112811-59-3 Usage
Uses
Used in Medical Industry:
1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid is used as an antibacterial agent for treating acute sinus, lung, or urinary tract infections, as well as sexually transmitted bacterial infections. It is administered orally in tablet form or by injection.
1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid is used as an alternative treatment option for patients who are unresponsive to other acute otitis media (AOM) therapies. In a study comparing Gatifloxacin with amoxicillin/clavulanate for the treatment of recurrent otitis media and AOM in treatment failures in children, both drugs were found to be well-tolerated and effective. Gatifloxacin was administered once daily and was as effective as amoxicillin/clavulanate, which was administered twice daily.
Common side effects associated with Gatifloxacin include nausea, vaginitis (irritation or inflammation of the vagina), diarrhea, headache, dizziness, and irregular heartbeats. In general, Gatifloxacin is considered a third-line treatment option for AOM due to its potential side effects and the availability of other effective treatments.
Antimicrobial activity
Gatifloxacin is an 8-methoxyfluoroquinolone with enhanced activity against Gram-positive, atypical agents, and some anerobes, and broad-spectrum activity against Gram-negative bacteria. It is bactericidal and produces a post-antibiotic effect in Gram-positive and Gramnegative bacteria.The in vitro antibacterial spectrum of gatifloxacin has been tested against a variety of clinically important microorganisms. It is two to four times more potent than ciprofloxacin and ofloxacin against staphylococci, streptococci, pneumococci, and enterococci. However, it is two times less potent than ciprofloxacin, but the same as or two times more potent than ofloxacin against Enterobacteriaceae. Gatifloxacin and ofloxacin have similar antipseudomonal activity, while ciprofloxacin is two to eight times more potent. Gatifloxacin is highly potent against Hemophilus influenzae, Legionella species, and Helicobacter pylori, and also has activity against Bacteroides fragilis and Clostridium difficile. Like other quinolones, it has poor activity against Mycobacterium avium intracellulare, but is 8–16 times more potent against Mycobacterium tuberculosis.Meyler's Side Effects of Drugs || Gatifloxacin
Pharmaceutical Applications
The spectrum includes Acinetobacter spp. and Aeromonas spp. but it is not very active against Ps. aeruginosa and other non-fermentative Gram-negative rods. It is more active against methicillin-susceptible strains of staphylococci than methicillin-resistant strains. It is also active against Chlamydia, Mycoplasma and Legionella spp. and has some activity against anaerobes.It is almost completely absorbed when given orally and is widely distributed throughout the body into many body tissues and fluids. The plasma half-life is 6–8 h. More than 70% of the drug is excreted unchanged in the urine. Renal clearance is reduced by 57% in moderate renal insufficiency and by 77% in severe renal insufficiency.Prolongation of the QTc interval in some patients and interference with diabetes mellitus have resulted in withdrawal of the drug in most countries for systemic usage. Gatifloxacin remains in use in North America only as an ophthalmic solution.
Biological Activity
Fluoroquinolone antibiotic. Inhibits bacterial type II topoisomerases (IC 50 values are 0.109 and 13.8 μ g/ml for E.coli DNA gyrase and S.aureus topoisomerase IV respectively). Displays potent activity against gram-positive and gram-negative bacteria. Stimulates short-term self-renewal in both human and mouse embryonic stem cells in vitro .
Mechanism of action
Gatifloxacin is a quinolone antimicrobial. It is an 8-methoxyfluoroquinolone with a 3-methylpiperazinyl substituent at C7. The antibacterial action of gatifloxacin results from inhibition of DNA gyrase and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription, and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division. The mechanism of action of fluoroquinolones including gatifloxacin is different from that of aminoglycoside, macrolide, and tetracycline antibiotics. Therefore, gatifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to gatifloxacin. There is no cross-resistance between gatifloxacin and the aforementioned classes of antibiotics. Cross-resistance has been observed between systemic gatifloxacin and some other fluoroquinolones.https://www.accessdata.fda.gov
Pharmacokinetics
Gatifloxacin ophthalmic solution 0.5% was administered to one eye of 6 healthy male subjects each in an escalated dosing regimen starting with a single 2 drop dose, then 2 drops 4 times daily for 7 days, and finally 2 drops 8 times daily for 3 days. At all time points, serum gatifloxacin levels were below the lower limit of quantification (5 ng/mL) in all subjects.
Side effects
Gatifloxacin is well absorbed from the gastrointestinal tract (oral availability almost 100%), and concomitant administration of a continental breakfast, 1050 kcal, had no effect on its availability. The standard dose is 400 mg od and both oral and intravenous formulations are available.Common side effectsWorsening of eye infectionEye irritationEye painChange in tasteThe following serious adverse reactions are described elsewhere in the labeling:Hypersensitivity [see Contraindications (4) and Warnings and Precautions (5.1)]Growth of Resistant Organisms With Prolonged Use [see Warnings and Precautions (5.2)]Corneal Endothelial Cell Injury [see Warnings and Precautions (5.3)]https://go.drugbank.com https://medlineplus.govhttps://www.accessdata.fda.gov
Check Digit Verification of cas no
The CAS Registry Mumber 112811-59-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,2,8,1 and 1 respectively; the second part has 2 digits, 5 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 112811-59:
(8*1)+(7*1)+(6*2)+(5*8)+(4*1)+(3*1)+(2*5)+(1*9)=93
93 % 10 = 3
So 112811-59-3 is a valid CAS Registry Number.
