- Method for the Preparation of Crystal Forms of Torsemide in a Pure State
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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.
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- METHOD FOR THE PREPARATION OF CRYSTAL FORMS OF TORSEMIDE IN A PURE STATE
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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.
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Page/Page column 7
(2008/06/13)
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- Process for the preparation of torsemide and related intermediates
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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.
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Page/Page column 3
(2008/06/13)
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- Process for the synthesis of torsemide, in particular of pure and stable form II
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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.
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- Process for the synthesis of torsemide, in particular of pure and stable form II
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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.
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- PREPARATION OF TORASEMIDE
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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.
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- PROCESS FOR THE PREPARATION OF MODIFICATION I OF N-(1-METHYLETHYLAMINOCARBONYL)-4-(3-METHYLPHENYLAMINO)-3-PYRIDINESULFONAMIDE
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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.
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- PROCESS FOR THE PREPARATION OF HIGHLY PURE TORSEMIDE
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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.
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Page/Page column 35
(2010/02/07)
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- Crystal modification of torasemide
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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.
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- Torsemide polymorphs
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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.
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- Design, synthesis and biological activity of a series of torasemide derivatives, potent blockers of the Na+ 2Cl- K+ co-transporter: In-vitro study
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Pharmacomodulation of the torasemide molecule, a loop diuretic inhibiting Na+ 2Cl- K+ co-transport in the thick ascending limb of the loop of Henle has been performed in order to obtain new long-acting diuretics. The aim of this study was to decrease the metabolism of the drug and to slow down its rate of excretion by increasing its hydrophobicity. The present study describes the synthesis and the inhibitory potency of new torasemide derivatives in the bioassay system of the cortical thick ascending limb of rabbit. A correlation between the lipophilicity (log P') of these substances and their activity as inhibitors of the Na+ Cl- K+ co-transporter was observed. The present design led to compounds more active than torasemide. Structure-activity relationships permit us to propose an interaction model between torasemide derivatives and the Na+ 2Cl- K+ co-transport system of the cortical thick ascending limb.
- Masereel,Lohrmann,Schynts,Pirotte,Greger,Delarge
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p. 589 - 593
(2007/10/02)
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- Chemistry and pharmacological properties of the pyridine-3-sulfonylurea derivative torasemide.
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Out of a series of pyridine-3-sulfonylureas with diuretic activity torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) has been proved to be one of the most active derivatives. In the rat, urinary volume and electrolyte excretions increased linearily with the logarithm of the dose, thus resembling the profile of a high ceiling diuretic. Experiments by oral and intravenous routes indicated that torasemide was equally potent both by oral and parenteral administration. Compared to furosemide, torasemide was 9-40 times more potent on weight basis in the rat. For the same natriuretic effect, however, potassium losses with torasemide were significantly less than with furosemide. The diuretic effect of torasemide lasted longer compared to that of furosemide. In accordance with the pharmacodynamic characteristics plasma elimination half-life of torasemide was about 1.5 h in the rat and bioavailability was nearly complete. Torasemide was 98-99% bound to plasma proteins. No in vitro interaction was found with the cumarine derivative warfarin.
- Delarge
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p. 144 - 150
(2007/10/02)
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