ES2686500T3 - Compuestos de piridilo sustituidos con heterocíclicos, útiles como inhibidores de cinasas - Google Patents
Compuestos de piridilo sustituidos con heterocíclicos, útiles como inhibidores de cinasas Download PDFInfo
- Publication number
- ES2686500T3 ES2686500T3 ES13700828.0T ES13700828T ES2686500T3 ES 2686500 T3 ES2686500 T3 ES 2686500T3 ES 13700828 T ES13700828 T ES 13700828T ES 2686500 T3 ES2686500 T3 ES 2686500T3
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- substituted
- alkyl
- hydrogen
- solvent
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- 125000000623 heterocyclic group Chemical group 0.000 title claims abstract description 37
- 125000004076 pyridyl group Chemical group 0.000 title claims abstract description 13
- 229940043355 kinase inhibitor Drugs 0.000 title description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
- -1 pyrazolopyridinyl Chemical group 0.000 claims abstract description 242
- 150000001875 compounds Chemical class 0.000 claims abstract description 238
- 150000003839 salts Chemical class 0.000 claims abstract description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 70
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 68
- 239000001257 hydrogen Substances 0.000 claims abstract description 65
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 58
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 54
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 51
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 42
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 40
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 33
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 31
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 29
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 28
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 27
- 101150105130 RORB gene Proteins 0.000 claims abstract description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 13
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- 125000005843 halogen group Chemical group 0.000 claims abstract description 10
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
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- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims abstract description 6
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- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 claims abstract description 6
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- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims abstract description 6
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims abstract description 5
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- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims abstract description 5
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- 125000003118 aryl group Chemical group 0.000 claims description 20
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
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- 238000000034 method Methods 0.000 description 76
- 239000000243 solution Substances 0.000 description 75
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- 238000006243 chemical reaction Methods 0.000 description 65
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
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Classifications
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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
- C07D413/14—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (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)
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| US201261586155P | 2012-01-13 | 2012-01-13 | |
| US201261586155P | 2012-01-13 | ||
| PCT/US2013/021093 WO2013106612A1 (en) | 2012-01-13 | 2013-01-11 | Heterocyclic-substituted pyridyl compounds useful as kinase inhibitors |
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| ES2686500T3 true ES2686500T3 (es) | 2018-10-18 |
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| WO (1) | WO2013106612A1 (OSRAM) |
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| WO2014058685A1 (en) | 2012-10-08 | 2014-04-17 | Merck Sharp & Dohme Corp. | Inhibitors of irak4 activity |
| EP2922840B1 (en) | 2012-11-08 | 2016-12-21 | Bristol-Myers Squibb Company | Bicyclic heterocycle substituted pyridyl compounds useful as kinase modulators |
| US9657009B2 (en) | 2012-11-08 | 2017-05-23 | Bristol-Myers Squibb Company | Heteroaryl substituted pyridyl compounds useful as kinase modulators |
| 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 |
| JP6720355B2 (ja) | 2015-06-24 | 2020-07-08 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | ヘテロアリール置換のアミノピリジン化合物 |
