NO326349B1 - CCR5-antagonister for behandling av AIDS, farmasoytisk preparat inneholdende disse, og deres anvendelse for fremstilling av medisin. - Google Patents
CCR5-antagonister for behandling av AIDS, farmasoytisk preparat inneholdende disse, og deres anvendelse for fremstilling av medisin. Download PDFInfo
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- NO326349B1 NO326349B1 NO20034311A NO20034311A NO326349B1 NO 326349 B1 NO326349 B1 NO 326349B1 NO 20034311 A NO20034311 A NO 20034311A NO 20034311 A NO20034311 A NO 20034311A NO 326349 B1 NO326349 B1 NO 326349B1
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- alkyl
- aryl
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- heteroaryl
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- DATRVIMZZZVHMP-QMMMGPOBSA-N tert-butyl (2s)-2-methylpiperazine-1-carboxylate Chemical compound C[C@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-QMMMGPOBSA-N 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
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- 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
- C07D401/14—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 three or more hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- AIDS & HIV (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27993801P | 2001-03-29 | 2001-03-29 | |
| PCT/US2002/009491 WO2002079194A1 (en) | 2001-03-29 | 2002-03-27 | Ccr5 antagonists useful for treating aids |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20034311D0 NO20034311D0 (no) | 2003-09-26 |
| NO20034311L NO20034311L (no) | 2003-11-26 |
| NO326349B1 true NO326349B1 (no) | 2008-11-17 |
Family
ID=23070981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20034311A NO326349B1 (no) | 2001-03-29 | 2003-09-26 | CCR5-antagonister for behandling av AIDS, farmasoytisk preparat inneholdende disse, og deres anvendelse for fremstilling av medisin. |
Country Status (30)
| Country | Link |
|---|---|
| US (5) | US6720325B2 (ja) |
| EP (2) | EP1373256B1 (ja) |
| JP (2) | JP4248251B2 (ja) |
| KR (1) | KR100613528B1 (ja) |
| CN (1) | CN100519554C (ja) |
| AR (1) | AR033452A1 (ja) |
| AT (2) | ATE466009T1 (ja) |
| AU (1) | AU2002255947B8 (ja) |
| BR (1) | BR0208398A (ja) |
| CA (1) | CA2442227C (ja) |
| CZ (1) | CZ20032636A3 (ja) |
| DE (2) | DE60236218D1 (ja) |
| DK (1) | DK1373256T3 (ja) |
| ES (2) | ES2242856T3 (ja) |
| HK (2) | HK1057363A1 (ja) |
| HU (1) | HUP0400349A3 (ja) |
| IL (1) | IL157551A0 (ja) |
| MX (1) | MXPA03008853A (ja) |
| MY (1) | MY128609A (ja) |
| NO (1) | NO326349B1 (ja) |
| NZ (1) | NZ527768A (ja) |
| PE (1) | PE20020996A1 (ja) |
| PL (1) | PL364560A1 (ja) |
| PT (1) | PT1373256E (ja) |
| RU (1) | RU2316553C2 (ja) |
| SI (1) | SI1373256T1 (ja) |
| SK (1) | SK287521B6 (ja) |
| TW (1) | TWI237638B (ja) |
| WO (1) | WO2002079194A1 (ja) |
| ZA (1) | ZA200307474B (ja) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60236218D1 (de) * | 2001-03-29 | 2010-06-10 | Schering Corp | CCR5 Antagonisten verwendbar für die Behandlung von Aids |
| DK1404667T3 (da) | 2001-07-02 | 2006-07-10 | Astrazeneca Ab | Piperidinderivater, der er anvendelige som modulatorer af chemokinreceptoraktivitet |
| SE0200844D0 (sv) | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
| SE0200843D0 (sv) | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
| TW200504033A (en) | 2002-10-23 | 2005-02-01 | Procter & Gamble | Melanocortin receptor ligands |
| ES2312856T3 (es) | 2002-12-13 | 2009-03-01 | Smithkline Beecham Corporation | Compuestos heterociclicos como antagonistas de ccr5. |
| PE20040769A1 (es) * | 2002-12-18 | 2004-11-06 | Schering Corp | Derivados de piperidina utiles como antagonisas ccr5 |
| SE0300957D0 (sv) | 2003-04-01 | 2003-04-01 | Astrazeneca Ab | Chemical compounds |
| US7652142B2 (en) * | 2003-11-03 | 2010-01-26 | Schering Corporation | Bipiperidinyl derivatives useful as inhibitors of chemokine receptors |
| JP2007520556A (ja) * | 2004-02-05 | 2007-07-26 | シェーリング コーポレイション | Ｃｃｒ３アンタゴニストとして有用なピペリジン誘導体 |
| SE0400925D0 (sv) * | 2004-04-06 | 2004-04-06 | Astrazeneca Ab | Chemical compounds |
