EA016527B1 - Триазолопиридазиновые модуляторы протеинкиназ - Google Patents
Триазолопиридазиновые модуляторы протеинкиназ Download PDFInfo
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- EA016527B1 EA016527B1 EA200970402A EA200970402A EA016527B1 EA 016527 B1 EA016527 B1 EA 016527B1 EA 200970402 A EA200970402 A EA 200970402A EA 200970402 A EA200970402 A EA 200970402A EA 016527 B1 EA016527 B1 EA 016527B1
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- Eurasian Patent Office
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- cancer
- methyl
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- 102000001253 Protein Kinase Human genes 0.000 title abstract description 31
- 108060006633 protein kinase Proteins 0.000 title abstract description 31
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- CJLRTXGWNOAMHX-UHFFFAOYSA-N tert-butyl 2-(7-methylquinolin-6-yl)acetate Chemical compound C1=CC=C2C=C(CC(=O)OC(C)(C)C)C(C)=CC2=N1 CJLRTXGWNOAMHX-UHFFFAOYSA-N 0.000 description 1
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- DYBIXDJMIONIDX-UHFFFAOYSA-N tert-butyl 3-(4-bromopyrazol-1-yl)azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1N1N=CC(Br)=C1 DYBIXDJMIONIDX-UHFFFAOYSA-N 0.000 description 1
- QSQWENQPOSRWLP-UHFFFAOYSA-N tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1N=CC(B2OC(C)(C)C(C)(C)O2)=C1 QSQWENQPOSRWLP-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
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- 238000004809 thin layer chromatography Methods 0.000 description 1
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- FERKWUXUTFCIFW-UHFFFAOYSA-N trimethyl-[2-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]methoxy]ethyl]silane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(COCC[Si](C)(C)C)N=C1 FERKWUXUTFCIFW-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D403/02—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 two hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86255206P | 2006-10-23 | 2006-10-23 | |
| US87138406P | 2006-12-21 | 2006-12-21 | |
| US91375207P | 2007-04-24 | 2007-04-24 | |
| US95283307P | 2007-07-30 | 2007-07-30 | |
| PCT/US2007/081832 WO2008051805A2 (en) | 2006-10-23 | 2007-10-18 | Triazolo-pyridazine protein kinase modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200970402A1 EA200970402A1 (ru) | 2009-10-30 |
| EA016527B1 true EA016527B1 (ru) | 2012-05-30 |
Family
ID=39031065
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200970402A EA016527B1 (ru) | 2006-10-23 | 2007-10-18 | Триазолопиридазиновые модуляторы протеинкиназ |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US8071581B2 (enExample) |
| EP (1) | EP2081937B1 (enExample) |
| JP (1) | JP2010507577A (enExample) |
| KR (1) | KR101083177B1 (enExample) |
| AU (1) | AU2007309237B2 (enExample) |
| BR (1) | BRPI0717317A2 (enExample) |
| CA (1) | CA2667453A1 (enExample) |
| DK (1) | DK2081937T3 (enExample) |
| EA (1) | EA016527B1 (enExample) |
| ES (1) | ES2393132T3 (enExample) |
| MX (1) | MX2009004060A (enExample) |
| PE (1) | PE20081256A1 (enExample) |
| PL (1) | PL2081937T3 (enExample) |
| PT (1) | PT2081937E (enExample) |
| TW (1) | TW200833692A (enExample) |
| WO (1) | WO2008051805A2 (enExample) |
Families Citing this family (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5420395B2 (ja) | 2006-04-07 | 2014-02-19 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｐ結合カセット輸送体の調節剤 |
