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nifurtimox

CAS No.
23256-30-6
Chemical Name:
nifurtimox
Synonyms
Lampit;BAY-2502;NIFURIMOX;Bayer-2502;Bayer 2502;Aids007325;nifurtimox;BAY-A-2502;Aids-007325;nifurtimox USP/EP/BP
CBNumber:
CB3903922
Molecular Formula:
C10H13N3O5S
Molecular Weight:
287.29
MDL Number:
MFCD00869254
MOL File:
23256-30-6.mol
MSDS File:
SDS
Last updated:2023-05-18 11:31:04

nifurtimox Properties

Melting point 177-183°C
Boiling point 550.3±50.0 °C(Predicted)
Density 1.4716 (rough estimate)
refractive index 1.6390 (estimate)
storage temp. room temp
solubility DMSO: ≥13mg/mL
pka -1.01±0.40(Predicted)
form powder
color yellow to orange
Water Solubility 33g/L(temperature not stated)
BCS Class 3
InChIKey ARFHIAQFJWUCFH-IZZDOVSWSA-N
FDA UNII M84I3K7C2O
NCI Drug Dictionary nifurtimox
ATC code P01CC01

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS08
Signal word  Warning
Hazard statements  H373
Precautionary statements  P260-P314-P501
WGK Germany  3
Toxicity LD50 in mice, rats (mg/kg): 3720, 4050 by gavage (Hoffmann)

nifurtimox price More Price(21)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich N3415 Nifurtimox ≥98% (HPLC) 23256-30-6 5mg $161 2024-03-01 Buy
Sigma-Aldrich N3415 Nifurtimox ≥98% (HPLC) 23256-30-6 25mg $646 2024-03-01 Buy
Cayman Chemical 21784 Nifurtimox ≥98% 23256-30-6 1mg $32 2024-03-01 Buy
Cayman Chemical 21784 Nifurtimox ≥98% 23256-30-6 5mg $116 2024-03-01 Buy
Cayman Chemical 21784 Nifurtimox ≥98% 23256-30-6 10mg $214 2024-03-01 Buy
Product number Packaging Price Buy
N3415 5mg $161 Buy
N3415 25mg $646 Buy
21784 1mg $32 Buy
21784 5mg $116 Buy
21784 10mg $214 Buy

nifurtimox Chemical Properties,Uses,Production

Pharmacology and mechanism of action

Nifurtimox is a nitrofuran derivative that has trypanocidal activity against both the trypomastigote forms (extracellular) and the amastigote forms (intracellular) of Trypanosoma (T.) cruzi. Under experimental conditions amastigotes are 10 times more sensitive to the drug than the trypomastigotes[1]. The mechanism of action of the drug is not clearly known. Its trypanocidal action may be related to its ability to undergo partial reduction to form chemically reactive radicals that cause production of superoxide anion, hydrogen peroxide and hydroxyl radicals. These free radicals react with cellular macromolecules and cause membrane injury, enzyme inactivation, damage to DNA, and mutagenesis [2].

Indications

Treatment of American trypanosomiasis (Chagas’ disease) due to Trypanosoma cruzi. The drug may also be used in patients with Trypanosoma brucei gambiense sleeping sickness who are refractory to other treatments.

Side effects

Side effects of nifurtimox are frequent and can be encountered in up to 40% in children, and up to 70% in adults treated for acute and chronic Chagas’ disease. Common side effects include anorexia, nausea, vomiting, abdominal pain, excitation, sleeping difficulties, dizziness, headache and joint and muscle pains [3]. During treatment, half of the patients may interrupt therapy because of side effects. Other rare side effects include skin eruptions and paraesthesia [4].

Contraindications and precautions

The drug should be given with caution to patients with a history of convulsions, brain injury, peripheral neuropathy and psychiatric illness. Dosage reductions may be considered in patients with liver diseases.

Interactions

Concomitant administration of nifurtimox with melarsoprol[5] or eflornithine[6]have been reported to have synergistic effects in experimental animals (mice) infected with Trypanosoma brucei species. The clinical implication of this is unknown.

Preparations

 Lampit (Bayer). Tablets 30 mg, 120 mg.

