Torasemide Chemical Properties

Melting point:

163-164°C

Density 

1.283±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

DMSO: soluble18mg/mL

pka

6.44(at 25℃)

form 

solid

color 

White

Water Solubility 

Soluble

Merck 

14,9552

BCS Class

1

InChIKey

NGBFQHCMQULJNZ-UHFFFAOYSA-N

CAS DataBase Reference

56211-40-6(CAS DataBase Reference)

EPA Substance Registry System

3-Pyridinesulfonamide, N-[[(1-methylethyl)amino]carbonyl]-4-[(3-methylphenyl)amino]- (56211-40-6)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36-36/37/38

Safety Statements 

26-37/39

WGK Germany 

2

RTECS 

UT7938000

HS Code 

2935904000

MSDS

• Language:English Provider:Torasemide

Torasemide Usage And Synthesis

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 chemicalbook of Tian Ye.

Description

Torasemide is a novel loop diuretic launched in 1993 after a 12-year gap from the last diuretic introduction. It is indicated for the treatment of hypertension and edema associated with chronic congestive heart failure, renal disease and hepatic cirrhosis. Torasemide exerts its major diuretic activity on the thick ascending limb of the Henle's loop to promote rapid and marked excretion of water, Na⁺, Cl^-, and to a lesser extent,K⁺ and Ca²⁺. Compared with other loop diuretics such as furosemide, torasemide has a stronger antihypertensive action, a higher bioavailability, a longer duration of action that is independent of the renal function, and has no side effects such as paradoxical antidiuresis. The mechanism of its vasodilating effect has been suggested to result from, at least in part, the competitive antagonism of the thromboxane A2 receptor.

Chemical Properties

Crystalline Solid

Originator

Hafslund Nycomed Germany; Italy (Norway)

Uses

Torasemide is a loop diuretic. Diuretics have been abused as performance-enhancing drugs and masking agents in doping in sports. Use of torsemide is effective for the treatment of edema associated with chronic renal failure. The pharmacology of torasemide is similar to that of frusemide,though torasemide has a longer duration of action with a plasma half-life of approximately 3.5 hours. It also causes a less marked loss of potassiumand calcium.

Definition

ChEBI: Torasemide is an N-sulfonylurea obtained by formal condensation of [(3-methylphenyl)amino]pyridine-3-sulfonic acid with the free amino group of N-isopropylurea. It is a potent loop diuretic used for the treatment of hypertension and edema in patients with congestive heart failure. It has a role as a loop diuretic and an antihypertensive agent. It is a N-sulfonylurea, an aminopyridine and a secondary amino compound. It is functionally related to a 4-aminopyridine.

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.

brand name

Torasemide is INN and BAN;Unat;Toradiur.

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.

Torasemide(56211-40-6)Related Product Information

• 3-Aminobenzenesulfonamide
• Sulfuryl chloride
• Benzenesulfonamide
• 3-Aminopyridine
• Urea
• 4-Dimethylaminopyridine
• Semicarbazide
• 2-Aminopyridine
• Sulfanilamide
• p-Toluenesulfonamide
• Torasemide Impurity 3
• Torsemide Related Compound 1
• Torasemide Impurity 4
• Torasemide intermediate,4-(3-methylphenyl)amino-3-pyridine sulfonamide (intermediate of torasemide)
• TORASEMIDE ANHYDROUS
• 4-Amino-3-pyridinesulfonamide
• 4-chloroyridine-3-sulfonamide (intermediate of torasemide)
• ISO-PROPYL-D7-AMINE