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Bumetanide

Product Name
Bumetanide
CAS No.
28395-03-1
Chemical Name
Bumetanide
Synonyms
3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid;bumex;Lixil;pf159;DONALD;burine;pf1593;burinex;Bufenox;fontego
CBNumber
CB9382992
Molecular Formula
C17H20N2O5S
Formula Weight
364.42
MOL File
28395-03-1.mol
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Bumetanide Property

Melting point:
230-2310C
Boiling point:
571.2±60.0 °C(Predicted)
Density 
1.2812 (rough estimate)
refractive index 
1.6510 (estimate)
storage temp. 
2-8°C
solubility 
Practically insoluble in water, soluble in acetone and in alcohol, slightly soluble in methylene chloride. It dissolves in dilute solutions of alkali hydroxides.
pka
pK1 3.6, pK2 7.7(at 25℃)
form 
Solid
color 
White to Light Yellow
Water Solubility 
Soluble in ethanol (10 mg/ml), DMSO (25 mg/ml), acetone, benzene, methanol, propylene glycol, and water (<1 mg/ml).
CAS DataBase Reference
28395-03-1(CAS DataBase Reference)
EPA Substance Registry System
Benzoic acid, 3-(aminosulfonyl)-5-(butylamino)-4-phenoxy- (28395-03-1)
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Safety

WGK Germany 
3
RTECS 
DG4910000
HS Code 
2935904000
Toxicity
LD50 i.v. in mice: 330 mg/kg (Oestergaard)
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
B3023
Product name
Bumetanide
Purity
≥98%
Packaging
1g
Price
$274
Updated
2024/03/01
Sigma-Aldrich
Product number
1078303
Product name
Bumetanide
Purity
United States Pharmacopeia (USP) Reference Standard
Packaging
125mg
Price
$436
Updated
2024/03/01
Alfa Aesar
Product number
J62302
Product name
Bumetanide, 98+%
Packaging
1g
Price
$123
Updated
2024/03/01
Alfa Aesar
Product number
J62302
Product name
Bumetanide, 98+%
Packaging
5g
Price
$401.65
Updated
2024/03/01
Cayman Chemical
Product number
14630
Product name
Bumetanide
Purity
≥98%
Packaging
1g
Price
$84
Updated
2024/03/01
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Bumetanide Chemical Properties,Usage,Production

Chemical Properties

Crystalline Solid

Originator

Burinex,Leo,UK,1973

Uses

antineoplastic, alkylating agent

Uses

Bumetanide is a diuretic.

Uses

Bumetanide is used for relieving edema associated with cardiac insufficiency, for liver and kidney diseases including nephrotic syndrome, for ascites, and hypertension.

Definition

ChEBI: A member of the class of benzoic acids that is 4-phenoxybenzoic acid in which the hydrogens ortho to the phenoxy group are substituted by butylamino and sulfamoyl groups. Bumetanide is a diuretic, and is used for treatment of oedema associated with congestive heart failure, hepatic and renal disease.

Manufacturing Process

Preparation of 3-Nitro-4-Phenoxy-5-Sulfamylbenzoic Acid: A mixture of 4- chloro-3-nitro-5-sulfamylbenzoic acid (140 grams), phenol (100 grams), sodium hydrogencarbonate (170 grams), and water (1.000 ml) was heated to 85°C while stirring and kept at this temperature for 16 hours. After cooling to 4°C, the precipitated sodium salt of 3-nitro-4-phenoxy-5-sulfamylbenzoic acid was filtered off and washed with ice water. The sodium salt was dissolved in boiling water (3,000 ml), and the 3-nitro-4-phenoxy-5-sulfamylbenzoic acid was precipitated by addition of 4N hydrochloric acid. After cooling, the acid was isolated by suction and dried. The melting point was 255°-256°C.
Preparation of 3-Amino-4-Phenoxy-5-Sulfamylbenzoic Acid: A suspension of 3- nitro-4-phenoxy-5-sulfamylbenzoic acid (20 grams) in water (100 ml) was adjusted to pH 8 by addition of 1N lithium hydroxide. The resulting solution was hydrogenated at room temperature and 1.1 atmospheres hydrogen pressure after addition of Pd on carbon catalyst (0.6 grams catalyst containing 10% Pd). After the hydrogen uptake had become negligible, the catalyst was removed by filtration, and the 3-amino-4-phenoxy-5-sulfamylbenzoic acid was precipitated from the filtrate by addition of 4N hydrochloric acid to pH 2.5. After recrystallization from aqueous ethanol and drying, the melting point was 255°-256°C.
Preparation of 3-n-Butylamino-4-Phenoxy-5-Sulfamylbenzoic Acid: To a suspension of 3-amino-4-phenoxy-5-sulfamyibenzoic acid (10 grams) in nbutanol (200 ml), concentrated sulfuric acid (2 ml) was added while stirring. The reaction mixture was heated under reflux under conditions in which the water formed during the reaction could be removed. When, after dilution with n-butanol, the NMR-spectrum of a sample of the reaction mixture showed at the two doublets of the aromatic protons in ring A that the butyl-3-amino-4- phenoxy-5-sulfamylbenzoate formed as an intermediate was more than 90% converted to the corresponding 3-n-butylaminobenzoate, 2 N sodium hydroxide (200 ml) was added and the boiling was continued for 45 minutes. After the saponification, the reaction mixture was neutralized to pH 8 by addition of concentrated hydrochloric acid.
By cooling, the sodium salt of 3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid precipitated. It was filtered off and recrystallized from water (100 ml). The sodium salt, crystallizing with 3 molecules of water, was then dissolved in boiling water (200 ml), 1N hydrochloric acid was added to pH 2.5, and after cooling the precipitated 3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid was collected by filtration. After recrystallization from aqueous ethanol and drying, the pure compounds were obtained with melting point 230°-231°C.

brand name

Bumex (Roche).

