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Temafloxacin (Omniflox) is a potent fluoroquinolone antibiotic and antimycobacterial agent that acts as a DNA topoisomerase inhibitor. It has broad antimicrobial activity against gram-positive and gram-negative bacteria, such as S. pneumoniae, M. hominis, and anaerobic bacteria, including B. fragilis. It was approved in 1992 for the treatment of lower respiratory tract infections, genital and urinary infections like prostatitis, and skin infections, but was withdrawn from sale in the United States shortly after its approval in 1992 because of serious adverse effects resulting in three deaths.
Physicochemical Properties
| Molecular Formula | C21H18F3N3O3 |
| Molecular Weight | 417.39 |
| Exact Mass | 417.13 |
| Elemental Analysis | C, 60.43; H, 4.35; F, 13.66; N, 10.07; O, 11.50 |
| CAS # | 108319-06-8 |
| Related CAS # | Temafloxacin hydrochloride;105784-61-0 |
| PubChem CID | 60021 |
| Appearance | Solid powder |
| Density | 1.427g/cm3 |
| Boiling Point | 608.9ºC at 760mmHg |
| Flash Point | 322.1ºC |
| Vapour Pressure | 1.11E-15mmHg at 25°C |
| Index of Refraction | 1.603 |
| LogP | 3.298 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 30 |
| Complexity | 721 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(C1=CN(C2=CC=C(F)C=C2F)C3=C(C=C(F)C(N4CC(C)NCC4)=C3)C1=O)O |
| InChi Key | QKDHBVNJCZBTMR-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H18F3N3O3/c1-11-9-26(5-4-25-11)19-8-18-13(7-16(19)24)20(28)14(21(29)30)10-27(18)17-3-2-12(22)6-15(17)23/h2-3,6-8,10-11,25H,4-5,9H2,1H3,(H,29,30) |
| Chemical Name | 1-(2,4-Difluorophenyl)-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid |
| Synonyms | trade name: Omniflox; A-62254; A62254; A 62254 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Quinolone |
| ln Vitro | Temafloxacin (0-64 µg/mL; 18–24 h) exhibits good antibacterial activity against gram-positive and gram-negative bacteria, with MIC ranges for E. Coli, P. aeruginosa, and S. aureus, respectively, of <0.004-0.5, 0.5-2, and 0.06-0.25 µg/mL[1]. |
| ln Vivo |
Temafloxacin (6.25, 25, 100 mg/kg; p.o. ; single dose) exhibits good anti-mouse pyelonephritis activity[1]. With the exception of the central nervous system (CNS), temafloxacin hydrochloride (100 mg/kg; p.o. or s.c.; single) exhibits rapid gastrointestinal absorption and excellent tissue and body fluid penetration and concentration[1]. |
| Cell Assay |
Cell Line: E. coli (16 strains), P. aeruginosa (13 strains), and S. aureus (17 strains). Concentration: 0-64 µg/mL Incubation Time: 18-24 h Result: MIC ranges of <0.004-0.5 (MIC 90%=0.06, =0.06), 0.5-2 (MIC 90%=1, MIC 50%=1), and 0.06-0.25 µg/mL (MIC 90%=0.125, MIC 50%=0.125) inhibited 16 strains of E. coli, P. aeruginosa, and S. aureus. 90% and 50% of the isolates are included in the MIC (unit: µg/mL). |
| Animal Protocol |
Animal Model: Female CF-1 mice (20-25 g) (murine pyelonephritis model)[1]. Dosage: 6.25, 25, 100 mg/kg Administration: Orally; single. Result: Reduced the number of viable bacteria in the kidneys of mice. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Studies in healthy volunteers indicate that the average bioavailability of temafloxacin exceeds 90%, with little intersubject variability. Metabolism / Metabolites Hepatic. Biological Half-Life Approximately 8 hours in patients with normal renal function. |
| References |
[1]. Comparative antibacterial activities of temafloxacin hydrochloride (A-62254) and two reference fluoroquinolones. Antimicrob Agents Chemother. 1987 Nov;31(11):1768-74. [2]. Pankey GA. Temafloxacin: an overview. Am J Med. 1991 Dec 30;91(6A):166S-172S. |
| Additional Infomation |
1-(2,4-difluorophenyl)-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid is a quinolone that is 4-oxo-1,4-dihydroquinoline-3-carboxylic acid which is substituted at positions 1, 6, and 7 by 2,4-difluorophenyl, fluorine, and 3-methylpiperazin-1-yl groups, respectively. It is a quinolone, an amino acid, a monocarboxylic acid, an organofluorine compound, a secondary amino compound, a tertiary amino compound, a N-arylpiperazine and a quinolone antibiotic. Temafloxacin is an antibiotic agent belonging to the fluoroquinolone drug class. It was first approved for use in the U.S. market in 1992, but was withdrawn shortly due to the reports of serious adverse reactions, such as allergic reactions and hemolyric anemia, resulting in three deaths. Drug Indication For the treatment of lower respiratory tract infections, genital and urinary infections like prostatitis, and skin infections. Mechanism of Action The bactericidal action of temafloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited. Pharmacodynamics Temafloxacin is a fluoroquinolone antibiotic drug, marketed as Omniflox by Abbot Laboratories, which was withdrawn from the market in 1992 due to fatal adverse effects. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such as E.coli and Neisseria gonorrhoea as well as gram-positive bacteria including S. pneumoniae and Staphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter. |
Solubility Data
| Solubility (In Vitro) | DMSO : < 1 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (1.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 10% DMSO+90% Corn Oil: ≥ 0.5 mg/mL (1.20 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3958 mL | 11.9792 mL | 23.9584 mL | |
| 5 mM | 0.4792 mL | 2.3958 mL | 4.7917 mL | |
| 10 mM | 0.2396 mL | 1.1979 mL | 2.3958 mL |