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Nalidixic acid

CAS No.
389-08-2
Chemical Name:
Nalidixic acid
Synonyms
neggram;Nalidixic acid BP93.CH.P.95;1,4-DIHYDRO-1-ETHYL-7-METHYL-4-OXO-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID;cybis;nalix;NOGRAM;uropan;uroneg;uroman;negram
CBNumber:
CB1194283
Molecular Formula:
C12H12N2O3
Molecular Weight:
232.24
MDL Number:
MFCD00006884
MOL File:
389-08-2.mol
Last updated:2023-10-07 17:44:49

Nalidixic acid Properties

Melting point 227-229 °C (lit.)
Boiling point 374.4°C (rough estimate)
Density 1.2243 (rough estimate)
refractive index 1.6660 (estimate)
storage temp. 2-8°C
solubility chloroform: 20 mg/mL, clear
form Powder
pka pKa 6.11± 0.02(Approximate)
color White to light yellow
Water Solubility 0.1 G/L (23 ºC)
Merck 14,6359
BRN 750515
Stability Stable. Incompatible with strong oxidizing agents.
CAS DataBase Reference 389-08-2(CAS DataBase Reference)
FDA UNII 3B91HWA56M
Proposition 65 List Nalidixic Acid
ATC code J01MB02
EPA Substance Registry System Nalidixic acid (389-08-2)

Pharmacokinetic data

Protein binding 93-97%
Excreted unchanged in urine 11-33 (80-90% as inactive metabolites)
Volume of distribution 0.47-0.55(L/kg)
Biological half-life 6-8 / 21

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictogramsGHS hazard pictograms
GHS07,GHS08
Signal word  Warning
Hazard statements  H302-H351
Precautionary statements  P202-P264-P270-P280-P301+P312-P308+P313
Hazard Codes  Xn
Risk Statements  63-42/43-40-20/21/22-22
Safety Statements  22-36/37-45-24-36
WGK Germany  2
RTECS  QN2885000
8-10-23
HS Code  29339190
Toxicity LD50 in mice (mg/kg): 3300 orally; 500 s.c.; 176 i.v. (Lesher, 1962)
NFPA 704
1
2 0

Nalidixic acid price More Price(38)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 97023 Nalidixic acid analytical standard 389-08-2 100mg $72.6 2024-03-01 Buy
TCI Chemical N0490 Nalidixic Acid >95.0%(T) 389-08-2 25g $63 2024-03-01 Buy
Alfa Aesar B25096 Nalidixic acid, 99% 389-08-2 5g $30.6 2024-03-01 Buy
Alfa Aesar B25096 Nalidixic acid, 99% 389-08-2 25g $98.5 2024-03-01 Buy
Cayman Chemical 19807 Nalidixic Acid ≥98% 389-08-2 10g $32 2024-03-01 Buy
Product number Packaging Price Buy
97023 100mg $72.6 Buy
N0490 25g $63 Buy
B25096 5g $30.6 Buy
B25096 25g $98.5 Buy
19807 10g $32 Buy

Nalidixic acid Chemical Properties,Uses,Production

Chemical Properties

Crystalline Powder

Originator

Neggram,Winthrop,US,1964

Uses

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.

Uses

Quinolone antibacterial.

Uses

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 stron

Definition

ChEBI: A monocarboxylic acid comprising 1,8-naphthyridin-4-one substituted by carboxylic acid, ethyl and methyl groups at positions 3, 1, and 7, respectively.

Manufacturing Process

A warm solution containing 41 grams of 4-hydroxy-7-methyl-1,8- naphthyridine-3-carboxylic acid and 39 grams of potassium hydroxide in 1 liter of ethanol and 200 cc of water was treated with 50 cc of ethyl iodide and the resulting mixture was refluxed gently overnight, acidified with hydrochloric acid and cooled. The resulting precipitate was collected and recrystallized twice from acetonitrile to yield 26 grams (56% yield) of 1-ethyl-7-methyl-4- oxo-1,8-naphthyridine-3-carboxylic acid, MP 229° to 230°C.
The starting material is prepared by reacting 2-amino-6-methylpyridine with ethoxymethylene-malonic acid diethyl ester and then reacting that product with sodium hydroxide.

brand name

Neggram(Sanofi Aventis).

