127254-12-0

Basic information

• Product Name: Sitafloxacin
• Synonyms: SITAFLOXACIN;spifloxacin;7-[(4S)-4-Amino-6-azaspiro[2.4]heptan-6-yl]-8-chloro-6-fluoro-1-[(2S)-2-fluorocyclopropyl]-4-oxoquinoline-3-carboxylic acid;3-Quinolinecarboxylic acid, 7-[(7S)-7-aMino-5-azaspiro[2.4]hept-5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxo-;Sitafloxacin anhydrous;7-((S)-7-Amino-5-azaspiro[2.4]heptan-5-yl)-8-chloro-6-fluoro-1-((1R,2S)-2-fluorocyclopropyl)-4;Sitafloxacfn;Sitfloxacfn
• CAS NO: 127254-12-0
• Molecular Formula: C₁₉H₁₈ClF₂N₃O₃
• Molecular Weight: 409.81
• EINECS: 1308068-626-2
• Product Categories: intermediates
• Mol File: 127254-12-0.mol

Chemical Properties

• Boiling Point: 629.2 °C at 760 mmHg
• Flash Point: 334.3 °C
• Appearance: /
• Density: 1.63 g/cm³
• Vapor Pressure: 1.06E-16mmHg at 25°C
• Refractive Index: 1.698
• PKA: 6.39±0.50(Predicted)
• CAS DataBase Reference: Sitafloxacin(CAS DataBase Reference)
• NIST Chemistry Reference: Sitafloxacin(127254-12-0)
• EPA Substance Registry System: Sitafloxacin(127254-12-0)

Safety Data

• Hazardous Substances Data: 127254-12-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Sitafloxacin is used as an oral antibiotic for the treatment of respiratory and urinary tract infections. Its broad-spectrum activity and effectiveness against resistant strains make it a valuable addition to the arsenal of antibiotics available for treating various bacterial infections.
Used in Antimicrobial Therapy:
Sitafloxacin is used as an antimicrobial agent for the treatment of Buruli ulcer, a necrotizing skin infection caused by Mycobacterium ulcerans. Its potential in treating this condition highlights its versatility and effectiveness in combating different types of bacterial infections.
Used in Combating Antibiotic Resistance:
Sitafloxacin's dual inhibition of bacterial type II topoisomerases, DNA gyrase and topoisomerase IV, makes it an attractive option for widespread activity and avoidance of resistance. The need for both encoding genes to acquire mutations simultaneously reduces the likelihood of resistance development, making it a promising candidate for addressing the growing issue of antibiotic resistance.
Brand Name:
Sitafloxacin is marketed under the trade name Gracevit in Japan.

References

http://www.biochempartner.com/product_details.aspx?item_id=6084 https://en.wikipedia.org/wiki/Sitafloxacin

Originator

Daiichi Sankyo (Japan)

Pharmaceutical Applications

A group 4 quinolone formulated for oral or intravenous use. In-vitro activity is similar to or better than that of moxifloxacin. The antibacterial spectrum covers Gram-positive and Gram-negative bacteria including anaerobes. It has a chlorine atom at the C-8 position, and therefore has potential for phototoxicity. Early interest in this compound has not been maintained, but it is available in Japan.

Side effects

As a class, the major adverse events for fluoroquinolones are cardiac arrhythmia (due to QT interval 622 Shridhar Hegde and Michelle Schmidt prolongation), major phototoxicity, CNS disturbances (seizures, dizziness, and headaches), and tendonitis. The GI side effects, common to most antimicrobials, include Clostridium difficile-associated diarrhea (CDAD) and alterations in glucose homeostasis. From the clinical safety profile of sitafloxacin (1,059 patients receiving either 50 mg b.i.d. or 100 mg b.i.d.), about a third of patients experienced an adverse event with the most common being diarrhea, liver enzyme elevations, and headaches; however, the risk of QT prolongation, hypoglycemia, and hepatotoxicity were all considered to be low. Phototoxicity appears to be the limiting toxicity, particularly in non-Asian patients.

InChI:InChI=1/C19H18ClF2N3O3/c20-14-15-8(17(26)9(18(27)28)5-25(15)12-4-10(12)21)3-11(22)16(14)24-6-13(23)19(7-24)1-2-19/h3,5,10,12-13H,1-2,4,6-7,23H2,(H,27,28)/t10-,12+,13+/m0/s1

Upstream product

• 127199-41-1 7-(S)-amino-5-<1(R)-phenylethyl>-5-azaspiro<2.4>heptane 
• 127199-45-5 (7S)-5-azaspiro[2.4]heptan-7-ylcarbamic acid tert-butyl ester 
• 127199-38-6 7-(S)-amino-5-<1(R)-phenylethyl>-4-oxo-5-azaspiro<2.4>heptane 
• 127199-42-2 7(S)-<(tert-butoxycarbonyl)amino>-5-<1(R)-phenylethyl>-5-azaspiro<2.4>heptane 
• 127199-27-3 8-chloro-6,7-difluoro-1-[(1R,2S)-cis-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 
• 127199-25-1 8-chloro-6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 
• 101987-86-4 ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate 
• 180506-32-5 (R)-5-Benzyl-7-hydroxy-5-aza-spiro[2.4]heptan-4-one 
• 144282-35-9 5-benzyl-7(S)-amino-5-azaspiro[2,4]heptane 
• 1432056-70-6 5-benzyl-7(S)-tert-butoxycarbonylamino-5-azaspiro[2,4]heptane 
• 129306-05-4 ethyl 1-(2-bromoacetyl)cyclopropanecarboxylate 

