EA014907B1 - ИНГИБИТОРЫ Mnk2 НА ОСНОВЕ 8-ГЕТЕРОАРИЛПУРИНА ДЛЯ ЛЕЧЕНИЯ МЕТАБОЛИЧЕСКИХ НАРУШЕНИЙ - Google Patents
ИНГИБИТОРЫ Mnk2 НА ОСНОВЕ 8-ГЕТЕРОАРИЛПУРИНА ДЛЯ ЛЕЧЕНИЯ МЕТАБОЛИЧЕСКИХ НАРУШЕНИЙ Download PDFInfo
- Publication number
- EA014907B1 EA014907B1 EA200801897A EA200801897A EA014907B1 EA 014907 B1 EA014907 B1 EA 014907B1 EA 200801897 A EA200801897 A EA 200801897A EA 200801897 A EA200801897 A EA 200801897A EA 014907 B1 EA014907 B1 EA 014907B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- amine
- purin
- ethyl
- pyridin
- phenyl
- Prior art date
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78080006P | 2006-03-09 | 2006-03-09 | |
| PCT/US2007/063699 WO2007104053A2 (en) | 2006-03-09 | 2007-03-09 | 8-heteroarylpurine mnk2 inhibitors for treating metabolic disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200801897A1 EA200801897A1 (ru) | 2009-02-27 |
| EA014907B1 true EA014907B1 (ru) | 2011-02-28 |
Family
ID=38371082
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200801897A EA014907B1 (ru) | 2006-03-09 | 2007-03-09 | ИНГИБИТОРЫ Mnk2 НА ОСНОВЕ 8-ГЕТЕРОАРИЛПУРИНА ДЛЯ ЛЕЧЕНИЯ МЕТАБОЛИЧЕСКИХ НАРУШЕНИЙ |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US7951803B2 (enExample) |
| EP (1) | EP1991547A2 (enExample) |
| JP (1) | JP2009529541A (enExample) |
| KR (1) | KR20080107466A (enExample) |
| CN (1) | CN101454325A (enExample) |
| AU (1) | AU2007222982A1 (enExample) |
| BR (1) | BRPI0709007A2 (enExample) |
| CA (1) | CA2646429A1 (enExample) |
| EA (1) | EA014907B1 (enExample) |
| MX (1) | MX2008011525A (enExample) |
| WO (1) | WO2007104053A2 (enExample) |
| ZA (1) | ZA200807715B (enExample) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007030438A2 (en) * | 2005-09-06 | 2007-03-15 | Pharmacopeia, Inc. | Aminopurine derivatives for treating neurodegenerative diseases |
| TWI398252B (zh) * | 2006-05-26 | 2013-06-11 | 諾華公司 | 吡咯并嘧啶化合物及其用途 |
| AU2007309167A1 (en) * | 2006-10-20 | 2008-05-02 | N.V. Organon | Purines as PKC-theta inhibitors |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| AU2009284098B2 (en) | 2008-08-22 | 2012-03-29 | Astex Therapeutics Ltd. | Pyrrolopyrimidine compounds as CDK inhibitors |
| JP2013519719A (ja) * | 2010-02-18 | 2013-05-30 | セントロ ナシオナル デ インベスティガシオネス オンコロヒカス（セエネイオ） | トリアゾロ［４，５−ｂ］ピリジン誘導体 |
| UY33227A (es) | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina como inhibidores de la cdk4/6 |
| MX2012009735A (es) * | 2010-02-26 | 2012-09-12 | Boehringer Ingelheim Int | 4-[cicloalquiloxi (hetero) arilamino] tieno [2,3-d] pirimidinas que tienen actividad inhibitoria de mnk1/mnk2 para composiciones farmaceuticas. |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
| EP2560488B1 (en) | 2010-04-23 | 2015-10-28 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120055A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US10280168B2 (en) | 2012-03-30 | 2019-05-07 | Agency For Science, Technology And Research | Bicyclic heteroaryl derivatives as MNK1 and MNK2 modulators and uses thereof |
| GB201205669D0 (en) | 2012-03-30 | 2012-05-16 | Agency Science Tech & Res | Bicyclic heterocyclic derivatives as mnk2 and mnk2 modulators and uses thereof |
| JP6306035B2 (ja) | 2012-11-09 | 2018-04-04 | エヴォテック・インターナショナル・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＥｖｏｔｅｃ Ｉｎｔｅｒｎａｔｉｏｎａｌ ＧｍｂＨ | 医薬組成物のためのスルホキシミン置換キナゾリン |