| WO2016210034A1 (en) * | 2015-06-24 | 2016-12-29 | Bristol-Myers Squibb Company | Heteroaryl substituted aminopyridine compounds |
| 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 |
| 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 |
| WO2018165338A2 (en) * | 2017-03-07 | 2018-09-13 | uBiome, Inc. | Therapeutic & diagnostics compositions targeting toll-like receptors and methods thereof |
| EA039189B1 (ru) | 2017-05-11 | 2021-12-15 | Бристол-Маерс Сквибб Компани | Тиенопиридины и бензотиофены в качестве ингибиторов irak4 |
| IL322809A (en) | 2017-09-22 | 2025-10-01 | Kymera Therapeutics Inc | Protein Decomposers and Their Uses |
| US11358948B2 (en) | 2017-09-22 | 2022-06-14 | Kymera Therapeutics, Inc. | CRBN ligands and uses thereof |
| US11065231B2 (en) | 2017-11-17 | 2021-07-20 | Arvinas Operations, 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 |
| US11512080B2 (en) | 2018-01-12 | 2022-11-29 | Kymera Therapeutics, Inc. | CRBN ligands and uses thereof |
| WO2019140380A1 (en) | 2018-01-12 | 2019-07-18 | Kymera Therapeutics, Inc. | Protein degraders and uses thereof |
| EP3817822A4 (en) | 2018-07-06 | 2022-07-27 | Kymera Therapeutics, Inc. | PROTEIN DEGRADANTS AND USES THEREOF |
| US11292792B2 (en) | 2018-07-06 | 2022-04-05 | Kymera Therapeutics, Inc. | Tricyclic CRBN ligands and uses thereof |
| TWI721483B (zh) | 2018-07-13 | 2021-03-11 | 美商基利科學股份有限公司 | 吡咯并[1,2-b]嗒𠯤衍生物 |
| 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 |
| CA3119773A1 (en) | 2018-11-30 | 2020-06-04 | 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 |
| US12304914B2 (en) | 2019-07-18 | 2025-05-20 | Bristol-Myers Squibb Company | Pyrazolo[3,4-d]pyrrolo[1,2-b]pyridazinyl compounds useful as IRAK4 inhibitors |
| US12286428B2 (en) | 2019-07-18 | 2025-04-29 | Bristol-Myers Squibb Company | Tricyclic heteroaryl compounds useful as IRAK4 inhibitors |
| ES3036306T3 (en) | 2019-07-23 | 2025-09-17 | Bristol Myers Squibb Co | Thienopyridinyl and thiazolopyridinyl compounds useful as irak4 inhibitors |
| ES2983263T3 (es) | 2019-08-06 | 2024-10-22 | Bristol Myers Squibb Co | Compuestos heterocíclicos bicíclicos útiles como inhibidores de IRAK4 |
| JP2023509366A (ja) | 2019-12-17 | 2023-03-08 | カイメラ セラピューティクス， インコーポレイテッド | Ｉｒａｋ分解剤およびそれらの使用 |
| US11591332B2 (en) | 2019-12-17 | 2023-02-28 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
| 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 |
| ES2977339T3 (es) | 2020-02-03 | 2024-08-22 | Bristol Myers Squibb Co | Compuestos heteroarílicos tricíclicos útiles como inhibidores de IRAK4 |
| 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 |
| MX2023007852A (es) | 2020-12-30 | 2023-07-07 | Kymera Therapeutics Inc | Degradadores de cinasas asociadas al receptor de interleucina-1 (irak) y usos de los mismos. |
| EP4291187A4 (en) | 2021-02-15 | 2025-01-15 | Kymera Therapeutics, Inc. | Irak4 degraders and uses thereof |
| CN117715904A (zh) | 2021-05-07 | 2024-03-15 | 凯麦拉医疗公司 | Cdk2降解剂和其用途 |
| EP4422635A4 (en) | 2021-10-29 | 2025-11-26 | Kymera Therapeutics Inc | IRAQ4 DEGRADATION AGENTS AND THEIR SYNTHESIS |
| AU2023214044A1 (en) | 2022-01-31 | 2024-08-08 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
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| EP1399440B1 (en) | 2001-06-15 | 2009-06-03 | Vertex Pharmaceuticals Incorporated | 5-(2-aminopyrimidin-4-yl)benzisoxazoles as protein kinase inhibitors |
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| RU2013148405A (ru) | 2011-04-29 | 2015-06-10 | Айкан Скул Оф Медисин Эт Маунт Синай | Ингибиторы киназ |
| JP6096219B2 (ja) | 2012-01-13 | 2017-03-15 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | キナーゼ阻害剤として有用なトリアゾリルまたはトリアジアゾリル置換されたピリジル化合物 |
| WO2013106614A1 (en) | 2012-01-13 | 2013-07-18 | Bristol-Myers Squibb Company | Triazolyl-substituted pyridyl compounds useful as kinase inhibitors |
-
2013
- 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 CN CN201380013438.7A patent/CN104159896B/zh active Active
- 2013-01-11 US US14/371,456 patent/US9242975B2/en active Active
- 2013-01-11 JP JP2014552311A patent/JP6109195B2/ja not_active Expired - Fee Related
- 2013-01-11 EP EP13700828.0A patent/EP2802576B1/en active Active
Also Published As
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|---|---|
| EP2802576A1 (en) | 2014-11-19 |
| CN104159896A (zh) | 2014-11-19 |
| US20150011532A1 (en) | 2015-01-08 |
| CN104159896B (zh) | 2017-05-24 |
| WO2013106612A1 (en) | 2013-07-18 |
| US9242975B2 (en) | 2016-01-26 |
| EP2802576B1 (en) | 2018-06-27 |
| JP2015503620A (ja) | 2015-02-02 |
| JP6109195B2 (ja) | 2017-04-05 |
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