5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
Sparfloxacin
CAS: 110871-86-8
Molecular Formula: C19H22F2N4O3
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Names and Identifiers
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Physico-chemical Properties
| Molecular Formula | C19H22F2N4O3 |
| Molar Mass | 392.4 |
| Density | 1.436±0.06 g/cm3(Predicted) |
| Melting Point | 265°C |
| Boling Point | 640℃ |
| Flash Point | >110°(230°F) |
| Water Solubility | Soluble in DMSO at 9mg/ml. Sparingly soluble in water |
| Vapor Presure | 4.2E-14mmHg at 25°C |
| Appearance | powder |
| Color | white to light yellow |
| BRN | 9170271 |
| pKa | pKa1 6.25, pKa2 9.30(at 25℃) |
| Storage Condition | Keep in dark place,Inert atmosphere,2-8°C |
| Refractive Index | 1.611 |
| Physical and Chemical Properties | Storage Conditions: Store at 0-5 ℃ WGK Germany:2 RTECS:VB1986500 |
| In vitro study | Sparfloxacin has a broad spectrum of potent antibacterial activity. For Gram-positive bacteria, such as staphylococci, streptococci and enterococci, The MICs of 90% of the tested strains are 0.1 to 0.78 micrograms/ml, for Gram-negative bacteria, for example, the Enterobacteriaceae family and Pseudomonas spp., the MICs are 0.0125 to 1.56 μg/ml. Its MICs are 0.025 to 0.78 μg/ml for glucose non-fermenting bacteria and 0.2 to 0.78 μg/ml for anaerobic biological MICs, MICs against Legionella is 0.0125 to 0.05 μg/ml. Sparfloxacin targets DNA gyrase to inhibit DNA synthesis. |
| In vivo study | Oral Sparfloxacin is effective in treating systemic infections in mice caused by Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. |
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Risk and Safety
| Hazard Symbols | Xi - Irritant |
| Risk Codes | 36/37/38 - Irritating to eyes, respiratory system and skin. |
| Safety Description | S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S36 - Wear suitable protective clothing. |
| WGK Germany | 2 |
| RTECS | VB1986500 |
| HS Code | 29339900 |
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Standard
Authoritative Data Verified Data
This product is 5-amino-1-cyclopropyl-7-(cis-3, 5-dimethyl-1-piperazinyl)-6, 8-difluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid. The content of sparfloxacin (C19H22F2N403) should be between 98.5% and 102.0% based on the dry product.
Last Update：2024-01-02 23:10:35
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Trait
Authoritative Data Verified Data
- This product is yellow crystalline powder; Odorless.
- This product is slightly soluble in acetonitrile, methanol or ethyl acetate, slightly soluble in ethanol, almost insoluble in water; Dissolved in O.lmol/L sodium hydroxide solution, slightly soluble in glacial acetic acid.
Last Update：2022-01-01 11:42:08
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Differential diagnosis
Authoritative Data Verified Data
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
- The infrared absorption spectrum of this product should be consistent with that of the control (Spectrum set 921).
Last Update：2022-01-01 11:42:08
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Exam
Authoritative Data Verified Data
absorbance
take this product, precision weighing, add 0.1 mol/L sodium hydroxide solution is dissolved and quantitatively diluted to make a solution containing 0401 mg per 1 ml, and the absorbance is measured at the wavelength of 440nm by ultraviolet-visible spectrophotometry (general rule), not more than 0.15.
