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41. 发明专利

MX2007011255A CLOHIDRATO DE DULOXETINA PURO. 未知
公开(公告)号：MX2007011255A
公开(公告)日：2007-10-18
申请号：MX2007011255
申请日：2006-03-14
申请人： TEVA PHARMA
发明人： INI SANTIAGO , LIBERMAN ANITA , ABRAMOV MILI
IPC分类号： C07D333/22 , A61K31/38 , A61P13/00 , A61P25/24 , A61P29/00
摘要： Se proporcionan HC1 de duloxetina quimica y/o enantiomericamente pura y procesos para preparar HC1 de duloxetina quimica y/o enantiomericamente pura (ver Formula I).

42. 发明专利

DE69929462T2 未知
公开(公告)号：DE69929462T2
公开(公告)日：2006-09-07
申请号：DE69929462
申请日：1999-11-24
申请人： TEVA PHARMA
发明人： SCHWARTZ EDUARD , NIDAM TAMAR , LIBERMAN ANITA , MENDELOVICI MARIOARA , ARONHIME JEHUDIT , SINGER CLAUDE , VALDMAN EVGENI
IPC分类号： A61P25/22 , C07C1/00 , A61K31/137 , A61P25/24 , C07C209/84 , C07C209/90 , C07C211/42

43. 发明专利

YU61602A POSTUPAK ZA DOBIJANJE LEFLUNOMIDA 未知
公开(公告)号：YU61602A
公开(公告)日：2006-01-16
申请号：YUP61602
申请日：2001-02-08
申请人： TEVA PHARMA
发明人： AVRUTOV ILYA , GERSHON NEOMI , LIBERMAN ANITA
IPC分类号： A61K31/42 , A61P3/10 , A61P11/02 , A61P11/06 , A61P17/06 , A61P27/02 , A61P29/00 , A61P35/00 , A61P37/06 , C07D261/18
摘要： Obezbeđen je postupak za sintezu lefluonomida iz 5-metilizoksazol-4-karboksilne kiseline i 4-trifluorometilanilina. Dalje je obezbeđen leflunomid pripremljen inventivnim postupkom, koji je gotovo potpuno bez nečistoća koje je teško izdvojiti, koje se obično nalaze u leflunomidu pripremljenom poznatim metodama, uključujući N-(4-trifluorometilfenil)-2-cijano-3-hidroksikrotonamid, 5-metil-N-(4-metilfenil)-izoksazol-4-karboksamid i N-(4-trifluorometilfenil)-3-metil-izoksazol-4-karboksamida. Pronalazak dalje obezbeđuje farmaceutske preparate i dozne oblike koji sadrže leflunomid visoke čistoće i metode tretiranja bolesti korišćenjem leflunomida.[A process for synthesizing leflunomide from 5-methylisoxazole-4-carboxylic acid and 4-trifluoromethylaniline is provided. Further provided is the leflunomide prepared by the inventive process, which is substantially free of difficult-to-separate impurities often found in leflunomide prepared by known methods, including N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide, 5-methyl-N-(4- methylphenyl)-isoxazole-4-carboxamide and N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4-carboxamide. The invention further provides pharmaceutical compositions and dosage forms containing highly pure leflunomide and methods of treating disease using the leflunomide.

44. 发明专利

AU2005201117A1 Novel synthesis and crystallization of piperazine ring-containing compounds 未知
公开(公告)号：AU2005201117A1
公开(公告)日：2005-04-07
申请号：AU2005201117
申请日：2005-03-15
申请人： TEVA PHARMA
发明人： FINKELSTEIN NINA , SINGER CLAUDE , LIBERMAN ANITA
IPC分类号： A61K31/55 , A61P25/24 , C07D401/04 , C07D487/12

