56211-40-6 Usage
Uses
Used in Pharmaceutical Industry:
Torasemide is used as a diuretic for the treatment of hypertension and edema associated with chronic congestive heart failure, renal disease, and hepatic cirrhosis. Its strong antihypertensive action, higher bioavailability, and longer duration of action make it a preferred choice in managing these conditions.
Used in Research and Forensic Applications:
Torasemide is used as an analytical reference standard in research and forensic applications, particularly in the study of diuretic abuse as performance-enhancing drugs and masking agents in sports doping.
Diuretics
Diuretics are drugs mainly acting on the kidneys to increase the excretion of water and electrolytes, and increase urine output. Their potency can be divided into:
1. potent diuretics (loop diuretics): including furosemide, bumetanide, ethacrynic acid.
2. Middle efficiency diuretics include: thiazide diuretics, such as hydrochlorothiazide, bendroflumethiazide and so on.
3. Inefficient diuretics include: retention of potassium diuretics spironolactone, triamterene and carbonic anhydrase inhibitor acetazolamide and the like.
Potent diuretics effect on medullary loop ramus crude segment medulla,they inhibit reabsorption of active chlorine, followed by inhibiting sodium reabsorption, and play a strong diuretic effect.
Torasemide is a potent diuretic, its mechanism of action is similar to furosemide, it has no effect on the proximal tubules, it does not cause an increase in the discharge of potassium. This product increase renal volume and sodium excretion is dose-dependent , it does not affect the calcium and potassium excretion, excretion and metabolism have no association with renal function, large doses have no significant toxicity. Sort diuretic strength by: bumetanide> torasemide> piretanide> furosemide. It is useful in the treatment of acute and chronic renal failure and essential hypertension. Adverse reactions of torasemide are similar to furosemide ,common adverse reactions are headache, dizziness, weakness, nausea, muscle spasms, but it produces lesser extent of potassium loss ,it has no effect on uric acid, blood glucose and lipid .
The above information is edited by the lookchem of Tian Ye.
Originator
Hafslund Nycomed
Germany; Italy (Norway)
Manufacturing Process
In a 100 ml three-necked flask equipped with magnetic stirrer, condenser,
thermometer and dropping funnel 3-sulfonylchloride-4-chloropyridine (10 g, 1
eq., 46.7 mmoles) was suspended in t-butyl-methyl ether (MTBE) (30 ml) at
room temperature. Ammonium hydroxide, 25% solution (13.5 ml, 2.13 eq.)
was dropped into the suspension in a rate such that the temperature is
allowed to increase to 22°-26°C, this temperature was maintained until all the
ammonium hydroxide was added. The suspension was then to cooled to room
temperature and was stirred for 1 h. The pH of the suspension was adjusted
to 80.1 by the addition of a few drops of ammonium hydroxide, 25% solution.
The suspension was filtered and washed with water (2 times 10 ml) and the
wet product (8 g) dried at 40°C, under the 1 mm Hg vacuum. 3-Sulfonamide-
4-chloropyridine was isolated in 74.4% yield, 6.7 g.
A mixture of 0.01 moles of 3-sulfonamido-4-chloropyridine, 0.02 mole of 3-
methylbenzylamine and 50 ml of dry ethanol was heated to reflux
temperature for 9 h. After distillation of the ethanol the residue was taken up
in an excess of diluted NaOH and the excess of amine was extracted by
means of ether.
The aqueous solution was then decolourized with charcoal and filtered, and
the filtrate was neutralized with acetic acid. The precipitated product was
separated and purified by crystallization from a mixture of water and acetone.The 3-sulfonamido-4-(3-methylbenzyl)amino-pyridine crystallized in the form
of beige coloured cristals having a melting point of 184°-186°C.
0.01 mole of 3-sulfonamido-4-(3-methylbenzyl)amino-pyridine was reacted
with 0.015 mole of isopropylisocyanate in the presence of 0.02 mole of
triethylamine and of 20 ml of dichloromethane, at room temperature for 20 h.
After evaporation under vacuum, the residue was taken up in an excess of
diluted Na2CO3, filtered off and acidified by means of acetic acid. After
precipitation of the product it was filtered and washed several times with ice
cold water. The 3-isopropylcarbamoylsulfonamido-4-(3-methylbenzyl)amino_x0002_pyridine (Torsemide) showing as a white powder, has a melting point of 147°-
149°C.
Therapeutic Function
Diuretic
Biochem/physiol Actions
Torsemide is a loop diuretic of the pyridine-sulfonylurea class with antialdosteronergic properties and inhibitor of the Na+/K+/2Cl- carrier system.
Clinical Use
Loop diuretic: Hypertension Oedema
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
concomitant use 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 (avoid
with pimozide) if hypokalaemia occurs; enhanced
hypotensive effect with phenothiazines.
Atomoxetine: hypokalaemia increases risk of
ventricular arrhythmias.
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
Torasemide is metabolised by the cytochrome P450 isoenzyme CYP2C9 to three inactive metabolites, M1, M3 and M5 by stepwise oxidation, hydroxylation or ring hydroxylation. The inactive metabolites are excreted in the urine.
