123447-62-1 Usage
Description
Prulifloxacin, also known as Sword, is a third-generation fluoroquinolone antibiotic. It is a lipophilic prodrug that rapidly hydrolyzes to its active metabolite, Ulifloxacin, after intestinal absorption. Prulifloxacin inhibits bacterial DNA replication by inhibiting DNA gyrase, exerting broad-spectrum antibacterial activity against several Gram-positive and Gram-negative organisms. It was introduced in Japan as an oral treatment for urinary tract infections (UTIs), respiratory tract infections (RTIs), and bacterial pneumoniae.
Uses
Used in Pharmaceutical Industry:
Prulifloxacin is used as an antibiotic for the treatment of various bacterial infections, including urinary tract infections (UTIs) and respiratory tract infections (RTIs). It is effective against both gram-positive and gram-negative bacteria, showing similar or greater activity compared to ciprofloxacin.
Used in Clinical Studies:
Prulifloxacin has demonstrated good efficacy in clinical studies for the treatment of uncomplicated lower urinary tract infections, acute exacerbations of chronic bronchitis, and complicated lower urinary tract infections.
Chemical Properties:
Prulifloxacin is an off-white solid with a plasma half-life of approximately 8 hours. It is mainly excreted in the urine and feces as unchanged NM 394. Phototoxicity in animal models is less severe than with other quinolones, and the drug is well-tolerated with an adverse effect profile similar to that of other fluoroquinolones.
Quinolone antibiotics
Prulifloxacin is a quinolone antibiotic, a fluoroquinolone antibiotics prodrug NM394 by the Japan Pharmaceutical Co. and Meiji Seika Kaisha, Ltd. joint research and development in the late eighties, and it was first approved for marketing in December 2002 in Japan. the dosage form is 100mg tablets, by inhibiting bacterial DNA topoisomerase ⅱ and ⅳ activity and bacterial DNA synthesis, completing sterilization, which is different from the traditional model, without drug resistance to other classes of antibiotics. It is used for the treatment of respiratory gram-positive bacteria and negative bacteria clinically, which is caused by infections, urogenital infections, otolaryngology infection, biliary tract infections, enteritis, skin and soft tissue infections and surgical infections. Notable features are as follows:
Anti-gram-positive bacteria are similar with ciprofloxacin. The anti-Gram-negative bacteria, led by pseudomonas aeruginosa, is better than the similar products, such as ciprofloxacin, ofloxacin, levofloxacin, resistance to green pus bacillus particularly high sensitivity, and the antibacterial abilitu is better than the gatifloxacin class and other antibiotics currently listed.
The oral absorption is good without savings and cerebrospinal fluid distribution,? and the side effects is little.
The half-life is as long as 8-9 hours, and the number of eating medication is few.
Rapid onset, time to peak within 0.5 to 1 hour, the effet is stronger (due to bacterial accumulation in good).
Indication
It is used for the treatment of prulifloxacin sensitive staphylococcus, streptococcus, Neisseria gonorrhoeae, (except typhoid, paratyphoid) pneumoniae, Enterococcus, Moraxella Alex Salmonella, E. coli, Shigella, Salmonella, lemon acid bacteria, Klebsiella pneumoniae, Serratia, Proteus, Vibrio cholerae, Pseudomonas aeruginosa, Streptococcus digestion, they can cause the following infections:
Superficial skin infections (acute superficial folliculitis, infectious impetigo), deep skin infections (cellulitis, erysipelas, boils, boils swollen disease, appendicitis, suppurative paronychia), chronic pyoderma (sebaceous cyst infection, purulent, etc.).
Superficial secondary infections, such as abscess, trauma, burns, and surgical trauma.
Acute respiratory infections (pharyngitis, tonsillitis, acute bronchitis), chronic respiratory disease secondary infection (chronic bronchitis, diffuse bronchiolitis, bronchiectasis, emphysema, pulmonary fibrosis, bronchial asthma, etc.) and pneumonia.
Cystitis, pyelonephritis, prostatitis.
Cholecystitis, cholangitis.