Related substances
take an appropriate amount of this product, add the mobile phase under the content measurement item to dissolve and dilute to prepare a solution containing about 0.2mg per 1ml as a test solution. Take 1ml accurately, put it in a 200ml measuring flask, dilute it to the scale with the mobile phase under the content measurement item, and shake it well to serve as a control solution. Determined by high performance liquid chromatography (General 0512). Sodium citrate buffer (weigh 2.104g of citric acid and 2.941g of sodium citrate, add water to 70% ML, adjust pH value to 2.4 with perchloric acid solution) as mobile phase A; acetonitrile was used as mobile phase B and the detection wavelength was 290mn. Perform linear gradient elution according to the following table, take an appropriate amount of sparfloxacin reference, dissolve and dilute with mobile phase A to make A solution containing about 0.3mg per 1 ml, and irradiate for 20 hours under illumination of 4500lx, as the system applicable solution, take 10ul injection liquid chromatograph, record chromatogram, sparfloxacin peak retention time is about 7 minutes, the resolution between the peak of sparfloxacin and its impurity peak at a relative retention time of about 0.9 shall meet the requirements, and the tailing factor of sparfloxacin peak shall not exceed 2.0. Accurately take 20 u1 of the test solution and the control solution respectively, inject them into the liquid chromatograph and record the chromatogram. If there are impurity peaks in the chromatogram of the test solution, the Peak area of the largest single impurity shall not be greater than the main peak area of the control solution (0.5% ) , and the peak area of other single impurity shall not be greater than 0.2 times (0.1%) of the main peak area of the control solution, the sum of each impurity peak area shall not be greater than 2 times (1.0%) of the main peak area of the control solution. The peaks in the chromatogram of the test solution which were 0.1 times smaller than the main peak area of the control solution were ignored.
residual solvents toluene and pyridine
about 0.5g of the sample was precisely weighed and placed in a top-empty bottle. 5ml of 2% sodium hydroxide solution was precisely added to dissolve the sample, and sealed to form the sample solution. Accurately weigh the appropriate amount of toluene and pyridine, add 2% sodium hydroxide solution for quantitative dilution to make a mixed solution containing toluene 89ug and pyridine 20ug per 1 ml, accurately weigh 5ml, and place in the top empty bottle, sealed as a control solution. According to the determination method of residual solvent (General 0861 second method), the capillary column with polyethylene glycol (PEG-20M)(or similar polarity) as the stationary liquid is used as the column, the initial temperature is 60°C, and the maintenance time is 5 minutes, the temperature was raised to 150°C at a rate of 20°C per minute for 6 minutes, the detector temperature was 230°C; The inlet temperature was 200°C. The Headspace bottle equilibration temperature was 85°C and the equilibration time was 30 minutes. Take the reference solution into the headspace, the separation degree of each component peak should meet the requirements. The test solution and the reference solution are respectively injected in the headspace, and the chromatogram is recorded. The residual amount of toluene and pyridine shall be calculated by the peak area according to the external standard method.
chloroform
about 0.5g of the sample was accurately weighed and placed in a top-empty bottle. 5ml of 2% sodium hydroxide solution was accurately added to dissolve the sample, and sealed to form the sample solution. The appropriate amount of chloroform was accurately weighed and diluted with 2% sodium hydroxide solution to make a solution containing about 6ug of chloroform per 1 ml. The solution was accurately weighed and placed in a top empty bottle, sealed, and used as a reference solution. According to the determination method of residual solvent (General 0861 second method), the capillary column with polyethylene glycol (PEG-20M)(or similar polarity) as the stationary liquid is used as the column, the initial temperature is 60°C, and the maintenance time is 10 minutes, the temperature was raised to 150°C at a rate of 20°C per minute for 5 minutes; The detector temperature was 230°C; And the inlet temperature was 200°C. The Headspace bottle equilibration temperature was 75°C and the equilibration time was 20 minutes. The test solution and the reference solution are injected in the headspace respectively, the chromatogram is recorded, and the peak area is calculated according to the external standard method. The residual amount of chloroform should be in accordance with the regulations.
loss on drying
take this product, dry to constant weight at 105°C, weight loss shall not exceed 1.0% (General rule 0831).
burning residue
take l.Og of this product, put it in a platinum crucible, and check it according to law (General rule 0841). The residue left shall not exceed 0.2%.
Heavy metals
The residue left under the item of taking the ignition residue shall not contain more than 20 parts per million of heavy metal when examined by law (General rule 0821, Law II).
