HRP20020521A2 - 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
- HRP20020521A2 HRP20020521A2 HR20020521A HRP20020521A HRP20020521A2 HR P20020521 A2 HRP20020521 A2 HR P20020521A2 HR 20020521 A HR20020521 A HR 20020521A HR P20020521 A HRP20020521 A HR P20020521A HR P20020521 A2 HRP20020521 A2 HR P20020521A2
- Authority
- HR
- Croatia
- Prior art keywords
- leflunomide
- solvent
- form iii
- crystals
- solution
- Prior art date
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- 229960000681 leflunomide Drugs 0.000 title claims description 143
- 238000000034 method Methods 0.000 title claims description 50
- 230000008569 process Effects 0.000 title description 10
- 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 claims description 149
- 239000002904 solvent Substances 0.000 claims description 42
- 239000013078 crystal Substances 0.000 claims description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 25
- 238000002425 crystallisation Methods 0.000 claims description 25
- 230000008025 crystallization Effects 0.000 claims description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 24
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- 239000000203 mixture Substances 0.000 claims description 22
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
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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 |
|---|---|---|---|
| US17123799P | 1999-12-16 | 1999-12-16 | |
| US17122899P | 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 |
|---|---|
| HRP20020521A2 true HRP20020521A2 (en) | 2004-08-31 |
Family
ID=27496942
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20020521A HRP20020521A2 (en) | 1999-12-16 | 2002-06-14 | Novel processes for making - and a new crystalline form of - leflunomide |
| HR20050176A HRP20050176A2 (en) | 1999-12-16 | 2005-02-23 | Novel processes for making - and a new crystalline form of-leflunomide |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20050176A HRP20050176A2 (en) | 1999-12-16 | 2005-02-23 | Novel processes for making - and a new crystalline form of-leflunomide |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US6610718B2 (zh) |
| EP (1) | EP1242077A4 (zh) |
| JP (1) | JP2003517011A (zh) |
| KR (1) | KR20020067545A (zh) |
| CN (1) | CN1411373A (zh) |
| AU (1) | AU779931B2 (zh) |
| CA (1) | CA2397601A1 (zh) |
| CZ (1) | CZ20022000A3 (zh) |
| HR (2) | HRP20020521A2 (zh) |
| HU (1) | HUP0204069A3 (zh) |
| IL (1) | IL149792A0 (zh) |
| PL (1) | PL356243A1 (zh) |
| SK (1) | SK8332002A3 (zh) |
| WO (1) | WO2001043742A1 (zh) |
| YU (1) | YU45102A (zh) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0903345B1 (de) * | 1997-08-08 | 2000-10-04 | Aventis Pharma Deutschland GmbH | Kristallform von 5-Methylisoxazol-4-carbonsäure-(4-trifluormethyl)-anilid |
| CA2397601A1 (en) * | 1999-12-16 | 2001-06-21 | Teva Pharmaceutical Industries, Ltd. | Novel processes for making- and a new crystalline form of- leflunomide |
| WO2001051089A1 (de) * | 2000-01-13 | 2001-07-19 | 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 |
| WO2008040149A1 (en) * | 2006-09-05 | 2008-04-10 | Dexian Dou | Composition and method for treating immune-mediated skin disorders |
| 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 |
| EP2170841A1 (en) | 2007-06-29 | 2010-04-07 | Merck Generics (UK) Limited | Process for introduction of hydroxyethoxy side chain in bosentan |
| US8530488B2 (en) | 2007-10-24 | 2013-09-10 | Generics [Uk] Limited | Crystalline forms of bosentan |
| CA2712860C (en) | 2008-02-08 | 2014-11-18 | Abhay Gaitonde | Process for preparing bosentan |
| CA2741928A1 (en) | 2008-11-03 | 2010-06-03 | Generics [Uk] Limited | Hplc method for the analysis of bosentan and related substances and use of these substances as reference standards and markers |
| 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 |
| CR20200220A (es) | 2013-11-15 | 2020-11-18 | Akebia Therapeutics Inc | FORMAS SÓLIDAS DE ÁCIDO {[5-(3-CLOROFENIL)-3-HIDROXIPIRIDIN-2-CARBONIL]AMINO}ACÉTICO, COMPOSICIONES, Y USOS DE LAS MISMAS (Divisional 2016-0222) |
