NO317299B1 - Sulfonamidholdige indolforbindelser, deres anvendelse samt farmasoytiske preparater inneholdende disse - Google Patents
Sulfonamidholdige indolforbindelser, deres anvendelse samt farmasoytiske preparater inneholdende disse Download PDFInfo
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- NO317299B1 NO317299B1 NO20005357A NO20005357A NO317299B1 NO 317299 B1 NO317299 B1 NO 317299B1 NO 20005357 A NO20005357 A NO 20005357A NO 20005357 A NO20005357 A NO 20005357A NO 317299 B1 NO317299 B1 NO 317299B1
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- Prior art keywords
- group
- indol
- bromo
- hydrates
- methyl
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- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
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- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
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- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11049870A JP2000247949A (ja) | 1999-02-26 | 1999-02-26 | スルホンアミド含有インドール化合物 |
| PCT/JP2000/001071 WO2000050395A1 (fr) | 1999-02-26 | 2000-02-24 | Composes indoles contenant un sulfonamide |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20005357D0 NO20005357D0 (no) | 2000-10-24 |
| NO20005357L NO20005357L (no) | 2000-12-22 |
| NO317299B1 true NO317299B1 (no) | 2004-10-04 |
Family
ID=12843091
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20005357A NO317299B1 (no) | 1999-02-26 | 2000-10-24 | Sulfonamidholdige indolforbindelser, deres anvendelse samt farmasoytiske preparater inneholdende disse |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US6469043B1 (fr) |
| EP (1) | EP1074542B1 (fr) |
| JP (3) | JP2000247949A (fr) |
| KR (1) | KR100627611B1 (fr) |
| CN (1) | CN1132814C (fr) |
| AT (1) | ATE325094T1 (fr) |
| AU (1) | AU766936B2 (fr) |
| CA (1) | CA2327253C (fr) |
| DE (1) | DE60027648T2 (fr) |
| DK (1) | DK1074542T3 (fr) |
| ES (1) | ES2259997T3 (fr) |
| HU (1) | HU228787B1 (fr) |
| NO (1) | NO317299B1 (fr) |
| NZ (1) | NZ507464A (fr) |
| PT (1) | PT1074542E (fr) |
| RU (1) | RU2208607C2 (fr) |
| WO (1) | WO2000050395A1 (fr) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1258252B1 (fr) * | 2000-02-03 | 2010-04-21 | Eisai R&D Management Co., Ltd. | Inhibiteurs de l'expression de l'integrine |
| AU2001288518A1 (en) * | 2000-08-30 | 2002-03-13 | Primecyte, Inc. | Methods for treating tumors using sulfonyl compounds |
| TWI283575B (en) | 2000-10-31 | 2007-07-11 | Eisai Co Ltd | Medicinal compositions for concomitant use as anticancer agent |
| ES2317368T3 (es) * | 2001-02-21 | 2009-04-16 | EISAI R&D MANAGEMENT CO., LTD. | Metodo para evaluar el efecto de un inhibidor de la angiogenesis a traves de la inhibicion de la expresion de la integrina. |
| EP1430894A4 (fr) * | 2001-09-05 | 2007-12-12 | Eisai R&D Man Co Ltd | Inhibiteur d'activation lymphocytaire et remede pour maladie auto-immune |
| DE60223936D1 (de) * | 2001-09-05 | 2008-01-17 | Eisai R&D Man Co Ltd | Mittel zur anregung des appetits und mittel zur behandlung von anorexie |
| WO2003074045A1 (fr) * | 2002-03-05 | 2003-09-12 | Eisai Co., Ltd. | Agent antitumoral comprenant une combinaison d'un compose heterocyclique contenant un sulfamide et d'un inhibiteur d'angiogenese |
| JP4928937B2 (ja) | 2003-03-28 | 2012-05-09 | スローン−ケッタリング・インスティテュート・フォー・キャンサー・リサーチ | ミグラスタチンアナログおよびその使用 |
| WO2004091664A1 (fr) * | 2003-04-18 | 2004-10-28 | Eisai Co., Ltd. | Inhibiteur de malate dehydogenase cytoplasmique |
| WO2005026119A1 (fr) * | 2003-09-10 | 2005-03-24 | Eisai Co., Ltd. | Procede de production d'un compose indole contenant un sulfone amide |
