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Acetazolamide

Basic information Description References Safety Supplier Related

Acetazolamide Basic information

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
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Sulfur & Selenium Compounds
  • ACETAMOX
  • Miscellaneous Enzyme
  • API
Mol File:
59-66-5.mol
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Acetazolamide Chemical Properties

Melting point:
256-261°C
Density 
1.610 (estimate)
refractive index 
1.6270 (estimate)
storage temp. 
Refrigerator
solubility 
Soluble in NH4OH (50 mg/mL), DMSO, Methanol and slightly soluble in Ethanol.
pka
7.2(at 25℃)
form 
solid
Water Solubility 
<0.1 g/100 mL at 22 ºC
λmax
265nm(H2O)(lit.)
Merck 
14,53
BRN 
212994
InChIKey
BZKPWHYZMXOIDC-UHFFFAOYSA-N
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)
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Safety Information

Hazard Codes 
Xi
Risk Statements 
36/38-36/37/38
Safety Statements 
26-36
RIDADR 
2811
WGK Germany 
2
RTECS 
AC8225000
TSCA 
Yes
HazardClass 
6.1
PackingGroup 
III
HS Code 
29350090
Hazardous Substances Data
59-66-5(Hazardous Substances Data)
Toxicity
LD50 oral in mouse: 4300mg/kg

MSDS

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Acetazolamide Usage And Synthesis

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 cardiac insufficiency, glaucoma, minor epileptic attacks, and altitude sickness.

Chemical Properties

White Solid

Originator

Diamox ,Lederle,US ,1953

Uses

carbonic anhydrase inhibitor, diuretic, antiglaucoma

Uses

Acetazolamide is used for epilepsy in the absence of attacks and also in conjunction with other antiepileptic drugs.

Manufacturing Process

According to REM, hydrazine hydrate is reacted with 2 mols of ammonium thiocyanate to produce 1,2-bis(thiocarbamoyl)hydrazine which by loss of ammonia 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 gas into a cooled (5-10°C) solution in 33% acetic acid (66 parts to 4 parts of mercapto compound) used as a reaction medium. Chlorine treatment is continued for two hours. The crude product can be dried and purified by recrystallization from ethylene chloride. The pure compound is a white crystalline solid, MP 194°C, with decomposition, when heated rapidly. The crude damp sulfonyl chloride is converted to the sulfonamide by addition to a large excess of liquid ammonia. The product is purified by recrystallization from water. The pure compound is a white, crystalline solid, MP 259°C, with decomposition. The yield of sulfonamide was 85% of theory based on mercapto compound.
An alternative process is described in US Patent 2,980,679 as follows. 15 grams of finely powdered 2-acetylamino-1,3,4-thiadiazole-5-mercaptain are suspended in 200 ml of water containing 4 grams of potassium bromide. From 0.5 to 1 gram of ferric chloride are subsequently added. The mass is energetically stirred and 52 grams of liquid bromide are added by increments for about 45 minutes, while keeping the reaction temperature below 10°C, and, preferably, at 4-8°C by employing a cooling bath. Stirring is continued for 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 with liquid ammonia. The reaction mixture is allowed to stand for a certain period, then the ammonia is evaporated, after which the residue is taken up with diluted ammonia and, after decolorizing with carbon, the sulfonamide is precipitated with hydrochloric acid. The yield of crude sulfonamide obtained with this process, with respect to the starting mercapto compound is abut 84%. If the amidation is carried out with 33% aqueous ammonia, the yield is slightly 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.

Mechanism of action

Acetazolamide is an aromatic sulfonamide used as a carbonic anhydrase inhibitor. It facilitates production of alkaline urine with an elevated biocarbonate, sodium, and potassium ion concentrations. By inhibiting carbonic anhydrase, the drug suppresses reabsorption of sodium ions in exchange for hydrogen ions, increases reflux of bicarbonate and sodium ions and reduces reflux of chloride ions. During this process, chloride ions are kept in the kidneys to cover of insufficiency of bicarbonate ions, and for keeping an ion balance. Electrolytic contents of fluid secreted by the kidneys in patients taking carbonic anhydrase inhibitors are characterized by elevated levels of sodium, potassium, and bicarbonate ions and a moderate increase in water level. 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 12 hours. As mentioned earlier, its diuretic action is limited because of the systemic acidosis it produces. Acetazolamide reduces 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.

Chemical 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 and hydrazine, 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 anhydride gives 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 medicine for its effects on aqueous humor production in the treatment of glaucoma, metabolic alkalosis, and for its diuretic action. It may be useful as an adjunctive treatment for syringomyelia in dogs. Acetazolamide’s use in small animals is complicated by a relatively high occurrence of adverse effects.
In horses, acetazolamide is used as an adjunctive treatment for hyperkalemic periodic paralysis (HYPP).
In humans, the drug has been used as adjunctive therapy for epilepsy and for acute high-altitude sickness.

Purification Methods

It is recrystallised from water. [Roblin & Clapp J Am Chem Soc 72 4890 1950, Beilstein 27 III/IV 8219.]

AcetazolamideSupplier

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