1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid

• ChemBase ID: 659
• Molecular Formular: C12H12N2O3
• Molecular Mass: 232.23528
• Monoisotopic Mass: 232.08479225
• SMILES: O=c1c2c(n(CC)cc1C(=O)O)nc(cc2)C
• Canonical SMILES: CCn1cc(C(=O)O)c(=O)c2c1nc(C)cc2
• InChI: InChI=1S/C12H12N2O3/c1-3-14-6-9(12(16)17)10(15)8-5-4-7(2)13-11(8)14/h4-6H,3H2,1-2H3,(H,16,17)
• InChIKey: MHWLWQUZZRMNGJ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
• IUPAC Traditional name: nalidixic acid; 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
• Brand Name: Cybis; Dixiben; Dixinal; Eucistin; Innoxalon; Jicsron; Nalidic acid; Nalidixan; Nalidixate; Nalidixic acid USP27; Nalidixin; Nalidixinic acid; Nalitucsan; Nalix; Nalurin; Naxuril; NegGram; Negram; Nevigramon; Nogram; Sicmylon; Unaserus; Urisal; Uronidix; Wintomylon; Wintron; naladixic acid
• Synonyms: 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid; NALDIXIC ACID; Nalidixic Acid; NegGram; Nevigramon; Nalidixin; Uronidix; 1,4-Dihydro-1-ethyl-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic Acid; Betaxina; Cybis; Dixiben; Eucistin; Nelidix; Win 18320; Wintomylon; 1,4-Dihydro-1-ethyl-7-methyl-1,8-naphthyridin-4-one-3-carboxylic acid; 1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid; Negram; Nalidixanum; Nalidixic acid; Nalidixic acid; 3-Carboxy-1-ethyl-7-methyl-1,8-naphthyridin-4-one; 1,4-Dihydro-1-ethyl-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid; 萘啶酮酸; 1,4-二氢-1-乙基-7-甲基-1,8-萘啶-4-酮-3-羧酸; 1-乙基-1,4-二氢-7-甲基-4-氧代-1,8-萘啶-3-羧酸; 萘啶酸

Database IDs

• CAS Number: 389-08-2
• EC Number: 206-864-7
• MDL Number: MFCD00006884
• Beilstein Number: 750515
• Merck Index: 146359
• PubChem SID: 24897719; 46507401; 24897864; 160964122
• PubChem CID: 4421

CALCULATED PROPERTIES

JChem

• Acid pKa: 5.950253
• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 1.0300463
• LogD (pH = 7.4): -0.25419375
• Log P: 1.0082526
• Molar Refractivity: 62.8245 cm^3
• Polarizability: 23.020437 Å^3
• Polar Surface Area: 70.5 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.95
• LOG S: -2.0
• Solubility (Water): 2.30e+00 g/l

PROPERTIES

Physical Property

• Solubility: 100 mg/L; Chloroform; chloroform: soluble20 mg/mL, clear; Ethanol; Methanol; Toluene
• Apperance: Pale Yellow Solid
• Melting Point: 227-229 °C(lit.); 227-229°C; 228-230 °C; 228-230°C; 229-230°C
• Hydrophobicity(logP): 2.1

Safety Information

• Storage Condition: -20°C; Refrigerator
• Storage Warning: Harmful
• RTECS: QN2885000
• European Hazard Symbols: X; Harmful (Xn)
• German water hazard class: 2
• Risk Statements: 22; 42/43
• Safety Statements: 22-36/37-45; 36
• TSCA Listed: 否
• GHS Pictograms: GHS07; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H302; H334
• GHS Precautionary statements: P261-P342 + P311; P264-P270-P301+P312-P330-P501A
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Faceshields, Gloves; Eyeshields, Faceshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Pharmacology Properties

• Mechanism of Action: DNA polymerase inhibitor

Product Information

• Purity: ≥98%; ≥99.0% (T); 99%
• Salt Data: Free Base
• Suitability: meets USP testing specifications
• Application(s): Antibacterial agent; Antibiotic; Antiseptic
• Empirical Formula (Hill Notation): C12H12N2O3