Therapeutic Function

Diuretic

Biological Activity

Loop diuretic that inhibits the Na + /2Cl - /K + (NKCC) cotransporter. More potent than furosemide (5-(Aminosulfonyl)-4-chloro-2-([2-furanylmethyl]amino)benzoic acid ).

Biochem/physiol Actions

Inhibitor of Na+/K+/Cl- cotransporter.

Clinical Use

A diuretic structurally related to furosemide is bumetanide. This compound also functions as a high-ceiling diuretic in the ascending limb of the loop of Henle. It has a duration of action of approximately 4 hours. The uses of this compound are similar to those described for furosemide. The dose of bumetanide is 0.5 to 2 mg/day given as a single dose.

Synthesis

Bumetanide, 3-butylamino-4-phenoxy-5-sulfamoylbenzoic acid (21.4.6), is synthesized from 4-chlorobenzoic acid. In the first stage of synthesis, it undergoes sulfonylchlorination by chlorosulfonic acid, forming 4-chloro-3-chlorosulfonylbenzoic acid (21.4.1), which is further nitrated with nitric acid to 4-chloro-3-chlorosulfonyl-5-nitrobenzoic acid (21.4.2). Reacting this with ammonia gives 5-aminosulfonyl-4-chloro-3-nitrobenzoic acid (21.4.3), which when reacted with sodium phenolate is transformed into 5-amino-sulfonyl-3-nitro-5-phenoxybenzoid acid (21.4.4). Reduction of the nitro group in this product by hydrogen using a palladium on carbon catalyst gives 3-amino-5-aminosulfonyl- 5-phenoxybenzoic acid (21.4.5). Finally, reacting this with butyl alcohol in the presence of sulfuric acid gives the desired bumetanide (21.4.6).

Drug interactions

Potentially hazardous interactions with other drugs
Analgesics: increased risk of nephrotoxicity with NSAIDs; antagonism of diuretic effect with NSAIDs.
Anti-arrhythmics: risk of cardiac toxicity with anti-arrhythmics if hypokalaemia occurs; effects of lidocaine and mexiletine antagonised.
Antibacterials: increased risk of ototoxicity with aminoglycosides, polymyxins and vancomycin; avoid with lymecycline.
Antidepressants: increased risk of hypokalaemia with reboxetine; enhanced hypotensive effect with MAOIs; increased risk of postural hypotension with tricyclics.
Antiepileptics: increased risk of hyponatraemia with carbamazepine.
Antifungals: increased risk of hypokalaemia with amphotericin.
Antihypertensives: enhanced hypotensive effect; increased risk of first dose hypotensive effect with alpha-blockers; increased risk of ventricular arrhythmias with sotalol if hypokalaemia occurs.
Antipsychotics: increased risk of ventricular arrhythmias with amisulpride or pimozide if hypokalaemia occurs - avoid with pimozide; enhanced hypotensive effect with phenothiazines.
Atomoxetine: increased risk of ventricular arrhythmias if hypokalaemia occurs.
Cardiac glycosides: increased toxicity if hypokalaemia occurs.
Cytotoxics: increased risk of ventricular arrhythmias due to hypokalaemia with arsenic trioxide; increased risk of nephrotoxicity and ototoxicity with platinum compounds.
Lithium: risk of toxicity.

Metabolism

About 80% of a dose of bumetanide is excreted in the urine, about 50% as unchanged drug, and 10-20% in the faeces. No active metabolites are known. In patients with chronic renal failure the liver takes more importance as an excretory pathway although the duration of action is not markedly prolonged.

storage

Store at RT

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Bumetanide Suppliers

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View Lastest Price from Bumetanide manufacturers

WUHAN FORTUNA CHEMICAL CO., LTD
Product
Bumetanide 28395-03-1
Price
US $0.00/KG
Min. Order
1KG
Purity
99%-101%, EP
Supply Ability
100kg
Release date
2021-11-02
Hebei Weibang Biotechnology Co., Ltd
Product
Bumetanide 28395-03-1
Price
US $10.00/KG
Min. Order
1KG
Purity
99%
Supply Ability
10 mt
Release date
2024-11-19
Wuhan Senwayer Century Chemical Co.,Ltd
Product
Bumetanide 28395-03-1
Price
US $0.00-0.00/g
Min. Order
1g
Purity
99%
Supply Ability
50kg
Release date
2023-02-09

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