Infectious enteritis, bacillary dysentery, salmonellosis, cholera.
The uterine infection, adnexitis.
Blepharitis, stye.
Otitis media, sinusitis.
Pharmacokinetics
After oral administration, Prulifloxacin is rapidly metabolized as an active form of drug, Ulifloxacin. The drug exerts good penetration into the target tissue with prolonged elimination half-life with once-daily administration.
After absorption, Cmax is generally achieved within one hour, and apparent Vss is 1231 L. About 45% of the administered drug is bound to plasma proteins. The drug is extensively metabolized by first-pass metabolism into active metabolites. The terminal half-life of Ulifloxacin is 10.6-12.1 hours. The drug is mainly excreted via the urine as unmetabolized drug.
Prulifloxacin Intermediate
Prulifloxacin Intermediate PL-7
Appearance: white to light yellow powder
Chemical name: 6,7-difluoro-2-mercapto-ethyl-4-hydroxy-quinoline-3-carboxylic acid ethyl ester CAS: 154330-68-4
?Molecular Formula: C14H13F2NO3S
Prulifloxacin intermediate PL-9
Appearance: white to light yellow powder
Chemical name: 6,7-difluoro-1-methyl-4-oxo--4H-(1,3) thiazine (3,2a) and quinoline-3-carboxylate CAS: 113046-72-
Molecular Formula:C14H11F2NO3S
Prulifloxacin Intermediate PL-10
Appearance: white to light yellow powder
Chemical Name: 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl) 4H-(1,3) thiazine (3,2a) and quinoline-3-carboxylate CAS: 113028-17-4
?Molecular Formula:C18H20FN3O3S
Prulifloxacin Intermediate PL-11
Appearance: white to light yellow powder
Chemical Name: 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-(1,3) thiazine (3,2a) and quinoline-3-carboxylic acid CAS : 112984-60-8
Molecular Formula:C16H16FN3O3S
Application:For the total synthesis of gatifloxacin antibacterials
Side effects
Abdominal cramp, Confusion, Diarrhoea, Drowsiness, Altered taste, Epigastric pain, Gastritis, Headache, Hot flashes, Increased bilirubin in the blood, Itching, Loss of appetite, Sedation, Skin rash, Sleep disorder, Vomiting, Nausea.
References
https://www.ncbi.nlm.nih.gov/pubmed/15456336
http://www.drugsupdate.com/generic/view/1110/Prulifloxacin
Originator
Nippon Shinyaku (Japan)
Pharmaceutical Applications
A lipophilic prodrug which is very rapidly metabolized by esterase into ulifloxacin, a 6-fluoro, 7-piperazinyl thiazetoquinoline.Ulifloxacin is moderately active against Staph. aureus (MIC 0.4–0.8 mg/L) and inactive against Str. pneumoniae (MIC 2–8 mg/L) as well as against Enterococcus spp. Against Enterobacteriaceae (MIC 0.05–0.8 mg/L) and Ps. aeruginosa (MIC 0.2–0.8 mg/L) activity is similar to that of ciprofloxacin. It is active against fastidious Gram-negative bacilli, but not against anaerobes and non-fermentative Gram-negative bacilli. Activity against Acinetobacter spp. is modest.Prulifloxacin is rapidly converted into ulifloxacin and after 3 h is no longer detected in blood. In volunteers receiving a single oral dose, peak plasma concentrations of 0.68 mg/L (300 mg dose) to 1.88 mg/L (for 400 mg dose) were attained between 0.67 and 1.25 h. The mean apparent elimination half-life was 8 h and the mean cumulative elimination rate in urine within 48 h was 31–46%. Other inactive metabolites account for 7% of the dose. Half the administered dose is eliminated in feces within 72 h as ulifloxacin and 4% as prulifloxacin. Protein binding is 45%.
