EA023132B1 - Бициклические азагетероциклические карбоксамиды - Google Patents
Бициклические азагетероциклические карбоксамиды Download PDFInfo
- Publication number
- EA023132B1 EA023132B1 EA201300186A EA201300186A EA023132B1 EA 023132 B1 EA023132 B1 EA 023132B1 EA 201300186 A EA201300186 A EA 201300186A EA 201300186 A EA201300186 A EA 201300186A EA 023132 B1 EA023132 B1 EA 023132B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- methyl
- ethyl
- methylamino
- amino
- azetidin
- Prior art date
Links
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- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
-
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
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Applications Claiming Priority (2)
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| US36896410P | 2010-07-29 | 2010-07-29 | |
| PCT/EP2011/003272 WO2012013282A1 (en) | 2010-07-29 | 2011-07-01 | Bicyclic azaheterocyclic carboxamides as inhibitors of the kinase p70s6k |
Publications (2)
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| EA201300186A1 EA201300186A1 (ru) | 2013-12-30 |
| EA023132B1 true EA023132B1 (ru) | 2016-04-29 |
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| EA201300186A EA023132B1 (ru) | 2010-07-29 | 2011-07-01 | Бициклические азагетероциклические карбоксамиды |
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| BR (1) | BR112013002090A2 (enExample) |
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| ES (1) | ES2557383T3 (enExample) |
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| SG (1) | SG187166A1 (enExample) |
| UA (1) | UA110113C2 (enExample) |
| WO (1) | WO2012013282A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| 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 |
| MX342288B (es) | 2010-04-22 | 2016-09-23 | Vertex Pharma | Proceso para producir compuestos de cicloalquilcarboxamido-indol. |
| WO2012016001A1 (en) * | 2010-07-29 | 2012-02-02 | Merck Patent Gmbh | Cyclic amine azaheterocyclic carboxamides |
| CA2818706C (en) * | 2010-11-24 | 2019-07-23 | Merck Patent Gmbh | Quinazoline carboxamide azetidines |
| ES2644536T3 (es) | 2011-09-12 | 2017-11-29 | Merck Patent Gmbh | Imidazol-aminas novedosas como moduladores de la actividad cinasa |
| JP6082011B2 (ja) | 2011-09-12 | 2017-02-15 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | キナーゼ活性のモジュレーターとして使用するためのアミノピリミジン誘導体 |
| ES2807539T3 (es) | 2012-11-16 | 2021-02-23 | Merck Patent Gmbh | Derivados de imidazol-piperidinilo como moduladores de la actividad de quinasa |
| ES2620119T3 (es) | 2012-11-16 | 2017-06-27 | Merck Patent Gmbh | Derivados heterocíclicos novedosos como moduladores de la actividad de quinasa |
| ES2821102T3 (es) * | 2012-11-29 | 2021-04-23 | Merck Patent Gmbh | Derivados de azaquinazolincarboxamida |
| AR095202A1 (es) | 2013-03-11 | 2015-09-30 | Merck Patent Gmbh | Heterociclos como moduladores de la actividad quinasa |
| CN103232401B (zh) * | 2013-04-12 | 2015-11-04 | 浙江工业大学 | 一种4-芳硫基喹唑啉类化合物的合成方法 |
| CN103254141B (zh) * | 2013-04-26 | 2016-02-24 | 浙江工业大学 | 4-[4-(2-二丙氨基乙酰氨基)苯胺基]-6-取代喹唑啉类化合物及制备和应用 |
| KR102410696B1 (ko) | 2014-04-03 | 2022-06-17 | 메르크 파텐트 게엠베하 | 암 치료법의 조합 |
| KR102447581B1 (ko) | 2014-04-15 | 2022-09-28 | 버텍스 파마슈티칼스 인코포레이티드 | 낭포성 섬유증 막전도 조절자 매개 질환 치료용 약제학적 조성물 |
| US20230220395A1 (en) * | 2020-04-21 | 2023-07-13 | University Of Massachusetts | Methods and compositions for treatment of age-related macular degeneration |
| MX2023005520A (es) | 2020-11-16 | 2023-05-23 | Merck Patent Gmbh | Combinaciones de inhibidores de cinasa para tratamiento de cancer. |
| WO2023039068A1 (en) * | 2021-09-08 | 2023-03-16 | Neubase Therapeutics, Inc. | Compositions and methods for synthesis of peptide nucleic acid intermediates |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004014861A1 (ja) * | 2002-08-09 | 2004-02-19 | Kyorin Pharmaceutical Co., Ltd. | 4-置換キノリン-8-カルボン酸アミド誘導体とその薬理上許容される付加塩 |
| WO2005120509A1 (en) * | 2004-06-04 | 2005-12-22 | Amphora Discovery Corporation | Quinoline- and isoquinoline-based compounds exhibiting atp-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| WO2010093419A1 (en) * | 2009-02-11 | 2010-08-19 | Merck Patent Gmbh | Novel amino azaheterocyclic carboxamides |