| USRE50453E1 (en) | 2006-04-07 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| US7645789B2 (en) | 2006-04-07 | 2010-01-12 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| US10022352B2 (en) | 2006-04-07 | 2018-07-17 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| PE20121506A1 (es) | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| US8198448B2 (en) | 2006-07-14 | 2012-06-12 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| US7683060B2 (en) | 2006-08-07 | 2010-03-23 | Incyte Corporation | Triazolotriazines as kinase inhibitors |
| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| GEP20125658B (en) | 2006-11-22 | 2012-10-10 | Incyte Corp | Imidazotriazines and imidazo pyrimidines as kinase inhibitors |
| PE20091468A1 (es) | 2008-02-28 | 2009-10-22 | Novartis Ag | DERIVADOS DE 3-METIL-IMIDAZO-[1,2-b]-PIRIDAZINA |
| SI2300455T1 (sl) * | 2008-05-21 | 2017-12-29 | Incyte Holdings Corporation | Soli 2-fluoro-n-metil-4-(7-(kinolin-6-il-metil)-imidazo(1,2-b)1,2,4) triazin-2-il)benzamid in postopki v zvezi z njihovo pripravo |
| DE102008028905A1 (de) * | 2008-06-18 | 2009-12-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo[4,3-b]pyridazinderivate |
| DE102008037790A1 (de) | 2008-08-14 | 2010-02-18 | Merck Patent Gmbh | Bicyclische Triazolderivate |
| DE102008038222A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Indazol-5-carbonsäurehydrazid-derivate |
| DE102008038220A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Oxadiazolderivate |
| DE102008038221A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | 7-Azaindolderivate |
| EP2356116A1 (en) * | 2008-11-20 | 2011-08-17 | OSI Pharmaceuticals, Inc. | Substituted pyrroloý2,3-b¨-pyridines and-pyrazines |
| EP2381777A4 (en) * | 2008-12-12 | 2012-08-08 | Ariad Pharma Inc | AZAINDOL DERIVATIVES AS KINASEHEMMER |
| DE102008063667A1 (de) * | 2008-12-18 | 2010-07-01 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-°[1,2,4]triazolo[4,3-b]pyrimidin-derivate |
| DE102008062825A1 (de) | 2008-12-23 | 2010-06-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo [4,3-b]pyridazin-derivate |
| WO2010092371A1 (en) * | 2009-02-10 | 2010-08-19 | Astrazeneca Ab | Triazolo [4,3-b] pyridazine derivatives and their uses for prostate cancer |
| JP2012519731A (ja) * | 2009-03-09 | 2012-08-30 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | ニコチン受容体およびｇａｂａａ受容体のアロステリックモジュレーターとしての置換複素環およびそれらの使用 |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| BR112012003262A8 (pt) | 2009-08-12 | 2016-05-17 | Novartis Ag | compostos de hidrazona heterocíclica e seus usos para tratar câncer e inflamação |
| IN2012DN01453A (enExample) | 2009-08-20 | 2015-06-05 | Novartis Ag | |
| PT3511330T (pt) * | 2009-12-31 | 2020-12-24 | Hutchison Medipharma Ltd | Intermediário sintético útil na preparação de inibidores de triazolopiridina c-met |
| MX2012008898A (es) | 2010-02-03 | 2012-11-06 | Incyte Corp | Imidazo - [1, 2 - b] [1, 2, 4] triazinas como inhibidores de c - met. |
| US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
| RU2569678C2 (ru) | 2010-04-22 | 2015-11-27 | Вертекс Фармасьютикалз Инкорпорейтед | Способ получения циклоалкилкарбоксамидо-индольных соединений |
| AR081039A1 (es) | 2010-05-14 | 2012-05-30 | Osi Pharmaceuticals Llc | Inhibidores biciclicos fusionados de quinasa |
| US20130072495A1 (en) | 2010-05-14 | 2013-03-21 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
| JP5960688B2 (ja) | 2010-05-17 | 2016-08-02 | インコゼン セラピューティクス プライベート リミテッド | プロテインキナーゼ調節物質としての新規３，５−二置換−３ｈ−［１，２，３］トリアゾロ［４，５−ｂ］ピリジン化合物 |
| US8513291B2 (en) * | 2010-06-01 | 2013-08-20 | Angion Biomedica Corp. | Cytochrome P450 inhibitors and uses thereof |
| US10414760B2 (en) | 2016-11-29 | 2019-09-17 | Angion Biomedica Corp. | Cytochrome P450 inhibitors and uses thereof |
