SK8332002A3 - Novel processes for making- and a new crystalline form of leflunomide - Google Patents
Novel processes for making- and a new crystalline form of leflunomide Download PDFInfo
- Publication number
- SK8332002A3 SK8332002A3 SK833-2002A SK8332002A SK8332002A3 SK 8332002 A3 SK8332002 A3 SK 8332002A3 SK 8332002 A SK8332002 A SK 8332002A SK 8332002 A3 SK8332002 A3 SK 8332002A3
- Authority
- SK
- Slovakia
- Prior art keywords
- leflunomide
- solvent
- form iii
- solution
- crystals
- Prior art date
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- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 title claims abstract description 157
- 238000000034 method Methods 0.000 title claims abstract description 52
- 230000008569 process Effects 0.000 title claims abstract description 15
- 229960000681 leflunomide Drugs 0.000 title claims description 80
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- 239000013078 crystal Substances 0.000 claims description 29
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 23
- 238000002425 crystallisation Methods 0.000 claims description 21
- 230000008025 crystallization Effects 0.000 claims description 21
- 239000000843 powder Substances 0.000 claims description 17
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
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- 238000010438 heat treatment Methods 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 claims description 5
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- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17122899P | 1999-12-16 | 1999-12-16 | |
| US17123799P | 1999-12-16 | 1999-12-16 | |
| US18264700P | 2000-02-15 | 2000-02-15 | |
| US20241600P | 2000-05-08 | 2000-05-08 | |
| PCT/US2000/033866 WO2001043742A1 (en) | 1999-12-16 | 2000-12-14 | Novel processes for making- and a new crystalline form of- leflunomide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK8332002A3 true SK8332002A3 (en) | 2003-04-01 |
Family
ID=27496942
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK833-2002A SK8332002A3 (en) | 1999-12-16 | 2000-12-14 | Novel processes for making- and a new crystalline form of leflunomide |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US6610718B2 (cs) |
| EP (1) | EP1242077A4 (cs) |
| JP (1) | JP2003517011A (cs) |
| KR (1) | KR20020067545A (cs) |
| CN (1) | CN1411373A (cs) |
| AU (1) | AU779931B2 (cs) |
| CA (1) | CA2397601A1 (cs) |
| CZ (1) | CZ20022000A3 (cs) |
| HR (2) | HRP20020521A2 (cs) |
| HU (1) | HUP0204069A3 (cs) |
| IL (1) | IL149792A0 (cs) |
| PL (1) | PL356243A1 (cs) |
| SK (1) | SK8332002A3 (cs) |
| WO (1) | WO2001043742A1 (cs) |
| YU (1) | YU45102A (cs) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT987256E (pt) * | 1997-08-08 | 2002-03-28 | Aventis Pharma Gmbh | Forma cristalina da n-(4-trifluorometilfenil)-5-metil-isoxazol-4-carboxamida |
| CN1411373A (zh) * | 1999-12-16 | 2003-04-16 | 特瓦制药工业有限公司 | 制备来氟米特的新方法和新晶形的来氟米特 |
| EP1255565A1 (de) * | 2000-01-13 | 2002-11-13 | MERCK PATENT GmbH | Pharmazeutische zubereitungen enthaltend 2-pyrrolidon als lösungsvermittler |
| US6723855B2 (en) * | 2000-02-15 | 2004-04-20 | Teva Pharmaceutical Industries Ltd. | Method for synthesizing leflunomide |
| US20050158371A1 (en) * | 2002-02-12 | 2005-07-21 | Sumitomo Pharmaceuticals Co., Ltd. | Novel external agent |
| WO2006103506A1 (en) * | 2005-03-31 | 2006-10-05 | Ranbaxy Laboratories Limited | Sertraline-containing pharmaceutical compositions and a process for preparation thereof |
| CN101563082A (zh) * | 2006-09-05 | 2009-10-21 | 窦德献 | 治疗免疫介导性皮肤病的组合物和方法 |
| CN101143834B (zh) * | 2006-09-15 | 2010-09-08 | 欣凯医药化工中间体（上海）有限公司 | N-(4-三氟甲基苯)-2-氰基-3-羟基丁烯酰胺钠盐的多晶型及其制备方法 |
| US8664390B2 (en) | 2007-06-29 | 2014-03-04 | Generics (Uk) Limited | Process for the introduction of hydroxyethoxy side chain in bosentan |
| CA2703230A1 (en) | 2007-10-24 | 2009-04-30 | Generics [Uk] Limited | Novel crystalline forms |
| WO2009098517A1 (en) | 2008-02-08 | 2009-08-13 | Generics [Uk] Limited | Process for preparing bosentan |
| NZ593117A (en) | 2008-11-03 | 2013-03-28 | Generics Uk Ltd | HPLC METHOD FOR THE ANALYSIS OF BOSENTAN AND RELATED SUBSTANCES AND USE OF THESE SUBSTANCES AS REFERENCE STANDARDS AND MARKERS Chromatography mass spectrometry fragmentation |
| CN101817797B (zh) * | 2009-02-26 | 2013-04-10 | 江苏亚邦爱普森药业有限公司 | 高纯度3-甲基-n-[4-(三氟甲基)苯基]-4-异噁唑甲酰胺的合成方法 |
| TW202435877A (zh) | 2013-11-15 | 2024-09-16 | 美商阿克比治療有限公司 | {[5-(3-氯苯基)-3-羥基吡啶-2-羰基]胺基}乙酸之固體型式，其組合物及用途 |
| US11801232B2 (en) * | 2019-11-27 | 2023-10-31 | Yale University | Targeting of ARID1A-deficient cancers by inhibiting de novo pyrimidine synthesis pathway |
| CN112898215B (zh) * | 2021-02-04 | 2022-11-08 | 美罗药业股份有限公司 | 一种来氟米特晶型i的制备方法 |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2854439A1 (de) * | 1978-12-16 | 1980-07-03 | Hoechst Ag | Ein isoxazolderivat, verfahren zu seiner herstellung, diese verbindung enthaltende mittel und verwendung |
| US5268382A (en) * | 1985-09-27 | 1993-12-07 | Hoechst Aktiengesellschaft | Medicaments to combat autoimmune diseases, in particular systemic lupus erythematosus |
| DE3534440A1 (de) * | 1985-09-27 | 1987-04-02 | Hoechst Ag | Arzneimittel gegen chronische graft-versus-host-krankheiten sowie gegen autoimmunerkrankungen, insbesondere systemischen lupus erythematodes |
| GB8619432D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
| JP2995086B2 (ja) * | 1990-05-18 | 1999-12-27 | ヘキスト・アクチエンゲゼルシヤフト | イソオキサゾール−４−カルボキサミド類およびヒドロキシアルキリデンシアノアセトアミド類を含有する製剤 |
| US5700823A (en) * | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| US5610173A (en) * | 1994-01-07 | 1997-03-11 | Sugen, Inc. | Formulations for lipophilic compounds |
| DE19610955A1 (de) * | 1996-03-20 | 1997-09-25 | Hoechst Ag | Kombinationspräparat, enthaltend 5-Methylisoxazol-4-carbonsäure-(4-trifluormethyl)- anilid und N-(4-Trifluormethylphenyl)-2-cyan-3- hydroxycrotonsäureamid |
| GB9624038D0 (en) * | 1996-11-19 | 1997-01-08 | Sandoz Ltd | Organic compounds |
| DE19711800A1 (de) * | 1997-03-21 | 1998-09-24 | Hoechst Ag | Verlängerung der Expression von transgenen Proteinen durch immunmodulierende Behandlung |
| PT987256E (pt) * | 1997-08-08 | 2002-03-28 | Aventis Pharma Gmbh | Forma cristalina da n-(4-trifluorometilfenil)-5-metil-isoxazol-4-carboxamida |
| EP0933633A1 (en) * | 1997-12-11 | 1999-08-04 | Hoechst Marion Roussel Deutschland GmbH | Process for obtaining L-dihydroorotic acid and use thereof |
| US7691890B2 (en) * | 1998-03-11 | 2010-04-06 | James W. Williams | Anti-viral uses of leflunomide products |
| US6303652B1 (en) * | 1998-08-21 | 2001-10-16 | Hughes Institute | BTK inhibitors and methods for their identification and use |
| US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| DE19908527C2 (de) * | 1999-02-26 | 2001-08-30 | Aventis Pharma Gmbh | Verfahren zur Kristallisation von N-(4-Trifluormethylphenyl)-5-methyl-isoxazol-4-carboxamid |
| CA2377278C (en) * | 1999-06-25 | 2010-03-23 | Vertex Pharmaceuticals Incorporated | Prodrugs of carbamate inhibitors of impdh |
