JP2011504474A - アルツハイマー氏病を治療するためのＭｎｋインヒビターの使用 - Google Patents
アルツハイマー氏病を治療するためのＭｎｋインヒビターの使用 Download PDFInfo
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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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- 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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- Psychiatry (AREA)
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- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07022695 | 2007-11-22 | ||
| PCT/EP2008/009880 WO2009065596A2 (en) | 2007-11-22 | 2008-11-21 | Use of mnk inhibitors for the treatment of alzheimer's disease |
Publications (2)
| Publication Number | Publication Date |
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| JP2011504474A true JP2011504474A (ja) | 2011-02-10 |
| JP2011504474A5 JP2011504474A5 (cg-RX-API-DMAC7.html) | 2011-12-22 |
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Family Applications (1)
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| JP2010534409A Pending JP2011504474A (ja) | 2007-11-22 | 2008-11-21 | アルツハイマー氏病を治療するためのＭｎｋインヒビターの使用 |
Country Status (5)
| Country | Link |
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| US (1) | US20100247517A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2219649A2 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2011504474A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2706203A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2009065596A2 (cg-RX-API-DMAC7.html) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013520471A (ja) * | 2010-02-26 | 2013-06-06 | ベーリンガー インゲルハイム 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 | 医薬組成物のためのｍｎｋｌ／ｍｎｋ２阻害活性を有する４−［シクロアルキルオキシ（ヘテロ）アリールアミノ］チエノ「２，３−ｄ］ピリミジン |
| JP2013520474A (ja) * | 2010-02-26 | 2013-06-06 | ベーリンガー インゲルハイム 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 | 医薬組成物のための置換アルキル基含有チエノピリミジン |
| JP2013520472A (ja) * | 2010-02-26 | 2013-06-06 | ベーリンガー インゲルハイム 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 | 医薬組成物のためのヘテロシクロアルキル含有チエノピリミジン |
| JP2018534316A (ja) * | 2015-11-20 | 2018-11-22 | ライフアークＬｉｆｅａｒｃ | Ｍｎｋ阻害剤としてのピロロピリミジン化合物 |
| JP2018534314A (ja) * | 2015-11-20 | 2018-11-22 | ライフアークＬｉｆｅａｒｃ | Ｍｎｋ阻害剤としての縮合チアゾロピリミジン誘導体 |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5301986B2 (ja) * | 2005-06-22 | 2013-09-25 | ベーリンガー インゲルハイム 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 | 医薬組成物用のチエノピリミジン類 |
| CA2651898A1 (en) * | 2006-04-07 | 2007-10-18 | Develogen Aktiengesellschaft | Thienopyrimidines having mnk1/mnk2 inhibiting activity for pharmaceutical compositions |
| EP1889847A1 (en) * | 2006-07-10 | 2008-02-20 | DeveloGen Aktiengesellschaft | Pyrrolopyrimidines for pharmaceutical compositions |
| JP2010528647A (ja) * | 2007-06-06 | 2010-08-26 | ドマンティス リミテッド | ポリペプチド、抗体可変ドメインおよびアンタゴニスト |
| AU2009286734A1 (en) | 2008-08-26 | 2010-03-04 | Boehringer Ingelheim International Gmbh | Thienopyrimidines for pharmaceutical compositions |
| ES2899000T3 (es) | 2011-07-18 | 2022-03-09 | Merck Patent Gmbh | Benzamidas |
| EP3134405B1 (en) | 2014-04-25 | 2019-08-28 | Pfizer Inc | Heteroaromatic compounds and their use as dopamine d1 ligands |
| KR20190117013A (ko) | 2017-02-14 | 2019-10-15 | 이펙터 테라퓨틱스, 인크. | 피페리딘-치환된 Mnk 억제제 및 그와 관련된 방법 |
| BR112021007745A2 (pt) | 2018-10-24 | 2021-07-27 | Effector Therapeutics, Inc. | formas cristalinas de inibidores de mnk |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002540112A (ja) * | 1999-03-23 | 2002-11-26 | アストラゼネカ アクチボラグ | ピリジンおよびピリミジン誘導体、およびサイトカインに媒介される疾患の阻害物質としてのそれらの使用 |
| WO2005042537A1 (en) * | 2003-10-22 | 2005-05-12 | Bristol-Myers Squibb Company | Phenyl-aniline substituted bicyclic compounds useful as kinase inhibitors |
| WO2005117890A2 (en) * | 2004-06-04 | 2005-12-15 | Astrazeneca Ab | Thienopyrimidines and thiazolopyrimidines for use in medicine |
| WO2006066937A2 (en) * | 2004-12-23 | 2006-06-29 | Develogen Aktiengesellschaft | Mnk1 or mnk2 inhibitors |
| WO2006136402A1 (en) * | 2005-06-22 | 2006-12-28 | Develogen Aktiengesellschaft | Thienopyrimidines for pharmaceutical compositions |
