Nadifloxacin Chemical Properties

Melting point:

245-2470C (dec)

Boiling point:

624.9±55.0 °C(Predicted)

Density 

1.46±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

DMSO (Slightly), Methanol (Sparingly, Heated)

pka

5.55±0.40(Predicted)

form 

White to yellow crystalline solid.

color 

White to Off-White

Merck 

14,6345

InChI

InChI=1S/C19H21FN2O4/c1-10-2-3-12-16-13(18(24)14(19(25)26)9-22(10)16)8-15(20)17(12)21-6-4-11(23)5-7-21/h8-11,23H,2-7H2,1H3,(H,25,26)

InChIKey

JYJTVFIEFKZWCJ-UHFFFAOYSA-N

SMILES

C12=CC(F)=C(N3CCC(O)CC3)C3=C1N(C(C)CC3)C=C(C(O)=O)C2=O

CAS DataBase Reference

124858-35-1(CAS DataBase Reference)

Safety Information

HS Code 

2933.99.7500

Toxicity

LD50 male, female mice and rats (mg/kg): 376.5, 420.6, 225.7, 240.5 i.v. (Hashimoto)

MSDS

• Language:English Provider:(+/-)-9-Fluoro-6,7-dihydro-8-(4-hydroxypiperidino)-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid

Nadifloxacin Usage And Synthesis

Abstract

Nadifloxacin(Nadibact Cream,124858-35-1) is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections. The medication works by inhibiting the enzyme DNA gyrase to prevent bacterial multiplication. It is mainly prescribed to treat acne vulgaris and other skin infections with susceptible bacteria.

Acne Treatment

Nadifloxacin(Nadibact Cream) from Japan Otsuka company developed the third generation quinolone antibacterial agents, The 1% ointment is used for the treatment of acne for the first time in the Japanese market in 1993 (known as acne, it is a common hair follicles, sebaceous glands, chronic inflammatory diseases, occurs in puberty), nadifloxacin is a novel DNA topoisomerase inhibitors, and also effective for G + bacteria, G-bacteria, anaerobes, but also produce b-lactamase bacteria and MRSA, effective against skin infections mainly Propionibacterium acnes bacteria about minimum inhibitory concentration is only 0.78mg/ml. currently used in the 1% ointment in the treatment of acne and folliculitis, high efficacy, efficiency up to 81.3%, side effects, only 56 cases have side effects from 3946 cases of patients, the ratio is about 1.42%.

Antibacterial Activity

Staphylococcus aureus, nadifloxacin minimum inhibitory concentration is the smallest of all eight kinds of antibiotics. When the concentration is 2mg/L, all clinical isolates are inhibited, while other antibacterial agents have been found more than 8mg/L MIC50 of resistant strains. Coagulase-negative staphylococci appear higher resistance. There are resistant strains of 4mg /L in Nadifloxacin but of over 8mg/L in the other seven antimicrobial drugs. It has strong antibacterial activity for propionibacterium acnes, nadifloxacin, penicillin, erythromycin, clindamycin and fusidic acid, in addition to the difloxacin and penicillin, it can produce resistance on the other antibacterial drugs. The results presented nadifloxacin Staphylococcus aureus and Propionibacterium have antibacterial activity, suggesting that effective treatment of acne infection.
All subjects of quinolones against MSSA strains have antibacterial activity. Nadifloxacin, the strongest antibacterial activity (MIC90≤0.1mg/L), have strong antibacterial activity. The MIC90 is four times lower, compared with Tuosu difloxacin (Tosufloxacin) Division and Pakistan difloxacin (Sparfloxacin). Compared with MSSA, Nadifloxacin(Nadibact Cream) antibacterial activity is lower than against MRSA, but it is still the strongest of all the tested quinolone antibacterial. In the 5-year period, the MIC90 of Nadifloxacin(Nadibact Cream) was 1.56mg/L, while the MIC90 of other quinolones drugs is more than 12.5mg/L.

Pharmacokinetics

Following a single topical application of 10 g nadifloxacin 1% cream to normal human back skin, the highest plasma concentration was determined to be 107 ng/mL with an elimination half-life of 19.4 hours. Approximately 0.09% of the administered dose was excreted in the urine over 48 hours post-dosing. The plasma concentration reached a steady state on Day 5 of repeated administration study when nadifloxacin 1% cream was applied at 5 g twice daily to normal healthy individuals for a period of 7 days. The plasma concentration reached a peak of 4.1 ng/ml at 8 hours post-final dosing with an elimination half-life of 23.2 hours. The urinary excretion rate reached 0.16% on Day 7.

