Patents Assigned to Zentiva A.S.
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Patent number: 7618953Abstract: The monosodium salt of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid in new amorphous forms, methods of preparation and a pharmaceutical formulation.Type: GrantFiled: February 28, 2005Date of Patent: November 17, 2009Assignee: Zentiva, a.s.Inventors: Jindrich Richter, Josef Jirman, Hana Petrickova
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Patent number: 7619087Abstract: A method of preparation of Oxycodone of formula I by reacting thebaine of formula II, or its analogue of formula III, wherein R represents a C2 to C5 alkyl, an alkylaryl, preferably benzyl, methoxybenzyl, or allyl, with hydrogen peroxide or peroxoacids in the presence of oxalic acid in admixture with acetic or formic acid. From the resulting crystalline precipitate of 14-hydroxycodeinone oxalate, by addition of a base, 14-hydroxycodeinone of formula IV is released, which is hydrogenated with hydrogen in the presence of a catalyst to yield Oxycodone (I): Oxycodone is transformed to hydrochloride, which is used as the active ingredient in analgesic formulations.Type: GrantFiled: August 16, 2005Date of Patent: November 17, 2009Assignee: Zentiva, a.s.Inventors: Vladislav Snuparek, Lubica Ratkovska, Bohumil Proksa
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Publication number: 20090192318Abstract: From the starting 4-bromomethyl-2?-(1-triphenylmethyltetrazol-5-yl)biphenyl, N-[(2?(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester of formula 7 is obtained via a reaction with L-valine benzyl ester, and is converted to valsartan of formula I via a reaction with valeryl chloride and removing of protective groups. The method consists in converting, with hydrochloric acid, N-[(2?-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester of formula 7, obtained in the first stage, to N-[(2?-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester hydrochloride of formula III, which is optionally re-crystallized.Type: ApplicationFiled: May 14, 2004Publication date: July 30, 2009Applicant: Zentiva, A.S.Inventors: Stanislav Radl, Jan Stach, Eva Dedinova
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Patent number: 7544840Abstract: The compound of formula (III), optionally its alkaline salt, is reacted with a compound of formula VII, wherein X is a leaving group, resulting in (S)-rivastigmine of formula II, which is then optionally converted into (S)-rivastigmine hydrogentartrade of formula I.Type: GrantFiled: October 21, 2003Date of Patent: June 9, 2009Assignee: Zentiva, a.s.Inventors: Hana Stepankova, Josef Hajicek, Stanislav Simek
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Publication number: 20090143600Abstract: A method of preparation of (S)—N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (I) or its pharmaceutically acceptable salt, in which (RS)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (III) is reacted with an optically active acid, after which a crystallization is made of that diastereoisomer which yields, by reaction with an inorganic or organic base, (S)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (S)-III, which is then demethylated using alkylchloroformates, followed by a hydrolysis and optional conversion of the compound of formula (I) to its salt.Type: ApplicationFiled: October 21, 2005Publication date: June 4, 2009Applicant: ZENTIVA, A.S.Inventors: Ludek Ridvan, Petr Hruby, Lukas Placek, Miroslav Kuchar
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Patent number: 7534895Abstract: The invention solves a new method of preparation of Carvedilol for pharmaceutical use. In the synthesis of Carvedilol a reaction of 4-(oxirane-2-ylmethoxy)-9H-arbazole (II) with 2-(2-methoxyphenoxy)ethylamine salts (IV) in the presence of a base, in an alcohol having the number of carbons C2 to C5 as a solvent, at an elevated temperature, is used. After processing of the crude reaction mixture crude Carvedilol is obtained, which is purified by crystallization from ethylacetate with an addition of activated carbon and the final substance is formulated by crystallization from ethylacetate.Type: GrantFiled: November 4, 2003Date of Patent: May 19, 2009Assignee: Zentiva, A.S.Inventors: Richard Hercek, Alojz Skoda, Bohumil Proksa
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Publication number: 20080319225Abstract: A method of preparation of (R)-(?)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide of formula I and its use for production tamsulosin. A protective group is introduced to N-[(1R)-2(4-methoxyphenyl)-1-methylethyl]-N-[(1R)-1-phenylethyl)]amine and the resulting amide of formula IX is chlorosulfonated and the resulting sulfochloride is converted to a sulfonamide of formula X, from which the compound of formula I is obtained by hydrogenation.Type: ApplicationFiled: February 3, 2005Publication date: December 25, 2008Applicant: ZENTIVA, A.S.Inventors: Josef Hajicek, Marketa Slavikova
