparation of quinolone carboxylic acid derivatives of general formula I, and intermediates thereof as illustrated in Scheme 1 wherein the key intermediate is a compound of formula IX. STR1
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(2008/06/13)

Support for synthesis and purification of compounds
A method for the preparation and purification of compounds using a novel support, a tetrabenzo[a,c,g,i]fluorene group (Tbf) comprising reacting a building block (A) containing a Tbf group (Tbf-A), with a second building block (B), to afford an intermediate compound (Tbg-A-B) followed by purifying the intermediate compound by adsorption on a carbon support, removing the intermediate compound from the support with a solvent and repeating the previous reactions using the required number of building blocks to synthesize the compounds followed by removal of the Tbf group to afford the desired compounds.
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(2008/06/13)

Use of tetrabenzo[a,c,g,i]fluorene as an anchor group for the solid/solution phase synthesis of the quinolone antibacterial, ciprofioxacin
The affinity of tetrabenzo[a,c,g,i]fluorene (Tbf) for charcoal has been applied successfully to provide an alternative to existing solid phase synthesis methodology. In a synthesis of the quinolone antibacterial, Ciprofloxacin, traditional solution phase synthesis has been coupled with efficient pseudo-solid phase purification.
Hay, Alastair M.,Hobbs-Dewitt, Sheila,MacDonald, Alasdair A.,Ramage, Robert
p. 1979 - 1985
(2007/10/03)

Electrochemical studies of 1-cyclopropyl-6-fluoro-1,4-dihydro-7-(N- piperazinyl)-4-oxo-3-quinoline carboxylic acid and its synthetic precursors
Electrochemical studies of 1-cyclopropyl-6-fluoro-1,4-dihydro-7-(N- piperazinyl)-4-oxo-3-quinoline carboxylic acid 5 and its synthetic precursors, viz., 2, 4-dichloro-5-fluoroacetophenone 1, 3-cyclopropylamino-2- (2,4-dichloro-5-fluorobenzoyl)acrylic acid methyl ester 2, 7-chloro-1- cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid methyl ester 3 and 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-quinoline-3- carboxylic acid 4 are reported. Plausible electrochemical mechanism for the reduction of the series of compounds is suggested based on cyclic voltammetry, coulometry and spectral studies. The role of resonance isomerism aided by intramolecular hydrogen bonding and aromaticity, in the electrochemistry of compounds 2-5, is discussed. The acid-base equilibria of the compounds are revisited based on PCMODEL MMX Molecular Energy Minimisation Software and cyclic voltammetry. An excellent electroanalytical method in differential pulse polarography for the quantitative analysis of the drug 5 and its synthetic precursors 14 is developed.
Srinivasu,Sunil Kumar,Ramachandraiah,Veera Reddy
p. 553 - 562
(2007/10/03)

Use of tetrabenzo[a,c,g,i]fluorene as an anchor group for the solid/solution phase synthesis of ciprofloxacinρ
The affinity of tetrabenzo[a,c,g,i]fluorene for charcoal has been applied successfully to provide an alternative to existing solid phase synthesis methodology. In a synthesis of the quinolone antibacterial, Ciprofloxacin, traditional solution phase synthesis has been coupled with efficient pseudo-solid phase purification.
Hay, Alastair M.,Hobbs-Dewitt, Sheila,MacDonald, Alasdair A.,Ramage, Robert
p. 8721 - 8724
(2007/10/03)

Regioselective nucleophilic substitution of halogen derivatives of 1-substituted 4-oxo-1,4-dihydroquinoline-3-carboxylic acids
The rate of the nucleophilic displacement of the fluoro atom of 7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate could be enhanced either by the introduction of further fluoro atom(s) into position(s) 6 and/or 8, or by the formation of a boron chelate (e.g. 3). The regioselectivity of the nucleophilic substitution of the chloro atom in 1-substituted 6-fluoro-7-chloro-4-oxo-1,4dihydroquinoline-3-carboxylic acids could also be enhanced by the formation of a boron chelate (e.g. 7).
Hermecz, Istvan,Vasvari-Debreczy, Lelle,Podanyi, Benjamin,Kereszturi, Geza,Balogh, Maria,Horvath, Agnes,Varkonyi, Peter
p. 1111 - 1116
(2007/10/03)

One-pot process for the preparation of 3-quinolonecarboxylic acid derivatives
The present invention relates to a one-pot process for the preparation of 7-heterocyclyl-substituted 3-quinolonecarboxylic acid derivatives. They possess a strong anti-microbial effect. They include active compounds such as, for example, ofloxacin, ciprofloxacin or enrofloxacin.
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(2008/06/13)