InChI:InChI=1/C19H22FN3O4/c1-10-8-22(6-5-21-10)16-14(20)7-12-15(18(16)27-2)23(11-3-4-11)9-13(17(12)24)19(25)26/h7,9-11,21H,3-6,8H2,1-2H3,(H,25,26)
112811-59-3Relevant articles and documents
A high-throughput impurity-free process for gatifloxacin
Villasante, F. Javier,Gude, Lourdes,Fernandez, Sara P.,Alonso, Olga,Garcia, Elena,Cosme, Antonio
, p. 900 - 903 (2008)
An improved process to obtain gatifloxacin (1) through use of boron chelate intermediates has been developed. The methodology involves an initial activation step which accelerates the formation of the first chelate under low-temperature conditions and prevents demethylation of the starting material. To increase the overall yield and to avoid the isolation and manipulation of the resulting intermediates, the process has been designed to be carried out in one pot. As a result, we present here an easy, scaleable and substantially impurity-free process to obtain gatifloxacin (1) in high yield.
Gatifloxacin and synthesis method thereof
-
Paragraph 0061; 0063-0064; 0065; 0067-0068; 0069; 0071-0072, (2020/03/23)
The invention relates to a gatifloxacin and a synthesis method thereof. The synthesis method comprises the following steps: uniformly mixing N,N-dimethylaminoethyl acrylate, 2,4,5-trifluoro-3-methoxybenzoylchloride, ethyl acetate and triethylamine, and carrying out a complete reaction so as to obtain a first intermediate; uniformly mixing the first intermediate with acetic acid and cyclopropylamine, and carrying out a complete reaction to obtain a second intermediate; uniformly mixing the second intermediate with a strong base, and carrying out a complete reaction to obtain gatifloxacin cyclization ester; carrying out an ester exchange reaction on the gatifloxacin cycliztion ester to so as to obtain a third intermediate; uniformly mixing the third intermediate with 2-methylpiperazine, carrying out a complete reaction, and hydrolyzing and acidifying the obtained reaction product to obtain the gatifloxacin, wherein the strong base is selected from at least one of sodium hydroxide and potassium hydroxide. The synthesis method of gatifloxacin adopts the sodium hydroxide and potassium hydroxide to carry out the cyclization reaction, so that the cyclization reaction time is greatly shortened, and the time cost for synthesizing gatifloxacin is reduced.
STREAMLINED SYNTHESES OF FLUOROQUINOLONES
-
Page/Page column 24, (2019/01/08)
Methods of synthesizing fluoroquinolones such as ciprofloxacin are provided. The methods utilize affordable materials, reduce the number of synthesis steps and provide high yields.
METHOD FOR PRODUCING QUINOLONE CARBOXYLIC ACID DERIVATIVE
-
Page/Page column 12, (2009/12/24)
The present invention relates to a method for producing a quinolone compound having high antibacterial activity and high safety, at high yield and in a simple manner. A quinolonecarboxylic acid derivative (1) of interest is produced through a one-pot manner by reacting a compound (2) with a salt of a cyclic amine (3) and with a boron derivative in a solvent in the presence of a base.
PROCESS FOR THE PREPARATION OF GATIFLOXACIN AND REGENERATION OF DEGRADATION PRODUCTS
-
Page/Page column title page; 4; 9-10, (2008/06/13)
The subject of the present invention are an improved synthesis process comprising a process for regeneration of a side product of gatifloxacin and an analysis method for process control in the synthesis of gatifloxacin (Formula I).
CRYSTALLINE FORM OF GATIFLOXACIN
-
Page/Page column 7-8, (2010/02/11)
The present invention relates to a crystalline form of gatifoxacin (formula I) obtainable by process that comprises recrystallisation of the crude gatifloxacin in methanol and which is stable with a water content ranging between 2.5 and 4.5% by weight, to a process for preparing it and to the use thereof as an active substance in the preparation of pharmaceutical formulations.
AN IMPROVED PROCESS FOR THE PREPARATION OF GATIFLOXACIN
-
Page/Page column 9-11, (2008/06/13)
The present invention relates to a process for the preparation of Gatifloxacin by reacting ethvl 1-cyclopropyl-6,7-difluoro-8- methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylate with aqueous hydrofluoroboric acid followed by condensation with 2-methyl piperazine in polar organic solvent resulting in an intermediate Cyclopropyl-7-(3-methylpiperazin-1-yl)-6-fluoro-8-methoxy-4-oxo- 1,4-dihydro-3-quinoline carboxylic acid boron difluoride chelate which upon hydrolysis yields Gatifloxacin.
PROCESS FOR PREPARING GATIFLOXACIN
-
Page/Page column 7-9, (2010/02/11)
This invention relates to a simplified process for preparing gatifloxacin. In said process the compound (II) is used as the starting compund, which is then made to react with 2-methylpiperazine after being silyated and activated in the form of boron chelate.Finally, the boron chelate is eliminated by treatment with a C1-C4 alkyl chain alcohol. One characteristic of the process described is that all the reactions are carried out without isolating the intermediate compounds formed ("one pot" process).
Novel crystalline forms of gatifloxacin
-
Page/Page column 12, (2008/06/13)
Provided are novel crystalline forms of gatifloxacin denominated forms A, B, C, D, E1, F, G, H, I, and J, and methods for their preparation. Also provided are methods for making known crystalline forms of gatifloxacin, in particular forms omega and T2RP.
PROCESS FOR PREPARING OMEGA-ANHYDROUS GATIFLOXACIN
-
Page 7-8, (2008/06/13)
Novel process to manufacture omega form and form-II of anhydrous Gatifloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-l-piperazinyl)-3-guinodine carboxylic acid) having structural formula (I) is disclosed. The invention does not require high temperature or use of column chromatography for purification. Moreover the solvents being used in the process can be recovered and recycled. These factors make the process industrially efficient.
