59-66-5 Usage
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
Chemical Properties
White Solid
Originator
Diamox ,Lederle,US ,1953
Uses
Different sources of media describe the Uses of 59-66-5 differently. You can refer to the following data:
1. 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.
2. carbonic anhydrase inhibitor, diuretic, antiglaucoma
3. 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.
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 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.
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.
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.
Purification Methods
It is recrystallised from water. [Roblin & Clapp J Am Chem Soc 72 4890 1950, Beilstein 27 III/IV 8219.]
Check Digit Verification of cas no
The CAS Registry Mumber 59-66-5 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 9 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 59-66:
(4*5)+(3*9)+(2*6)+(1*6)=65
65 % 10 = 5
So 59-66-5 is a valid CAS Registry Number.
InChI:InChI=1/C4H6N4O3S2/c1-2(9)6-3-7-8-4(12-3)13(5,10)11/h1H3,(H2,5,10,11)(H,6,7,9)
59-66-5Relevant articles and documents
Visible Light-Induced Amide Bond Formation
Song, Wangze,Dong, Kun,Li, Ming
supporting information, p. 371 - 375 (2019/11/29)
A metal-, base-, and additive-free amide bond formation reaction was developed under an organic photoredox catalyst. This green approach showed excellent functional selectivity without affecting other functional groups such as alcohols, phenols, ethers, esters, halogens, or heterocycles. This method featured a broad substrate scope, good compatibility with water and air, and high yields (≤95%). The potential utilities were demonstrated by the synthesis of important drug molecules such as paracetamol, melatonin, moclobemide, and acetazolamide.
Preparation process for intermediate of acetazolamide
-
Paragraph 0052; 0053, (2017/09/13)
The invention especially relates to a preparation process for an intermediate of acetazolamide, belonging to the field of medicine synthesis. The process comprises the following steps: with thiosemicarbazide and carbon disulfide as reactants and a mixture of pyridine and piperidine as a solvent, carrying out a reaction; and then successively carrying out purification and drying so as to obtain 2-amino-5-mercapto-1,3,4-thiadiazole, i.e., the intermediate of acetazolamide.
Compositions and methods for the suppression of carbonic anhydrase activity
-
Page/Page column 27; 28, (2016/04/05)
The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for treating or preventing or modulating carbonic anhydrase activity in a disease may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of glaucoma, epileptic seizures, Idiopathic intracranial hypertension (pseudotumor cerebri), altitude sickness, cystinuria, periodic paralysis and dural ectasia, congestive heart failure, drug induced edema, diuretic, intermittent claudication resulting from obstructed arteries in the limbs, and vascular dementia.
Key intermediate aqiang 2-acetyl-5-chlorosulfonyl -1, 3, 4-thiadiazole method for preparing the non-chlorine (by machine translation)
-
Paragraph 0037, (2017/01/02)
The invention discloses a preparation method of non-chlorine gas of acetazolamide key intermediate 2-acetamido-5-chlorosulfonyl-1, 3, 4-thiadiazole. The preparation method comprises the steps of firstly adding hydrochloric acid into a reactor and then dropwise adding hydrogen peroxide to perform reaction so as to obtain a reaction solution; adding 2-acetamido-5-sulfydryl-1, 3, 4-thiadiazole into the obtained reaction solution in batch to perform reaction and obtaining a reactant after reaction is completed; directly conducting suction filtration, washing and drying on the reactant and performing drying to obtain the intermediate 2-acetamido-5-chlorosulfonyl-1, 3, 4-thiadiazole. The preparation method is more moderate in operate and more environment-friendly, and the obtained intermediate 2-acetamido-5-chlorosulfonyl-1, 3, 4-thiadiazole is good in color and luster and high in purity.
COMPOSITIONS AND METHODS FOR SUPPRESSION OF CARBONIC ANHYDRASE ACTIVITY
-
Paragraph 0098; 0099, (2013/12/03)
Provided are the compounds of formula (I) or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula (I), and methods for treating or preventing or modulating carbonic anhydrase activity in a disease may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral admimstration, syrup, or injection. Such compositions may be used to treatment of glaucoma, epileptic seizures, Idiopathic intracranial hypertension (pseudotumor cerebri), altitude sickness, cystinuria, periodic paralysis and dural ectasia, congestive heart failure, drug induced edema, diuretic, intermittent claudication resulting from obstructed arteries in the limbs, and vascular dementia.