Family Cites Families (15)
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|---|---|---|---|---|
| GB9613021D0 (en) * | 1996-06-21 | 1996-08-28 | Pharmacia Spa | Bicyclic 4-aralkylaminopyrimidine derivatives as tyrosine kinase inhibitors |
| AR016817A1 (es) * | 1997-08-14 | 2001-08-01 | Smithkline Beecham Plc | Derivados de fenilurea o feniltiourea, procedimiento para su preparacion, coleccion de compuestos, compuestos intermediarios, composicion farmaceutica,metodo de tratamiento y uso de dichos compuestos para la manufactura de un medicamento |
| WO2001083456A1 (en) * | 2000-04-27 | 2001-11-08 | Yamanouchi Pharmaceutical Co., Ltd. | Condensed heteroaryl derivatives |
| TW200306819A (en) | 2002-01-25 | 2003-12-01 | Vertex Pharma | Indazole compounds useful as protein kinase inhibitors |
| WO2004014873A1 (ja) * | 2002-08-09 | 2004-02-19 | Kyorin Pharmaceutical Co., Ltd. | 4-置換キナゾリン-8-カルボン酸アミド誘導体とその薬理上許容される付加塩 |
| JP2006522124A (ja) | 2003-04-03 | 2006-09-28 | 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 | プロテインキナーゼのインヒビターとして有用な組成物 |
| JP2007507531A (ja) | 2003-09-30 | 2007-03-29 | アイアールエム・リミテッド・ライアビリティ・カンパニー | タンパク質キナーゼ阻害剤としての化合物および組成物 |
| JP4800216B2 (ja) | 2003-10-24 | 2011-10-26 | エグゼリクシス， インコーポレイテッド | ｐ７０Ｓ６キナーゼモジュレーターおよび使用方法 |
| KR20060117329A (ko) | 2003-11-21 | 2006-11-16 | 노파르티스 아게 | 단백질 키나제 저해제로서의 1ｈ-이미다조퀴놀린 유도체 |
| US8044057B2 (en) | 2003-12-09 | 2011-10-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Methods for suppressing an immune response or treating a proliferative disorder |
| AU2005249380C1 (en) | 2004-04-23 | 2012-09-20 | Exelixis, Inc. | Kinase modulators and methods of use |
| WO2006071819A1 (en) | 2004-12-28 | 2006-07-06 | Exelixis, Inc. | [1h-pyrazolo[3, 4-d]pyrimidin-4-yl]-piperidine or -piperazine compounds as serine-theoronine kinase modulators (p70s6k, atk1 and atk2) for the treatment of immunological, inflammatory and proliferative diseases |
| GB0501999D0 (en) | 2005-02-01 | 2005-03-09 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| WO2006136821A1 (en) | 2005-06-22 | 2006-12-28 | Astex Therapeutics Limited | Pharmaceutical compounds |
| UA99284C2 (ru) | 2007-05-11 | 2012-08-10 | Елі Ліллі Енд Компані | ИНГИБИТОРЫ р70 S6-КИНАЗЫ |
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2011
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- 2011-07-01 EA EA201300186A patent/EA023132B1/ru not_active IP Right Cessation
- 2011-07-01 WO PCT/EP2011/003272 patent/WO2012013282A1/en not_active Ceased
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2012
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004014861A1 (ja) * | 2002-08-09 | 2004-02-19 | Kyorin Pharmaceutical Co., Ltd. | 4-置換キノリン-8-カルボン酸アミド誘導体とその薬理上許容される付加塩 |
| WO2005120509A1 (en) * | 2004-06-04 | 2005-12-22 | Amphora Discovery Corporation | Quinoline- and isoquinoline-based compounds exhibiting atp-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| WO2010093419A1 (en) * | 2009-02-11 | 2010-08-19 | Merck Patent Gmbh | Novel amino azaheterocyclic carboxamides |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112013002090A2 (pt) | 2016-05-24 |
| CN103003250B (zh) | 2016-02-17 |
| KR101852644B1 (ko) | 2018-04-26 |
| CA2806610A1 (en) | 2012-02-02 |
| US8710044B2 (en) | 2014-04-29 |
| CA2806610C (en) | 2018-08-28 |
| EP2598492A1 (en) | 2013-06-05 |
| CN103003250A (zh) | 2013-03-27 |
| NZ604379A (en) | 2015-01-30 |
| UA110113C2 (xx) | 2015-11-25 |
| JP5894157B2 (ja) | 2016-03-23 |
| ES2557383T3 (es) | 2016-01-25 |
| EA201300186A1 (ru) | 2013-12-30 |
| KR20130096714A (ko) | 2013-08-30 |
| HK1183302A1 (zh) | 2013-12-20 |
| AU2011285247A1 (en) | 2013-03-14 |
| AR082414A1 (es) | 2012-12-05 |
| WO2012013282A1 (en) | 2012-02-02 |
| SG187166A1 (en) | 2013-02-28 |
| WO2012013282A8 (en) | 2012-03-29 |
| IL224072A0 (en) | 2013-03-05 |
| JP2013532668A (ja) | 2013-08-19 |
| CL2013000263A1 (es) | 2013-09-06 |
| EP2598492B1 (en) | 2015-10-28 |
| US20130137677A1 (en) | 2013-05-30 |
| MX2013001054A (es) | 2013-02-21 |
| AU2011285247B2 (en) | 2016-08-04 |
| IL224072A (en) | 2016-02-29 |
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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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