SITAFLOXACIN ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H18ClF2N3O3
Molecular Weight	409.814
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N[C@@H]1CN(CC12CC2)C3=C(Cl)C4=C(C=C3F)C(=O)C(=CN4[C@@H]5C[C@@H]5F)C(O)=O

InChI

InChIKey=PNUZDKCDAWUEGK-CYZMBNFOSA-N

InChI=1S/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

HIDE SMILES / InChI

Molecular Formula	C19H18ClF2N3O3
Molecular Weight	409.814
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21504249
Curator's Comment: description was created based on several sources, including http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1597 https://www.ncbi.nlm.nih.gov/pubmed/18806900 https://www.ncbi.nlm.nih.gov/pubmed/10588315

Sitafloxacin hydrate (DU-6859a, Gracevit), a new-generation, broad-spectrum oral fluoroquinolone that is very active against many Gram-positive, Gram-negative and anaerobic clinical isolates, including strains resistant to other fluoroquinolones, was recently approved in Japan for the treatment of respiratory and urinary tract infections. This is a new quinolone oral antibacterial to inhibit DNA replication of bacteria at the time of infection, and shows antibacterial action. Sitafloxacin is active against methicillin-resistant staphylococci, Streptococcus pneumoniae and other streptococci with reduced susceptibility to levofloxacin and other quinolones and enterococci. Sitafloxacin has also demonstrated activity against clinical isolates of Klebsiella pneumoniae (including about 67% of strains producing extended-spectrum, beta-lactamases and resistant to ciprofloxacin), Enterobacter cloacae, Pseudomonas aeruginosa with some activity against quinolone-resistant strains and Acinetobacter baumannii. The in vitro activity against anaerobes is comparable to imipenem or metronidazole. Sitafloxacin showed dual inhibitory activity against both enzymes: Streptococcus pneumoniae DNA gyrase and topoisomerase IV.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Topoisomerase IV 62 Target ID: CHEMBL2363033 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10588315	Inhibitor 8297
DNA gyrase 26 Target ID: CHEMBL2311225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10588315	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Respiratory infections 12 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1597	Curative	Approved 8429	Gracevit(R) Approved Use It is usually used in the treatment of various infections such as respiratory infection, urologic infection, gynecologic infection, otorhinological infections, and dental infection. Launch Date 2008
Urologic infection 3 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1597	Curative	Approved 8429	Gracevit(R) Approved Use It is usually used in the treatment of various infections such as respiratory infection, urologic infection, gynecologic infection, otorhinological infections, and dental infection. Launch Date 2008
Gynecologic infections 18 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1597	Curative	Approved 8429	Gracevit(R) Approved Use It is usually used in the treatment of various infections such as respiratory infection, urologic infection, gynecologic infection, otorhinological infections, and dental infection. Launch Date 2008
Otorhinological infections 5 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1597	Curative	Approved 8429	Gracevit(R) Approved Use It is usually used in the treatment of various infections such as respiratory infection, urologic infection, gynecologic infection, otorhinological infections, and dental infection. Launch Date 2008
Dental infection 3 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1597	Curative	Approved 8429	Gracevit(R) Approved Use It is usually used in the treatment of various infections such as respiratory infection, urologic infection, gynecologic infection, otorhinological infections, and dental infection. Launch Date 2008