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Publication number: 20080171784Abstract: Stabilization of the pharmaceutical active solid substance atorvastatin alone or in a mixture with other solid substances embedded in a gaseous mixture is carried out in such a manner that in the surrounding gaseous mixture a partial pressure of oxygen of at most 2 kPa, preferably less than 1 kPa, more preferably less than 0.4 kPa is maintained. The corresponding partial pressure is achieved either by use of oxygen absorbers, by packaging under a pressure of 0.3-10 kPa, or by packaging under a slight overpressure of an inert gas, preferably nitrogen, the gas being introduced, by means of nozzles, into the cavities, optionally also into the space of the press roller and of the wiper station.Type: ApplicationFiled: August 5, 2004Publication date: July 17, 2008Applicant: ZENTIVA, A.S.Inventors: Pavel Sebek, Alena Prokopova, Eduard Svoboda, Stanislav Radl, Jan Stach, Martin Svoboda, Andrej Kovacik, Adrian Danko, Roman Petro, Miroslav Strizinec
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Patent number: 7282517Abstract: A method of manufacturing glimepiride of formula I wherein trans-4-methylcyclohexylamine pivalate of formula VII is reacted, either directly or after conversion to trans-4-methylcyclohexylamine or to its another salt, with an alkyl [4-(2-{[(3-ethyl-4-methyl-2-oxo-2,5-dihydro-1H-pyrrol-1 yl)carbonyl]amino)ethyl)phenyl]-sulfonyl carbamate of general formula IV wherein R is a C1-C5 alkyl, giving glimepiride of formula I, trans-4-Methylcyclohexylamine pivalate of formula VIIType: GrantFiled: February 20, 2004Date of Patent: October 16, 2007Assignee: Zentiva, a.s.Inventors: Stanislav Radl, Kamal Jarrah
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Patent number: 7276604Abstract: The present invention relates to a crystalline, hydrated form of the sodium salt of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid. The hydrate contains from 6.4 up to 22 weight % of sodium and 15 up to 23 weight % of crystalline water if the sodium content is lower than 7.5 weight %, based on the whole molecule, or 4.5 up to 18 weight % of crystalline water if the sodium content is equal to or higher than 13 weight %, based on the anhydrous substance. Due to stability in humid environments, the hydrate is useful as an active substance for the treatment of diseases associated with bone resorption disorders.Type: GrantFiled: October 21, 2003Date of Patent: October 2, 2007Assignee: Zentiva A.S.Inventors: Jindrich Richter, Josef Jirman
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Publication number: 20070155765Abstract: A method of preparation of the hemi-calcium salt of rosuvastatin of formula (I) consists in extracting an aqueous solution of the sodium or potassium salt of (E)-7-[4-(4-fluorophenyl)-6isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxy-6-heptenoic acid, with optional admixture of sodium or potassium hydroxide or other sodium or potassium salts having inorganic anions, with an organic solvent, incompletely miscible with water, selected from the series of R1COOR2, R1COR2 and R1OH, wherein R1 and R2 independently represent hydrogen or a residue of a C1-C10 aliphatic hydrocarbon, C6 aromatic hydrocarbon, C5 or C6cyclic hydrocarbon, or a combination of an aliphatic and aromatic or cyclic hydrocarbon, the extract being subsequently shaken with an aqueous solution of an inorganic or C1-C5 organic calcium salt, and the product of formula I is further isolated by cooling and/or adding an anti-solvent and filtration, and optionally, is converted into its amorphous form.Type: ApplicationFiled: December 17, 2004Publication date: July 5, 2007Applicant: Zentiva, A.S.Inventors: Pavel Sebek, Stanislav Radl, Jan Stach
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Publication number: 20070142332Abstract: The monosodium salt of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid in new amorphous forms, methods of preparation and a pharmaceutical formulation.Type: ApplicationFiled: February 28, 2005Publication date: June 21, 2007Applicant: ZENTIVA , A.S.Inventors: Jindrich Richter, Josef Jirman, Hana Petrichova
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Patent number: 7208608Abstract: A method of manufacturing an amorphous form of the hemi-calcium salt of (3R, 5R) 7-[3-phenyl-4-phenylcarbamoyl-2-(4-fluorophenyl)-5-isopropyl-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid of formula (I), in which (3R, 5R) 7-[3-phenyl-4-phenylcarbamoyl-2-(4-fluorophenyl)-5-isopropyl-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid or its salt with a cation M+ wherein M30 is either a cation of an alkali metal or an ammonium cation of formula RnN(+)H(4?n) wherein R is lower C1–C5 alkyl, n may reach values ranging between 0 and 3, is, without isolating the intermediate in the form of the hemi-calcium salt or of another salt, acid or lactone, converted, in a solution, by the treatment with the calcium salt or calcium hydroxide, or a calcium C1–C5 alcoholate, to the hemi-calcium salt, and the latter is precipitated with a C1–C5hydrocarbon or dialkylether of formula R1OR2, wherein each of R1 and R2 is a C1–C5 alkyl group.Type: GrantFiled: January 30, 2003Date of Patent: April 24, 2007Assignee: Zentiva A. S.Inventors: Stanislav Radl, Jan Stach