| EP4772247A2 (en) | 2013-08-14 | 2026-07-08 | Novartis AG | Combination therapy comprising ribociclib and fulvestrant for the treatment of cancer |
| US20150051208A1 (en) * | 2013-08-14 | 2015-02-19 | Boehringer Ingelheim International Gmbh | Pyridinones |
| US10093660B2 (en) | 2013-12-04 | 2018-10-09 | Evotec Internatonal Gmbh | Sulfoximine substituted quinazolines for pharmaceutical compositions |
| WO2015091156A1 (en) | 2013-12-17 | 2015-06-25 | Boehringer Ingelheim International Gmbh | Sulfoximine substituted pyrrolotriazines for pharmaceutical compositions |
| JP6479854B2 (ja) | 2014-05-07 | 2019-03-06 | エヴォテック・インターナショナル・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＥｖｏｔｅｃ Ｉｎｔｅｒｎａｔｉｏｎａｌ ＧｍｂＨ | 医薬組成物のためのスルホキシイミン置換キナゾリン |
| CN105001096B (zh) * | 2015-07-21 | 2017-07-21 | 沈阳化工研究院有限公司 | 一种制备4‑氨基‑n‑烷基苄胺的方法 |
| CN106008506B (zh) * | 2016-06-27 | 2018-02-13 | 山东大学 | 取代嘌呤类衍生物及其制备方法与应用 |
| PL3984523T3 (pl) | 2018-12-07 | 2026-02-02 | Neurocrine Biosciences, Inc. | Antagonista receptora crf1, jego formulacje farmaceutyczne i postacie stałe do leczenia wrodzonego przerostu nadnerczy |
| US12383536B2 (en) | 2019-09-27 | 2025-08-12 | Neurocrine Biosciences, Inc. | CRF receptor antagonists and methods of use |
| ES3039926T3 (en) | 2019-12-04 | 2025-10-27 | Neurocrine Biosciences Inc | Crf receptor antagonists and methods of use |
| TW202329937A (zh) | 2021-12-03 | 2023-08-01 | 美商英塞特公司 | 雙環胺ｃｋ１２抑制劑 |
| US12084453B2 (en) | 2021-12-10 | 2024-09-10 | Incyte Corporation | Bicyclic amines as CDK12 inhibitors |
| US20250289806A1 (en) * | 2022-04-28 | 2025-09-18 | University Of Miami | Compounds for proliferative disorders |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003006465A1 (en) * | 2001-07-13 | 2003-01-23 | Cv Therapeutics, Inc. | Partial and full agonist of a adenosine receptors |
| WO2007030438A2 (en) * | 2005-09-06 | 2007-03-15 | Pharmacopeia, Inc. | Aminopurine derivatives for treating neurodegenerative diseases |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5554512A (en) * | 1993-05-24 | 1996-09-10 | Immunex Corporation | Ligands for flt3 receptors |
| JP4249804B2 (ja) | 1995-04-03 | 2009-04-08 | ノバルティス・アクチエンゲゼルシャフト | ピラゾール誘導体およびその製造法 |
| ZA9810490B (en) * | 1997-12-03 | 1999-05-20 | Dainippon Pharmaceutical Co | 2-Aryl-8-oxodihydropurine derivative process for the preparation thereof pharmaceutical composition containing the same and intermediate therefor |
| SE0102147D0 (sv) | 2001-06-18 | 2001-06-18 | Pharmacia Ab | New methods |
| AU2002363175A1 (en) | 2001-10-29 | 2003-05-12 | Develogen Aktiengesellschaft Fur Entwicklungsbiologische Forschung | Mnk kinase homologous proteins involved in the regulation of energy homeostasis and organelle metabolism |
| US7105526B2 (en) * | 2002-06-28 | 2006-09-12 | Banyu Pharmaceuticals Co., Ltd. | Benzimidazole derivatives |
| JP5704785B2 (ja) * | 2004-07-19 | 2015-04-22 | ザ・ジョンズ・ホプキンス・ユニバーシティ | 免疫抑制のためのｆｌｔ３阻害剤 |
| BRPI0517272A (pt) * | 2004-10-29 | 2008-10-07 | Tibotec Pharm Ltd | derivados de pirimidina bicìclicos de inibição de hiv |
| US7884109B2 (en) * | 2005-04-05 | 2011-02-08 | Wyeth Llc | Purine and imidazopyridine derivatives for immunosuppression |
| BRPI0610514A2 (pt) * | 2005-04-05 | 2016-11-16 | Pharmacopeia Inc | composto, composição farmacêutica, e, método de tratamento de um distúrbio |
