NO313961B1 - IL-8-reseptor-antagonister, anvendelse derav samt farmasöytiske preparater - Google Patents
IL-8-reseptor-antagonister, anvendelse derav samt farmasöytiske preparater Download PDFInfo
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- NO313961B1 NO313961B1 NO19993586A NO993586A NO313961B1 NO 313961 B1 NO313961 B1 NO 313961B1 NO 19993586 A NO19993586 A NO 19993586A NO 993586 A NO993586 A NO 993586A NO 313961 B1 NO313961 B1 NO 313961B1
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- Prior art keywords
- urea
- cyano
- bromophenyl
- benzimidazolin
- mmol
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/14—Thiadiazoles; Hydrogenated thiadiazoles condensed with carbocyclic rings or ring systems
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- 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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- 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
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/26—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65848—Cyclic amide derivatives of acids of phosphorus, in which two nitrogen atoms belong to the ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3599197P | 1997-01-23 | 1997-01-23 | |
| US4282997P | 1997-04-08 | 1997-04-08 | |
| PCT/US1998/001291 WO1998032439A1 (fr) | 1997-01-23 | 1998-01-23 | Antagonistes du recepteur de l'il-8 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO993586D0 NO993586D0 (no) | 1999-07-22 |
| NO993586L NO993586L (no) | 1999-09-21 |
| NO313961B1 true NO313961B1 (no) | 2003-01-06 |
Family
ID=26712688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19993586A NO313961B1 (no) | 1997-01-23 | 1999-07-22 | IL-8-reseptor-antagonister, anvendelse derav samt farmasöytiske preparater |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US6300325B1 (fr) |
| EP (1) | EP0991406A4 (fr) |
| JP (1) | JP2001511130A (fr) |
| KR (1) | KR20000070368A (fr) |
| CN (1) | CN1217660C (fr) |
| AU (1) | AU726858B2 (fr) |
| BR (1) | BR9807083A (fr) |
| CA (1) | CA2278504A1 (fr) |
| HU (1) | HUP0001943A3 (fr) |
| IL (1) | IL131004A0 (fr) |
| NO (1) | NO313961B1 (fr) |
| NZ (1) | NZ336861A (fr) |
| PL (1) | PL334756A1 (fr) |
| TR (1) | TR199901710T2 (fr) |
| WO (1) | WO1998032439A1 (fr) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6218539B1 (en) | 1996-06-27 | 2001-04-17 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
| JP2002518300A (ja) * | 1998-06-17 | 2002-06-25 | スミスクライン・ビーチャム・コーポレイション | Ｉｌ−８受容体アンタゴニスト |
| DE19842363A1 (de) * | 1998-09-16 | 2000-03-30 | Forssmann Wolf Georg | Verwendung von Chemokinen zur Stammzellmobilisation und von Chemokin-Antagonisten zur Vermeidung von Tumormetastasierung |
| ME00275B (fr) | 1999-01-13 | 2011-02-10 | Bayer Corp | DIPHENYLUREES A SUBSTITUANTS ω-CARBOXYARYLES, INHIBITRICES DE KINASE RAF |
| US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| IL144144A0 (en) | 1999-01-13 | 2002-05-23 | Bayer Ag | Omega-carboxy aryl substituted diphenyl ureas as p38 kinase inhibitors |
| AR029637A1 (es) * | 1999-05-28 | 2003-07-10 | Smithkline Beecham Corp | Compuestos de guanidina, antagonistas de los receptores de la il-8, una composicion farmaceutica que los contiene y el uso de los mismos para la manufactura de un medicamento |
| CO5190696A1 (es) * | 1999-06-16 | 2002-08-29 | Smithkline Beecham Corp | Antagonistas de los receptores il-8 |
| US7001911B2 (en) | 2000-06-28 | 2006-02-21 | Bristol-Myers Squibb Company | Fused cyclic modulators of nuclear hormone receptor function |
| MXPA02012605A (es) | 2000-06-28 | 2003-05-14 | Squibb Bristol Myers Co | Moduladores selectivos del receptor androgeno y metodo para su identificacion, dise°o y uso. |
