RU2419623C2 - НОВЫЕ ПРОИЗВОДНЫЕ 5-ЗАМЕЩЕННОГО 7-АМИНО-[1,3]ТИАЗОЛО[4,5-d] ПИРИМИДИНА - Google Patents
НОВЫЕ ПРОИЗВОДНЫЕ 5-ЗАМЕЩЕННОГО 7-АМИНО-[1,3]ТИАЗОЛО[4,5-d] ПИРИМИДИНА Download PDFInfo
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- RU2419623C2 RU2419623C2 RU2007140551/04A RU2007140551A RU2419623C2 RU 2419623 C2 RU2419623 C2 RU 2419623C2 RU 2007140551/04 A RU2007140551/04 A RU 2007140551/04A RU 2007140551 A RU2007140551 A RU 2007140551A RU 2419623 C2 RU2419623 C2 RU 2419623C2
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- amino
- thiazolo
- pyrimidin
- formula
- thio
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Classifications
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Landscapes
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| WO2014142056A1 (ja) | 2013-03-12 | 2014-09-18 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ピロリジン－３－イル酢酸誘導体の塩およびその結晶 |
| EP3049086A4 (en) * | 2013-09-27 | 2017-02-22 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| US20180222922A1 (en) * | 2015-06-08 | 2018-08-09 | The Johns Hopkins University | Radiofluorinated 7-amino-5-thio-thiazolo[4,5-d]pyrimidines for imaging fractalkine receptor (cx3cr1) |
| US11267817B2 (en) | 2017-05-02 | 2022-03-08 | Drexel University | Substituted pyrrolo[1,2-a]quinoxalin-4(5H)-ones as CX3CR1 antagonists |
| GB201807898D0 (en) | 2018-05-15 | 2018-06-27 | Kancera Ab | New processes and products with increased chiral purity |
| GB201811169D0 (en) * | 2018-07-06 | 2018-08-29 | Kancera Ab | New compounds |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000009511A1 (en) * | 1998-08-13 | 2000-02-24 | Astrazeneca Ab | Novel thiazolopyrimidine compounds |
| WO2001058906A1 (en) * | 2000-02-11 | 2001-08-16 | Astrazeneca Ab | Pyrimidine compounds and their use as modulators of chemokine receptor activity |
| WO2002076990A1 (en) * | 2001-03-27 | 2002-10-03 | Astrazeneca Ab | Thiazolopyrimidine derivatives and use thereof as antagonists of the cx3 cr1 receptor |
| RU2197493C2 (ru) * | 1997-07-18 | 2003-01-27 | Ф.Хоффманн-Ля Рош Аг | Производные 5h-тиазол[3,2-а]пиримидина, промежуточные продукты и лекарственное средство |
| RU2003110575A (ru) * | 2000-09-15 | 2005-01-27 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Производные пиразола, используемые в качестве ингибиторов ротеинкиназы |
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| US4639433A (en) * | 1985-08-14 | 1987-01-27 | Eli Lilly And Company | Glycopeptide derivatives |
| US4643987A (en) * | 1985-08-14 | 1987-02-17 | Eli Lilly And Company | Modified glycopeptides |
| ZA909847B (en) * | 1989-12-13 | 1992-08-26 | Lilly Co Eli | Glycopeptide derivatives |
| US5202328A (en) * | 1991-03-06 | 1993-04-13 | Merck & Co., Inc. | Substituted fused pyrimidinones |
| US5840684A (en) * | 1994-01-28 | 1998-11-24 | Eli Lilly And Company | Glycopeptide antibiotic derivatives |
| WO1999051608A1 (en) * | 1998-04-03 | 1999-10-14 | Du Pont Pharmaceuticals Company | THIAZOLO[4,5-d]PYRIMIDINES AND PYRIDINES AS CORTICOTROPIN RELEASING FACTOR (CRF) ANTAGONISTS |
| CA2330619A1 (en) | 1998-05-01 | 1999-11-11 | Eli Lilly And Company | N1-modified glycopeptides |
| SE9903544D0 (sv) | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| GB2359081A (en) * | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| GB2359551A (en) | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| SE0004110L (sv) * | 2000-11-10 | 2002-05-11 | Forsheda Ab | Tätningsring |
| SE0101322D0 (sv) | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
| GB0221828D0 (en) | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0221829D0 (en) | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| EP1589901A4 (en) * | 2002-12-20 | 2006-08-09 | Generipharm Inc | INTRAKUTANE INJECTION |
| WO2005033115A1 (en) * | 2003-10-07 | 2005-04-14 | Astrazeneca Ab | New 2-substituted, 4-amino-thiazolo[4,5-d] pyrimidines, useful as chemokine receptor antagonists, esp. cx3cr1 |
| US20090239882A1 (en) * | 2004-12-17 | 2009-09-24 | Astrazeneca Ab | Thiazolopyramidine Compounds for the Modulation of Chemokine Receptor Activity |
| AR053347A1 (es) * | 2005-04-06 | 2007-05-02 | Astrazeneca Ab | Derivados de [1,3]tiazolo[4,5-d]pirimidin-2(3h)-ona 5,7-sustituidos |
-
2006
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2197493C2 (ru) * | 1997-07-18 | 2003-01-27 | Ф.Хоффманн-Ля Рош Аг | Производные 5h-тиазол[3,2-а]пиримидина, промежуточные продукты и лекарственное средство |
| WO2000009511A1 (en) * | 1998-08-13 | 2000-02-24 | Astrazeneca Ab | Novel thiazolopyrimidine compounds |
| WO2001058906A1 (en) * | 2000-02-11 | 2001-08-16 | Astrazeneca Ab | Pyrimidine compounds and their use as modulators of chemokine receptor activity |
| RU2003110575A (ru) * | 2000-09-15 | 2005-01-27 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Производные пиразола, используемые в качестве ингибиторов ротеинкиназы |
| WO2002076990A1 (en) * | 2001-03-27 | 2002-10-03 | Astrazeneca Ab | Thiazolopyrimidine derivatives and use thereof as antagonists of the cx3 cr1 receptor |
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