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
• Article Data: 6

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

Description

Different sources of media describe the Description of 127254-12-0 differently. You can refer to the following data:
1. Sitafloxacin (Trade name: Gracevit in Japan) belongs to a new generation, broad-spectrum oral fluoroquinolone antibiotics. It is highly active against various kinds of gram-negative, gram-positive and anaerobic clinical isolates, even including strains that are resistant to other kinds of fluoroquinolone antibiotics. It has been listed in Japan for the treatment of respiratory and urinary tract infections. It also shows potential for the treatment of Buruli ulcer. Its mechanism of action is through inhibiting the Topoisomerase II ligase domain of bacteria, causing DNA fragmentation to inhibit the DNA synthesis of bacteria.
2. Sitafloxacin hydrate is the newest member (fourth generation) of the fluoroquinolone family of antibiotics that exhibits broad spectrum activity against many Gram-positive, Gramnegative, and anaerobic clinical isolates, including strains resistant to other fluoroquinolones. Since the launch of the first fluoroquinolone norfloxacin (patented in 1978), 20 other versions have made it to market with ciprofloxacin and levofloxacin experiencing the most prevalent usage. The mechanism of action involves inhibition of bacterial type II topoisomerases, both DNA gyrase and topoisomerase IV. By inhibiting these enzymes and preventing DNA supercoiling, cell division is disrupted leading to cell death. In Gram-negative bacteria, the primary target appears to be gyrase, whereas topoisomerase IV is involved in Gram-positive bacteria. Dual inhibition is attractive for widespread activity and avoidance of resistance as both encoding genes would have to acquire mutations.

References

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

Originator

Daiichi Sankyo (Japan)

Uses

Antibacterial (DNA-gyrase inhibitor).

Brand name

Gracevit

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

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

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.

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.