JP2007508290A - ＧＳＫ−３阻害剤としての置換２Ｈ−［１，２，４］トリアゾロ［４，３−ａ］ピラジン - Google Patents
ＧＳＫ−３阻害剤としての置換２Ｈ−［１，２，４］トリアゾロ［４，３−ａ］ピラジン Download PDFInfo
- Publication number
- JP2007508290A JP2007508290A JP2006530734A JP2006530734A JP2007508290A JP 2007508290 A JP2007508290 A JP 2007508290A JP 2006530734 A JP2006530734 A JP 2006530734A JP 2006530734 A JP2006530734 A JP 2006530734A JP 2007508290 A JP2007508290 A JP 2007508290A
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- JP
- Japan
- Prior art keywords
- independently
- alkyl
- triazolo
- substituted
- pyrazin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- BNKVGZXDUVAYFS-UHFFFAOYSA-N ethyl 4-[(6-tert-butyl-3-oxo-2h-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1NC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 BNKVGZXDUVAYFS-UHFFFAOYSA-N 0.000 claims 2
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Classifications
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Landscapes
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- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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Applications Claiming Priority (2)
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| US51022403P | 2003-10-10 | 2003-10-10 | |
| PCT/IB2004/003137 WO2005035532A1 (en) | 2003-10-10 | 2004-09-27 | Substituted 2h-[1,2,4]triazolo[4,3-a]pyrazines as gsk-3 inhibitors |
Publications (2)
| Publication Number | Publication Date |
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| JP2007508290A true JP2007508290A (ja) | 2007-04-05 |
| JP2007508290A5 JP2007508290A5 (https=) | 2007-10-11 |
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Country Status (10)
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| US (1) | US7709473B2 (https=) |
| EP (1) | EP1678180B1 (https=) |
| JP (1) | JP2007508290A (https=) |
| AT (1) | ATE369370T1 (https=) |
| BR (1) | BRPI0415185A (https=) |
| CA (1) | CA2541832C (https=) |
| DE (1) | DE602004008098T8 (https=) |
| ES (1) | ES2288270T3 (https=) |
| MX (1) | MXPA06004043A (https=) |
| WO (1) | WO2005035532A1 (https=) |
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| JP2011006404A (ja) * | 2009-05-27 | 2011-01-13 | Toyama Chem Co Ltd | ３，６−ジクロロ−２−ピラジンカルボニトリルの製造法 |
| JP2011520819A (ja) * | 2008-05-15 | 2011-07-21 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | 置換イミダゾ−およびトリアゾロピリミジン類、イミダゾ−およびピラゾロピラジン類およびイミダゾトリアジン類 |
| KR20170016465A (ko) * | 2014-06-17 | 2017-02-13 | 치아타이 티안큉 파마수티컬 그룹 주식회사 | PI3K 억제제로 사용되는 피리디노[1,2-a]피리미돈 유사체 |
| JP2017518382A (ja) * | 2014-06-17 | 2017-07-06 | リーシン ファーマシューティカル カンパニー リミテッド | ｍＴＯＲ／ＰＩ３Ｋ阻害剤としてのピリド［１，２−ａ］ピリミジノン類似体 |
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| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| DE102007012645A1 (de) * | 2007-03-16 | 2008-09-18 | Bayer Healthcare Ag | Substituierte Imidazo- und Triazolopyrimidine |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002080064A1 (en) * | 2001-03-28 | 2002-10-10 | Sony Computer Entertainment Inc. | Content distribution system |