Check Digit Verification of cas no
The CAS Registry Mumber 56211-40-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,6,2,1 and 1 respectively; the second part has 2 digits, 4 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 56211-40:
(7*5)+(6*6)+(5*2)+(4*1)+(3*1)+(2*4)+(1*0)=96
96 % 10 = 6
So 56211-40-6 is a valid CAS Registry Number.
InChI:InChI=1/C16H20N4O3S/c1-12(2)10-18-16(21)20-24(22,23)15-11-17-9-8-14(15)19-13-6-4-3-5-7-13/h3-9,11-12H,10H2,1-2H3,(H,17,19)(H2,18,20,21)
56211-40-6Relevant articles and documents
Method for the Preparation of Crystal Forms of Torsemide in a Pure State
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, (2008/06/13)
A method for the preparation of crystal form 1 of polymorphous crystalline torsemide, wherein torsemide is dissolved in an ethanol-water mixture with heating, after which the torsemide is subsequently cooled and dried once crystal separation has been performed. Drying takes place in a blade drier, for example, with the crystals being subjected to mechanical stress, wherein the crystals of crystalline form 2 are transformed into crystalline form 1.
METHOD FOR THE PREPARATION OF CRYSTAL FORMS OF TORSEMIDE IN A PURE STATE
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Page/Page column 7, (2008/06/13)
A method for the preparation of crystal form 1 of polymorphous crystalline torsemide, wherein torsemide is dissolved in an ethanol-water mixture with heating, after which the torsemide is subsequently cooled and dried once crystal separation has been performed. Drying takes place in a blade drier, for example, with the crystals being subjected to mechanical stress, wherein the crystals of crystalline form 2 are transformed into crystalline form 1.
Process for the preparation of torsemide and related intermediates
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Page/Page column 3, (2008/06/13)
A process for preparing torsemide or salts thereof comprising: a) reacting II with isopropyl isocyanate in the presence of an alkali carbonate or bicarbonate and an organic solvent to form an alkali torsemide mixture, b) recovering the alkali torsemide mixture, and c) if desired, recovering the torsemide by acidification of the alkali torsemide mixture.
PROCESS FOR THE PREPARATION OF MODIFICATION I OF N-(1-METHYLETHYLAMINOCARBONYL)-4-(3-METHYLPHENYLAMINO)-3-PYRIDINESULFONAMIDE
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Page 5-6, (2008/06/13)
The invention relates to a new process for the preparation of modification I of torasemide by precipitation with acids from an alkaline extract of the original reaction mixture of the last phase in the synthesis of torasemide.
Process for the synthesis of torsemide, in particular of pure and stable form II
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Page 4, (2008/06/13)
The present invention relates to a new process for the synthesis of torsemide, in particular of pure and stable form II, which comprises direct synthesis of torsemide from 4-(3-methylphenylamino)-3-pyridine-sulphonamide. The new process envisages fewer steps than the processes described in the prior art, with improved yields and good quality from the chemical and preferably polymorphous points of view.
Process for the synthesis of torsemide, in particular of pure and stable form II
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Page 7, (2010/02/07)
The present invention relates to a new process for the synthesis of torsemide, in particular of pure and stable form II, which comprises direct synthesis of torsemide from 4-(3-methylphenylamino)-3-pyridine-sulphonamide. The new process envisages fewer steps than the processes described in the prior art, with improved yields and good quality from the chemical and preferably polymorphous points of view.
PREPARATION OF TORASEMIDE
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Page 9, (2010/02/09)
The stable polymorphic form of torasemide, Modification I, is prepared from other, less stable torasemide forms, by forming a solution of the starting polymorphic form of torasemide in water and methanol, stirring for at least 20 hours and then phase separating the solid torasemide modification I from the liquid medium.
PROCESS FOR THE PREPARATION OF HIGHLY PURE TORSEMIDE
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Page/Page column 46-47, (2010/02/07)
The present invention provides a novel process for the preparation of highly pure torsemide [1] by reacting of 4-m-tolylamino-3-pyridinesulfonamide [2] with phenyl isopropylcarbamate in the presence of lithium base (F I, II). The present invention also provides a novel intermediate - torsemide lithium, also in hydrate or solvate form - which is a stable, solid compound, and may be simply isolated from the reaction mixture to give after acidification practically pure torsemide [1] without further purification steps.
Crystal modification of torasemide
-
, (2008/06/13)
The present invention relates to the characterization of a new crystal modification III of torasemide, to a process for the preparation thereof by the use of controlled acidifying of alkaline solutions of torasemide with inorganic or organic acids with or without addition of a crystal seed, to its use a raw material for the preparation of the crystal modification I of torasemide and of pharmaceutically acceptable salts of torasemide as well as to pharmaceutical forms containing this new crystal modification III of torasemide.
Torsemide polymorphs
-
, (2008/06/13)
The present invention is directed to the novel forms of torsemide, designated Form V, amorphous torsemide, Dupont Form 2 solvent adduct, Dupont Form 2 ethanol adduct and Dupont Form 2 isopropanol adduct. Methods for their preparation are also disclosed. The present invention also relates to processes for making torsemide modification I. Pharmaceutical compositions containing the new forms of torsemide and methods of using them are also disclosed.
