Acetazolamide CAS 59-66-5
Introduction：Basic information about Acetazolamide CAS 59-66-5, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Acetazolamide Basic informationDescription References
| Product Name: | Acetazolamide |
| Synonyms: | N-(5-[AMINOSULFONYL]-1,3,4-THIADIAZOL-2-YL)ACETAMIDE;N-[5-(AMINOSULFONYL)-1,3,4-THIADIOZOL-2-YL]-ACETAMIDE;N-(5-SULFAMOYL-1,3,4-THIADIAZOL-2-YL)ACETAMIDE;N-(5-SULFAMOYL-1,3,4-THIADIAZOL-2-YL)ETHANAMIDE;DIACARB;LABOTEST-BB LT00012571;2-ACETAMINO-1,3,4-THIADIAZOLE-5-SULFONAMIDE;2-acetamido-5-sulfamoyl-1,3,4-thiadiazole |
| CAS: | 59-66-5 |
| MF: | C4H6N4O3S2 |
| MW: | 222.25 |
| EINECS: | 200-440-5 |
| Product Categories: | Furans;Isotope;ACETAMOX;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Miscellaneous Enzyme;API;59-66-5 |
| Mol File: | 59-66-5.mol |
Acetazolamide Chemical Properties
| Melting point | 258-259 °C |
| density | 1.610 (estimate) |
| refractive index | 1.6270 (estimate) |
| storage temp. | 2-8°C |
| solubility | Soluble in NH4OH (50 mg/mL), DMSO, Methanol and slightly soluble in Ethanol. |
| form | solid |
| pka | 7.2(at 25℃) |
| color | White to Off-White |
| biological source | synthetic |
| Water Solubility | <0.1 g/100 mL at 22 ºC |
| λmax | 265nm(H2O)(lit.) |
| Merck | 14,53 |
| BRN | 212994 |
| BCS Class | 4 |
| Stability: | Hygroscopic |
| InChI | 1S/C4H6N4O3S2/c1-2(9)6-3-7-8-4(12-3)13(5,10)11/h1H3,(H2,5,10,11)(H,6,7,9) |
| InChIKey | BZKPWHYZMXOIDC-UHFFFAOYSA-N |
| SMILES | CC(=O)Nc1nnc(s1)S(N)(=O)=O |
| CAS DataBase Reference | 59-66-5(CAS DataBase Reference) |
| NIST Chemistry Reference | 2-Acetylamino-1,3,4-thiadiazole-5-sulfonamide(59-66-5) |
| EPA Substance Registry System | Acetazolamide (59-66-5) |
Safety Information
| Hazard Codes | Xi |
| Risk Statements | 36/38-36/37/38 |
| Safety Statements | 26-36 |
| RIDADR | 2811 |
| WGK Germany | 2 |
| RTECS | AC8225000 |
| TSCA | TSCA listed |
| HazardClass | 6.1 |
| PackingGroup | III |
| HS Code | 29350090 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Eye Irrit. 2 Skin Irrit. 2 |
| Hazardous Substances Data | 59-66-5(Hazardous Substances Data) |
| Toxicity | LD50 oral in mouse: 4300mg/kg |
| Description | Acetazolamide is a drug used for the treatment of glaucoma,epilepsy,altitude sickness,periodic paralysis, chronic macular edema, idiopathic intracranial hypertension, andheart failure. It can also been used for the treatment of altitude sickness, increased intracranial pressure and neuromuscular disorders. In addition, it also has significant effect of diuretic. It belongs to the carbonic anhydrase inhibitorfamilies of medication. It works by decreasing the amount ofhydrogen ionsandbicarbonatein the body. |
| References | Forwand, S. A., et al. "Effect of acetazolamide on acute mountain sickness." New England Journal of Medicine279.16(1968):839. Cox, S. N., E. Hay, and A. C. Bird. "Treatment of chronic macular edema with acetazolamide." Archives of Ophthalmology 106.9(1988):1190. Supuran, Claudiu T. "Acetazolamide for the treatment of idiopathic intracranial hypertension." Expert Review of Neurotherapeutics15.8(2015):851. Kassamali, R, and D. A. Sica. "Acetazolamide: a forgotten diuretic agent." Cardiology in Review 19.6(2011):276. Lucas, M., and M. Brown. "Acetazolamide Reduces Hospital Admissions and Length of Stay in Refractory Heart Failure Patients." Heart Lung & Circulation 20.Suppl 2(2011):S6-S6. https://www.rxlist.com/acetazolamide-drug.htm https://en.wikipedia.org/wiki/Acetazolamide |
| Description | Acetazolamide is a weak diuretic with limited use in edema associated with cardiacinsufficiency, glaucoma, minor epileptic attacks, and altitude sickness. |
| Chemical Properties | White Solid |
| Originator | Diamox ,Lederle,US ,1953 |
| Uses | Acetazolamide acts as a carbonic anhydrase inhibitor which increases cerebral blood flow. It inhibits water permeability of membranes by interacting with aquaporins. It is used for the medical treatment of glaucoma, epileptic seizure, idiopathic intracranial hypertension, altitude sickness, cystinuria. |
| Uses | carbonic anhydrase inhibitor, diuretic, antiglaucoma |
| Uses | Acetazolamide is used for epilepsy in the absence of attacks and also in conjunction withother antiepileptic drugs. |
