EA016791B1 - Замещенные 8-[6-амино-3-пиридил]ксантины - Google Patents
Замещенные 8-[6-амино-3-пиридил]ксантины Download PDFInfo
- Publication number
- EA016791B1 EA016791B1 EA200900010A EA200900010A EA016791B1 EA 016791 B1 EA016791 B1 EA 016791B1 EA 200900010 A EA200900010 A EA 200900010A EA 200900010 A EA200900010 A EA 200900010A EA 016791 B1 EA016791 B1 EA 016791B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- meoh
- pyridyl
- gradient
- compound according
- xanthine
- Prior art date
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
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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
- C07D403/14—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 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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
Landscapes
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Applications Claiming Priority (4)
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|---|---|---|---|
| US80503006P | 2006-06-16 | 2006-06-16 | |
| US80556406P | 2006-06-22 | 2006-06-22 | |
| US11/811,823 US7884100B2 (en) | 2006-06-16 | 2007-06-12 | Substituted 8-[6-amino-3-pyridyl]xanthines |
| PCT/US2007/013849 WO2007149277A2 (en) | 2006-06-16 | 2007-06-13 | Substituted 8-[6-amino-3-pyridyl]xanthines |
Publications (2)
| Publication Number | Publication Date |
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| EA200900010A1 EA200900010A1 (ru) | 2009-10-30 |
| EA016791B1 true EA016791B1 (ru) | 2012-07-30 |
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| EA200900010A EA016791B1 (ru) | 2006-06-16 | 2007-06-13 | Замещенные 8-[6-амино-3-пиридил]ксантины |
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| Country | Link |
|---|---|
| US (2) | US7884100B2 (enExample) |
| EP (1) | EP2029143B1 (enExample) |
| JP (1) | JP5417558B2 (enExample) |
| KR (1) | KR101413404B1 (enExample) |
| CN (1) | CN103145712A (enExample) |
| AU (1) | AU2007261568B2 (enExample) |
| BR (1) | BRPI0712001B8 (enExample) |
| CA (1) | CA2655598C (enExample) |
| DK (1) | DK2029143T3 (enExample) |
| EA (1) | EA016791B1 (enExample) |
| ES (1) | ES2548437T3 (enExample) |
| HU (1) | HUE026457T2 (enExample) |
| IL (1) | IL195916A (enExample) |
| MX (1) | MX2008015954A (enExample) |
| MY (1) | MY152178A (enExample) |
| NZ (1) | NZ597222A (enExample) |
| PL (1) | PL2029143T3 (enExample) |
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| US7317017B2 (en) * | 2002-11-08 | 2008-01-08 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| RU2357969C2 (ru) * | 2003-08-25 | 2009-06-10 | АДЕНОЗАЙН ТЕРАПЬЮТИКС, ЭлЭлСи | Новые замещенные 8-гетероарилксантины и фармацевтическая композиция на их основе |
| WO2006091898A2 (en) * | 2005-02-25 | 2006-08-31 | Adenosine Therapeutics, Llc | Pyrazolyl substituted xanthines |
| US7579348B2 (en) * | 2005-02-25 | 2009-08-25 | Pgxhealth, Llc | Derivatives of 8-substituted xanthines |
| WO2006091936A2 (en) * | 2005-02-25 | 2006-08-31 | Adenosine Therapeutics, Llc | Methods for the synthesis of unsymmetrical cycloalkyl substituted xanthines |
| US7884100B2 (en) | 2006-06-16 | 2011-02-08 | Pgxhealth, Llc | Substituted 8-[6-amino-3-pyridyl]xanthines |
| US7875608B2 (en) * | 2007-12-17 | 2011-01-25 | Thompson Robert D | Substituted 8-[6-amino-3pyridyl]xanthines |
| WO2022246392A1 (en) | 2021-05-18 | 2022-11-24 | Purnovate, Inc. | Cyclic amide-containing pyridyl xanthines as a 2b antagonists |
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| US20050065341A1 (en) * | 2003-08-25 | 2005-03-24 | Guoquan Wang | Substituted 8-heteroaryl xanthines |
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| US6117878A (en) * | 1998-02-24 | 2000-09-12 | University Of Virginia | 8-phenyl- or 8-cycloalkyl xanthine antagonists of A2B human adenosine receptors |
| US6060481A (en) | 1998-05-28 | 2000-05-09 | The Penn State Research Foundation | Method for improving insulin sensitivity using an adenosine receptor antagonist |
| GB9817623D0 (en) | 1998-08-13 | 1998-10-07 | Glaxo Group Ltd | Pharmaceutical compounds |