DETAILS

MP Biomedicals - 05224670

MP Biomedicals Rare Chemical collection

DrugBank - DB00779

• Drug Groups: approved
• Description: A synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA gyrase. [PubChem]
• Indication: For the treatment of urinary tract infections caused by susceptible gram-negative microorganisms, including the majority of E. Coli, Enterobacter species, Klebsiella species, and Proteus species.
• Pharmacology: Nalidixic acid is a quinolone antibacterial agent for oral administration. Nalidixic acid has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. Nalidixic acid is bactericidal and is effective over the entire urinary pH range. Conventional chromosomal resistance to nalidixic acid taken in full dosage has been reported to emerge in approximately 2 to 14 percent of patients during treatment; however, bacterial resistance to nalidixic acid has not been shown to be transferable via R factor.
• Toxicity: ORAL (LD₅₀): Acute: 1160 mg/kg [Rat]. 572 mg/kg [Mouse]. Toxic psychosis, convulsions, increased intracranial pressure, or metabolic acidosis may occur in patients taking more than the recommended dosage. Vomiting, nausea, and lethargy may also occur following overdosage.
• Affected Organisms: Enteric bacteria and other eubacteria
• Biotransformation: Hepatic. 30% of administered dose is metabolized to the active metabolite, hydroxynalidixic acid. Rapid conjugation of parent drug and active metabolite to inactive metabolites. Metabolism may vary widely among individuals. In the urine, hydroxynalidixic acid represents 80 to 85% of the antibacterial activity.
• Absorption: Following oral administration, nalidixic acid is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 96%. Absorption may be delayed if taken with antacids.
• Half Life: 1.1 to 2.5 hours in healthy adult patients, and up to 21 hours in patients with impaired renal function.
• Protein Binding: Nalidixic acid is 93% bound to protein in the blood, and the active metabolite, hydroxynalidixic acid is 63% bound.
• Elimination: Following oral administration, NegGram is rapidly absorbed from the gastrointestinal tract, partially metabolized in the liver, and rapidly excreted through the kidneys.; Approximately four percent of NegGram is excreted in the feces.
• External Links: RxList; Drugs.com

Selleck Chemicals - S2328

Research Area: Infection
Biological Activity:
Nalidixic acid(NegGram) is a synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA gyrase. Evidence exists that the active metabolite, hydroxynalidixic acid, binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis. [1]

Sigma Aldrich - 70162

Other Notes
Inhibitor of bacterial DNA synthesis1

Sigma Aldrich - N5035

Biochem/physiol Actions
Used to modulate (inhibit) bacterial DNA gyrase-dependent processes such as DNA polymerization, (ATP-dependen)t DNA supercoiling, and chromosome fragmentation.

Sigma Aldrich - N8878

Application
Used to modulate (inhibit) bacterial DNA gyrase-dependent processes such as DNA polymerization, (ATP-dependen)t DNA supercoiling, and chromosome fragmentation.
包装
5, 25, 100 g in poly bottle

Toronto Research Chemicals - N275600

Antibacterial.

REFERENCES

• http://www.drugbank.ca/drugs/DB00779
• Bourguignon, G.J., et al.: Antimicrob. Agents Chemother., 4, 479 (1973)
• Grubb, P.E., et al.: Anal. Profiles Drug Subs., 8, 371 (1973)
• Wright, H.T., et al.: Science, 213, 455 (1973)
• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, EID000
• Aldrich Library of 13C and 1H FT NMR Spectra, 1992, 3, 473B, (nmr)
• Aldrich Library of FT-IR Spectra, 1st edn., 1985, 2, 889B, (ir)
• Lesher, G.Y. et al., J. Med. Chem., 1962, 5, 1063
• Santielli, A.A. et al., J. Med. Chem., 1975, 18, 1038, (synth)
• Lesher, G.Y., Kirk-Othmer Encycl. Chem. Technol., 3rd edn., Wiley, 1978, 2, 782, (rev)
• Grubb, P.E., Anal. Profiles Drug Subst., 1979, 8, 371, (rev)
• Huber, C.P. et al., Acta Cryst. B, 1980, 36, 497, (cryst struct)
• Koch, H. et al., Pharm. Int., 1980, 1, 108, (rev, pharmacol)
• Negwer, M., Organic-Chemical Drugs and their Synonyms, 6th edn., Akademie-Verlag, 1987, 2267
• Morrissey, R.E. et al., Drug Chem. Toxicol., 1991, 14, 45, (tox)
• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 184