| AR085183A1 (es) | 2010-07-30 | 2013-09-18 | Lilly Co Eli | Compuesto 6-(1-metil-1h-pirazol-4-il)-3-(2-metil-2h-indazol-5-iltio)-[1,2,4]triazol[4,3-b]piridazina, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para tratar cancer |
| WO2012107500A1 (en) | 2011-02-10 | 2012-08-16 | Novartis Ag | [1, 2, 4] triazolo [4, 3 -b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| JP2014513724A (ja) | 2011-05-16 | 2014-06-05 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 融合二環キナーゼ阻害剤 |
| UY34329A (es) | 2011-09-15 | 2013-04-30 | Novartis Ag | Compuestos de triazolopiridina |
| EP2760866B1 (en) | 2011-09-27 | 2017-12-13 | Genfit | Derivatives of 6-substituted triazolopyridazines as rev-erb agonists |
| KR101869534B1 (ko) * | 2012-03-05 | 2018-06-20 | 한국화학연구원 | 신규한 트리아졸로 피리다진 유도체 및 그의 용도 |
| CN104321322A (zh) | 2012-03-30 | 2015-01-28 | 理森制药股份公司 | 作为c-met蛋白激酶调节剂的新型3,5-二取代-3h-咪唑并[4,5-b]吡啶和3,5-二取代-3h-[1,2,3]三唑并[4,5-b]吡啶化合物 |
| AU2013290444B2 (en) | 2012-07-16 | 2018-04-26 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of (R)-1-(2,2-diflurorbenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl) cyclopropanecarboxamide and administration thereof |
| CN103122000B (zh) * | 2012-09-03 | 2013-12-25 | 中美冠科生物技术（太仓）有限公司 | 用作抗肿瘤药物的高选择性的c-Met激酶抑制剂 |
| HK1213887A1 (zh) | 2012-10-16 | 2016-07-15 | Janssen Pharmaceutica N.V. | RORγt的苯基连接的喹啉基调节剂 |
| WO2014062655A1 (en) | 2012-10-16 | 2014-04-24 | Janssen Pharmaceutica Nv | HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt |
| MY189505A (en) | 2012-10-16 | 2022-02-16 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of roryt |
| WO2014133526A1 (en) | 2013-02-28 | 2014-09-04 | Empire Technology Development Llc | Colored pigment particles for electrophoretic displays |
| US9303043B2 (en) * | 2013-03-13 | 2016-04-05 | Greentech, Inc. | Process for making benzoxazepin compounds |
| US20140303121A1 (en) | 2013-03-15 | 2014-10-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| CN105073747B (zh) | 2013-03-15 | 2017-06-06 | 普莱希科公司 | 杂环化合物及其应用 |
| US9221804B2 (en) | 2013-10-15 | 2015-12-29 | Janssen Pharmaceutica Nv | Secondary alcohol quinolinyl modulators of RORγt |
| US9328095B2 (en) | 2013-10-15 | 2016-05-03 | Janssen Pharmaceutica Nv | Heteroaryl linked quinolinyl modulators of RORgammat |
| US9403816B2 (en) | 2013-10-15 | 2016-08-02 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of RORγt |
| US9284308B2 (en) | 2013-10-15 | 2016-03-15 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of RORγt |
| US10555941B2 (en) | 2013-10-15 | 2020-02-11 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORγt |
| CA2926339A1 (en) | 2013-10-15 | 2015-04-23 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of roryt |
| CA2927182A1 (en) | 2013-10-15 | 2015-04-23 | Janssen Pharmaceutica Nv | Quinolinyl modulators of ror.gamma.t |
| GB201321745D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| WO2015134854A2 (en) * | 2014-03-06 | 2015-09-11 | Oyagen, Inc. | Small molecule vif dimerization antagonists as anti-hiv agents and for use as hiv/aids therapeutics |
| PL3925607T5 (pl) | 2014-04-15 | 2026-06-01 | Vertex Pharmaceuticals Incorporated | Kompozycje farmaceutyczne do leczenia chorób, w których pośredniczy mukowiscydozowy przezbłonowy regulator przewodnictwa |
| CA2957785C (en) | 2014-08-11 | 2023-01-03 | Angion Biomedica Corporation | Cytochrome p450 inhibitors and uses thereof |
| CA2970819A1 (en) | 2014-12-31 | 2016-07-07 | Angion Biomedica Corp. | Methods and agents for treating disease |
| CA2980460A1 (en) * | 2015-04-13 | 2016-10-20 | Five Prime Therapeutics, Inc. | Combination therapy for cancer |
| CR20180109A (es) | 2015-07-20 | 2018-05-03 | Genzyme Corp | Inhibidores de receptor del factor estimulador de colonias 1 (csf-1r) |