| WO2002088078A2 (en) * | 2001-04-30 | 2002-11-07 | Vertex Pharmaceuticals Incorporated | INHIBITORS OF GSK-3 AND CRYSTAL STRUCTURES OF GSK-3β PROTEIN AND PROTEIN COMPLEXES |
| WO2003072580A1 (en) * | 2002-02-28 | 2003-09-04 | Sanofi-Aventis | 1-[ALKYL], 1-[HETEROARYL)ALKYL] AND 1-[ARYL)ALKYL]-7-(PYRIMIDIN-4-YL)-IMADAZO[1,2-a]PYRIMIDIN-5(1H)-ONE DERIVATIVES |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1235910A (en) * | 1968-12-10 | 1971-06-16 | Ici Ltd | Pharmaceutical compositions |
| FR2662163A1 (fr) * | 1990-05-16 | 1991-11-22 | Lipha | Nouvelles 8-amino-1,2,4-triazolo(4,3-a) pyrazines, procedes de preparation et medicaments les contenant. |
| BRPI0407926A (pt) | 2003-03-27 | 2006-02-21 | Pfizer Prod Inc | 4-amino[1,2,4]triazol[4,3-a]quinoxalinas substituìdas |
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2004
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- 2004-09-27 EP EP04769486A patent/EP1678180B1/en not_active Expired - Lifetime
- 2004-09-27 WO PCT/IB2004/003137 patent/WO2005035532A1/en not_active Ceased
- 2004-09-27 BR BRPI0415185-2A patent/BRPI0415185A/pt not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002080064A1 (en) * | 2001-03-28 | 2002-10-10 | Sony Computer Entertainment Inc. | Content distribution system |
| WO2002088078A2 (en) * | 2001-04-30 | 2002-11-07 | Vertex Pharmaceuticals Incorporated | INHIBITORS OF GSK-3 AND CRYSTAL STRUCTURES OF GSK-3β PROTEIN AND PROTEIN COMPLEXES |
| WO2003072580A1 (en) * | 2002-02-28 | 2003-09-04 | Sanofi-Aventis | 1-[ALKYL], 1-[HETEROARYL)ALKYL] AND 1-[ARYL)ALKYL]-7-(PYRIMIDIN-4-YL)-IMADAZO[1,2-a]PYRIMIDIN-5(1H)-ONE DERIVATIVES |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011520819A (ja) * | 2008-05-15 | 2011-07-21 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | 置換イミダゾ−およびトリアゾロピリミジン類、イミダゾ−およびピラゾロピラジン類およびイミダゾトリアジン類 |
| JP2011006404A (ja) * | 2009-05-27 | 2011-01-13 | Toyama Chem Co Ltd | ３，６−ジクロロ−２−ピラジンカルボニトリルの製造法 |
| KR20170016465A (ko) * | 2014-06-17 | 2017-02-13 | 치아타이 티안큉 파마수티컬 그룹 주식회사 | PI3K 억제제로 사용되는 피리디노[1,2-a]피리미돈 유사체 |
| JP2017518382A (ja) * | 2014-06-17 | 2017-07-06 | リーシン ファーマシューティカル カンパニー リミテッド | ｍＴＯＲ／ＰＩ３Ｋ阻害剤としてのピリド［１，２−ａ］ピリミジノン類似体 |
| JP2017519821A (ja) * | 2014-06-17 | 2017-07-20 | チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッド | ＰＩ３Ｋ阻害剤としてのピリド［１，２−ａ］ピリミドン類似体 |
| KR102495840B1 (ko) | 2014-06-17 | 2023-02-03 | 치아타이 티안큉 파마수티컬 그룹 주식회사 | PI3K 억제제로 사용되는 피리디노[1,2-a]피리미돈 유사체 |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE369370T1 (de) | 2007-08-15 |
| MXPA06004043A (es) | 2006-06-28 |
| WO2005035532A1 (en) | 2005-04-21 |
| EP1678180A1 (en) | 2006-07-12 |
| DE602004008098D1 (de) | 2007-09-20 |
| CA2541832C (en) | 2009-11-24 |
| DE602004008098T8 (de) | 2008-04-17 |
| ES2288270T3 (es) | 2008-01-01 |
| US7709473B2 (en) | 2010-05-04 |
| CA2541832A1 (en) | 2005-04-21 |
| US20070249612A1 (en) | 2007-10-25 |
| EP1678180B1 (en) | 2007-08-08 |
| BRPI0415185A (pt) | 2006-11-28 |
| DE602004008098T2 (de) | 2007-12-13 |
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