| CN1411373A (zh) * | 1999-12-16 | 2003-04-16 | 特瓦制药工业有限公司 | 制备来氟米特的新方法和新晶形的来氟米特 |
| US6723855B2 (en) * | 2000-02-15 | 2004-04-20 | Teva Pharmaceutical Industries Ltd. | Method for synthesizing leflunomide |
| AU2001251011A1 (en) * | 2000-03-27 | 2001-10-08 | The General Hospital Corporation | Treatments for immune-mediated ear disorders |
| US20020077485A1 (en) * | 2000-08-14 | 2002-06-20 | Ilya Avrutov | Micronized leflunomide |
| DK1401801T3 (da) * | 2000-08-24 | 2007-03-05 | Univ Tennessee Res Foundation | Selektive androgenreceptormodulatorer og fremgangsmåder til anvendelse deraf |
| JP4212278B2 (ja) * | 2001-03-01 | 2009-01-21 | 日本たばこ産業株式会社 | 移植片拒絶反応抑制剤 |
| US20040229849A1 (en) * | 2002-09-24 | 2004-11-18 | Jost-Price Edward Roydon | Methods and reagents for the treatment of diseases and disorders associated with increased levels of proinflammatory cytokines |
| CA2535346A1 (en) * | 2003-08-13 | 2005-03-03 | Medtronic, Inc. | Active agent delivery systems, including a single layer of a miscible polymer blend, medical devices, and methods |
| EP1684820A2 (en) * | 2003-08-13 | 2006-08-02 | Medtronic, Inc. | Active agent delivery systems including a miscible polymer blend, medical devices, and methods |
| US20050053600A1 (en) * | 2003-09-09 | 2005-03-10 | Lane Thomas E. | Methods for treating rheumatoid arthritis |
-
2000
- 2000-12-14 CN CN00817283A patent/CN1411373A/zh active Pending
- 2000-12-14 KR KR1020027007575A patent/KR20020067545A/ko not_active Ceased
- 2000-12-14 IL IL14979200A patent/IL149792A0/xx unknown
- 2000-12-14 HU HU0204069A patent/HUP0204069A3/hu unknown
- 2000-12-14 YU YU45102A patent/YU45102A/sh unknown
- 2000-12-14 HR HR20020521A patent/HRP20020521A2/hr not_active Application Discontinuation
- 2000-12-14 WO PCT/US2000/033866 patent/WO2001043742A1/en not_active Application Discontinuation
- 2000-12-14 EP EP00989253A patent/EP1242077A4/en not_active Withdrawn
- 2000-12-14 US US09/736,727 patent/US6610718B2/en not_active Expired - Fee Related
- 2000-12-14 PL PL00356243A patent/PL356243A1/xx not_active Application Discontinuation
- 2000-12-14 CZ CZ20022000A patent/CZ20022000A3/cs unknown
- 2000-12-14 JP JP2001544880A patent/JP2003517011A/ja active Pending
- 2000-12-14 CA CA002397601A patent/CA2397601A1/en not_active Abandoned
- 2000-12-14 SK SK833-2002A patent/SK8332002A3/sk unknown
- 2000-12-14 AU AU25788/01A patent/AU779931B2/en not_active Ceased
- 2000-12-14 HR HR20050176A patent/HRP20050176A2/xx not_active Application Discontinuation
-
2003
- 2003-04-08 US US10/410,493 patent/US6806373B2/en not_active Expired - Fee Related
-
2004
- 2004-07-22 US US10/897,778 patent/US20050004191A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0204069A2 (hu) | 2003-04-28 |
| KR20020067545A (ko) | 2002-08-22 |
| CN1411373A (zh) | 2003-04-16 |
| HRP20050176A2 (en) | 2005-08-31 |
| HUP0204069A3 (en) | 2005-01-28 |
| US20030203952A1 (en) | 2003-10-30 |
| HRP20020521A2 (en) | 2004-08-31 |
| US6610718B2 (en) | 2003-08-26 |
| IL149792A0 (en) | 2002-11-10 |
| AU779931B2 (en) | 2005-02-17 |
| EP1242077A4 (en) | 2006-01-04 |
| PL356243A1 (en) | 2004-06-28 |
| EP1242077A1 (en) | 2002-09-25 |
| CZ20022000A3 (cs) | 2003-02-12 |
| AU2578801A (en) | 2001-06-25 |
| YU45102A (sh) | 2006-01-16 |
| US20050004191A1 (en) | 2005-01-06 |
| US6806373B2 (en) | 2004-10-19 |
| US20010031878A1 (en) | 2001-10-18 |
| WO2001043742A1 (en) | 2001-06-21 |
| CA2397601A1 (en) | 2001-06-21 |
| JP2003517011A (ja) | 2003-05-20 |
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