| US10717735B2 (en) | 2017-10-13 | 2020-07-21 | Plexxikon Inc. | Solid forms of a compound for modulating kinases |
| GB201905721D0 (en) | 2019-04-24 | 2019-06-05 | Univ Dundee | Compounds |
| CN113861198B (zh) * | 2020-06-30 | 2024-08-02 | 上海医药集团股份有限公司 | 咪唑并[4,5-b]吡嗪类化合物、其制备方法及应用 |
| US11530216B2 (en) | 2020-12-23 | 2022-12-20 | Genzyme Corporation | Deuterated colony stimulating factor-1 receptor (CSF-1R) inhibitors |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002083139A1 (en) * | 2001-04-10 | 2002-10-24 | Merck & Co., Inc. | Inhibitors of akt activity |
| WO2002083675A2 (en) * | 2001-04-10 | 2002-10-24 | Merck Sharp & Dohme Limited | Inhibitors of akt activity |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100932677B1 (ko) * | 2001-08-10 | 2009-12-22 | 요코하마 티엘오 가부시키가이샤 | 열전달 장치 |
| RS55630B1 (sr) * | 2005-12-21 | 2017-06-30 | Janssen Pharmaceutica Nv | Triazolopiridazini kao modulatori tirozin kinaze |
| CA2651979A1 (en) * | 2006-05-30 | 2007-12-06 | Pfizer Products Inc. | Triazolopyridazine derivatives |
| PE20121506A1 (es) * | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
-
2007
- 2007-10-18 EA EA200970402A patent/EA016527B1/ru not_active IP Right Cessation
- 2007-10-18 PL PL07854193T patent/PL2081937T3/pl unknown
- 2007-10-18 DK DK07854193.5T patent/DK2081937T3/da active
- 2007-10-18 MX MX2009004060A patent/MX2009004060A/es not_active Application Discontinuation
- 2007-10-18 KR KR1020097007986A patent/KR101083177B1/ko not_active Expired - Fee Related
- 2007-10-18 PT PT07854193T patent/PT2081937E/pt unknown
- 2007-10-18 AU AU2007309237A patent/AU2007309237B2/en not_active Ceased
- 2007-10-18 US US12/442,987 patent/US8071581B2/en not_active Expired - Fee Related
- 2007-10-18 JP JP2009533536A patent/JP2010507577A/ja not_active Withdrawn
- 2007-10-18 ES ES07854193T patent/ES2393132T3/es active Active
- 2007-10-18 BR BRPI0717317-2A2A patent/BRPI0717317A2/pt not_active IP Right Cessation
- 2007-10-18 EP EP07854193A patent/EP2081937B1/en active Active
- 2007-10-18 CA CA002667453A patent/CA2667453A1/en not_active Abandoned
- 2007-10-18 WO PCT/US2007/081832 patent/WO2008051805A2/en not_active Ceased
- 2007-10-22 TW TW096139481A patent/TW200833692A/zh unknown
- 2007-10-23 PE PE2007001436A patent/PE20081256A1/es not_active Application Discontinuation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002083139A1 (en) * | 2001-04-10 | 2002-10-24 | Merck & Co., Inc. | Inhibitors of akt activity |
| WO2002083675A2 (en) * | 2001-04-10 | 2002-10-24 | Merck Sharp & Dohme Limited | Inhibitors of akt activity |
Also Published As
| Publication number | Publication date |
|---|---|
| MX2009004060A (es) | 2009-06-19 |
| CA2667453A1 (en) | 2008-05-02 |
| AU2007309237B2 (en) | 2012-03-22 |
| ES2393132T3 (es) | 2012-12-18 |
| PL2081937T3 (pl) | 2013-01-31 |
| KR101083177B1 (ko) | 2011-11-11 |
| PE20081256A1 (es) | 2008-10-13 |
| EP2081937B1 (en) | 2012-09-12 |
| PT2081937E (pt) | 2012-10-15 |
| KR20090069303A (ko) | 2009-06-30 |
| EA200970402A1 (ru) | 2009-10-30 |
| JP2010507577A (ja) | 2010-03-11 |
| WO2008051805A2 (en) | 2008-05-02 |
| US20100120739A1 (en) | 2010-05-13 |
| WO2008051805A3 (en) | 2008-07-10 |
| EP2081937A2 (en) | 2009-07-29 |
| US8071581B2 (en) | 2011-12-06 |
| BRPI0717317A2 (pt) | 2013-10-22 |
| DK2081937T3 (da) | 2012-10-01 |
| AU2007309237A1 (en) | 2008-05-02 |
| TW200833692A (en) | 2008-08-16 |
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| Date | Code | Title | Description |
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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) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |