CN104159896B - 用作激酶抑制剂的杂环取代的吡啶基化合物 - Google Patents
用作激酶抑制剂的杂环取代的吡啶基化合物 Download PDFInfo
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- CN104159896B CN104159896B CN201380013438.7A CN201380013438A CN104159896B CN 104159896 B CN104159896 B CN 104159896B CN 201380013438 A CN201380013438 A CN 201380013438A CN 104159896 B CN104159896 B CN 104159896B
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Classifications
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261586155P | 2012-01-13 | 2012-01-13 | |
| US61/586,155 | 2012-01-13 | ||
| PCT/US2013/021093 WO2013106612A1 (en) | 2012-01-13 | 2013-01-11 | Heterocyclic-substituted pyridyl compounds useful as kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104159896A CN104159896A (zh) | 2014-11-19 |
| CN104159896B true CN104159896B (zh) | 2017-05-24 |
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| CN201380013438.7A Active CN104159896B (zh) | 2012-01-13 | 2013-01-11 | 用作激酶抑制剂的杂环取代的吡啶基化合物 |
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| Country | Link |
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| US (1) | US9242975B2 (enExample) |
| EP (1) | EP2802576B1 (enExample) |
| JP (1) | JP6109195B2 (enExample) |
| CN (1) | CN104159896B (enExample) |
| ES (1) | ES2686500T3 (enExample) |
| WO (1) | WO2013106612A1 (enExample) |
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| EP2903617B1 (en) * | 2012-10-08 | 2019-01-30 | Merck Sharp & Dohme Corp. | Inhibitors of irak4 activity |
| WO2014074657A1 (en) | 2012-11-08 | 2014-05-15 | Bristol-Myers Squibb Company | Bicyclic heterocycle substituted pyridyl compounds useful as kinase modulators |
| PE20150953A1 (es) | 2012-11-08 | 2015-06-20 | Bristol Myers Squibb Co | Compuestos de piridilo sustituidos con heteroarilo utiles como moduladores de cinasa |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| TWI667233B (zh) | 2013-12-19 | 2019-08-01 | 德商拜耳製藥公司 | 新穎吲唑羧醯胺,其製備方法、含彼等之醫藥製劑及其製造醫藥之用途 |
| UY35935A (es) | 2014-01-03 | 2015-06-30 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Compuestos de nicotinamida sustituida con heteroarilo como inhibidores de quinasa y moduladores de irak-4 |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| CN108026099B (zh) * | 2015-06-24 | 2020-07-10 | 百时美施贵宝公司 | 经杂芳基取代的氨基吡啶化合物 |
| KR102641263B1 (ko) | 2015-06-24 | 2024-02-26 | 브리스톨-마이어스 스큅 컴퍼니 | 헤테로아릴 치환된 아미노피리딘 화합물 |
| EP3313840B1 (en) * | 2015-06-24 | 2019-07-24 | Bristol-Myers Squibb Company | Heteroaryl substituted aminopyridine compounds |
| TWI825663B (zh) * | 2016-10-14 | 2023-12-11 | 美商林伯士拉克許米公司 | Tyk2抑制劑及其用途 |
| JOP20180011A1 (ar) | 2017-02-16 | 2019-01-30 | Gilead Sciences Inc | مشتقات بيرولو [1، 2-b]بيريدازين |
| EP3790889A4 (en) * | 2017-03-07 | 2022-06-08 | Psomagen, Inc. | DIAGNOSTIC AND THERAPEUTIC COMPOSITIONS TARGETING TOLL-LIKE RECEPTORS AND METHODS THEREOF |
| TW201900640A (zh) | 2017-05-11 | 2019-01-01 | 美商必治妥美雅史谷比公司 | 作為irak4抑制劑之噻吩并吡啶及苯并噻吩 |
| EP3684366A4 (en) | 2017-09-22 | 2021-09-08 | Kymera Therapeutics, Inc. | CRBN LIGANDS AND USES OF THE LATEST |
| EP3684365A4 (en) | 2017-09-22 | 2021-09-08 | Kymera Therapeutics, Inc. | PROTEIN DEGRADATION AGENTS AND USES OF SUCH |
| WO2019099926A1 (en) | 2017-11-17 | 2019-05-23 | Arvinas, Inc. | Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 4 polypeptides |
| WO2019111218A1 (en) | 2017-12-08 | 2019-06-13 | Cadila Healthcare Limited | Novel heterocyclic compounds as irak4 inhibitors |