| WO2007109851A1 (en) * | 2006-03-29 | 2007-10-04 | Velacor Therapeutics Pty Ltd | Treatment of neurodegenerative diseases |
| WO2007115822A1 (en) * | 2006-04-07 | 2007-10-18 | Develogen Aktiengesellschaft | Thienopyrimidines having mnkl /mnk2 inhibiting activity for pharmaceutical compositions |
| WO2007118984A1 (fr) * | 2006-03-30 | 2007-10-25 | Neurokin | Utilisation de la ( s ) -roscovitine pour la prevention et/ou le traitement de maladies neurologiques |
| WO2007127273A2 (en) * | 2006-04-24 | 2007-11-08 | Alltech, Inc. | Methods and compositions for altering cell function |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW370529B (en) * | 1992-12-17 | 1999-09-21 | Pfizer | Pyrazolopyrimidines |
| EP0729758A3 (en) * | 1995-03-02 | 1997-10-29 | Pfizer | Pyrazolopyrimidines and pyrrolopyrimidines for the treatment of neuronal and other diseases |
| AU2005204358B2 (en) * | 2004-01-05 | 2008-09-04 | Merz Pharma Gmbh & Co. Kgaa | Memantine for the treatment of mild and mild-to-moderate Alzheimer's disease |
| WO2007059905A2 (en) * | 2005-11-25 | 2007-05-31 | Develogen Aktiengesellschaft | Thienopyrimidines treating inflammatory diseases |
| EP2044051B1 (en) * | 2006-06-22 | 2010-01-27 | BIOVITRUM AB (publ) | Pyridine and pyrazine derivatives as mnk kinase inhibitors |
-
2008
- 2008-11-21 CA CA2706203A patent/CA2706203A1/en not_active Abandoned
- 2008-11-21 JP JP2010534409A patent/JP2011504474A/ja active Pending
- 2008-11-21 EP EP08852675A patent/EP2219649A2/en not_active Withdrawn
- 2008-11-21 WO PCT/EP2008/009880 patent/WO2009065596A2/en not_active Ceased
- 2008-11-21 US US12/744,374 patent/US20100247517A1/en not_active Abandoned
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002540112A (ja) * | 1999-03-23 | 2002-11-26 | アストラゼネカ アクチボラグ | ピリジンおよびピリミジン誘導体、およびサイトカインに媒介される疾患の阻害物質としてのそれらの使用 |
| WO2005042537A1 (en) * | 2003-10-22 | 2005-05-12 | Bristol-Myers Squibb Company | Phenyl-aniline substituted bicyclic compounds useful as kinase inhibitors |
| WO2005117890A2 (en) * | 2004-06-04 | 2005-12-15 | Astrazeneca Ab | Thienopyrimidines and thiazolopyrimidines for use in medicine |
| WO2006066937A2 (en) * | 2004-12-23 | 2006-06-29 | Develogen Aktiengesellschaft | Mnk1 or mnk2 inhibitors |
| WO2006136402A1 (en) * | 2005-06-22 | 2006-12-28 | Develogen Aktiengesellschaft | Thienopyrimidines for pharmaceutical compositions |
| WO2007109851A1 (en) * | 2006-03-29 | 2007-10-04 | Velacor Therapeutics Pty Ltd | Treatment of neurodegenerative diseases |
| WO2007118984A1 (fr) * | 2006-03-30 | 2007-10-25 | Neurokin | Utilisation de la ( s ) -roscovitine pour la prevention et/ou le traitement de maladies neurologiques |
| WO2007115822A1 (en) * | 2006-04-07 | 2007-10-18 | Develogen Aktiengesellschaft | Thienopyrimidines having mnkl /mnk2 inhibiting activity for pharmaceutical compositions |
| WO2007127273A2 (en) * | 2006-04-24 | 2007-11-08 | Alltech, Inc. | Methods and compositions for altering cell function |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013520471A (ja) * | 2010-02-26 | 2013-06-06 | ベーリンガー インゲルハイム 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 | 医薬組成物のためのｍｎｋｌ／ｍｎｋ２阻害活性を有する４−［シクロアルキルオキシ（ヘテロ）アリールアミノ］チエノ「２，３−ｄ］ピリミジン |
| JP2013520474A (ja) * | 2010-02-26 | 2013-06-06 | ベーリンガー インゲルハイム 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 | 医薬組成物のための置換アルキル基含有チエノピリミジン |
| JP2013520472A (ja) * | 2010-02-26 | 2013-06-06 | ベーリンガー インゲルハイム 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 | 医薬組成物のためのヘテロシクロアルキル含有チエノピリミジン |
| JP2018534316A (ja) * | 2015-11-20 | 2018-11-22 | ライフアークＬｉｆｅａｒｃ | Ｍｎｋ阻害剤としてのピロロピリミジン化合物 |
| JP2018534314A (ja) * | 2015-11-20 | 2018-11-22 | ライフアークＬｉｆｅａｒｃ | Ｍｎｋ阻害剤としての縮合チアゾロピリミジン誘導体 |
| JP2021073306A (ja) * | 2015-11-20 | 2021-05-13 | ライフアークＬｉｆｅａｒｃ | Ｍｎｋ阻害剤としての縮合チアゾロピリミジン誘導体 |
| JP7181647B2 (ja) | 2015-11-20 | 2022-12-01 | ライフアーク | Ｍｎｋ阻害剤としての縮合チアゾロピリミジン誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20100247517A1 (en) | 2010-09-30 |
| WO2009065596A2 (en) | 2009-05-28 |
| CA2706203A1 (en) | 2009-05-28 |
| EP2219649A2 (en) | 2010-08-25 |
| WO2009065596A3 (en) | 2009-08-20 |
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