Process for making antimicrobial compounds
The present invention provides a process for making a compound having a structure according to Formula (I) STR1 wherein A1, A2 and A3 are independently carbon or nitrogen and R1, R3, R4 and R6 are known quinolone substituents; and wherein one of R1, R3 or R6 may be a lactam-containing moiety; or a protected form, salt, pharmaceutically-acceptable salt, biohydrolyzable ester, or solvate thereof; the process comprising reacting one or more organosilicon compounds with a compound having a structure according to Formula (II) STR2 wherein A1, A2 and A3, R1, R3, R4 and R6 as described above; wherein one of R1, R3 or R6 may be a lactam-containing moiety; and X is a leaving group; or a protected form, salt, biohydrolyzable ester, or solvate thereof. The compounds prepared according to the processes of the invention are themselves useful as antimicrobials, or they may be used as intermediates for making other quinolone-containing antimicrobials.
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(2008/06/13)

Quinolone antibiotics: Study of reactivity and impurity profile of piperazine with chloro-fluoro-quinolone carboxylic acid in aqueous medium
The reaction of 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,2-dihydroquinoline-3-carboxyli c acid with piperazine in water was studied. The product ciprofloxacin was isolated and the impurity formed in the reaction was isolated and characterized as 1-cyclopropyl-7-chloro-6-piperazinyl-4-oxo-1,2-dihydroquinoline-3-carb oxylic acid. Similarly norfloxacin was also synthesised.
Kalkote,Sathe,Kharul,Chavan,Ravindranathan
p. 6785 - 6786
(2007/10/03)

A solid phase approach to quinolones using the DIVERSOMER technology
The first example of a library of the quinolone antibacterial agents prepared by solid phase organic synthesis is described. Results of these studies and the parallel synthesis, isolation, purification and analysis of eight quinolones are discussed.
MacDonald, Alasdair A.,DeWitt, Sheila H.,Hogan, Eleonora M.,Ramage, Robert
p. 4815 - 4818
(2007/10/03)

Process for making antimicrobial quinolonyl lactams
The present invention provides methods of making compounds of the structure wherein (I) Q is a quinolone moiety; (II) B is a beta-lactam moiety; (III) L, L1, and L2 together comprise a carbamate-containing linking moiety comprising the steps of: (1) Reacting a lactam compound of the formula B-L4 -H with phosgene to form an intermediate compound of the formula B--L4 --C(=O)--Cl, where L4 is oxygen; and (2) Coupling said intermediate compound with a quinolone compound of the formula Q-L3 -R44 ; wherein L3 is nitrogen; R44 is hydrogen, Si(R45)3, or Sn(R45)3 ; and R45 is lower alkyl. Preferably, the process additionally comprises steps prior to the reacting and coupling steps where esters of the lactam and quinolone compounds are made. Also preferably, the coupling step comprises adding a solution containing the quinolone compound to a solution containing the intermediate compound. The process steps are also preferably performed at a temperature of from about -80° C. to about 0° C. Preferred antimicrobial compounds made by these processes are those where the beta-lactam moiety is a penem.
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(2008/06/13)

Preparation of quinolinecarboxylic acids
STR1 is reacted with an amine STR2 to give the compound of the formula STR3 Because the starting material (I) has F in 7-position rather than Cl, the reaction proceeds at relatively low temperature with minimum side reactions.
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(2008/06/13)

Baron chelates of quinoline carboxylic acids
The invention relates to a new process for the preparation of compounds of the general Formula I STR1 /wherein R stands for piperazinyl, 4-methyl-piperazinyl or 4-ethyl-piperazinyl group/ and pharmaceutically acceptable salts thereof which comprises reacting a compound of the general Formula II STR2 /wherein R1 and R2 stand for halogen, for an aliphatic acyloxy group containing 2 to 6 carbon atoms and optionally substituted by halogen, or for an aromatic acyloxy group containing 7 to 11 carbon atoms/ with a piperazine derivative of the general Formula STR3 /wherein R3 stands for hydrogen, methyl or ethyl/ or a salt thereof and subjecting the compound of the general Formula IV STR4 thus obtained /wherein R, R1 and R2 are as stated above/ to hydrolysis after or without isolation and if desired converting the compound of the general Formula I thus obtained into a salt thereof or setting free the same from its salt. The compounds of the general Formula I are known antibacterial agents. The advantage of the present invention is that it makes the desired compounds of the general Formula I available in a simple manner, with high yields and in a short reaction time.
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(2008/06/13)