| EP1666463B1 (fr) * | 2003-09-10 | 2010-11-03 | Eisai R&D Management Co., Ltd. | Cristal d'un compose d'indole contenant un sulfonamide et procede de production de celui-ci |
| JP4897490B2 (ja) * | 2003-11-13 | 2012-03-14 | サッター・ウエスト・ベイ・ホスピタルズ | 転移抑制のための抗ｐｅｃａｍ治療 |
| US8957056B2 (en) * | 2004-05-25 | 2015-02-17 | Sloan-Kettering Instiute For Cancer Research | Migrastatin analogs in the treatment of cancer |
| US8772269B2 (en) | 2004-09-13 | 2014-07-08 | Eisai R&D Management Co., Ltd. | Use of sulfonamide-including compounds in combination with angiogenesis inhibitors |
| WO2006030941A1 (fr) | 2004-09-13 | 2006-03-23 | Eisai R & D Management Co., Ltd. | Utilisation concomitante d'un compose contenant du sulfonamide et d'un inhibiteur d'angiogenese |
| US8188141B2 (en) * | 2004-09-23 | 2012-05-29 | Sloan-Kettering Institute For Cancer Research | Isomigrastatin analogs in the treatment of cancer |
| CN101163468A (zh) | 2005-02-28 | 2008-04-16 | 卫材R&D管理有限公司 | 磺酰胺化合物的新联合用途 |
| EP2308839B1 (fr) * | 2005-04-20 | 2017-03-01 | Takeda Pharmaceutical Company Limited | Composés hétérocycliques condensés |
| CN101360422B (zh) * | 2005-11-23 | 2013-10-23 | 得克萨斯大学体系董事会 | 致癌Ras特异性细胞毒化合物及其使用方法 |
| US7625896B2 (en) * | 2005-11-25 | 2009-12-01 | Hoffman-La Roche Inc. | Pyridylsulfonamide derivatives |
| WO2007086605A1 (fr) * | 2006-01-27 | 2007-08-02 | Eisai R & D Management Co., Ltd. | Procédé de prédiction de l'effet d'un composé de sulfonamide |
| EP2015070A4 (fr) | 2006-04-20 | 2010-04-21 | Eisai R&D Man Co Ltd | Nouveau marqueur contre la sensibilité à un composé de sulfonamide |
| DE102007012284A1 (de) * | 2007-03-16 | 2008-09-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue substituierte Arylsulfonylglycine, deren Herstellung und deren Verwendung als Arzneimittel |
| DE102007035334A1 (de) | 2007-07-27 | 2009-01-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue substituierte Arylsulfonylglycine, deren Herstellung und deren Verwendung als Arzneimittel |
| DE102007035333A1 (de) | 2007-07-27 | 2009-01-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue substituierte Arylsulfonylglycine, deren Herstellung und deren Verwendung als Arzneimittel |
| DE102007042154A1 (de) | 2007-09-05 | 2009-03-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Arylsulfonylaminomethyphosphonsäure-Derivate, deren Herstellung und deren Verwendung als Arzneimittel |
| US20090142832A1 (en) * | 2007-11-29 | 2009-06-04 | James Dalton | Indoles, Derivatives, and Analogs Thereof and Uses Therefor |
| JP2012136435A (ja) * | 2009-03-30 | 2012-07-19 | Eisai R & D Management Co Ltd | 腫瘍組織の感受性を検査する方法 |
| KR102083041B1 (ko) | 2012-02-22 | 2020-05-27 | 샌포드 번햄 프레비즈 메디컬 디스커버리 인스티튜트 | 술폰아미드 화합물 및 ｔｎａｐ 억제제로서 용도 |
| CN104098498A (zh) * | 2014-07-30 | 2014-10-15 | 天津市斯芬克司药物研发有限公司 | 一种吲唑类化合物及其制备方法 |
| RU2748835C1 (ru) * | 2017-11-27 | 2021-05-31 | Совет Научных И Прикладных Исследований | Индол(сульфонил)-n-гидроксибензамидные производные в качестве селективных ингибиторов hdac |
| US11807606B2 (en) | 2018-01-25 | 2023-11-07 | Dana-Farber Cancer Institute, Inc. | Sulfonamide derivatives for protein degradation |
| EP3953331A4 (fr) * | 2019-04-10 | 2022-12-28 | Peloton Therapeutics, Inc. | Pyrazolesulfonamides en tant qu'agents antitumoraux |
| WO2024039689A1 (fr) * | 2022-08-15 | 2024-02-22 | Recursion Pharmaceuticals, Inc. | Modulateurs de rbm39 hétérocycliques |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9115160D0 (en) * | 1991-07-12 | 1991-08-28 | Erba Carlo Spa | Methylen-oxindole derivatives and process for their preparation |
| JP3545461B2 (ja) * | 1993-09-10 | 2004-07-21 | エーザイ株式会社 | 二環式ヘテロ環含有スルホンアミド誘導体 |
| AU683492B2 (en) | 1993-09-10 | 1997-11-13 | Eisai R&D Management Co., Ltd. | Bicyclic heterocyclic sulfonamide and sulfonic ester derivatives |
| JP3690831B2 (ja) | 1995-02-27 | 2005-08-31 | エーザイ株式会社 | インドール含有スルホンアミド誘導体 |
| WO1997030706A1 (fr) | 1996-02-26 | 1997-08-28 | Eisai Co., Ltd. | Compositions contenant un agent antitumoral |
| JP3868534B2 (ja) | 1996-05-24 | 2007-01-17 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | スルホンアミド誘導体の製造法および中間体 |
| EP1258252B1 (fr) | 2000-02-03 | 2010-04-21 | Eisai R&D Management Co., Ltd. | Inhibiteurs de l'expression de l'integrine |
-
1999
- 1999-02-26 JP JP11049870A patent/JP2000247949A/ja active Pending
-
2000
- 2000-02-24 RU RU2000129508/04A patent/RU2208607C2/ru not_active IP Right Cessation
- 2000-02-24 JP JP2000600978A patent/JP3866041B2/ja not_active Expired - Fee Related
- 2000-02-24 ES ES00905321T patent/ES2259997T3/es not_active Expired - Lifetime
- 2000-02-24 AU AU26916/00A patent/AU766936B2/en not_active Ceased
- 2000-02-24 CA CA002327253A patent/CA2327253C/fr not_active Expired - Fee Related
- 2000-02-24 PT PT00905321T patent/PT1074542E/pt unknown
- 2000-02-24 WO PCT/JP2000/001071 patent/WO2000050395A1/fr active IP Right Grant
- 2000-02-24 CN CN008002290A patent/CN1132814C/zh not_active Expired - Fee Related
- 2000-02-24 EP EP00905321A patent/EP1074542B1/fr not_active Expired - Lifetime
- 2000-02-24 HU HU0101434A patent/HU228787B1/hu not_active IP Right Cessation
- 2000-02-24 US US09/647,215 patent/US6469043B1/en not_active Expired - Lifetime
- 2000-02-24 DE DE60027648T patent/DE60027648T2/de not_active Expired - Lifetime
- 2000-02-24 DK DK00905321T patent/DK1074542T3/da active
- 2000-02-24 KR KR1020007011026A patent/KR100627611B1/ko not_active IP Right Cessation
- 2000-02-24 AT AT00905321T patent/ATE325094T1/de active
- 2000-02-24 NZ NZ507464A patent/NZ507464A/en not_active IP Right Cessation
- 2000-10-24 NO NO20005357A patent/NO317299B1/no not_active IP Right Cessation
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2002
- 2002-03-18 US US10/098,420 patent/US6673787B2/en not_active Expired - Lifetime
- 2002-03-18 US US10/098,421 patent/US6638964B2/en not_active Expired - Lifetime
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2010
- 2010-04-02 JP JP2010085696A patent/JP2010180229A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN1132814C (zh) | 2003-12-31 |
| ES2259997T3 (es) | 2006-11-01 |
| US20020128483A1 (en) | 2002-09-12 |
| EP1074542B1 (fr) | 2006-05-03 |
| NZ507464A (en) | 2003-10-31 |
| CN1294579A (zh) | 2001-05-09 |
| DK1074542T3 (da) | 2006-08-14 |
| JP3866041B2 (ja) | 2007-01-10 |
| US6673787B2 (en) | 2004-01-06 |
| HUP0101434A3 (en) | 2001-10-29 |
| ATE325094T1 (de) | 2006-06-15 |
| US6469043B1 (en) | 2002-10-22 |
| CA2327253A1 (fr) | 2000-08-31 |
| NO20005357D0 (no) | 2000-10-24 |
| RU2208607C2 (ru) | 2003-07-20 |
| EP1074542A4 (fr) | 2002-02-06 |
| KR20010042434A (ko) | 2001-05-25 |
| WO2000050395A1 (fr) | 2000-08-31 |
| CA2327253C (fr) | 2007-10-16 |
| JP2000247949A (ja) | 2000-09-12 |
| PT1074542E (pt) | 2006-07-31 |
| AU766936B2 (en) | 2003-10-23 |
| KR100627611B1 (ko) | 2006-09-25 |
| EP1074542A1 (fr) | 2001-02-07 |
| HU228787B1 (en) | 2013-05-28 |
| US20020128480A1 (en) | 2002-09-12 |
| US6638964B2 (en) | 2003-10-28 |
| JP2010180229A (ja) | 2010-08-19 |
| AU2691600A (en) | 2000-09-14 |
| DE60027648D1 (de) | 2006-06-08 |
| DE60027648T2 (de) | 2007-04-05 |
| HUP0101434A2 (hu) | 2001-09-28 |
| NO20005357L (no) | 2000-12-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ERR | Erratum |
Free format text: SULFONAMIDHOLDIGE INDOLFORBINDELSER, DERES ANVENDELSE SAMT FARMASOYTISKE PREPARATER INNEHOLDENDE DISSE |
|
| MM1K | Lapsed by not paying the annual fees |