PubMed

Title	Date	PubMed
In vitro and in vivo antimycobacterial activities of a new quinolone, DU-6859a.	1994 Dec	7695276
Pharmacokinetics and tolerance of DU-6859a, a new fluoroquinolone, after single and multiple oral doses in healthy volunteers.	1995 Jan	7695301
[In vitro anti-MAC activities of new quinolones in focus (2)].	1996 Sep	8999137
Sitafloxacin: DU 6859, DU 6859A, Gracevit, sitafloxacin hydrate.	2003	12568642
In vitro antibacterial activity and pharmacodynamics of new quinolones.	2003 Apr	12687416
Comparative antimicrobial activities of gatifloxacin, sitafloxacin and levofloxacin against Mycobacterium tuberculosis replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines.	2003 Aug	12865388
Effects of disruption of heat shock genes on susceptibility of Escherichia coli to fluoroquinolones.	2003 Aug 12	12911840
A randomized controlled trial (volunteer study) of sitafloxacin, enoxacin, levofloxacin and sparfloxacin phototoxicity.	2003 Dec	14674902
Pharmacological evaluation of garenoxacin, a novel des-F(6)-quinolone antimicrobial agent: effects on the central nervous system.	2003 Feb	12696183
Activities of sitafloxacin (DU-6859a), either singly or in combination with rifampin, against Mycobacterium ulcerans infection in mice.	2003 Feb	12678414
Detection of mutations in quinolone resistance-determining regions in levofloxacin- and methicillin-resistant Staphylococcus aureus: effects of the mutations on fluoroquinolone MICs.	2003 Jun	12812718
In-vitro activity of sitafloxacin (DU-6859a), either singly or in combination with rifampin analogs, against Mycobacterium leprae.	2003 Mar	12673400
In vivo susceptibility of Mycobacterium leprae to sitafloxacin (DU-6859a), either singly or in combination with rifampicin analogues.	2003 Mar	12636987
Novel antibacterial agents for the treatment of serious Gram-positive infections.	2003 Mar	12605562
Adverse drug reactions: implications for the development of fluoroquinolones.	2003 May	12702700
A topological-substructural molecular design (TOPS-MODE) approach to determining pharmacokinetics and pharmacological properties of 6-fluoroquinolone derivatives.	2003 Sep	12957633
Fluoroquinolones as chemotherapeutics against mycobacterial infections.	2004	15544510
In vitro activity of older and newer fluoroquinolones against efflux-mediated high-level ciprofloxacin-resistant Streptococcus pneumoniae.	2004 Aug	15288320
In vivo experimental approach for the risk assessment of fluoroquinolone antibacterial agents-induced long QT syndrome.	2004 Feb 20	14975708
Investigational new drugs for the treatment of resistant pneumococcal infections.	2005 Aug	16050791
In vitro activities of 11 fluoroquinolones against 226 Campylobacter jejuni strains isolated from Finnish patients, with special reference to ciprofloxacin resistance.	2005 Dec	16223936
Quantitative assessment of the hepatic pharmacokinetics of the antimicrobial sitafloxacin in humans using in vivoF magnetic resonance spectroscopy.	2005 Feb	15676049
Acyl glucuronidation of fluoroquinolone antibiotics by the UDP-glucuronosyltransferase 1A subfamily in human liver microsomes.	2005 Jun	15769885
Reproducibility of gemifloxacin and comparison fluoroquinolone MIC results using Sensititre commercial dry-form panels.	2005 Mar	15766610
Characterization of fluoroquinolone and carbapenem susceptibilities in clinical isolates of levofloxacin-resistant Pseudomonas aeruginosa.	2005 May	15870499
Determination of in vitro synergy when three antimicrobial agents are combined against Mycobacterium tuberculosis.	2005 Oct	16150578
In vitro activities of 11 fluoroquinolones against 816 non-typhoidal strains of Salmonella enterica isolated from Finnish patients with special reference to reduced ciprofloxacin susceptibility.	2005 Sep 5	16143044
Fluoroquinolones: an important class of antibiotics against tuberculosis.	2006	16475933
Mutagenesis induced by 12 quinolone antibacterial agents in Escherichia coli WP2uvrA/pKM101.	2006 Apr	16171969
In vitro activity of sitafloxacin compared with several fluoroquinolones against Streptococcus anginosus and Streptococcus constellatus.	2006 Feb	16417990
Antimicrobial activity of picolinic acid against extracellular and intracellular Mycobacterium avium complex and its combined activity with clarithromycin, rifampicin and fluoroquinolones.	2006 Jan	16303883
New trends in development of antimycobacterial compounds.	2006 Jun	16789877
The potent antibacterial activity of Sitafloxacin against fluoroquinolone-resistant clinical isolates of Vibrio cholerae O1.	2007	17446687
History and evolution of antibiotic resistance in coagulase-negative staphylococci: Susceptibility profiles of new anti-staphylococcal agents.	2007 Dec	18516271
Skin and skin structure infections: treatment with newer generation fluoroquinolones.	2007 Jun	18360639
Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium.	2007 Jun	17266725
Successful treatment of Mycobacterium ulcerans osteomyelitis with minor surgical debridement and prolonged rifampicin and ciprofloxacin therapy: a case report.	2008 Apr 27	18439310
Effects of treatment with antimicrobial agents on the human colonic microflora.	2008 Dec	19337440
Sitafloxacin hydrate for bacterial infections.	2008 Jul	18806900
Dual-targeting properties of the 3-aminopyrrolidyl quinolones, DC-159a and sitafloxacin, against DNA gyrase and topoisomerase IV: contribution to reducing in vitro emergence of quinolone-resistant Streptococcus pneumoniae.	2008 Jul	18390884
Quinolones: action and resistance updated.	2009	19747119
Quinolones with enhanced bactericidal activity induce autolysis in Streptococcus pneumoniae.	2009	19468224
[In vitro susceptibilities to levofloxacin and various antibacterial agents of 12,919 clinical isolates obtained from 72 centers in 2007].	2009 Aug	19860322
Convulsant activity of sitafloxacin and its interactions with anti-inflammatory drugs in mice.	2009 Aug	19688249
[Pharmacological profile and clinical efficacy of sitafloxacin, a novel quinolone antibacterial agent].	2009 Jan	19145050
[Clinical position of sitafloxacin in outpatient chemotherapy. (discussion)].	2009 Jun	19882979
Comparative mutant prevention concentration and mutant selection window of sitafloxacin versus other quinolones using strains of Haemophilus influenzae with decreasing susceptibility to levofloxacin.	2009 May	19150226
Susceptibility and bactericidal activity of 8 oral quinolones against conventional-fluoroquinolone-resistant Streptococcus pneumoniae clinical isolates.	2009 Sep	19679241
In vivo efficacy of sitafloxacin in a new murine model of non-typeable Haemophilus influenzae pneumonia by sterile intratracheal tube.	2009 Sep	19394203
[In vitro activity of sitafloxacin against clinical isolates in 2009].	2010 Dec	21425595

