Sitafloxacin

Base Information

• Chemical Name: Sitafloxacin
• CAS No.: 127254-12-0
• Deprecated CAS: 155421-11-7,163157-04-8,167355-47-7
• Molecular Formula: C19H18ClF2N3O3
• Molecular Weight: 409.82
• UNII: 3GJC60U4Q8
• Nikkaji Number: J482.678G
• Wikipedia: Sitafloxacin
• Wikidata: Q3962322
• NCI Thesaurus Code: C76923
• ChEMBL ID: CHEMBL108821
• Mol file: 127254-12-0.mol

Synonyms:7-((7S)-amino-5-azaspiro(2,4)heptan-5-yl)-8-chloro-6-fluoro-1-((1R,2R)-cis-2-fluoro-1-cyclopropyl)-1,4-dihydro-4-oxoquinolone-3-carboxylic acid;7-(7-amino-5-azaspiro(2.4)heptan-5-yl)-8-chloro-6-fluoro-1-(2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid sesquihydrate;DU 6859;DU 6859A;DU-6859;DU-6859A;sitafloxacin

Chemical Property of Sitafloxacin

Chemical Property:

• Vapor Pressure: 1.06E-16mmHg at 25°C
• Refractive Index: 1.698
• Boiling Point: 629.2 °C at 760 mmHg
• PKA: 6.39±0.50(Predicted)
• Flash Point: 334.3 °C
• PSA: 88.56000
• Density: 1.63 g/cm³
• LogP: 3.46790
• XLogP3: 0.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 3
• Exact Mass: 409.1004755
• Heavy Atom Count: 28
• Complexity: 761

Purity/Quality:

99% ^*data from raw suppliers

7-((S)-7-Amino-5-azaspiro[2.4]heptan-5-yl)-8-chloro-6-fluoro-1-((1R,2S)-2-fluorocyclopropyl)-4-oxo-1,4-dihydroquinoline-3-carboxylicacid 97% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC12CN(CC2N)C3=C(C=C4C(=C3Cl)N(C=C(C4=O)C(=O)O)C5CC5F)F
• Isomeric SMILES: C1CC12CN(C[C@H]2N)C3=C(C=C4C(=C3Cl)N(C=C(C4=O)C(=O)O)[C@@H]5C[C@@H]5F)F
• Recent ClinicalTrials: A Study to Evaluate the Efficacy and Safety of Sitafloxacin in Adult Subjects With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
• Recent NIPH Clinical Trials: VAS third-line eradication study
• Description: 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. 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.
• Uses: Antibacterial (DNA-gyrase inhibitor).

Technology Process of Sitafloxacin

There total 19 articles about Sitafloxacin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.3%

C26H30ClF2N3O5 → sitafloxacin (127254-12-0,127199-06-8,127254-10-8,127254-11-9,155421-11-7,163157-04-8,167355-47-7,273401-03-9)

Guidance literature:

With trifluoroacetic acid; In chloroform; at 20 - 25 ℃; Cooling with ice;

Reference yield: 97.0%

7-[7-(s)-tert-butoxycarbonylamino-5-azaspiro[2,4]-hept-5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid → sitafloxacin (127254-12-0,127199-06-8,127254-10-8,127254-11-9,155421-11-7,163157-04-8,167355-47-7,273401-03-9)

Guidance literature:

With hydrogenchloride; In dichloromethane; water; at 0 - 30 ℃; for 1h; Solvent;

Reference yield: 87.0%

C20H17BClF2N3O4 → sitafloxacin (127254-12-0,127199-06-8,127254-10-8,127254-11-9,155421-11-7,163157-04-8,167355-47-7,273401-03-9)

Guidance literature:

With trifluoroacetic acid; at 20 ℃; for 0.833333h; Cooling with ice;

DOI:10.14233/ajchem.2014.17864

upstream raw materials:

7-(S)-amino-5-<1(R)-phenylethyl>-5-azaspiro<2.4>heptane

(7S)-5-azaspiro[2.4]heptan-7-ylcarbamic acid tert-butyl ester

7-(S)-amino-5-<1(R)-phenylethyl>-4-oxo-5-azaspiro<2.4>heptane

7(S)-<(tert-butoxycarbonyl)amino>-5-<1(R)-phenylethyl>-5-azaspiro<2.4>heptane

Refernces

• 1、 -. "Method for preparing sitafloxacin". Paragraph 0022; 0023; 0026; 0029. . Retrieved 2017/06/28.
• 2、 -. "A Sitafloxacine intermediate, Sitafloxacine preparation method and Sitafloxacine pharmaceutical composition". Paragraph 0024; 0060-0061. . Retrieved 2017/01/19.