| JP7569688B2 (ja) | 2017-12-22 | 2024-10-18 | ハイバーセル,インコーポレイテッド | ホスファチジルイノシトールリン酸キナーゼ阻害剤としてのアミノピリジン誘導体 |
| IL315310A (en) | 2017-12-26 | 2024-10-01 | Kymera Therapeutics Inc | Irak degraders and uses thereof |
| EP3737666A4 (en) | 2018-01-12 | 2022-01-05 | Kymera Therapeutics, Inc. | PROTEIN DEGRADATION AGENTS AND ASSOCIATED USES |
| EP3737675A4 (en) | 2018-01-12 | 2022-01-05 | Kymera Therapeutics, Inc. | Crbn ligands and uses thereof |
| WO2020010177A1 (en) | 2018-07-06 | 2020-01-09 | Kymera Therapeutics, Inc. | Tricyclic crbn ligands and uses thereof |
| EP3817822A4 (en) | 2018-07-06 | 2022-07-27 | Kymera Therapeutics, Inc. | PROTEIN DEGRADANTS AND USES THEREOF |
| TWI898556B (zh) | 2018-07-13 | 2025-09-21 | 美商基利科學股份有限公司 | 吡咯并[1,2-b]嗒衍生物 |
| TWI727392B (zh) | 2018-08-13 | 2021-05-11 | 美商基利科學股份有限公司 | 噻二唑irak4抑制劑 |
| WO2020106059A1 (ko) | 2018-11-21 | 2020-05-28 | 한국화학연구원 | Irak4 저해제로서 신규의 삼중고리 화합물 |
| KR102329235B1 (ko) | 2018-11-21 | 2021-11-22 | 한국화학연구원 | Irak4 저해제로서 신규의 삼중고리 화합물 |
| SG11202105424PA (en) | 2018-11-30 | 2021-06-29 | Kymera Therapeutics Inc | Irak degraders and uses thereof |
| TW202112767A (zh) | 2019-06-17 | 2021-04-01 | 美商佩特拉製藥公司 | 作為磷脂酸肌醇磷酸激酶抑制劑之胺基吡啶衍生物 |
| WO2021011724A1 (en) | 2019-07-18 | 2021-01-21 | Bristol-Myers Squibb Company | Tricyclic heteroaryl compounds useful as irak4 inhibitors |
| KR20220035447A (ko) | 2019-07-18 | 2022-03-22 | 브리스톨-마이어스 스큅 컴퍼니 | IRAK4 억제제로서 유용한 피라졸로[3,4-d]피롤로[1,2-b]피리다지닐 화합물 |
| JP7573596B2 (ja) | 2019-07-23 | 2024-10-25 | ブリストル-マイヤーズ スクイブ カンパニー | Irak4阻害剤として有用なチエノピリジニルおよびチアゾロピリジニル化合物 |
| EP4076524A4 (en) | 2019-12-17 | 2023-11-29 | Kymera Therapeutics, Inc. | IRAQ DEGRADERS AND USES THEREOF |
| MX2022007576A (es) | 2019-12-17 | 2022-09-23 | Kymera Therapeutics Inc | Degradadores de cinasas asociadas al receptor de interleucina-1 (irak) y usos de los mismos. |
| WO2021158495A1 (en) * | 2020-02-03 | 2021-08-12 | Bristol-Myers Squibb Company | Benzo[5,6][1,4]dioxino[2,3-b]pyridine compounds useful as irak4 inhibitors |
| JP7682191B2 (ja) | 2020-02-03 | 2025-05-23 | ブリストル-マイヤーズ スクイブ カンパニー | Irak4阻害剤として有用な三環ヘテロアリール化合物 |
| TW202210483A (zh) | 2020-06-03 | 2022-03-16 | 美商凱麥拉醫療公司 | Irak降解劑之結晶型 |
| AU2021413371A1 (en) | 2020-12-30 | 2023-07-13 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
| AU2022220043A1 (en) | 2021-02-15 | 2023-08-31 | Kymera Therapeutics, Inc. | Irak4 degraders and uses thereof |
| US12097261B2 (en) | 2021-05-07 | 2024-09-24 | Kymera Therapeutics, Inc. | CDK2 degraders and uses thereof |
| CN118302168A (zh) | 2021-10-29 | 2024-07-05 | 凯麦拉医疗公司 | Irak4降解剂和其制备 |
| EP4472967A2 (en) | 2022-01-31 | 2024-12-11 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004065378A1 (en) * | 2003-01-17 | 2004-08-05 | Warner-Lambert Company Llc | 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation |
| WO2009044162A1 (en) * | 2007-10-05 | 2009-04-09 | Cancer Research Technology Limited | Pyrazin-2-yl-pyridin-2-yl-amine and pyrazin-2-yl-pyrimidin-4-yl-amine compounds and their use |
| CN101562977A (zh) * | 2006-12-15 | 2009-10-21 | 艾博特公司 | 新的二唑化合物 |
| CN101594909A (zh) * | 2006-09-07 | 2009-12-02 | 比奥根艾迪克Ma公司 | 用于治疗炎性病症、细胞增殖性失调、免疫失调的irak调节剂 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6825190B2 (en) | 2001-06-15 | 2004-11-30 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors and uses thereof |
| AUPR688101A0 (en) | 2001-08-08 | 2001-08-30 | Luminis Pty Limited | Protein domains and their ligands |
| GB0211019D0 (en) | 2002-05-14 | 2002-06-26 | Syngenta Ltd | Novel compounds |