| US20090023723A1 (en) * | 2005-09-21 | 2009-01-22 | Pharmacopeia Drug Discovery, Inc. | Purinone derivatives for treating neurodegenerative diseases |
| AU2006304897B2 (en) * | 2005-10-18 | 2012-07-12 | Janssen Pharmaceutica N.V. | Method of inhibiting FLT3 kinase |
| US7989459B2 (en) * | 2006-02-17 | 2011-08-02 | Pharmacopeia, Llc | Purinones and 1H-imidazopyridinones as PKC-theta inhibitors |
| US7902187B2 (en) * | 2006-10-04 | 2011-03-08 | Wyeth Llc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| TW200831104A (en) * | 2006-10-04 | 2008-08-01 | Pharmacopeia Inc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| AU2007309167A1 (en) * | 2006-10-20 | 2008-05-02 | N.V. Organon | Purines as PKC-theta inhibitors |
| US20080119496A1 (en) * | 2006-11-16 | 2008-05-22 | Pharmacopeia Drug Discovery, Inc. | 7-Substituted Purine Derivatives for Immunosuppression |
| US20080220256A1 (en) * | 2007-03-09 | 2008-09-11 | Ues, Inc. | Methods of coating carbon/carbon composite structures |
-
2007
- 2007-03-09 EP EP07758270A patent/EP1991547A2/en not_active Withdrawn
- 2007-03-09 CA CA002646429A patent/CA2646429A1/en not_active Abandoned
- 2007-03-09 KR KR1020087024592A patent/KR20080107466A/ko not_active Withdrawn
- 2007-03-09 JP JP2008558554A patent/JP2009529541A/ja active Pending
- 2007-03-09 BR BRPI0709007-2A patent/BRPI0709007A2/pt not_active IP Right Cessation
- 2007-03-09 US US11/684,262 patent/US7951803B2/en not_active Expired - Fee Related
- 2007-03-09 ZA ZA200807715A patent/ZA200807715B/xx unknown
- 2007-03-09 WO PCT/US2007/063699 patent/WO2007104053A2/en not_active Ceased
- 2007-03-09 AU AU2007222982A patent/AU2007222982A1/en not_active Abandoned
- 2007-03-09 MX MX2008011525A patent/MX2008011525A/es unknown
- 2007-03-09 CN CNA2007800157773A patent/CN101454325A/zh active Pending
- 2007-03-09 EA EA200801897A patent/EA014907B1/ru not_active IP Right Cessation
-
2011
- 2011-05-27 US US13/118,166 patent/US20110230480A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003006465A1 (en) * | 2001-07-13 | 2003-01-23 | Cv Therapeutics, Inc. | Partial and full agonist of a adenosine receptors |
| WO2007030438A2 (en) * | 2005-09-06 | 2007-03-15 | Pharmacopeia, Inc. | Aminopurine derivatives for treating neurodegenerative diseases |
Non-Patent Citations (1)
| Title |
|---|
| KNAUF U. ET AL.: "Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1and 2", MOLECULAR AND CELLULAR BIOLOGY, AMERICAN SOCIETY FOR MICROBIOLOGY, WASHINGTON, US, vol. 21, no. 16, August 2001 (2001-08), pages 5500-5511, XP002310601, ISSN 0270-7306, abstract, fig. 6 * |
Also Published As
| Publication number | Publication date |
|---|---|
| MX2008011525A (es) | 2008-09-18 |
| WO2007104053A3 (en) | 2007-11-01 |
| WO2007104053A2 (en) | 2007-09-13 |
| BRPI0709007A2 (pt) | 2011-06-21 |
| ZA200807715B (en) | 2009-11-25 |
| KR20080107466A (ko) | 2008-12-10 |
| US20080032971A1 (en) | 2008-02-07 |
| AU2007222982A1 (en) | 2007-09-13 |
| CA2646429A1 (en) | 2007-09-13 |
| US20110230480A1 (en) | 2011-09-22 |
| US7951803B2 (en) | 2011-05-31 |
| EA200801897A1 (ru) | 2009-02-27 |
| JP2009529541A (ja) | 2009-08-20 |
| EP1991547A2 (en) | 2008-11-19 |
| CN101454325A (zh) | 2009-06-10 |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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