ES2775449T3 - Nuevos derivados de cianoindolina sustituida como inhibidores de nik - Google Patents
Nuevos derivados de cianoindolina sustituida como inhibidores de nik Download PDFInfo
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- ES2775449T3 ES2775449T3 ES17701110T ES17701110T ES2775449T3 ES 2775449 T3 ES2775449 T3 ES 2775449T3 ES 17701110 T ES17701110 T ES 17701110T ES 17701110 T ES17701110 T ES 17701110T ES 2775449 T3 ES2775449 T3 ES 2775449T3
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- Prior art keywords
- alkyl
- substituted
- group
- cycloalkyl
- atoms
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- 239000003112 inhibitor Substances 0.000 title description 13
- JXAAHLCOCLPRHW-UHFFFAOYSA-N 2,3-dihydroindole-1-carbonitrile Chemical class C1=CC=C2N(C#N)CCC2=C1 JXAAHLCOCLPRHW-UHFFFAOYSA-N 0.000 title description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 602
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 323
- 125000001424 substituent group Chemical group 0.000 claims abstract description 306
- 150000001875 compounds Chemical class 0.000 claims abstract description 255
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 189
- 239000001257 hydrogen Substances 0.000 claims abstract description 189
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 181
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 174
- 125000005843 halogen group Chemical group 0.000 claims abstract description 169
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 126
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 69
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- 125000003118 aryl group Chemical group 0.000 claims abstract description 30
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 26
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- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims description 116
- 229910052799 carbon Inorganic materials 0.000 claims description 110
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- 239000012453 solvate Substances 0.000 claims description 100
- 229910052757 nitrogen Inorganic materials 0.000 claims description 87
- 125000004432 carbon atom Chemical group C* 0.000 claims description 82
- 229910052760 oxygen Inorganic materials 0.000 claims description 77
- 125000005842 heteroatom Chemical group 0.000 claims description 76
- -1 3,6-dihydro-2H-pyran-4-yl Chemical group 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 49
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
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- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 86
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 49
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
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- 239000003054 catalyst Substances 0.000 description 25
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 25
- 235000019341 magnesium sulphate Nutrition 0.000 description 25
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 23
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- 239000007858 starting material Substances 0.000 description 20
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 19
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- 229910052794 bromium Inorganic materials 0.000 description 16
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 16
- 239000003446 ligand Substances 0.000 description 16
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- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 15
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
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- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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| CN108697710B (zh) | 2016-01-22 | 2022-02-18 | 杨森制药有限公司 | 作为nik抑制剂的新颖的经取代的氰基吲哚啉衍生物 |