Therapeutic Function

Antibacterial

Antimicrobial activity

It displays good activity in vitro against a wide range of Enterobacteriaceae.

General Description

Cream-colored powder.

Air & Water Reactions

Insoluble in water.

Health Hazard

SYMPTOMS: Ingestion of Nalidixic acid may cause nausea, vomiting, abdominal pain, allergic reactions and possible liver damage.

Fire Hazard

Flash point data for Nalidixic acid are not available, but Nalidixic acid is probably combustible.

Pharmaceutical Applications

A 1,8 naphthyridone derivative available for oral administration.

Pharmacokinetics

Oral absorption: >90%
Cmax 1 g oral: c. 25 mg/L
Plasma half-life:c.1.5h
Volume of distribution :0.4 L/kg
Plasma protein binding: 93%
The plasma concentrations achieved after oral administration vary widely. In infants with acute shigellosis, absorption is much impaired by diarrhea. Administration with an alkaline compound leads to higher plasma concentrations, partly as the result of enhanced solubility (nalidixic acid is much more soluble at higher pH) and absorption and partly because of reduced tubular reabsorption.
It is rapidly metabolized, principally to the hydroxy acid, which is bacteriologically active, and glucuronide conjugates, which are not. The entire administered dose appears in the urine over a 24 h period. Elimination is reduced by probenecid. In the presence of renal impairment there is little accumulation of the active compound because it continues to be metabolized. However, elimination of metabolites is progressively delayed as renal function declines. About 4% of a dose appears in the feces.

Clinical Use

1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (NegGram) occurs as a pale buff crystalline powder that is sparingly soluble in water and ether but solublein most polar organic solvents.Nalidixic acid is useful in the treatment of urinary tractinfections in which Gram-negative bacteria predominate.The activity against indole-positive Proteus spp. is particularlynoteworthy, and nalidixic acid and its congeners representimportant alternatives for the treatment of urinary tractinfections caused by strains of these bacteria resistant toother agents. Nalidixic acid is rapidly absorbed, extensivelymetabolized, and rapidly excreted after oral administration.The 7-hydroxymethyl metabolite is significantly more activethan the parent compound. Further metabolism of theactive metabolite to inactive glucuronide and 7-carboxylicacid metabolites also occurs. Nalidixic acid possesses at1/2elim of 6 to 7 hours. It is eliminated, in part, unchanged inthe urine and 80% as metabolites.

Side effects

Adverse reactions are generally those common to all quinolones: gastrointestinal tract and CNS disturbances and skin rashes, including eruptions related to photosensitivity. About half of the reported CNS reactions involve visual disturbances, hallucinations or disordered sensory perception. Severe excitatory states, including acute psychoses and convulsions, are usually observed in patients receiving high dosages. The drug should be avoided in patients with psychiatric disorders or epilepsy.
Acute intracranial hypertension has been observed in children, some of whom have also manifested cranial nerve palsies. Hemorrhage has occurred in patients who were also receiving warfarin, presumably due to displacement of the anticoagulant from its protein binding sites by the nalidixic acid. Hemolytic anemia has been described several times in infants with or without glucose-6-phosphate dehydrogenase deficiency; in adults, death has occurred from autoimmune hemolytic anemia. Arthralgia and severe metabolic acidosis have rarely been reported.

Safety Profile

Poison by intravenous and intraperitoneal routes. Moderately toxic by ingestion and subcutaneous routes. An experimental teratogen. Human systemic effects: convulsions, hyperglycemia, sweating, and blood changes in children. Experimental reproductive effects.Questionable carcinogen with experimental carcinogenic and tumorigenic data. Human mutation data reported. Used as an antibacterial agent and urinary tract antiseptic. When heated to decomposition it emits toxic fumes of NOx.

Synthesis

Nalidixic acid, 1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthiridin-3- carboxylic acid (33.2.4), is synthesized by the following scheme. In the first stage, the reaction of 2-amino-6-methylpyridine and diethyl ethoxymethylenemalonate forms the substituted product (33.2.1), which when heated cyclizes to ethyl ester of 4-hydroxy -7-methyl-1,8-napthiridin-3-carboxylic acid (33.2.2). Hydrolyzing the resulting product with a base gives the corresponding acid (33.2.3). Alkylating this with ethyl iodide in the presence of potassium hydroxide gives nalidixic acid.