| US20040077605A1 (en) | 2001-06-20 | 2004-04-22 | Salvati Mark E. | Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function |
| DE10038709A1 (de) * | 2000-08-09 | 2002-02-28 | Aventis Pharma Gmbh | Substituierte und unsubstituierte Benzooxathiazole sowie daraus abgeleitete Verbindungen |
| US6953679B2 (en) | 2000-09-19 | 2005-10-11 | Bristol-Myers Squibb Company | Method for the preparation of fused heterocyclic succinimide compounds and analogs thereof |
| US20030204085A1 (en) * | 2001-02-02 | 2003-10-30 | Taveras Arthur G. | 3, 4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor antagonists |
| US20040106794A1 (en) * | 2001-04-16 | 2004-06-03 | Schering Corporation | 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands |
| US7132445B2 (en) * | 2001-04-16 | 2006-11-07 | Schering Corporation | 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands |
| EP2050450A1 (fr) | 2001-04-18 | 2009-04-22 | Euro-Celtique S.A. | Dérivés de 1-pipéridine-2-cyanoimino-1,3-dihydro-2H-benzimidazole en tant que analogues de la nociceptine avec activité modulante ORL1 pour le traitement de la douleur |
| MXPA04003439A (es) * | 2001-10-12 | 2004-07-08 | Schering Corp | Compuestos de maleimida 3,4 disustituidos como antagonistas de receptor de quimiocina cxc. |
| ES2310622T3 (es) | 2001-12-19 | 2009-01-16 | Bristol-Myers Squibb Company | Compuestos heterociclicos condensados y analogos de los mismos, moduladores de la funcion de los receptores nucleares de hormonas. |
| US6878709B2 (en) * | 2002-01-04 | 2005-04-12 | Schering Corporation | 3,4-di-substituted pyridazinediones as CXC chemokine receptor antagonists |
| MXPA04007832A (es) | 2002-02-11 | 2005-09-08 | Bayer Pharmaceuticals Corp | Aril-ureas con actividad inhibitoria de angiogenesis. |
| WO2003068229A1 (fr) | 2002-02-11 | 2003-08-21 | Bayer Pharmaceuticals Corporation | N-oxydes de pyridine, de quinoline, et d'isoquinoline en tant qu'inhibiteurs de kinase |
| JP4733350B2 (ja) * | 2002-03-18 | 2011-07-27 | シェーリング コーポレイション | ケモカイン媒介疾患の併用治療 |
| US7115644B2 (en) * | 2002-09-13 | 2006-10-03 | Boehringer Ingelheim Pharmaceuticals Inc. | Heterocyclic compounds |
| EP1551818B1 (fr) * | 2002-10-09 | 2009-02-04 | Schering Corporation | Thiadiazoledioxydes et thiadiazoleoxides convenant comme ligands des recepteurs des cxc- et cc-chimiokines |
| TW200418812A (en) * | 2002-10-29 | 2004-10-01 | Smithkline Beecham Corp | IL-8 receptor antagonists |
| PL1626714T3 (pl) | 2003-05-20 | 2007-12-31 | Bayer Healthcare Llc | Diarylowe pochodne mocznika do schorzeń, w których pośredniczy PDGFR |
| US8637553B2 (en) | 2003-07-23 | 2014-01-28 | Bayer Healthcare Llc | Fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions |
| EP1694659B8 (fr) * | 2003-12-19 | 2008-10-08 | Schering Corporation | Utilisation de thiadiazoles comme ligands des recepteurs aux chimiokines cxc et cc |
| CA2550540A1 (fr) * | 2003-12-22 | 2005-07-28 | Schering Corporation | Dioxydes d'isothiazole en tant que ligands du recepteur de la chimiokine cxc et cc |
| GB0403038D0 (en) | 2004-02-11 | 2004-03-17 | Novartis Ag | Organic compounds |
| KR20070011475A (ko) | 2004-05-12 | 2007-01-24 | 쉐링 코포레이션 | Ｃｘｃｒ1 및 ｃｘｃｒ2 케모카인 길항제 |
| EP1812008A4 (fr) * | 2004-10-20 | 2008-10-29 | Smithkline Beecham Corp | Antagonistes du récepteur il-8 |
| WO2006047302A1 (fr) * | 2004-10-21 | 2006-05-04 | Transtech Pharma, Inc. | Composes bissulfonamide utilises en tant qu'agonistes du galr1, compositions, et procedes d'utilisation associes |
| EP1912971A2 (fr) * | 2005-06-29 | 2008-04-23 | Shering Corporation | Oxadiazoles di-substitutees utilisees en tant que ligands des recepteurs des chimiokines cxc |
