Bumetanide CAS 28395-03-1
Introduction：Basic information about Bumetanide CAS 28395-03-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Bumetanide Basic information
| Product Name: | Bumetanide |
| Synonyms: | 3-(aminosulfonyl)-5-(butylamino)-4-phenoxy-benzoicaci;3-(butylamino)-4-phenoxy-5-sulfamoyl-benzoicaci;3-Butyuamino-4-phenoxy-5-sutfamoylbenzoicacid;RO 10-6338;3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid;3-(AMINOSULFONYL)-5-(BUTYLAMINO)-4-PHENOXYBENZOIC ACID;BUMETANIDE;bumex |
| CAS: | 28395-03-1 |
| MF: | C17H20N2O5S |
| MW: | 364.42 |
| EINECS: | 249-004-6 |
| Product Categories: | Inhibitors;Ion transporter and other ion channel;Antibiotics;THIOPLEX;Aromatics Compounds;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;APIs;28395-03-1 |
| Mol File: | 28395-03-1.mol |
Bumetanide Chemical Properties
| 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). |
| Major Application | pharmaceutical (small molecule) |
| InChI | InChI=1S/C17H20N2O5S/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23) |
| InChIKey | MAEIEVLCKWDQJH-UHFFFAOYSA-N |
| SMILES | C(O)(=O)C1=CC(NCCCC)=C(OC2=CC=CC=C2)C(S(N)(=O)=O)=C1 |
| CAS DataBase Reference | 28395-03-1(CAS DataBase Reference) |
| EPA Substance Registry System | Benzoic acid, 3-(aminosulfonyl)-5-(butylamino)-4-phenoxy- (28395-03-1) |
Safety Information
| WGK Germany | 3 |
| RTECS | DG4910000 |
| HS Code | 2935904000 |
| Storage Class | 11 - Combustible Solids |
| Toxicity | LD50 i.v. in mice: 330 mg/kg (Oestergaard) |
| 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 andkidney 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 associatedwith 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 to85°C while stirring and kept at this temperature for 16 hours. After cooling to4°C, the precipitated sodium salt of 3-nitro-4-phenoxy-5-sulfamylbenzoic acidwas filtered off and washed with ice water. The sodium salt was dissolved inboiling water (3,000 ml), and the 3-nitro-4-phenoxy-5-sulfamylbenzoic acidwas precipitated by addition of 4N hydrochloric acid. After cooling, the acidwas 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) wasadjusted to pH 8 by addition of 1N lithium hydroxide. The resulting solutionwas hydrogenated at room temperature and 1.1 atmospheres hydrogenpressure after addition of Pd on carbon catalyst (0.6 grams catalyst containing10% Pd). After the hydrogen uptake had become negligible, the catalyst wasremoved by filtration, and the 3-amino-4-phenoxy-5-sulfamylbenzoic acid wasprecipitated from the filtrate by addition of 4N hydrochloric acid to pH 2.5.After recrystallization from aqueous ethanol and drying, the melting point was255°-256°C. Preparation of 3-n-Butylamino-4-Phenoxy-5-Sulfamylbenzoic Acid: To asuspension 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 thewater formed during the reaction could be removed. When, after dilution with n-butanol, the NMR-spectrum of a sample of the reaction mixture showed atthe 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 sodiumhydroxide (200 ml) was added and the boiling was continued for 45 minutes.After the saponification, the reaction mixture was neutralized to pH 8 byaddition of concentrated hydrochloric acid. By cooling, the sodium salt of 3-n-butylamino-4-phenoxy-5-sulfamylbenzoicacid precipitated. It was filtered off and recrystallized from water (100 ml).The sodium salt, crystallizing with 3 molecules of water, was then dissolved inboiling water (200 ml), 1N hydrochloric acid was added to pH 2.5, and aftercooling the precipitated 3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid wascollected 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 aduration 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 asa single dose. |
| Synthesis | Bumetanide, 3-butylamino-4-phenoxy-5-sulfamoylbenzoic acid (21.4.6), issynthesized from 4-chlorobenzoic acid. In the first stage of synthesis, it undergoes sulfonylchlorinationby chlorosulfonic acid, forming 4-chloro-3-chlorosulfonylbenzoic acid(21.4.1), which is further nitrated with nitric acid to 4-chloro-3-chlorosulfonyl-5-nitrobenzoicacid (21.4.2). Reacting this with ammonia gives 5-aminosulfonyl-4-chloro-3-nitrobenzoicacid (21.4.3), which when reacted with sodium phenolate is transformed into5-amino-sulfonyl-3-nitro-5-phenoxybenzoid acid (21.4.4). Reduction of the nitro group inthis 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 presenceof 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 |
Bumetanide Preparation Products And Raw materials
| Raw materials | Ammonium hydroxide-->Sodium borohydride-->Phenol-->Sodium bisulfite-->Chlorosulfonic acid-->Benzenesulfonamide-->4-Chlorobenzoic acid-->Butyl formate-->m-Carboxybenzenesulfonyl chloride-->1-Butanol-->Hydrogen-->Sodium bicarbonate-->Benzoic acid, 3-(aminosulfonyl)-5-(butylamino)-4-phenoxy-, methyl ester-->butyl 3-aminosulphonyl-5-butylamino-4-phenoxybenzoate-->3-amino-5-(aminosulphonyl)-4-phenoxybenzoic acid |
| Preparation Products | sodium 3-(aminosulphonyl)-5-(butylamino)-4-phenoxybenzoate |