| 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 |
| DE3534440A1 (de) * | 1985-09-27 | 1987-04-02 | Hoechst Ag | Arzneimittel gegen chronische graft-versus-host-krankheiten sowie gegen autoimmunerkrankungen, insbesondere systemischen lupus erythematodes |
| US5268382A (en) * | 1985-09-27 | 1993-12-07 | Hoechst Aktiengesellschaft | Medicaments to combat autoimmune diseases, in particular systemic lupus erythematosus |
| GB8619432D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
| BR9008022A (pt) * | 1990-05-18 | 1993-04-06 | Hoechst Ag | Amida de acido isoxazol-4-carboxilico e amidas de acido hidroxialquilideno-cianoacetico,medicamentos contendo estes compostos e sua aplicacao |
| US5610173A (en) * | 1994-01-07 | 1997-03-11 | Sugen, Inc. | Formulations for lipophilic compounds |
| US5700823A (en) * | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| 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 |
| EP0903345B1 (de) * | 1997-08-08 | 2000-10-04 | Aventis Pharma Deutschland GmbH | Kristallform von 5-Methylisoxazol-4-carbonsäure-(4-trifluormethyl)-anilid |
| 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 |
| DE60005017T2 (de) * | 1999-06-25 | 2004-06-09 | Vertex Pharmaceuticals Inc., Cambridge | Prodrugs von impdh-inhibierenden carbamaten |
| CA2397601A1 (en) * | 1999-12-16 | 2001-06-21 | Teva Pharmaceutical Industries, Ltd. | Novel processes for making- and a new crystalline form of- leflunomide |
| US6723855B2 (en) * | 2000-02-15 | 2004-04-20 | Teva Pharmaceutical Industries Ltd. | Method for synthesizing leflunomide |
| WO2001072298A1 (en) * | 2000-03-27 | 2001-10-04 | The General Hospital Corporation | Treatments for immune-mediated ear disorders |
| US20020077485A1 (en) * | 2000-08-14 | 2002-06-20 | Ilya Avrutov | Micronized leflunomide |
| SI1401801T1 (sl) * | 2000-08-24 | 2007-04-30 | Univ Tennessee Res Foundation | Selektivni modulatorji androgenskega receptorja in postopki za njihovo uporabo |
| 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 CA CA002397601A patent/CA2397601A1/en not_active Abandoned
- 2000-12-14 AU AU25788/01A patent/AU779931B2/en not_active Ceased
- 2000-12-14 IL IL14979200A patent/IL149792A0/xx unknown
- 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 KR KR1020027007575A patent/KR20020067545A/ko not_active Application Discontinuation
- 2000-12-14 CN CN00817283A patent/CN1411373A/zh active Pending
- 2000-12-14 YU YU45102A patent/YU45102A/sh unknown
- 2000-12-14 PL PL00356243A patent/PL356243A1/xx not_active Application Discontinuation
- 2000-12-14 WO PCT/US2000/033866 patent/WO2001043742A1/en not_active Application Discontinuation
- 2000-12-14 HU HU0204069A patent/HUP0204069A3/hu unknown
- 2000-12-14 SK SK833-2002A patent/SK8332002A3/sk unknown
- 2000-12-14 CZ CZ20022000A patent/CZ20022000A3/cs unknown
- 2000-12-14 JP JP2001544880A patent/JP2003517011A/ja active Pending
-
2002
- 2002-06-14 HR HR20020521A patent/HRP20020521A2/hr 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
-
2005
- 2005-02-23 HR HR20050176A patent/HRP20050176A2/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1242077A1 (en) | 2002-09-25 |
| US20010031878A1 (en) | 2001-10-18 |
| CN1411373A (zh) | 2003-04-16 |
| SK8332002A3 (en) | 2003-04-01 |
| WO2001043742A1 (en) | 2001-06-21 |
| HUP0204069A3 (en) | 2005-01-28 |
| YU45102A (sh) | 2006-01-16 |
| US20030203952A1 (en) | 2003-10-30 |
| AU779931B2 (en) | 2005-02-17 |
| IL149792A0 (en) | 2002-11-10 |
| US6610718B2 (en) | 2003-08-26 |
| US6806373B2 (en) | 2004-10-19 |
| JP2003517011A (ja) | 2003-05-20 |
| HUP0204069A2 (hu) | 2003-04-28 |
| EP1242077A4 (en) | 2006-01-04 |
| CZ20022000A3 (cs) | 2003-02-12 |
| CA2397601A1 (en) | 2001-06-21 |
| KR20020067545A (ko) | 2002-08-22 |
| AU2578801A (en) | 2001-06-25 |
| HRP20050176A2 (en) | 2005-08-31 |
| US20050004191A1 (en) | 2005-01-06 |
| PL356243A1 (en) | 2004-06-28 |
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