Preparation of sulfonamides from N-silylamines
Naredla, Rajasekhar Reddy,Klumpp, Douglas A.
supporting information, p. 5945 - 5947 (2013/10/22)
Sulfonamides have been prepared in high yields by the reactions of N-silylamines with sulfonyl chlorides and fluorides. In a competition experiment, the sulfonyl chlorides were found to be far more reactive than sulfonyl fluorides. The chemistry may be used to prepare aliphatic, aromatic, tertiary, secondary, and primary sulfonamides. It may also be done in the absence of solvent and the byproduct trimethylsilyl chloride recovered in good yield. Primary sulfonamides were synthesized from the sulfonyl chloride with aminotriphenyl silane (Ph3SiNH2), a conversion demonstrated with the synthesis of the carbonic anhydrase inhibitor, acetazolamide.
Synthesis and hydrolysis kinetic study of few co-drugs of propranolol and other antihypertensive drugs
Baidya, Mayukh,Das, Amit Kumar
body text, p. 173 - 178 (2012/01/13)
The different acyl halide analogs of propranolol were synthesized by reacting Propanolol with different acyl anhydrides in toluene medium. The derivatives were reacted with thionyl chloride to get propranolol hemi acyl chloride. Finally the co-drugs were synthesized by reacting propranolol hemi acyl chloride with different classes of antihypertensive drugs like Nifedepine (PSN,PMN,PPN), Hydrochlorthiazide (PSH, PMH, PPH) and Acetazolamide(PSA, PMA, PPA) by ester linkage. The structure of the synthesized derivative of propranolol analogs were confirmed by M P, TLC, IR and NMR data.
GIAO/DFT 13C NMR Chemical Shifts of 1,3,4-thiadiazoles
Loghmani-Khouzani, Hossein,Rauckyte, Teresa,Osmialowski, Borys,Gawinecki, Ryszard,Kolehmainen, Erkki
, p. 2217 - 2225 (2008/02/10)
1H, 13C and 15N NMR spectra of 2-acetylamino-1,3,4-thiadiazole and its 5-substituted derivatives have been measured and assigned based on reference data, as well as homo- and heteronuclear 2 D NMR experiments. In addition, the GIAO/DFT approach at the B3LYP level of theory using the 6-311G basis set was used to calculate the 13C NMR chemical shifts. Although this method gives reliable results for 2-arylhydrazones of 1,3-diphenylpropanetrione, 2-phenacylpyridines, (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines, 4-fluoroanilines, (1Z,3Z)-1,4-di(pyridin-2-yl)buta-1,3-dienediols and their tautomeric forms, the calculated chemical shifts for the 1,3,4-thiadiazoles studied are less satisfactory. Presence of the sulfur atom(s) seems to be responsible for such behavior.
Synthesis of certain diarylsulfonylureas as antitumor agents
Youssef,Al-Abdullah,El-Khamees
, p. 404 - 418 (2007/10/03)
A new series of N-aryl-N′-heteroaryl or N,N′-diheteroaryl sulfonylurea or sulfonylthiourea was synthesized and screened for their antitumor activity at the National Cancer Institute (NCI). N-(3-Chlorophenyl)-N′-(6-methyl-uracil-2-sulfonyl)urea (28) with GI50, TGI, LC50 (MG-MID) values of 66.1, 83.2, 93.3 μM, respectively is the most active compound in this study. It showed a remarkable activity more than sulofenur against HL-60 (TB) and RPMI-8226 leukemia, HOP-92 Non small lung cancer, KM12 colon cancer, SF-295 CNS cancer, PC-3 prostate cancer, OVCAR-4 Ovarian cancer, CAKI-1 and UO-31 Renal cancer, and MDA-MB-435 Breast cancer with GI50 values of 0.3, 2.7, 6.9, 14.7, 8.2, 9.3, 2.0, 2.1, 3.4, 11.3 μM, respectively.
Process and device for producing liquid dosage formulations of medicinal compounds on demand from tablets and capsules
-
, (2008/06/13)
The present invention provides a process for preparing liquid pharmaceutical formulations on demand from tablets and capsules.