Synthesis
The synthesis of
prulifloxacin (22)started with the treatment of 3,4-
difluoroaniline (183) with carbon disulfide in the presence of
TEA to give the triethylammonium dithiocarbamate, which
by reaction with ethyl chloroformate and TEA in
chloroform, was converted into isothiocyanate 184 in 74%
yield. Reaction of 184 with diethyl malonate in the presence
of KOH in dioxane yielded methylenemalonate 185
potassium salt, which was ethylated with ethyl sulfate in
ethanol to give compound 186 in excellent yield. 6,7-
Difluoroquinoline 187 was obtained with the highest yield
and regioselectivity when precursor 186 was heated in
refluxing xylene. To suppress the side reaction in the
subsequent chlorination, quinoline 187 was acylated to give
188 with acetyl chloride in chloroform. Chlorination of 188
with sulfuryl chloride gave compound 189 in 79% yield.
Compound 189 was treated with sodium acetate in THF to
afford cyclized compound 190, which was condensed with
piperazine in DMF to give compound 191. The hydrolysis
of ester 191 with KOH in hot t-butanol gave free acid 192,
which was finally condensed with 4-(bromomethyl)-5-
methyl-1, 3-dioxol-2-one (163) by treatment of potassium
bicarbonate in DMF to give prulifloxacin (22).
Check Digit Verification of cas no
The CAS Registry Mumber 123447-62-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,3,4,4 and 7 respectively; the second part has 2 digits, 6 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 123447-62:
(8*1)+(7*2)+(6*3)+(5*4)+(4*4)+(3*7)+(2*6)+(1*2)=111
111 % 10 = 1
So 123447-62-1 is a valid CAS Registry Number.
InChI:InChI=1/C21H22FN3O6S/c1-10-16(31-21(29)30-10)9-23-3-5-24(6-4-23)15-8-14-12(7-13(15)22)18(26)17(20(27)28)19-25(14)11(2)32-19/h7-8,11,17,19H,3-6,9H2,1-2H3,(H,27,28)
123447-62-1Relevant articles and documents
Studies on synthesis of the antibacterial agent NM441. II. Selection of a suitable base for alkylation of 1-substituted piperazine with 4- (bromomethyl)-5-methyl-1,3-dioxol-2-one
Fujii,Nishida,Abiru,Yamamoto,Kise
, p. 1872 - 1877 (1995)
Diisopropylamine (DIPA), N,N-diisopropylethylamine (DIPEA), tributylamine (TNBA) and 7-(1-piperazinyl)-4-quinolone-3-carboxylic acid (2) were titrated in water-dimethylformamide (DMF) mixtures containing 45-98% DMF. Apparent pK(a) values in anhydrous DMF (pK(DMF)) were calculated by extrapolation from the variation in the half-neutralization pH values in aqueous DMF. The validity of the relative basicity derived from the pK(DMF)S was confirmed by examination of the kinetics of esterification of a derivative of 2 with 4- (bromomethyl)-5-methyl-1,3-dioxol-2-one (DMDO-Br). Relative basicities in DMF were: the carboxylate anion of 2 >> DIPA > DIPEA > TNBA > the amino group in the piperazinyl part of 2. This order is clearly different from that observed in water. We concluded that DIPEA is a suitable agent to suppress the undesired esterification during the reaction to mask the amino group of 2 with a DMDO group, because it does not remove a proton from the carboxyl group, but only from the protonated amino group.
CRYSTALLINE FORM OF PRULIFLOXACIN AND PROCESSES FOR ITS PREPARATION
-
, (2012/01/14)
The present invention relates to a crystalline polymorphic form of 6-fluoro-1-methyl-7- {4-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl]piperazin-1-yl}-4-oxo-4H-[1,3]-thiazeto-[3,2- a]-quinoline-3-carboxylic acid (prulifloxacin). More specifically, the invention relates to a crystalline form of prulifloxacin (herein referred to as Form A), and a method for preparing the crystalline Form A. The present invention further provides a pharmaceutical formulation comprising the novel form of prulifloxacin.
PROCESS FOR THE PREPARATION OF PURE PRULIFLOXACIN
-
Page/Page column 6, (2008/12/07)
The present invention relates to a process for the preparation of prulifloxacin. The present invention further relates to prulifloxacin having purity of about 99% or above.