References

1. Webster LT Jr (1990). Drugs used in the chemotherapy of profozoal infections. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 8th edn, edited by A.G.Gilman, T.W.Rall, A.S.Nies, P.Taylor, (New York: Pergamon Press), pp. 1010–1011.
2. Docampo R, Moreno SNJ, Stoppani AOM, Leon W, Cruz FS, Villalta F, Muniz RFA (1981). Mechanism of nifurtimox toxicity in different forms of Trypanosoma cruzi. Biochem Pharmacol, 30, 1947–1981.
3. Gutteridge WE (1985). Existing chemotherapy and its limitations. Br Med Bull, 41, 162–168.
4. Wegner DHG, Rohwedder RW (1972). The effects of nifurtimox in acute Chagas’ infection. Arzneimittelforschung, 22, 1624–1635.
5. Jennings FW (1991). Chemotherapy of CNS-trypanosomiasis: the combined use of the arsenicals and nitro-compounds. Trop Med Parasitol, 42, 139–142.
6. Jennings FW (1988). The potentiation of arsenicals with difluoromethylornithine (DFMO): experimental studies in murine trypanosomiasis. Bull Soc Pathol Exot, 81, 595–607.

Description

Nifurtimox is manufactured by Bayer and marketed under the trade name Lampits.It is a nitrofuran derivative that was developed specifically for the treatment of American trypanosomiasis (Chagas'disease) (Packachanian, 1957). Nifurtimox is one of two drugs approved for use in treatment of Chagasdisease. It was shown to be the most active and least toxic of this group of agents in preclinical studies and was evaluated in clinical trials in the 1960s and subsequently marketed for use in Chagas’ disease in Latin America in the late 1960s and early 1970s. Although the use of nifurtimox for Chagas’ disease has decreased with the availability of benznidazole, a potentially more active and less toxic agent, there has been a resurgence of interest in and use of nifurtimox for the treatment of second-stage human African trypanosomiasis (HAT)caused by Trypanosoma brucei gambiense.

Chemical Properties

Orange Solid

Uses

Antiprotozoal (Trypanosoma). Showing anti-Trypanosoma cruzi activity.

Uses

The nitrofuran nifurtimoxis the most effective drug against T. cruzi, being cidal against the trypomastigote and amastigote forms. It is active against both the extra- and intracellular form of the parasite. In combination with corticosteroids it has prevented myocardial inflammation and destroyed the parasites within the heart. Side effects of the drug tend to be mild and include nausea, vomiting, insomnia, nervous excitation, vertigo, and skin rashes. Cardiac symptoms are treated symptomatically. Benznidazole (2, C12H12N4O3, N-benzyl-2-nitro-1 imidazoleacetamide, RO 7-1051), an alternative drug, can prevent the spread of the parasites from one tissue to another although relapses are common. Primaquine can destroy the extracellular trypanosomes in the blood, but is not effective against the intracellular forms of the parasite.

Indications

Nifurtimox (Lampit) is a nitrofuran derivative whose likely mechanism of action for killing of trypanosomes is through the production of activated forms of oxygen. Nifurtimox is reduced to the nitro anion radical, which reacts with oxygen to produce superoxide and hydrogen peroxide. The free radical metabolites, an absence of parasite catalase, and a peroxide deficiency lead to lipid peroxidation and cell damage. This production of activated oxygen results in toxicity to the protozoal cells.

Definition

ChEBI: Nifurtimox is a nitrofuran antibiotic.

General Description

Nifurtimox acts as a hypoxia-activated cytotoxin, which specifically kills clonogenic tumor cells under hypoxic conditions. It is used to treat Chagas disease and African trypanosomiasis. Nifurtimox inhibits neuroblastoma and medulloblastoma cell growth.

Pharmaceutical Applications

A water-soluble synthetic compound available for oral use. It exhibits antibacterial activity typical of the group, but its most notable property is its activity against trypanosomes, especially Trypanosoma cruzi.
A plasma concentration of 0.5–1 mg/L is achieved c. 2 h after an oral dose of 15 mg/kg. The plasma half-life is 2–4 h. In common with other nitrofurans, it is rapidly and extensively metabolized, so that less than 1% of a dose is excreted intact in the urine. In renal failure, clearance is somewhat reduced but the half-life is unchanged.
Adverse events are common. Many patients experience anorexia, which may be combined with vomiting and abdominal pain. There may also be neurological reactions such as restlessness, insomnia, headache and disorientation.
It is used in the treatment of Chagas disease (South American trypanosomiasis). It has also found some use in the treatment of African sleeping sickness in combination with eflornithine.