Drug resistance

Inoculant in 108CFU/ml 2-5 when generations have clindamycin drug resistance, the drug concentration of 16-25 generations increased from 0.03μg/ml to 0.25μg/ml. When inoculant is 106CFU/ml, 14-25 on behalf of the concentration of clindamycin increased from 0.02μg/ml to0.10μg/ml. Nadifloxacin group,s results is that the 18-25 make drug concentration generations increased from 0.3μg/ml to 2.00μg/ml when inoculants at 108CFU/ml,16-25 make drug concentration generations increased from 0.2μg/ml to 1.00μg/ml when inoculants at 106CFU/ml. Explaining how the resistance. The use of the drug, which is more than 5 times the drug concentration of sensitive bacteria, cannot inhibit the growth of drug resistant bacteria. The P.acne to clindamycin and nadifloxacin has drug resistance almost at the same rate.
Application: One kind of quinolone antibacterial drugs, a broad spectrum antibiotic,Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and other aerobic and Propionibacterium acnes, Bacteroides fragilis and other anaerobic bacteria We have good antibacterial activity. Its efficacy is better than conventional antibiotic tetracycline, erythromycin, and clindamycin.

Application

One kind of quinolone antibacterial drugs, a broad spectrum antibiotic,Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and other aerobic and Propionibacterium acnes, Bacteroides fragilis and other anaerobic bacteria We have good antibacterial activity. Its efficacy is better than conventional antibiotic tetracycline, erythromycin, and clindamycin.

References

[1] https://en.wikipedia.org/wiki/Nadifloxacin
[2] https://www.pharmacygeoff.md/Nadibact_Cream_Nadifloxacin_1_w_w_10g_Tube_p_923.html
[3] JACOBSMICHAEL R AppelbaumPeter C. Nadifloxacin: a quinolone for topical treatment of skin infections and potential for systemic use of its active isomer, WCK 771.[J]. Expert Opinion on Pharmacotherapy, 2006. DOI:10.1517/14656566.7.14.1957.
[4] KUWAHARAKEIICHI. Nadifloxacin, an antiacne quinolone antimicrobial, inhibits the production of proinflammatory cytokines by human peripheral blood mononuclear cells and normal human keratinocytes.[J]. Journal of dermatological science, 2005. DOI:10.1016/j.jdermsci.2005.01.002.
[5] MARK HUTCHINS. Glycosides of Nadifloxacin—Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus[J]. Molecules, 2022. DOI:10.3390/molecules27051504.

Description

Nadifloxacin, one of the three new fluoroquinolone antibiotics launched in 1993 is indicated for topical treatment of acne vulgaris and other skin infections. Nadifloxacin has a potent and broad spectrum of activity against aerobic Gram-positive and -negative bacteria and against anaerobic bacteria. It produces significant improvement in patients with Propionibacterium acnes infection and does not appear to cause cross-resistance to other antibiotic agents. Its potent antimicrobial activity has also been demonstrated in the Pseudomonas aeruginosa burn wound infection model in mice. Nadifloxacin exerts its antibiotic activity by inhibiting the formation of supercoiled DNA by DNA gyrase.

Chemical Properties

Off-White Crystalline Solid

Originator

Otsuka (Japan)

Uses

Nadifloxacin is a topical fluorinated quinolone antibacterial used to treat skin conditions such as acne and other dermal infections caused by bacteria. This drug belongs to a class of calcium salt of polyacrylic acid crosslinked with divinyl glycol with minimal AEs.

Definition

ChEBI: Nadifloxacin is a pyridoquinoline, a hydroxypiperidine, a heteroarylpiperidine and a quinolone antibiotic. It has a role as an antibacterial drug. It is effective against the Gram-positive bacteria S. aureus and P. acnes, as well as Gram-negative bacteria.

brand name

Acuatim

Pharmaceutical Applications

A lipophilic tricyclic fluorobenzoquinoline with a 4- hydroxylpiperinyl moiety at the C-8 position, formulated as a cream for topical use. It is active against many Grampositive bacteria involved in skin infections, including Propionibacterium acnes (MIC 0.25–2.0 mg/L), and Staph. aureus (MIC 0.015–2 mg/L). It appears to inhibit the generation of reactive oxygen species by neutrophils. The sodium salt is used as a 1% cream for use in acne vulgaris and cutaneous staphylococcal infections.

Nadifloxacin(124858-35-1)Related Product Information

• Kresoxim-methyl
• Thiophanate-methyl
• Butylparaben
• 3-Hydroxybenzoic acid
• METSULFURON METHYL
• Salicylic acid
• 2'-Hydroxy-3-phenylpropiophenone
• 4-Hydroxybenzoic acid
• 3,5-Dihydroxybenzoic acid
• Methyl salicylate
• Methylparaben
• 2,3,4-Trihydroxybenzoic acid
• Tribenuron methyl
• Methyl
• Fluorine
• 3-Piperidin-1-ylaniline
• 4-FLUORO-2,6-DIMETHYLANILINE
• Benzaldehyde, 3-fluoro-5-methyl- (9CI)