45. 发明专利

PL366289A1 NOVEL SYNTHESIS AND CRYSTALLIZATION OF PIPERAZINE RING-CONTAINING COMPOUNDS 未知
公开(公告)号：PL366289A1
公开(公告)日：2005-01-24
申请号：PL36628900
申请日：2000-04-18
申请人： TEVA PHARMA
发明人： SINGER CLAUDE , LIBERMAN ANITA , FINKELSTEIN NINA
IPC分类号： A61K31/55 , A61P25/24 , C07D401/04 , C07D471/14
摘要： The present invention is directed to methods for the preparation of piperazine ring-containing compounds, particularly mirtazapine. According to the present invention, the mirtazapine intermediate 1-(3-carboxypyridyl-2)-4-methyl-2-phenyl-piperazine is made by hydrolyzing 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine with a base where the base is present in a ratio of up to about 12 moles of the base per one mole of 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine. The mirtazapine intermediate 1-(3-carboxypyridly-2)-4-methyl-2-phenyl-piperazine may be made by hydrolyzing 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine with potassium hydroxide at a temperature of at least about 130 DEG C. The method of the present invention also includes reacting 2-amino-3-hydroxymethyl pyridine with N-methyl-1-phenyl-2, 2'-iminodiethyl chloride to form 1-(3-hydroxymethylpyridyl-2)-4-methyl-2-phenyl piperazine, and adding sulfuric acid to the 1-(3-hydroxymethylpyridyl-2)-phenyl-4-methylpiperazine to form mirtazapine. The present invention also relates to new processes for recrystallization of mirtazapine form crude mirtazapine.

46. 发明专利

HRP20040630A2 A NOVEL POLYMORPH OF SERTRALINE HYDROCHLORIDE AND COMPOSITION CONTAINING THEREOF, NOVEL METHODS FOR PREPARATION OF SERTRALINE HYDROCHLORIDE POLYMORPHS AND AMORPHOUS FORM 未知
公开(公告)号：HRP20040630A2
公开(公告)日：2004-10-31
申请号：HRP20040630
申请日：2004-07-12
申请人： TEVA PHARMA
发明人： ARONHIME JUDITH , LIBERMAN ANITA , VALDMAN EVGENI , NIDAM TAMAR , MENDELOVICI MARIOARA , SINGER CLAUDE , SCHWARTZ EDUARD
IPC分类号： A61P25/24 , A61K31/13 , A61P25/28 , C07C20060101 , C07C209/82 , C07C209/84 , C07C211/00 , C07C211/42
摘要： The present invention is directed to forms II, III, V, VI, VII, VIII, IX and X of sertraline hydrochloride and novel methods for their preparation. According to the present invention, sertraline hydrochloride polymorph II may be produced by slurrying sertraline hydrochloride polymorph VI in aprotic organic solvent. Sertraline hydrochloride polymorphic form III may be produced by heating sertraline hydrochloride polymorphs V and VI. Sertraline hydrochloride forms V and VI may be produced from either sertraline hydrochloride or sertraline base by crystallization. Sertraline hydrochloride Form VII may be produced by suspending sertraline hydrochloride polymorph V in water, followed by filtration. Sertraline hydrochloride Forms VIII and IX may be produced by suspending sertraline base in water followed by acidification and filtration. Sertraline hydrochloride Form X may be produced by suspending sertraline hydrochloride in benzyl alcohol with heating, followed by filtration.

47. 发明专利

YU74101A NOVA SINTEZA I KRISTALIZACIJA JEDINJENJA KOJA SADRŽE PRSTEN PIPERAZINA 未知
公开(公告)号：YU74101A
公开(公告)日：2004-09-03
申请号：YUP74101
申请日：2000-04-18
申请人： TEVA PHARMA
发明人： SINGER CLAUDE , LIBERMAN ANITA , FINKELSTEIN NINA
IPC分类号： A61K31/55 , A61P25/24 , C07D401/04 , C07D471/14
摘要： Predmetni pronalazak je usmeren na postupke za pripremanje jedinjenja koja sadrže prsten piperazina, a posebno na mirtazapin. Prema predmetnom pronalasku, intermedijer mirtazapina, 1-(3-karboksipiridil-2)-4-metil-2-fenil-piperazin se dobija hidrolizom 1-(3-cijanopiridil-2)-4-metil-2-fenil-piperazina pomoću baze, pri čemu je baza prisutna u odnosu koji se kreće do oko 12 molova baze na jedan mol 1-(3-cijanopiridil-2)-4-metil-2-fenil-piperazina. Intermedijer mirtazapina, 1-(3-karboksipiridil-2)-4-metil-2-fenil-piperazin, može se dobiti hidrolizom 1-(3-cijanopiridil-2)-4-metil-2-fenil-piperazina pomoću kalijum-hidroksida pri temperaturi od oko bar 130В°C. Postupak predmetnog pronalaska takodje obuhvata reakciju 2-amino-3-hidroksimetil piridina sa N-metil-1-fenil-2,2'-iminodietil hloridom, kako bi se dobio 1-(3-hidroksimetilpiridil-2)-4-metil-2-fenil piperazin, kao i dodavanje sumporne kiseline 1-(3-hidroksimetilpiridil-2)-4-metil-2-fenil piperazinu, kako bi se dobio mirtazapin. Predmetni pronalazak se takodje odnosi na nove postupke za rekristalizaciju mirtazapina iz sirovog mirtazapina.