| Definition | ChEBI: Acetazolamide is a sulfonamide, a member of thiadiazoles and a monocarboxylic acid amide. It has a role as a diuretic, an anticonvulsant and an EC 4.2.1.1 (carbonic anhydrase) inhibitor. It is a conjugate acid of an acetazolamide(1-). It derives from a hydride of a 1,3,4-thiadiazole. |
| Manufacturing Process | According to REM, hydrazine hydrate is reacted with 2 mols of ammoniumthiocyanate to produce 1,2-bis(thiocarbamoyl)hydrazine which by loss ofammonia and rearrangement produces 5-amino-2-mercapto-1,3,4-thiadiazole.That compound is acetyled with acetic anhydride. Then, as described in US Patent 2,554,816, the 2-acetylamido-5-mercapto-1,3,4-thiadiazole is converted to the sulfonyl chloride by passing chlorine gasinto a cooled (5-10°C) solution in 33% acetic acid (66 parts to 4 parts ofmercapto compound) used as a reaction medium. Chlorine treatment iscontinued for two hours. The crude product can be dried and purified byrecrystallization from ethylene chloride. The pure compound is a whitecrystalline solid, MP 194°C, with decomposition, when heated rapidly. Thecrude damp sulfonyl chloride is converted to the sulfonamide by addition to alarge excess of liquid ammonia. The product is purified by recrystallizationfrom water. The pure compound is a white, crystalline solid, MP 259°C, withdecomposition. The yield of sulfonamide was 85% of theory based onmercapto compound. An alternative process is described in US Patent 2,980,679 as follows. 15grams of finely powdered 2-acetylamino-1,3,4-thiadiazole-5-mercaptain aresuspended in 200 ml of water containing 4 grams of potassium bromide. From0.5 to 1 gram of ferric chloride are subsequently added. The mass isenergetically stirred and 52 grams of liquid bromide are added by incrementsfor about 45 minutes, while keeping the reaction temperature below 10°C,and, preferably, at 4-8°C by employing a cooling bath. Stirring is continuedfor a further 10 minutes, then the 2-acetylamino-1,3,4-thiadiazole-5-sulfobromide is collected on a funnel equipped with a porous diaphragm,thoroughly washed with cold water and finally subjected to amidation withliquid ammonia. The reaction mixture is allowed to stand for a certain period,then the ammonia is evaporated, after which the residue is taken up withdiluted ammonia and, after decolorizing with carbon, the sulfonamide isprecipitated with hydrochloric acid. The yield of crude sulfonamide obtainedwith this process, with respect to the starting mercapto compound is abut84%. If the amidation is carried out with 33% aqueous ammonia, the yield isslightly lower. |
| Brand name | Diamox (Duramed). |
| Therapeutic Function | Carbonic anhydrase inhibitor, Diuretic, Antiglaucoma |
| General Description | White to yellowish-white fine crystalline powder. No odor or taste. |
| Air & Water Reactions | Insoluble in water. |
| Reactivity Profile | A weak acid and a diazo derivative. Azo, diazo, azido compounds can detonate. This applies in particular to organic azides that have been sensitized by the addition of metal salts or strong acids. Toxic gases are formed by mixing materials of this class with acids, aldehydes, amides, carbamates, cyanides, inorganic fluorides, halogenated organics, isocyanates, ketones, metals, nitrides, peroxides, phenols, epoxides, acyl halides, and strong oxidizing or reducing agents. Flammable gases are formed by mixing materials in this group with alkali metals. Explosive combination can occur with strong oxidizing agents, metal salts, peroxides, and sulfides. |
| Fire Hazard | Flash point data for Acetazolamide are not available; however, Acetazolamide is probably combustible. |
| Biochem/physiol Actions | Inhibits water permeability of membranes by interacting with aquaporins |
| Mechanism of action | Acetazolamide is an aromatic sulfonamide used as a carbonic anhydrase inhibitor. It facilitatesproduction of alkaline urine with an elevated biocarbonate, sodium, and potassium ion concentrations.By inhibiting carbonic anhydrase, the drug suppresses reabsorption of sodium ionsin exchange for hydrogen ions, increases reflux of bicarbonate and sodium ions and reducesreflux of chloride ions. During this process, chloride ions are kept in the kidneys to cover ofinsufficiency of bicarbonate ions, and for keeping an ion balance. Electrolytic contents of fluidsecreted by the kidneys in patients taking carbonic anhydrase inhibitors are characterized byelevated levels of sodium, potassium, and bicarbonate ions and a moderate increase in waterlevel. Urine becomes basic, and the concentration of bicarbonate in the plasma is reduced. |