Last Update：2022-01-01 11:42:09
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Content determination
Authoritative Data Verified Data
measured by high performance liquid chromatography (General 0512).
chromatographic conditions and system suitability test
silica gel bonded with octa-alkyl silane as filler; Sodium citrate buffer (weigh 2.941g of citric acid and 70% g of sodium citrate, add water to 2.4, adjust pH to with perchloric acid solution)-Acetonitrile (70:30) as mobile phase; The detection wavelength was 298nm. Take an appropriate amount of sparfloxacin control, add mobile phase to dissolve and dilute to make about 0.lmg solution, irradiated at 4500LX illumination for 20 hours, as the system applicable solution, the amount of 10u1 injection of human liquid chromatography, recording the chromatogram, sparfloxacin peak retention time of about 7 minutes, the resolution between the sparfloxacin peak and its impurity peak at a relative retention time of about 0.9 should be satisfactory.
assay
take about 50mg of this product, weigh it accurately, put it in a 100ml measuring flask, add an appropriate amount of methanol, fully shake to dissolve it, dilute it to the scale with methanol, and shake it well, take 2ml accurately, put it in a 25ml measuring flask, dilute it to scale with mobile phase, shake well, use it as a sample solution, take 20ul accurately and inject it into human liquid chromatograph, record chromatogram; an appropriate amount of sparfloxacin reference substance was taken and determined by the same method. According to the external standard method to calculate the peak area, that is.
Last Update：2022-01-01 11:42:10
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Category
Authoritative Data Verified Data
quinolones.
Last Update：2022-01-01 11:42:10
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Content determination
Authoritative Data Verified Data
light shielding, sealed storage.
Last Update：2022-01-01 11:42:11
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Sparfloxacin tablets
Authoritative Data Verified Data
This product contains sparfloxacin (C19H22F2N403) should be 90.0% ~ 110.0% of the label amount.
trait
This product is light yellow or yellow or film-coated tablets, yellow after removing the coating.
identification
(1) in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the control solution.
(2) take an appropriate amount of fine powder of this product, add 0.1% sodium hydroxide solution to dissolve sparfloxacin and dilute it into a solution containing about 7.5ug sparfloxacin per 1 ml, filter it, and take the filtrate, there is an absorption maximum at a wavelength of 0401 nm as determined by UV-Vis spectrophotometry (general).
examination
- Related Substances: Take 10 tablets of this product, grind them finely, and accurately weigh an appropriate amount of fine powder (equivalent to 20mg of sparfloxacin), A solution containing about 0.2mg of sparfloxacin per 1 ml was prepared by dissolving and diluting the mobile phase under the item of content measurement. The solution was filtered and the filtrate was collected as a test solution. The Peak area of the largest single impurity shall not be greater than the main peak area of the control solution (0.5% ) , and the peak area of other single impurity shall not be greater than 0.2 times (0.1%) of the main peak area of the control solution, the sum of each impurity peak area shall not be greater than 3 times (1.5%) of the main peak area of the control solution.
- dissolution dissolution of this product, according to the dissolution and release determination method (General rule 0931 The first method), with acetic acid sodium acetate buffer (pH 4.5)900ml as the dissolution medium, speed is 100 revolutions per minute, according to the law, after 45 minutes, take the appropriate amount of solution, filtration, precision take the appropriate amount of filtrate, A solution containing about 6ug sparfloxacin per 1 ml was prepared by quantitative dilution with dissolution medium, and the absorbance was measured at the wavelength of 298nm according to ultraviolet-visible spectrophotometry (General rule 0401); in addition, an appropriate amount of sparfloxacin reference substance was accurately weighed, dissolved with dissolution medium and quantitatively diluted to prepare a solution containing about 6ug per 1 ml, which was determined by the same method to calculate the dissolution amount of each tablet. The limit is 80% of the labeled amount and shall be in accordance with the provisions.
- others shall be in accordance with the relevant provisions under the item of tablets (General rule 0101).
Content determination
Take 20 tablets of this product, precise weighing, fine grinding, precise weighing appropriate amount (about 0.lg equivalent to sparfloxacin), put it in a 200ml measuring flask, add the appropriate amount of methanol and shake to dissolve sparfloxacin, dilute to the scale with methanol, shake, filter, take a precise amount of filtrate 2ml, put in a 25ml measuring flask, dilute to the scale with mobile phase, shake, as a test solution. According to the method under the sparfloxacin determination, obtained.
category
with sparfloxacin.
specification
(1)0.lg (2)0.15g (3)0.2g
storage
light shielding, sealed storage.