Relevant articles and documents

Preparation method of sitafloxacin hydrate

The invention discloses a preparation method of sitafloxacin hydrate. The method comprises the following steps: taking ethyl 4-bromoacetoacetate used as a raw material, enabling ethyl 4-bromoacetoacetate to be fully reacted with 1,2-dibromoethane and preparing the obtained product into a compound II in the presence of carbonyl reduction enzyme; taking the compound II, enabling the compound II to carry out cyclization reaction with benzylamine in a solvent in the presence of cesium carbonate, enabling the obtained product to be reacted with DPPA and preparing a compound IV; reducing nitrine group of the compound IV to prepare a compound V; connecting primary amine group of the compound V with a BOC protection group to obtain a compound VI; reducing the compound VI through Pd/C, enabling theobtained product to be reacted with 8-chlorine-6,7-difluoro-1-[(1R,2s)-2-fluorocyclopropyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester to prepare a compound VIII; and carrying out deprotection of the compound VIII to obtain sitafloxacin hydrate. The sitafloxacin hydrate is few in preparation steps, simple in post-treatment and relatively high in yield.

Method for preparing sitafloxacin

The invention discloses a method for preparing sitafloxacin. The method comprises the following steps: (1) dissolving a compound II and a compound III in acetonitrile, adding triethylamine, heating to reflux, slowly cooling to the temperature of 0 DEG C after reaction is completed, filtering, drying, thereby obtaining a light yellow compound IV; (2) dissolving a compound IV in a non-protonic solvent, slowly adding the compound into the pre-cooled hydrochloric acid, standing and layering the reaction solution after reaction is completed, regulating the pH value of an aqueous phase by using a strong alkaline solution, regulating the pH value by using ammonium hydroxide, performing vacuum concentration on the system at room temperature so as to remove ammonia gas, separating out lots of white solids, filtering and drying, thereby obtaining sitafloxacin. According to the method for preparing sitafloxacin, disclosed by the invention, impurities produced in the reaction process can be effectively reduced, and the method is simple and convenient in after-treatment, good in refining effect, high in yield and suitable for industrial production.

A Sitafloxacine intermediate, Sitafloxacine preparation method and Sitafloxacine pharmaceutical composition

The invention discloses a sitafloxacin intermediate, a preparation method of sitafloxacin and a sitafloxacin pharmaceutical composition. The preparation method can be used for solving the problems of low yield, troublesome aftertreatment, poor safety and higher cost in the existing sitafloxacin preparation. The preparation method disclosed by the invention is simple in process, easily available in raw materials, lower in cost, the solvent after reaction is easy to treat, high yield and quite suitable for large-scale industrial production. The sitafloxacin pharmaceutical composition obtained by virtue of the preparation method provided by the invention can be used for further improving the product dissolution effect, improving the in-vivo bioavailability of the sitafloxacin and enhancing the exertion of medical effect.

A method for synthesizing Sitafloxacine (by machine translation)

The invention is in the field of organic synthesis, relates to a method for synthesizing Sitafloxacine. Compared with the prior art, the technical scheme of the invention the-west he sand star production rate, SSR, RRS and RSR isomer content is low, production can be carried out directly. (by machine translation)

Synthesis and characterization of sitafloxacin

The convenient protocol for the synthesis of sitafloxacin is described. Reaction of ethyl 3-(3-choloro-2,4,5-trifluorophenyl)-3-oxopropanoate with triethylorthoformate and (1R,2S)-(-)-cis-1,2 fluorine cyclopropane amino-p-toluene sulfonic acid salt by condensation under sodium hydrogen condition. The reaction mixture take place hydrolysis of ester in hydrochloric acid solution. Subsequence reacted with (S)-N[(oxoboryl) methylene] -5-azaspiro[2,4]heptan-7-amine by condensation. In the end taken off the protection group gives sitafloxacin and total conversion about 52-65%. The structure of sitafloxacin was characterized by 1H NMR, 13C NMR, IR, MS and elemental analysis.

(Fluorocyclopropyl)quinolones. 2. Synthesis and stereochemical structure- activity relationships of chiral 7-(7-amino-5-azaspiro[2.4]heptan-5-yl)-1- (2-fluorocyclopropyl)quinolone antibacterial agents

A series of novel chiral 7-(7-amino-5-azaspiro[2.4]heptan-5-yl)-8-chloro- 1-(2-fluorocyclopropyl)-quinolones were synthesized as a continuation of a research project of 1-(2-fluorocyclopropyl)-quinolones by considering stereochemical and physicochemical properties of the molecule. Absolute configurations of the 1-(cis-2-fluorocyclopropyl) moiety and the 7-(7-amino- 5-azaspiro-[2.4]heptan-5-yl) moiety were determined by X-ray crystallographic analysis. Stereochemical structure-activity relationship studies indicated that 1-[(1R,2S)-2-fluorocyclopropyl] and 7-[(7S)-amino-5-azaspiro[2.4]heptan- 5-yl] derivatives are more potent against Gram-positive and Gram-negative bacteria than the other stereoisomers and 7-[(7S)-7-amino-5-azaspiro[2.4]- heptan-5-yl]-8-chloro-1-[(1R,2S)-2-fluorocyclopropyl]quinolone (33) is the most potent of all stereoisomers. Pharmacokinetic profiles and physicochemical properties of the selected compounds were also examined, and it was found that 33 (DU-6859a) possesses moderate lipophilicity and good pharmacokinetic profiles.