| Clinical Use | Acetazolamide was the first of the carbonic anhydrase inhibitors to be introduced as an orally effective diuretic, with a diuretic effect that lasts approximately 8 to 12hours. As mentioned earlier, its diuretic action is limited because of the systemic acidosis it produces. Acetazolamidereduces the rate of aqueous humor formation and is used primarily for reducing intraocular pressure in the treatment of glaucoma. The dose is 250 mg to 1 g per day. |
| Safety Profile | Poison by subcutaneous and intravenous routes. Moderately toxic by intraperitoneal route. Human systemic effects by ingestion: dyspnea. An experimental teratogen by many routes. Other experimental reproductive effects. When heated to decomposition it emits very toxic fumes of NOx, and SOx,. A carbonic anhydrase inhibitor and dmretic used to treat glaucoma. |
| Synthesis | Acetazolamide is 5-acetamido-1,3,4-thiadiazole-2-sulfonamide (9.7.5).The synthesis of acetazolamide is based on the production of 2-amino-5-mercapto-1,3,4-thiadiazole (9.7.2), which is synthesized by the reaction of ammonium thiocyanate andhydrazine, forming hydrazino-N,N-bis-(thiourea) (9.7.1), which cycles into thiazole (9.7.2) upon reaction with phosgene. Acylation of (9.7.2) with acetic anhydridegives 2-acetylamino-5-mercapto-1,3,4-thiadiazol (9.7.3). The obtained product is chlorinated to give 2-acetylamino-5-mercapto-1,3,4-thiadiazol-5-sulfonylchloride(9.7.4), which is transformed into acetazolamide upon reaction with ammonia (9.7.5)[24,25]. |
| Veterinary Drugs and Treatments | Acetazolamide has been used principally in veterinary medicinefor its effects on aqueoushumor production in the treatment ofglaucoma, metabolic alkalosis, and for its diuretic action. It maybe useful as an adjunctive treatment for syringomyelia in dogs.Acetazolamide’s use in small animals is complicated by a relativelyhigh occurrence of adverse effects. In horses, acetazolamide is used as an adjunctive treatment forhyperkalemic periodic paralysis (HYPP). In humans, the drug has been used as adjunctive therapy for epilepsyand for acute high-altitude sickness. |
| Drug interactions | Potentially hazardous interactions with other drugs Analgesics: high dose aspirin reduces excretion (risk of toxicity). Anti-arrhythmics: increased toxicity if hypokalaemia occurs. Antibacterials: effects of methenamine antagonised. Antiepileptics: increased risk of osteomalacia with phenytoin and phenobarbital; concentration of carbamazepine and possibly fosphenytoin and phenytoin increased. Antihypertensives: enhanced hypotensive effect. Antipsychotics: increased risk of ventricular arrhythmias due to hypokalaemia. Atomoxetine: increased risk of ventricular arrhythmias due to hypokalaemia. Beta-blockers: increased risk of ventricular arrhythmias due to hypokalaemia with sotalol. Cardiac glycosides: increased toxicity if hypokalaemia occurs. Ciclosporin: possibly increases ciclosporin concentration. Cytotoxics: alkaline urine increases methotrexate excretion; increased risk of ventricular arrhythmias due to hypokalaemia with arsenic trioxide; increased risk of nephrotoxicity and ototoxicity with platinum compounds. Lithium: lithium excretion increased. |
| Metabolism | Acetazolamide is tightly bound to carbonic anhydrase and accumulates in tissues containing this enzyme, particularly red blood cells and the renal cortex. It is also bound to plasma proteins. It is excreted unchanged in the urine, renal clearance being enhanced in alkaline urine. |
| storage | Store at -20°C |
| Purification Methods | It is recrystallised from water. [Roblin & Clapp J Am Chem Soc 72 4890 1950, Beilstein 27 III/IV 8219.] |
Acetazolamide Preparation Products And Raw materials
| Raw materials | Acetyl chloride-->Sulfuryl chloride-->Sodium metabisulfite-->Ammonium thiocyanate-->2-Acetylamino-5-mercapto-1,3,4-thiadiazole-->Butanedioic acid,1-[1-[[(1-methylethyl)amino]methyl]-2-(1-naphthalenyloxy)ethyl] ester-->Benzoic acid, 2-[[[[5-(acetylamino)-1,3,4-thiadiazol-2-yl]sulfonyl]amino]carbonyl]-, 1-[[(1-methylethyl)amino]methyl]-2-(1-naphthalenyloxy)ethyl ester-->5-AMINO-1,3,4-THIADIAZOLE-2-SULFONAMIDE-->2-ACETAMIDO-5-BENZYLTHIO-1 3 4--->2-(ACETAMIDO)-5-(CHLOROSULFONYL)-1,3,4-THIADIAZOLE |
