Torasemide

Bezeichnung:Torasemide

CAS-Nr56211-40-6

Englisch Name:Torasemide

CBNumberCB1397929

SummenformelC16H20N4O3S

Molgewicht348.42

MOL-Datei56211-40-6.mol

Torasemide physikalisch-chemischer Eigenschaften

Schmelzpunkt	163-164°C
Dichte	1.283±0.06 g/cm3(Predicted)
storage temp.	Keep in dark place,Inert atmosphere,Room temperature
Löslichkeit	DMSO: soluble18mg/mL
pka	6.44(at 25℃)
Aggregatzustand	solid
Farbe	White
Wasserlöslichkeit	Soluble
Merck	14,9552
BCS Class	1
InChIKey	NGBFQHCMQULJNZ-UHFFFAOYSA-N
CAS Datenbank	56211-40-6(CAS DataBase Reference)
EPA chemische Informationen	3-Pyridinesulfonamide, N-[[(1-methylethyl)amino]carbonyl]-4-[(3-methylphenyl)amino]- (56211-40-6)

Sicherheit

Kennzeichnung gefährlicher	Xi
R-Sätze:	36-36/37/38
S-Sätze:	26-37/39
WGK Germany	2
RTECS-Nr.	UT7938000
HS Code	2935904000

Gefahreninformationscode (GHS)

Torasemide Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R36:Reizt die Augen.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S37/39:Bei der Arbeit geeignete Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
Beschreibung
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.
Chemische Eigenschaften
Crystalline Solid
Originator
Hafslund Nycomed Germany; Italy (Norway)
Verwenden
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.
Trademarks
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
Arzneimittelwechselwirkung
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.
Stoffwechsel
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 Upstream-Materialien And Downstream Produkte

Torasemide Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

56211-40-6, Torasemide Verwandte Suche:

Send Inquriy