7-[(1R,5S)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl]-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid

• ChemBase ID: 567
• Molecular Formular: C20H15F3N4O3
• Molecular Mass: 416.3533096
• Monoisotopic Mass: 416.10962502
• SMILES: Fc1c(N2C[C@H]3[C@H](C3N)C2)nc2n(cc(c(=O)c2c1)C(=O)O)c1c(F)cc(F)cc1
• Canonical SMILES: NC1[C@@H]2[C@H]1CN(C2)c1nc2c(cc1F)c(=O)c(cn2c1ccc(cc1F)F)C(=O)O
• InChI: InChI=1S/C20H15F3N4O3/c21-8-1-2-15(13(22)3-8)27-7-12(20(29)30)17(28)9-4-14(23)19(25-18(9)27)26-5-10-11(6-26)16(10)24/h1-4,7,10-11,16H,5-6,24H2,(H,29,30)/t10-,11+,16?
• InChIKey: WVPSKSLAZQPAKQ-SOSAQKQKSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 7-[(1R,5S)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl]-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
• IUPAC Traditional name: trovafloxacin
• Brand Name: Trovan
• Synonyms: TVFX; Trovafloxacin mesylate; Trovafloxacin

Database IDs

• CAS Number: 147059-72-1
• PubChem SID: 46508751; 160964030
• PubChem CID: 62959

CALCULATED PROPERTIES

JChem

• Acid pKa: 5.4131193
• H Acceptors: 7
• H Donor: 2
• LogD (pH = 5.5): -0.057143982
• LogD (pH = 7.4): 0.13973176
• Log P: 0.13645041
• Molar Refractivity: 101.0404 cm^3
• Polarizability: 36.818485 Å^3
• Polar Surface Area: 99.76 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.86
• LOG S: -3.77
• Solubility (Water): 7.04e-02 g/l

PROPERTIES

Physical Property

• Solubility: 12.3 mg/L
• Hydrophobicity(logP): 3.7

DETAILS

DrugBank - DB00685

• Drug Groups: approved
• Description: Trovafloxacin (sold as Trovan by Pfizer) is a broad spectrum antibiotic that inhibits the uncoiling of supercoiled DNA in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It was withdrawn from the market due to the risk of hepatotoxicity. It had better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones. [Wikipedia]
• Indication: For treatment of infections caused by susceptible strains of the designated microorganisms in uncomplicated urethral gonorrhea in males and endocervical and rectal gonorrhea in females caused by Neisseria gonorrhoeae as well as non gonoccocal urethritis and cervicitis due to Chlamydia trachomatis.
• Pharmacology: Trovafloxacin is a broad spectrum antibiotic that inhibits DNA supercoiling in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It is not used widely due to the risk of hepatotoxicity. It tends to have better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones. Mechanism of action of fluoroquinolones including trovafloxacin is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines. Therefore fluoroquinolones may be active against pathogens that are resistant to these antibiotics. There is no cross-resistance between trovafloxacin and the mentioned classes of antibiotics. The overall results obtained from in vitro synergy studies, testing combinations of trovafloxacin with beta-lactams and aminoglycosides, indicate that synergy is strain specific and not commonly encountered. This agrees with results obtained previously with other fluoroquinolones. Resistance to trovafloxacin in vitro develops slowly via multiple-step mutation in a manner similar to other fluoroquinolones. Resistance to trovafloxacin in vitro occurs at a general frequency of between 1x10^-7 to 10^-10. Although cross-resistance has been observed between trovafloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to trovafloxacin.
• Toxicity: Symptoms of overdose include convulsions, decreased activity, diarrhea, sleepiness, tremors, and/or vomiting.
• Affected Organisms: Enteric bacteria and other eubacteria
• Biotransformation: Metabolism Trovafloxacin is metabolized by conjugation (the role of cytochrome P450 oxidative metabolism of trovafloxacin is minimal). The major metabolites include the ester glucuronide, which appears in the urine (13% of the administered dose); and the N -acetyl metabolite, which appears in the feces and serum (9% and 2.5% of the administered dose, respectively). Other minor metabolites include diacid, hydroxycarboxylic acid, and sulfamate, which have been identified in both the feces and the urine in small amounts (< 4% of the administered dose).
• Absorption: Well-absorbed from the gastrointestinal tract after oral administration and does not depend on concomitant food intake. The absolute bioavailability is approximately 88%.
• Half Life: Following oral administration, half-life ranged from 9.1 hours to 12.2 hours over the dosage range of 100 to 200 mg tablets. Following intravenous infusion, half-life ranged from 9.4 to 12.7 hours over a dosage range of 100 to 300 mg.
• Protein Binding: The mean plasma protein bound fraction is approximately 76%, and is concentration-independent.
• Elimination: Approximately 50% of an oral dose is excreted unchanged (43% in the feces and 6% in the urine).
• External Links: Wikipedia; RxList; Drugs.com