Patents

Sample Use Guides

In Vivo Use Guide

for adults: 1 tablet (50 mg of sitafloxacin) at a time, twice daily, or 2 tablets (100 mg) at a time, once daily. If the effect is insufficient, the dosage may be increased to 2 tablets (100 mg) at a time, twice daily.

Route of Administration: Oral

In Vitro Use Guide

The minimum inhibitory concentration of sitafloxacin (STFX) at which 90% of isolates (MIC90) was 0.5 microg/mL for methicillin-susceptible Staphylococcus aureus. STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90 of STFX was 0.03 microg/mL. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL. The MIC90 of STFX was 2 microg/mL for Enterococcus faecalis. The MIC90 of STFX for Escherichia coli was 2 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 4 microg/mL. The MIC90 of STFX for P. aeruginosa isolates recovered from respiratory infections was 4 microg/mL. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less. The MIC90 of STFX was 0.015 microg/mL for Moraxella catarrhalis. The MIC90(s) of STFX ranged from 0.03 to 0.25 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:18:44 GMT 2023` Edited by `admin` on `Fri Dec 15 16:18:44 GMT 2023`
Record UNII	3GJC60U4Q8
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SITAFLOXACIN ANHYDROUS

Common Name

English

Sitafloxacin [WHO-DD]

Common Name

English

SITAFLOXACIN [MI]

Common Name

English

sitafloxacin [INN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

J01MA21