Biochem/physiol Actions

Nifurtimox is a nitrofurane derivative used to treat diseases caused by trypanosomes. Nifurtimox was discovered empirically and its mechanism of action is unclear. It is believed that nifurtimox exerts its biological activity through the bioreduction of the nitro-group to a nitro-anion radical which undergoes redox-cycling with molecular oxygen.

Mechanism of action

The drug is given orally and is well absorbed from the gastrointestinal tract. It is rapidly metabolized, and only low levels are found in blood and tissues.The drug is excreted in the urine, primarily in the form of metabolites.

Clinical Use

Nifurtimox is trypanocidal and exerts an effect on the trypomastigote and amastigote forms of T. cruzi. It is effective in the treatment of the acute form of Chagas’ disease but is less effective once the disease becomes chronic. The drug is moderately well tolerated, and treatment generally lasts 3 to 4 months. Cure rates of 80 to 90% have been reported. Since much of the tissue damage caused by the disease is irreversible, early diagnosis and treatment are important. Nifurtimox has also been used in T. gambiense infection with meningoencephalopathic involvement.

Side effects

Although side effects occur in approximately half the patients treated with nifurtimox, it is necessary to discontinue treatment in only a minority. Nausea, vomiting, abdominal pain, skin rashes, headache, insomnia, convulsions, and myalgia all have been reported.

Synthesis

Nifurtimox, 1,1-dioxide 4-[(5-nitrofuryliden)amino]-3-methylthiomorpholine (37.4.7), is made by the following scheme. Interaction of 2-mercaptoethanol with propylene oxide in the presence of potassium hydroxide gives (2-hydroxyethyl)-(2-hydroxypropylsulfide) (37.4.3), which undergoes intramolecular dehydration using potassium bisulfate to make 2-methyl-1,4-oxithiane (37.4.4). Oxidation of this using hydrogen peroxide gives 2-methyl-1,4-oxithian-4,4-dioxide (37.4.5), which when reacted with hydrazine transforms to 4-amino-3-methyltetrahydro-1,4-thiazin-1,1-dioxide (37.4.6). Reacting this with 5-nitrofurfurol gives the corresponding hydrazone?athe desired nifurtimox.

Synthesis_23256-30-6

nifurtimox Preparation Products And Raw materials

Raw materials

Preparation Products

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23256-30-6(nifurtimox)Related Search:

NIFURIMOX 4-[(5-Nitrofurfurylidene)amino]-3-methylthiomorpholine 1,1-dioxide BAY-2502 Bayer 2502 Bayer-2502 Lampit 3-Methyl-N-[(5-nitro-2-furanyl)methylene]-4-thiomorpholinamine 1,1-dioxide Aids007325 Aids-007325 nifurtimox 3-Methyl-N-[(5-nitro-furan-2-yl)Methylene]-4-thioMorpholinaMine1,1-dioxide 3-Methyl-N-[(5-nitro-2-furanyl)Methylene]- (RS)-3-methyl-N-[(1E)-(5-nitro-2-furyl)methylene]thiomorpholin-4-amine 1,1-dioxide 3-Methyl-4-(5′-nitrofurylidene-amino)-tetrahydro-4H-1,4-thiazine-1,1-dioxide Thiomorpholine, 3-methyl-4-((5-nitrofurfurylidene)amino)-,1,1-dioxide (E)-N-(3-methyl-1,1-dioxo-1,4-thiazinan-4-yl)-1-(5-nitrofuran-2-yl)methanimine BAY-A-2502 4-Thiomorpholinamine, 3-methyl-N-[(5-nitro-2-furanyl)methylene]-, 1,1-dioxide nifurtimox USP/EP/BP (±)-Nifurtimox Lampit LDH,Lactate Dehydrogenase,Parasite,inhibit,Inhibitor,Nifurtimox 3-Methyl-4-(((5-nitrofuran-2-yl)methylene)amino)thiomorpholine 1,1-dioxide 23256-30-6 Heterocycles Intermediates & Fine Chemicals Pharmaceuticals Sulfur & Selenium Compounds