Synthesis_389-08-2

Drug interactions

Potentially hazardous interactions with other drugs
Aminophylline and theophylline: possibly increased risk of convulsions.
Analgesics: increased risk of convulsions with NSAIDs.
Antibacterials: possibly antagonised by nitrofurantoin.
Anticoagulants: anticoagulant effect of coumarins enhanced.
Antimalarials: manufacturer of artemether with lumefantrine advises avoid.
Ciclosporin: increased risk of nephrotoxicity.
Cytotoxics: increases risk of melphalan toxicity

Metabolism

Nalidixic acid is partially metabolised in the liver to hydroxynalidixic acid, which has antibacterial activity similar to that of nalidixic acid and accounts for about 30% of active drug in the blood. Both nalidixic acid and hydroxynalidixic acid are rapidly metabolised to inactive glucuronide and dicarboxylic acid derivatives; the major inactive metabolite 7-carboxynalidixic acid is usually only detected in urine.

Purification Methods

Nalidixic acid crystallises from H2O or EtOH as a pale buff powder. It is soluble at 23o in CHCl3 (3.5%), toluene (0.16%), MeOH (0.13%), EtOH (0.09%), H2O (0.01%) and Et2O (0.01%). It inhibits nucleic acid and protein synthesis in yeast. [Lesher et al. J Med & Pharm Chem 5 1063 1962.]

1824-81-3
389-08-2
Synthesis of Nalidixic acid from 2-Amino-6-methylpyridine
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View Lastest Price from Nalidixic acid manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Nalidixic acid pictures 2023-10-07 Nalidixic acid
389-08-2
US $0.00 / kg 1kg 0.99 20 tons Hebei Yanxi Chemical Co., Ltd.
Nalidixic acid pictures 2022-08-17 Nalidixic acid
389-08-2
US $20.00 / kg 1kg 99% 5000 Ton Hebei Duling International Trade Co. LTD
Nalidixic acid pictures 2021-08-12 Nalidixic acid
389-08-2
US $15.00-10.00 / KG 1KG 99%+ HPLC Monthly supply of 1 ton Zhuozhou Wenxi import and Export Co., Ltd
  • Nalidixic acid pictures
  • Nalidixic acid
    389-08-2
  • US $0.00 / kg
  • 0.99
  • Hebei Yanxi Chemical Co., Ltd.
  • Nalidixic acid pictures
  • Nalidixic acid
    389-08-2
  • US $20.00 / kg
  • 99%
  • Hebei Duling International Trade Co. LTD
  • Nalidixic acid pictures
  • Nalidixic acid
    389-08-2
  • US $15.00-10.00 / KG
  • 99%+ HPLC
  • Zhuozhou Wenxi import and Export Co., Ltd
uroman uroneg uropan Win18,320 Wintomylon Nalidixic acid, Antibiotic for Culture Media Use Only Nalidixic acid, 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 NOGRAM NALIDIXIC ACID NALADIXIC ACID 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 1-ETHYL-7-METHYL-1,8-NAPHTHYRIDINE-4-ONE-3-CARBOXYLIC ACID 3-Carboxy-1-ethyl-7-methyl-1,8-naphthidin-4-one 3-carboxy-1-ethyl-7-methyl-1,8-naphthyridin-4-one 8-Naphthyridine-3-carboxylicacid,1-ethyl-1,4-dihydro-7-methyl-4-oxo-1 acide1-etil-7-metil-1,8-naftiridin-4-one-3-carbossilico acidenalidixico acidenalidixique betaxina cybis dixiben eucisten innoxalon kusnarin Naldixicacid Nalidicacid nalidicron Nalidixan Nalidixin Nalidixinicacid nalitucsan nalix nalurin Narigix Naxuril nci-c56199 negram Nevigramon nicelate nsc-82174 poleon specifen specifin uralgin uriben uriclar Urisal urodixin NALIDIXIC ACID FREE ACID NALIDIXIC ACID, USP NALIDIXIC ACID HIGH PURITY GRADE 98+% Nalidixic acid, 99.50% NALIDIXICACID,CRYSTAL,REAGENT 1,8-Naphthyridine-3-carboxylicacid,1-ethyl-1,4-dihydro-7-methyl-4-oxo- 1-aethyl-7-methyl-1,8-naphthyridin-4-on-3-karbonsaeure 1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxilicacid