93107-08-5

Usage

Uses

Used in Pharmaceutical Industry:
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid hydrochloride is used as an antimicrobial and immunomodulatory agent for the treatment of various bacterial infections. Its range of activity includes most strains of bacterial pathogens capable of inducing respiratory, urinary tract, gastrointestinal, and abdominal infections. It functions by inhibiting DNA gyrase (a type II topoisomerase) and topoisomerase IV, the enzymes responsible for negative supercoiling of chromosomes and DNA strand separation, thus blocking the initiation of bacterial replication.
Used in Postexposure Inhalational Anthrax Management:
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid hydrochloride is used as a therapeutic agent in the management of postexposure inhalational anthrax, a severe bacterial infection caused by the bacterium Bacillus anthracis.
Used in Radiation Combined Injury Management:
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid hydrochloride is also used in the management of radiation combined injury resulting from nuclear disasters, where it plays a crucial role in mitigating the effects of radiation exposure and promoting recovery.

Mechanism of action

Ciprofloxacin hydrochloride is a new type of quinolone antibacterial drug. Its mechanism of action is that it can combine with bacterial DNA gyrase subunit A, thereby inhibiting the cleavage and linking functions of the enzyme, preventing the replication of bacterial DNA, and showing antibacterial effect.

Biological Activity

ciprofloxacin (hydrochloride) is a fluoroquinolone antibiotic that has antimicrobial and immunomodulatory activities [1].ciprofloxacin functions by inhibiting dna gyrase and topoisomerase iv, the enzymes responsible for negative supercoiling of chromosomes and dna strand separation, thus blocking initiation of bacterial replication. topoisomerase iv is the primary target of ciprofloxacin in s. aureus [2].ciprofloxacin (hydrochloride) is a fluoroquinolone antibiotic that acts as an antimicrobial and immunomodulatory agent. in b6d2f1/j mice received radiation combined injury (ci), ciprofloxacin significantly reduced pro-inflammatory cytokine and chemokine concentrations (il-6 and kc), and enhanced il-3 production. cip also inhibited ci-induced apoptosis and autophagy in ileal villi, systemic bacterial infection, and iga production [1]. ciprofloxacin (hydrochloride) had been approved by fda for management of postexposure inhalational anthrax. in animals after exposure to aerosolized b. anthracis, ciprofloxacin significantly improved survival rate. ciprofloxacin inhibited the growth of b. anthracis with mic90 of 0.06 μg/ml. in the usamriid rhesus monkey model of inhalational anthrax, the maximum concentration (cmax) of ciprofloxacin was 1.74 μg/ml and the minimum concentration (cmin) was 0.17 μg/ml [3].

references

[1]. fukumoto r, cary lh, gorbunov nv, et al. ciprofloxacin modulates cytokine/chemokine profile in serum, improves bone marrow repopulation, and limits apoptosis and autophagy in ileum after whole body ionizing irradiation combined with skin-wound trauma. plos one. 2013;8(3):e58389.[2]. drlica k, zhao x. dna gyrase, topoisomerase iv, and the 4-quinolones. microbiol mol biol rev. 1997 sep;61(3):377-92.[3]. meyerhoff a, albrecht r, meyer jm, et al. us food and drug administration approval of ciprofloxacin hydrochloride for management of postexposure inhalational anthrax. clin infect dis. 2004 aug 1;39(3):303-8.

InChI:InChI=1/C17H18FN3O3.ClH/c18-13-7-11-14(8-15(13)20-5-3-19-4-6-20)21(10-1-2-10)9-12(16(11)22)17(23)24;/h7-10,19H,1-6H2,(H,23,24);1H

Upstream product

• 110-85-0 piperazine 
• 93107-30-3 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 
• 85721-33-1 ciprofloxacin 
• 86393-33-1 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid 
• 104600-30-8 ethyl 2-(2,4-dichloro-5-fluoro-benzoyl)-3-cyclopropylamino-acrylate 
• 86483-54-7 ethyl 1-cyclopropyl-7-chloro-6-fluoro-1,4-dihydro-4-oxo-3-quinoline-carboxylate 
• 86483-51-4 ethyl 2,4-dichloro-5-fluoro-benzoyl-acetate 
• 86483-53-6 3-Cyclopropylamino-2-(2,4-dichlor-5-fluorbenzoyl)acrylsaeure-ethylester 
• 86393-34-2 2,4-dichloro-5-fluorobenzoyl chloride 
• 105392-26-5 3-Cyclopropylamino-2-(2,4-dichlor-5-fluorbenzoyl)acrylsaeure-methylester 
• 104599-90-8 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid methyl ester 
• 86483-50-3 diethyl 2,4-dichloro-5-fluoro-benzoyl-malonate 
• 72396-25-9 N-(Cyclopropylamino)acrylsaeure-methylester 
• 67-68-5 dimethyl sulfoxide 

Downstream Products

• 103222-12-4 Desethyleneciprofloxacin 
• 86393-33-1 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid 
• 105394-83-0 1-cyclopropyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one 
• 85721-33-1 ciprofloxacin 

Relevant academic research and scientific papers

Preparation method of quinolone carboxylic acid derivative or phthalazinone carboxylic acid derivative

The invention belongs to the field of pharmaceutical chemicals, relates to a preparation method of a quinolone carboxylic acid derivative or a phthalazinone carboxylic acid derivative, and particularly relates to a preparation method of a 7-substituted-3-quinolone carboxylic acid derivative or a 7-substituted-1,5-phthalazinone carboxylic acid derivative. The preparation method comprises the following steps: (1) in an organic solvent, carrying out coupling reaction on a boron chelate II and organic amine III in the presence of an organosilicon compound to obtain a compound IV; and (2) mixing the compound IV with hydrochloric acid, and then filtering and separating the precipitated compound I. Compared with conventional methods, the preparation method provided by the invention has the advantages that the conditions are milder, the hydrolysis of the substrate quinoline carboxylic acid boric acid ester can be reduced, and meanwhile, the influence of a byproduct HF on the product purity is avoided. The method is high in yield and high in purity; compared with the traditional alkali, the organic silicon is more suitable for industrial preparation of the 7-substituted-3-quinolone carboxylic acid derivative or the 7-substituted-1,5-phthalazinone carboxylic acid derivative.

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.

Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards.

A Rapid Total Synthesis of Ciprofloxacin Hydrochloride in Continuous Flow

Within a total residence time of 9 min, the sodium salt of ciprofloxacin was prepared from simple building blocks via a linear sequence of six chemical reactions in five flow reactors. Sequential offline acidifications and filtrations afforded ciprofloxacin and ciprofloxacin hydrochloride. The overall yield of the eight-step sequence was 60 %. No separation of intermediates was required throughout the synthesis when a single acylation reaction was applied to remove the main byproduct, dimethylamine.

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.

ANHYDROUS CIPROFLOXACIN HYDROCHLORIDE

The present invention provides a new anhydrous crystalline form of ciprofloxacin hydrochloride that is substantially free from solvent molecules, and processes of preparation thereof.

An expeditious synthesis of quinolone antibacterials

A facile and rapid synthesis of ciprofloxacin under microwave irradiation is described. The product ciprofloxacin was isolated and the impurity was characterized as the product of substitution of fluorine instead of chlorine in acid 1. Similarly norfloxacin was synthesized.

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

Cycloaracylation of Enamines, I. - Synthesis of 4-Quinolone-3-carboxylic Acids

Starting with o-halobenzoyl chlorides 4 and open-chain secondary enamines 5, a new synthesis of 4-quinolone-3-carboxylic acids 12 is described.The reaction of 7-haloquinolone-3-carboxylic acids 12a-k with aliphatic amines 14 produces highly active antibacterial 7-aminoquinolone-3-carboxylic acids 15.The main product of the 1-cyclopropyl series, "ciprofloxacin" (15a), is being developed as a broad-spectrum chemotherapeutic agent.