48. 发明专利

HU0301865A2 A METHOD FOR SYNTHESIZING LEFLUNOMIDE 未知
公开(公告)号：HU0301865A2
公开(公告)日：2003-09-29
申请号：HU0301865
申请日：2001-02-08
申请人： TEVA PHARMA
发明人： AVRUTOV ILYA , GERSHON NEOMI , LIBERMAN ANITA
IPC分类号： A61K31/42 , A61P3/10 , A61P11/02 , A61P11/06 , A61P17/06 , A61P27/02 , A61P29/00 , A61P35/00 , A61P37/06 , C07D261/18 , C07D261/10
摘要： A process for synthesizing leflunomide from 5-methylisoxazole-4-carboxylic acid and 4-trifluoromethylaniline is provided. Further provided is the leflunomide prepared by the inventive process, which is substantially free of difficult-to-separate impurities often found in leflunomide prepared by known methods, including N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide, 5-methyl-N-(4-methylphenyl)-isoxazole-4-carboxamide and N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4-carboxamide. The invention further provides pharmaceutical compositions and dosage forms containing highly pure leflunomide and methods of treating disease using the leflunomide.

49. 发明专利

ZA200206494B A method for synthesizing leflunomide. 未知
公开(公告)号：ZA200206494B
公开(公告)日：2003-08-20
申请号：ZA200206494
申请日：2002-08-14
申请人： TEVA PHARMA
发明人： AVRUTOV ILYA , GERSHON NEOMI , LIBERMAN ANITA
IPC分类号： A61K31/42 , A61P3/10 , A61P11/02 , A61P11/06 , A61P17/06 , A61P27/02 , A61P29/00 , A61P35/00 , A61P37/06 , C07D261/18 , A61K , C07D
摘要： A process for synthesizing leflunomide from 5-methylisoxazole-4-carboxylic acid and 4-trifluoromethylaniline is provided. Further provided is the leflunomide prepared by the inventive process, which is substantially free of difficult-to-separate impurities often found in leflunomide prepared by known methods, including N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide, 5-methyl-N-(4-methylphenyl)-isoxazole-4-carboxamide and N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4-carboxamide. The invention further provides pharmaceutical compositions and dosage forms containing highly pure leflunomide and methods of treating disease using the leflunomide.

50. 发明专利

SK12992002A3 A method for synthesizing leflunomide 未知
公开(公告)号：SK12992002A3
公开(公告)日：2003-05-02
申请号：SK12992002
申请日：2001-02-08
申请人： TEVA PHARMA
发明人： AVRUTOV ILYA , GERSHON NEOMI , LIBERMAN ANITA
IPC分类号： A61K31/42 , A61P3/10 , A61P11/02 , A61P11/06 , A61P17/06 , A61P27/02 , A61P29/00 , A61P35/00 , A61P37/06 , C07D261/18 , C07D261/08
摘要： A process for synthesizing leflunomide from 5-methylisoxazole-4-carboxylic acid and 4-trifluoromethylaniline is provided. Further provided is the leflunomide prepared by the inventive process, which is substantially free of difficult-to-separate impurities often found in leflunomide prepared by known methods, including N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide, 5-methyl-N-(4-methylphenyl)-isoxazole-4-carboxamide and N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4-carboxamide. The invention further provides pharmaceutical compositions and dosage forms containing highly pure leflunomide and methods of treating disease using the leflunomide.

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