Last Update：2022-01-01 11:42:12
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Sparfloxacin capsules
Authoritative Data Verified Data
This product contains sparfloxacin (C19H22F2N403) should be 90.0% ~ 110.0% of the label amount.
trait
The content of this product is yellow particles, powder or crystalline powder.
identification
(1) in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the control solution.
(2) take an appropriate amount of the contents of this product, add 0.1% sodium hydroxide solution to dissolve and dilute sparfloxacin into a solution containing about 7.5ug sparfloxacin per 1 ml, and filter it, the filtrate was measured by UV-Vis spectrophotometry (General 0401), and had a maximum absorption at a wavelength of 291nm.
examination
- Related Substances: take the contents of this product, grind it finely, and accurately weigh an appropriate amount of fine powder (equivalent to 20mg of sparfloxacin), A solution containing about 0.2mg of sparfloxacin per 1 ml was prepared by dissolving and diluting the mobile phase under the item of content measurement. The solution was filtered and the filtrate was collected as a test solution. The Peak area of the largest single impurity shall not be greater than the main peak area of the control solution (0.5% ) , and the peak area of other single impurity shall not be greater than 0.2 times (0.1%) of the main peak area of the control solution, the sum of each impurity peak area shall not be greater than 3 times (1.5%) of the main peak area of the control solution.
- dissolution dissolution of this product, according to the dissolution and release determination method (General rule 0931 second method), with acetic acid-sodium acetate buffer (pH 4.5)900ml as the dissolution medium, the rotation speed is 50 rpm, and the operation is carried out according to law. After 45 minutes, the appropriate amount of the solution is taken, filtered, and the appropriate amount of the filtrate is taken, the solution containing sparfloxacin Gfxg in 1 ml was prepared by quantitative dilution with dissolution medium, and the absorbance was measured by ultraviolet-visible spectrophotometry (General rule 0401) at the wavelength of 298mn; in addition, an appropriate amount of sparfloxacin reference substance was accurately weighed, dissolved and quantitatively diluted with dissolution medium to make a solution containing about 6mg per lm l, which was determined by the same method to calculate the dissolution amount of each granule. The limit is 80% of the labeled amount and shall be in accordance with the provisions.
- others should comply with the relevant provisions under the capsule (General 0103).
Content determination
take the content under the item of loading amount difference, mix evenly, accurately weigh the appropriate amount (about equivalent to sparfloxacin O.lg ), put it in a 200ml measuring flask, add an appropriate amount of methanol and shake it thoroughly to dissolve sparfloxacin, dilute it with methanol to the scale, shake it well, filter it, and take 2ml of continued filtrate with precision, in a 25ml measuring flask, dilute to the scale with the mobile phase, shake well, as a test solution, according to the method under the item of sparfloxacin, obtained.
category
with sparfloxacin.
specification
(1)0.lg (2)0.2g
storage
light shielding, sealed storage.