| KR20030031466A (ko) * | 2000-02-17 | 2003-04-21 | 씨브이 쎄러퓨틱스, 인코포레이티드 | 포유동물 세포 증식을 조절하기 위한 a2b 아데노신수용체 길항 물질의 동정 및 사용 방법 |
| US7317017B2 (en) * | 2002-11-08 | 2008-01-08 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| NZ532816A (en) | 2001-11-09 | 2005-11-25 | Cv Therapeutics Inc | A2B adenosine receptor antagonists |
| US6977300B2 (en) | 2001-11-09 | 2005-12-20 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| US7304070B2 (en) | 2001-11-09 | 2007-12-04 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| KR20040080939A (ko) | 2002-02-01 | 2004-09-20 | 킹 파머슈티칼스 리서치 앤드 디벨로프먼트 아이엔씨 | 8-헤테로아릴 크산틴 아데노신 에이투비 수용체 길항제 |
| US7034070B2 (en) * | 2002-09-27 | 2006-04-25 | Vincent Chuang | Arylalkyl aminofunctional silanes for epoxy laminates |
| US7148229B2 (en) | 2003-02-19 | 2006-12-12 | Hoffman-La Roche Inc. | Sulfonamide substituted xanthine derivatives |
| ES2387653T3 (es) | 2004-09-01 | 2012-09-27 | Gilead Sciences, Inc. | Procedimiento de cicatrización de heridas utilizando antagonistas del receptor de adenosina A2B |
| US20060053029A1 (en) | 2004-09-03 | 2006-03-09 | Butler Keith R | Methods and systems for providing an enterprise supply management portal |
| MX2007004373A (es) | 2004-10-15 | 2007-08-08 | Cv Therapeutics Inc | Metodo para prevenir y tratar el remoldeo de las vias respiratorias e inflamacion pulmonar utilizando antagonistas de receptor adenosina a2b. |
| US7601723B2 (en) * | 2005-02-25 | 2009-10-13 | Pgx Health, Llc | Pyridyl substituted xanthines |
| WO2006091898A2 (en) | 2005-02-25 | 2006-08-31 | Adenosine Therapeutics, Llc | Pyrazolyl substituted xanthines |
| US7579348B2 (en) * | 2005-02-25 | 2009-08-25 | Pgxhealth, Llc | Derivatives of 8-substituted xanthines |
| WO2006091936A2 (en) * | 2005-02-25 | 2006-08-31 | Adenosine Therapeutics, Llc | Methods for the synthesis of unsymmetrical cycloalkyl substituted xanthines |
| EP2301937A1 (en) | 2005-06-16 | 2011-03-30 | Cv Therapeutics, Inc. | Prodrugs of A2b adenosine receptor antagonists |
| WO2007109547A2 (en) * | 2006-03-17 | 2007-09-27 | Cv Therapeutics, Inc. | Method of preventing and treating hepatic disease using a2b adenosine receptor antagonists |
| WO2007149115A1 (en) * | 2006-06-15 | 2007-12-27 | Targeted Genetics Corporation | Methods for treating target joints in inflammatory arthritis using aav vectors encoding a tnf antagonist |
| US7884100B2 (en) | 2006-06-16 | 2011-02-08 | Pgxhealth, Llc | Substituted 8-[6-amino-3-pyridyl]xanthines |
| US7767685B2 (en) | 2006-06-29 | 2010-08-03 | King Pharmaceuticals Research And Development, Inc. | Adenosine A2B receptor antagonists |
| US7875608B2 (en) * | 2007-12-17 | 2011-01-25 | Thompson Robert D | Substituted 8-[6-amino-3pyridyl]xanthines |
| CA2718983C (en) | 2008-03-26 | 2015-12-08 | Advinus Therapeutics Pvt. Ltd. | Heterocyclic compounds as adenosine receptor antagonist |
-
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050065341A1 (en) * | 2003-08-25 | 2005-03-24 | Guoquan Wang | Substituted 8-heteroaryl xanthines |
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| DK2029143T3 (en) | 2015-09-21 |
| IL195916A (en) | 2015-06-30 |
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| US8258142B2 (en) | 2012-09-04 |
| JP5417558B2 (ja) | 2014-02-19 |
| EP2029143A2 (en) | 2009-03-04 |
| CA2655598A1 (en) | 2007-12-27 |
| CA2655598C (en) | 2014-10-28 |
| US7884100B2 (en) | 2011-02-08 |
| HUE026457T2 (en) | 2016-05-30 |
| EA200900010A1 (ru) | 2009-10-30 |
| IL195916A0 (en) | 2009-09-01 |
| JP2010500284A (ja) | 2010-01-07 |
| KR20090029268A (ko) | 2009-03-20 |
| MX2008015954A (es) | 2009-03-06 |
| BRPI0712001B8 (pt) | 2021-05-25 |
| BRPI0712001A2 (pt) | 2012-01-10 |
| PT2029143E (pt) | 2015-10-20 |
| ES2548437T3 (es) | 2015-10-16 |
| MY152178A (en) | 2014-08-15 |
| AU2007261568B2 (en) | 2013-05-16 |
| CN103145712A (zh) | 2013-06-12 |
| EP2029143A4 (en) | 2009-07-15 |
| US20110082139A1 (en) | 2011-04-07 |
| KR101413404B1 (ko) | 2014-06-27 |
| NZ597222A (en) | 2013-06-28 |
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