| EP1907399B1 (fr) * | 2005-06-29 | 2010-10-27 | Schering Corporation | Oxadiazolopyrazines 5,6-di-substituées et thiadiazolopyrazines comme ligands récepteurs de cxc-chimiokine |
| NZ572069A (en) * | 2006-04-21 | 2011-09-30 | Smithkline Beecham Corp | IL-8 RECEPTOR ANTAGONIST N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N'-(3-fluoro-2-methylphenyl)urea |
| CA2650007A1 (fr) * | 2006-04-21 | 2007-11-01 | Smithkline Beecham Corporation | Antagonistes du recepteur de l'il-8 |
| CL2007001829A1 (es) * | 2006-06-23 | 2008-01-25 | Smithkline Beecham Corp | P-toluensulfonato de n-[4-cloro-2-hidroxi-3-(piperazina-1-sulfonil)fenil]-n-(2-cloro-3-fluorofenil)urea;procedimiento de preparacion;composicion farmaceutica;combinacion farmaceutica;y uso en el tratamiento de una enfermedad mediada por la quiimioquina il-8, tales como asma y epoc. |
| TW200813033A (en) * | 2006-07-07 | 2008-03-16 | Schering Corp | 3, 4-di-substituted cyclobutene-1, 2-diones as CXC-chemokine receptor ligands |
| US8648086B2 (en) | 2009-08-24 | 2014-02-11 | Ascepion Pharmaceuticals, Inc. | 5,6-bicyclic heteroaryl-containing urea compounds as kinase inhibitors |
| CN111362878B (zh) * | 2020-03-18 | 2023-09-19 | 湖南复瑞生物医药技术有限责任公司 | 一种4-氨基-1,3-二氢-苯并咪唑-2-酮的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK160941C (da) | 1988-06-28 | 1991-10-21 | Novo Nordisk As | Kondenserede 2,3-dihydroxypyraziner, fremgangsmaade til deres fremstilling og farmaceutiske praeparater, hvori forbindelserne indgaar |
| EP0809492A4 (fr) * | 1995-02-17 | 2007-01-24 | Smithkline Beecham Corp | Antagonistes des recepteurs d'il-8 |
| WO1997049399A1 (fr) | 1996-06-27 | 1997-12-31 | Smithkline Beecham Corporation | Antagonistes des recepteurs d'il-8 |
| WO1997049287A1 (fr) | 1996-06-27 | 1997-12-31 | Smithkline Beecham Corporation | Antagonistes des recepteurs d'il-8 |
-
1998
- 1998-01-23 AU AU61339/98A patent/AU726858B2/en not_active Ceased
- 1998-01-23 BR BR9807083-5A patent/BR9807083A/pt not_active Application Discontinuation
- 1998-01-23 IL IL13100498A patent/IL131004A0/xx unknown
- 1998-01-23 CN CN988035650A patent/CN1217660C/zh not_active Expired - Fee Related
- 1998-01-23 EP EP98905988A patent/EP0991406A4/fr not_active Withdrawn
- 1998-01-23 WO PCT/US1998/001291 patent/WO1998032439A1/fr not_active Application Discontinuation
- 1998-01-23 PL PL98334756A patent/PL334756A1/xx unknown
- 1998-01-23 HU HU0001943A patent/HUP0001943A3/hu unknown
- 1998-01-23 NZ NZ336861A patent/NZ336861A/xx unknown
- 1998-01-23 US US09/341,378 patent/US6300325B1/en not_active Expired - Fee Related
- 1998-01-23 CA CA002278504A patent/CA2278504A1/fr not_active Abandoned
- 1998-01-23 JP JP53213898A patent/JP2001511130A/ja not_active Ceased
- 1998-01-23 TR TR1999/01710T patent/TR199901710T2/xx unknown
- 1998-01-23 KR KR1019997006601A patent/KR20000070368A/ko not_active Ceased
-
1999
- 1999-07-22 NO NO19993586A patent/NO313961B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AU6133998A (en) | 1998-08-18 |
| KR20000070368A (ko) | 2000-11-25 |
| EP0991406A4 (fr) | 2000-12-13 |
| JP2001511130A (ja) | 2001-08-07 |
| BR9807083A (pt) | 2000-04-18 |
| WO1998032439A1 (fr) | 1998-07-30 |
| US6300325B1 (en) | 2001-10-09 |
| CN1251038A (zh) | 2000-04-19 |
| CA2278504A1 (fr) | 1998-07-30 |
| NO993586L (no) | 1999-09-21 |
| TR199901710T2 (xx) | 1999-09-21 |
| PL334756A1 (en) | 2000-03-13 |
| HUP0001943A3 (en) | 2002-12-28 |
| AU726858B2 (en) | 2000-11-23 |
| EP0991406A1 (fr) | 2000-04-12 |
| IL131004A0 (en) | 2001-01-28 |
| NZ336861A (en) | 2001-01-26 |
| NO993586D0 (no) | 1999-07-22 |
| HUP0001943A2 (hu) | 2001-01-29 |
| CN1217660C (zh) | 2005-09-07 |
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