| ATE530530T1 (de) | 2002-06-28 | 2011-11-15 | Astellas Pharma Inc | Diaminopyrimidincarbonsäureamidderivat |
| CN1820001A (zh) | 2003-07-10 | 2006-08-16 | 神经能质公司 | 经取代的杂环二芳基胺类似物 |
| GB0402653D0 (en) | 2004-02-06 | 2004-03-10 | Cyclacel Ltd | Compounds |
| US7521457B2 (en) | 2004-08-20 | 2009-04-21 | Boehringer Ingelheim International Gmbh | Pyrimidines as PLK inhibitors |
| FR2896503B1 (fr) | 2006-01-23 | 2012-07-13 | Aventis Pharma Sa | Nouveaux derives soufres d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases |
| KR20100020454A (ko) | 2007-06-08 | 2010-02-22 | 바이엘 크롭사이언스 소시에떼아노님 | 살진균제 헤테로사이클릴-피리미디닐-아미노 유도체 |
| WO2009046416A1 (en) | 2007-10-05 | 2009-04-09 | Targegen Inc. | Anilinopyrimidines as jak kinase inhibitors |
| CN102458402B (zh) | 2009-06-12 | 2013-10-02 | 百时美施贵宝公司 | 用作激酶调节剂的烟酰胺化合物 |
| JP2012254939A (ja) * | 2009-10-07 | 2012-12-27 | Astellas Pharma Inc | オキサゾール化合物 |
| JP5770198B2 (ja) | 2009-10-30 | 2015-08-26 | ヤンセン ファーマシューティカ エヌ.ベー. | オピオイド受容体調節因子としてのフェノキシ置換ピリミジン |
| US20190192510A1 (en) | 2010-02-01 | 2019-06-27 | Nippon Chemiphar Co., Ltd. | Gpr119 agonist |
| JP2014515029A (ja) | 2011-04-29 | 2014-06-26 | アイカーン・スクール・オブ・メディシン・アト・マウント・シナイ | キナーゼ阻害剤 |
| US9242976B2 (en) | 2012-01-13 | 2016-01-26 | Bristol-Myers Squibb Company | Thiazolyl- or thiadiazolyl-substituted pyridyl compounds useful as kinase inhibitors |
| WO2013106614A1 (en) | 2012-01-13 | 2013-07-18 | Bristol-Myers Squibb Company | Triazolyl-substituted pyridyl compounds useful as kinase inhibitors |
-
2013
- 2013-01-11 JP JP2014552311A patent/JP6109195B2/ja active Active
- 2013-01-11 CN CN201380013438.7A patent/CN104159896B/zh active Active
- 2013-01-11 ES ES13700828.0T patent/ES2686500T3/es active Active
- 2013-01-11 WO PCT/US2013/021093 patent/WO2013106612A1/en not_active Ceased
- 2013-01-11 US US14/371,456 patent/US9242975B2/en active Active
- 2013-01-11 EP EP13700828.0A patent/EP2802576B1/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004065378A1 (en) * | 2003-01-17 | 2004-08-05 | Warner-Lambert Company Llc | 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation |
| CN101594909A (zh) * | 2006-09-07 | 2009-12-02 | 比奥根艾迪克Ma公司 | 用于治疗炎性病症、细胞增殖性失调、免疫失调的irak调节剂 |
| CN101562977A (zh) * | 2006-12-15 | 2009-10-21 | 艾博特公司 | 新的二唑化合物 |
| WO2009044162A1 (en) * | 2007-10-05 | 2009-04-09 | Cancer Research Technology Limited | Pyrazin-2-yl-pyridin-2-yl-amine and pyrazin-2-yl-pyrimidin-4-yl-amine compounds and their use |
Non-Patent Citations (3)
| Title |
|---|
| IRAK-4 inhibitors. Part 1: A series of amides;George M. Buckley,等;《Bioorganic & Medicinal Chemistry Letters》;20080601;第18卷(第11期);第3211-3214页 * |
| IRAK-4 inhibitors. Part II: A structure-based assessment of imidazo[1,2-a]pyridine binding;George M. Buckley,等;《Bioorganic & Medicinal Chemistry Letters》;20080601;第18卷(第11期);第3291-3295页 * |
| IRAK-4 inhibitors. Part III: A series of imidazo[1,2-a]pyridines;George M. Buckley,等;《Bioorganic & Medicinal Chemistry Letters》;20080615;第18卷(第12期);第3656-3660页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| US9242975B2 (en) | 2016-01-26 |
| JP6109195B2 (ja) | 2017-04-05 |
| EP2802576A1 (en) | 2014-11-19 |
| EP2802576B1 (en) | 2018-06-27 |
| WO2013106612A1 (en) | 2013-07-18 |
| JP2015503620A (ja) | 2015-02-02 |
| ES2686500T3 (es) | 2018-10-18 |
| US20150011532A1 (en) | 2015-01-08 |
| CN104159896A (zh) | 2014-11-19 |
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