Last Update：2022-01-01 11:42:13
5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid - Reference Information
| introduction | sparfloxacin (Sparfloxacin) is a fluoroquinolone antibacterial drug developed by Japan Japan pharmaceutical co., ltd. it introduces amino groups at the 5 positions of the parent oxyquinoline skeleton to enhance the antibacterial activity of the drug against gram-positive bacteria compared with other fluoroquinolone antibacterial drugs. fluorine is added to the 6 and 8 positions, there is 3 5-dimethylpiperazinyl at the 7 position, which weakens the interaction with fenbufen, theophylline, and probenecid. |
| pharmacological effects | this product is a synthetic third-generation quinolone drug. It shows broad-spectrum antibacterial effect on gram-positive bacteria, negative bacteria, anaerobic bacteria, chlamydia, mycoplasma and acid-fast bacilli. This product specifically inhibits the DNA synthesis of Escherichia coli, and its mechanism of action is the same as ciprofloxacin. No cross-resistance with other antibiotics |
| biological activity | Sparfloxacin (AT-4140, CI-978, PD 131501) is a quinolone antibiotic with broad-spectrum and effective antibacterial activity. |
| use | the activity of gram-negative bacteria is the same or slightly inferior to ciprofloxacin, but the activity of gram-positive bacteria, anaerobic bacteria, chlamydia and mycoplasma is better than the latter. It is suitable for infections caused by gram-negative and positive bacteria, anaerobic bacteria, mycoplasma, chlamydia and other sensitive bacteria. In addition, there may be good prospects in the treatment of tuberculosis. |
| production method | 2,3,4,5-tetrafluorobenzoic acid is dissolved in 1,2-dichloroethane, and the mixture of fuming nitric acid and concentrated sulfuric acid (1:1, volume ratio) is added dropwise at 60 ℃, and the mixture is left overnight after the reaction at 70 ℃. The reaction liquid is poured into water and left to layer. The water layer was extracted with dichloroethane, the extract was concentrated, and the residue was recrystallized with tetrahydrofuran to obtain nitrification product (I) with 60% yield. The nitrification product, together with thionyl chloride and several drops of dimethylformamide, is refluxed until the solid is completely soluble. The unreacted thionyl chloride is distilled, the residual solution is dissolved in toluene, and added to the mixed solution of magnesium strips and absolute ethanol, carbon tetrachloride, diethyl malonate and toluene at -5-0 ℃. After the reaction, the room temperature is overnight. Pour the mixture of ice water and concentrated hydrochloric acid, and let it stand and layer. The water layer was extracted with toluene. The extract is washed with saturated salt water, dried, and concentrated under reduced pressure. Add water and concentrated sulfuric acid to the residual liquid, reflux, and cool. Extraction with dichloromethane, the extract is washed with saturated salt water, dried, and concentrated to obtain esterification product (II) with 90% yield. Esterification product (1I), triethyl orthoformate and acetic anhydride were refluxed together and concentrated under reduced pressure to obtain condensation product (III) with 95% yield. (Ⅲ), ethanol and cyclopropylamine are refluxed together. Recover ethanol, add dimethylformamide and anhydrous sodium carbonate, and react at 90°C. Cooling and filtration to obtain cyclization product (Ⅳ) with 71% yield. Iron powder, water and concentrated hydrochloric acid are refluxed, and the ethanol solution of the cyclization product (Ⅳ) is added dropwise to 85 ℃ for refluxing. Hot filtration, washing iron mud with ethanol. The filtrate and lotion are combined to evaporate ethanol. Cooling, filtration and ethanol recrystallization to obtain reduction product (V) with 74.8% yield. The reduction product (V) was refluxed in 6mol/L hydrochloric acid and cooled to room temperature to neutral with 20% sodium hydroxide. Cooling, filtration, water washing and recrystallization with ethanol to obtain hydrolysate (Ⅵ) with 95% yield. Hydrolysate (Ⅵ), acetic anhydride and acetic acid are mixed, several drops of concentrated sulfuric acid are added, and reflux is carried out. After concentration under reduced pressure, wash with water and recrystallize with chloroform to obtain acylation product (VII) with 90% yield. Acylation product (VII), cis2, 6-dimethylpiperazine and pyridine, refluxed together. Concentrate until dry, wash with water, recrystallize with ethanol to obtain condensation product (Ⅷ) with 84% yield. The condensation product (Ⅷ) was reacted with 5% sodium hydroxide at 110 ℃. Dilute with water, dilute hydrochloric acid to Ph = 9. Filtration, recrystallization with ammonia to obtain sparfloxacin with 91% yield and melting point 267~270 ℃ (decomposition). |
Last Update：2024-04-09 21:48:26
![5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid](http://res.chembk.com/assets/str/2d/1/11/110871-86-8.png)
Supplier List
Multiple SpecificationsSpot supply
Product Name: Sparfloxacin Visit Supplier Webpage Request for quotationCAS: 110871-86-8
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
Multiple SpecificationsSpot supply
Product Name: Sparfloxacin Visit Supplier Webpage Request for quotationCAS: 110871-86-8
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
View History