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Publication number: 20070088162Abstract: A method of preparation of Oxycodone of formula I by reacting thebaine of formula II, or its analogue of formula III, wherein R represents a C2 to C5 alkyl, an alkylaryl, preferably benzyl, methoxybenzyl, or allyl, with hydrogen peroxide or peroxoacids in the presence of oxalic acid in admixture with acetic or formic acid. From the resulting crystalline precipitate of 14-hydroxycodeinone oxalate, by addition of a base, 14-hydroxycodeinone of formula IV is released, which is hydrogenated with hydrogen in the presence of a catalyst to yield Oxycodone (I): Oxycodone is transformed to hydrochloride, which is used as the active ingredient in analgesic formulations.Type: ApplicationFiled: August 16, 2005Publication date: April 19, 2007Applicant: ZENTIVA, A.S.Inventors: Vladislav Snuparek, Lubica Ratkovska, Bohumil Proksa
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Patent number: 7198802Abstract: A tablet, obtainable by direct comprising the active ingredient 4-amino-1-hydroxybutylidene-1,1-bis-phosphonic (alendronic) acid or its pharmaceutically acceptable salts in an amount of 5 to 140 mg, based on the pure acid, a dry binder, a disintegrating agent, a lubricant, the tablet comprising, as the diluent, a combination of at least two diluents except lactose.Type: GrantFiled: June 29, 2001Date of Patent: April 3, 2007Assignee: Zentiva A.S.Inventor: Dagmar Jasprova
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Publication number: 20060167077Abstract: The invention solves a new method of preparation of Carvedilol for pharmaceutical use. In the synthesis of Carvedilol a reaction of 4-(oxirane-2-ylmethoxy)-9H-arbazole (II) with 2-(2-methoxyphenoxy)ethylamine salts (IV) in the presence of a base, in an alcohol having the number of carbons C2 to C5 as a solvent, at an elevated temperature, is used. After processing of the crude reaction mixture crude Carvedilol is obtained, which is purified by crystallization from ethylacetate with an addition of activated carbon and the final substance is formulated by crystallization from ethylacetate.Type: ApplicationFiled: November 4, 2003Publication date: July 27, 2006Applicant: ZENTIVA, A.S.Inventors: Richard Hercek, Alojz Skoda, Bohumil Proksa
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Publication number: 20060148762Abstract: The present invention relates to a crystalline, hydrated form of the sodium salt of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid. The hydrate contains from 6.4 up to 22 weight % of sodium and 15 up to 23 weight % of crystalline water if the sodium content is lower than 7.5 weight %, based on the whole molecule, or 4.5 up to 18 weight % of crystalline water if the sodium content is equal to or higher than 13 weight %, based on the anhydrous substance. Due to stability in humid environments, the hydrate is useful as an active substance for the treatment of diseases associated with bone resorption disorders.Type: ApplicationFiled: October 21, 2003Publication date: July 6, 2006Applicant: Zentiva, A.S.Inventors: Jindrich Richter, Josef Jirman
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Publication number: 20060122417Abstract: The compound of formula (III), optionally its alkaline salt, is reacted with a compound of formula VII, wherein X is a leaving group, resulting in (S)-rivastigmine of formula II, which is then optionally converted into (S)-rivastigmine hydrogentartrade of formula I.Type: ApplicationFiled: October 21, 2003Publication date: June 8, 2006Applicant: ZENTIVA, A.S.Inventors: Hana Stepankova, Josef Hajicek, Stanislav Simek
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Patent number: 7009057Abstract: A method for obtaining antidiabetic of formula (I), wherein the method comprises condensing of a 4-derivatized phenol or phenolate of general formula (II), wherein R is an amino group-containing organic residue, selected from the group comprising a residue of the following formula —NHR3, wherein R3 is hydrogen or a protecting group, which is removed before further treatment, and a residue of general formula (A), wherein Rb represents a carboxy group either in the free acid form or in the form of a salt or ester or another functional derivative or the nitrile group CN, and M represents a hydrogen or alkali metal atom, with a pyridine base of general formula (III, wherein Z is a leaving group other than a halogen, wherein, before or after carrying out the condensation, the following operations are carried out: (a) diazotizing the amino group present in organic residue R; (b) converting the diazotised residue R into a derivative of 2-halopropionate or 2-halopropionitrile of formula (B), wherein Rb is as definedType: GrantFiled: April 25, 2002Date of Patent: March 7, 2006Assignee: Zentiva A.S.Inventors: Ale{hacek over (s)} Halama, Ludmila Hejtmánková, Petr Lustig, Jind{hacek over (r)}ich Richter, Lucie Sr{hacek over (sn)}ová, Josef Jirman
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Publication number: 20060041136Abstract: A method for manufacturing hydrogen sulphate (alpha S) of the alpha-(2-chlorophenyl)-6,7dihydrothieno[3,2-c]pyridine-5(4H)-acetic acid methyl ester (clopidogrel hydrogen sulphate) of formula I, in crystalline Form I, wherein the compound of formula is separated out of a solution of clopidogrel in the form of the free base or salt in a solvent selected from the series of primary, secondary or tertiary C1-C5 alcohols, their esters with C1-C4 carboxylic acids, or optionally of mixtures thereof.Type: ApplicationFiled: August 26, 2003Publication date: February 23, 2006Applicant: Zentiva, A.S.Inventors: Miroshlav Veverka, Stefan Vodny, Eva Veverkova, Josef Hajicek, Hana Stepankova