| GEP20094680B (en) * | 2004-04-13 | 2009-05-10 | Incyte Corp | Piperazinylpiperidine derivatives as chemokine receptor antagonists |
| US8143404B2 (en) * | 2004-09-13 | 2012-03-27 | Ono Pharmaceutical Co., Ltd | Nitrogenous heterocylic derivative and medicine containing the same as an active ingredient |
| US7635698B2 (en) | 2004-12-29 | 2009-12-22 | Millennium Pharmaceuticals, Inc. | Compounds useful as chemokine receptor antagonists |
| WO2006071875A1 (en) | 2004-12-29 | 2006-07-06 | Millennium Pharmaceuticals, Inc. | Compounds useful as chemokine receptor antagonists |
| CA2594114A1 (en) * | 2005-01-06 | 2006-07-13 | Schering Corporation | Synthesis of ccr5 receptor antagonists |
| CA2594109A1 (en) * | 2005-01-06 | 2006-07-13 | Schering Corporation | Preparation of pharmaceutical salts of piperazine compounds |
| PE20061012A1 (es) * | 2005-02-23 | 2006-10-03 | Schering Corp | Derivados piperidinil piperazina como inhibidores de receptores quiomicina |
| US7705019B2 (en) | 2005-02-23 | 2010-04-27 | Schering Corporation | Piperidinyl piperidine derivatives useful as inhibitors of chemokine receptors |
| EP2402316A1 (en) | 2005-07-21 | 2012-01-04 | AstraZeneca AB (Publ) | Piperidine derivatives |
| US7462485B2 (en) * | 2005-10-07 | 2008-12-09 | Glaser Lawrence F | Modified erythrocytes and uses thereof |
| TW200745087A (en) * | 2006-02-24 | 2007-12-16 | Schering Corp | CCR5 antagonists useful for treating HIV |
| WO2008030853A2 (en) * | 2006-09-06 | 2008-03-13 | Incyte Corporation | Combination therapy for human immunodeficiency virus infection |
| CA2673233A1 (en) * | 2006-12-22 | 2008-07-03 | Schering Corporation | Process for preparing ccr-5 receptor antagonists utilizing 4-substituted 1-cyclopropane-sulfonyl-piperidinyl compounds |
| US20110059154A1 (en) * | 2008-02-29 | 2011-03-10 | Strizki Julie M | Ccr5 antagonists as prophylactics for preventing hiv infection and methods of inhibiting transmission of same |
| US11629196B2 (en) | 2020-04-27 | 2023-04-18 | Incelldx, Inc. | Method of treating SARS-CoV-2-associated hypercytokinemia by administering a human monoclonal antibody (PRO-140) that inhibits CCR5/CCL5 binding interactions |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5368854A (en) | 1992-08-20 | 1994-11-29 | Schering Corporation | Use of IL-10 to treat inflammatory bowel disease |
| WO1994018192A1 (en) | 1993-02-12 | 1994-08-18 | Merck & Co., Inc. | Piperazine derivatives as hiv protease inhibitors |
| IL117149A0 (en) | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
| US5889006A (en) | 1995-02-23 | 1999-03-30 | Schering Corporation | Muscarinic antagonists |
| EP1103275B1 (en) | 1995-06-07 | 2003-09-10 | Kimberly-Clark Worldwide, Inc. | Inhibition of exoprotein in absorbent article |
| NZ321575A (en) | 1995-10-30 | 1999-05-28 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4- substituted piperazine derivatives |
| TW531537B (en) | 1995-12-27 | 2003-05-11 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4-substituted piperidine derivatives |
| US5952349A (en) | 1996-07-10 | 1999-09-14 | Schering Corporation | Muscarinic antagonists for treating memory loss |
| US5977138A (en) | 1996-08-15 | 1999-11-02 | Schering Corporation | Ether muscarinic antagonists |
| JP2002510327A (ja) | 1997-07-25 | 2002-04-02 | メルク エンド カンパニー インコーポレーテッド | 環状アミンケモカイン受容体活性調節剤 |
| US6066636A (en) | 1998-06-30 | 2000-05-23 | Schering Corporation | Muscarinic antagonists |
| EP1013276A1 (en) * | 1998-12-23 | 2000-06-28 | Pfizer Inc. | Aminoazacycloalkanes as CCR5 modulators |
| CZ20013940A3 (cs) | 1999-05-04 | 2002-04-17 | Schering Corporation | Piperazinové deriváty uľitečné jako CCR5 antagonisté |
| RU2266281C2 (ru) | 1999-05-04 | 2005-12-20 | Шеринг Корпорейшн | Производные пиперидина, фармацевтическая композиция на их основе и способ лечения инфекции вирусом hiv |
| DE60236218D1 (de) * | 2001-03-29 | 2010-06-10 | Schering Corp | CCR5 Antagonisten verwendbar für die Behandlung von Aids |
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