| US11001569B2 (en) | 2016-01-22 | 2021-05-11 | Janssen Pharmaceutica Nv | 6-membered heteroaromatic substituted cyanoindoline derivatives as NIK inhibitors |
| US11136311B2 (en) | 2016-06-30 | 2021-10-05 | Janssen Pharmaceutica Nv | Heteroaromatic derivatives as NIK inhibitors |
| AU2017289317B2 (en) | 2016-06-30 | 2021-04-01 | Janssen Pharmaceutica Nv | Cyanoindoline derivatives as NIK inhibitors |
| WO2018019204A1 (zh) | 2016-07-26 | 2018-02-01 | 深圳市塔吉瑞生物医药有限公司 | 用于抑制蛋白酪氨酸激酶活性的氨基嘧啶类化合物 |
| AU2018339722B2 (en) * | 2017-09-30 | 2022-06-30 | Haihe Biopharma Co., Ltd | Compound having ERK kinase inhibitory activity and use thereof |
| TW202045008A (zh) | 2019-02-01 | 2020-12-16 | 印度商皮埃企業有限公司 | 4-取代的異噁唑/異噁唑啉(雜)芳基脒化合物、及其製備與用途 |
| CA3135929A1 (en) * | 2019-04-02 | 2020-10-08 | Hinova Pharmaceuticals Inc. | Aromatic amine compound and use thereof in preparation of ar and brd4 dual inhibitors and regulators |
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| EP4393508A4 (en) * | 2021-08-23 | 2024-12-04 | Osaka University | COMPOSITION FOR SUPPRESSING TRANSDIFFERENTIATION OF MATURE HEPATOCYTES |
| US20240158394A1 (en) | 2022-09-14 | 2024-05-16 | Halia Therapeutics, Inc. | Nek7 inhibitors |
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| AU770600B2 (en) | 1999-10-07 | 2004-02-26 | Amgen, Inc. | Triazine kinase inhibitors |
| CA2400447C (en) | 2000-02-17 | 2008-04-22 | Amgen Inc. | Kinase inhibitors |
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| EP2315751A1 (en) | 2008-06-26 | 2011-05-04 | Amgen Inc. | Alkynyl alcohols as kinase inhibitors |
| TWI546290B (zh) | 2008-06-27 | 2016-08-21 | 賽基艾維洛米斯研究股份有限公司 | 雜芳基化合物及其用途 |
| US20110183975A1 (en) * | 2008-10-07 | 2011-07-28 | Yasuhiro Goto | Novel 6-azaindole aminopyrimidine derivatives having nik inhibitory activity |
| CN102753177A (zh) | 2009-08-17 | 2012-10-24 | 纪念斯隆-凯特琳癌症中心 | 热休克蛋白结合化合物、组合物以及其制备和使用方法 |
| WO2011153553A2 (en) | 2010-06-04 | 2011-12-08 | The Regents Of The University Of California | Methods and compositions for kinase inhibition |
| US8791136B2 (en) | 2010-07-29 | 2014-07-29 | Rigel Pharmaceuticals, Inc. | Substituted pyridine, pyridazine, pyrazine and pyrimidine compounds and methods for using the same |
| EP2696683A4 (en) * | 2011-04-12 | 2014-08-13 | Alzheimer S Inst Of America Inc | COMPOSITIONS AND THERAPEUTIC APPLICATIONS OF IKK-MEDIATED KINASE EPSILON AND TANK BINDING KINASE-1 HEMMER |
| TWI663166B (zh) | 2013-04-24 | 2019-06-21 | 健生藥品公司 | 新化合物 |
| MX370588B (es) | 2013-08-30 | 2019-12-16 | Ptc Therapeutics Inc | Inhibidores de la bmi-1 de pirimidina sustituida. |
| TWI704146B (zh) | 2013-09-26 | 2020-09-11 | 比利時商健生藥品公司 | 用作ＮＩＫ抑制劑之新的1-(４-嘧啶基)-１Ｈ-吡唑並[３,２-ｃ]吡啶衍生物 |
| TWI627173B (zh) | 2013-09-26 | 2018-06-21 | 比利時商健生藥品公司 | 作為ＮＩＫ抑制劑的新穎３－（１Ｈ－吡唑－４－基）－１Ｈ－吡咯并［２，３－ｃ］吡啶衍生物 |
| EP3489232A3 (en) | 2014-04-04 | 2019-07-31 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
| CA2946164A1 (en) | 2014-05-22 | 2015-11-26 | The University Of Sydney | Omega-3 analogues |
| WO2016022645A1 (en) | 2014-08-06 | 2016-02-11 | Merck Sharp & Dohme Corp. | Heterocyclic cgrp receptor antagonists |
| WO2016049211A1 (en) | 2014-09-26 | 2016-03-31 | Gilead Sciences, Inc. | Aminotriazine derivatives useful as tank-binding kinase inhibitor compounds |
| CN106928216A (zh) | 2015-12-31 | 2017-07-07 | 中国科学院上海药物研究所 | 具有erk激酶抑制活性的化合物、其制备方法和用途 |
| US11001569B2 (en) | 2016-01-22 | 2021-05-11 | Janssen Pharmaceutica Nv | 6-membered heteroaromatic substituted cyanoindoline derivatives as NIK inhibitors |
| CN108697710B (zh) | 2016-01-22 | 2022-02-18 | 杨森制药有限公司 | 作为nik抑制剂的新颖的经取代的氰基吲哚啉衍生物 |
| FI3429591T3 (fi) | 2016-03-16 | 2023-06-15 | Kura Oncology Inc | Substituoituja tieno[2,3-d]pyrimidiinijohdannaisia meniini-mll:n estäjinä ja käyttömenetelmiä |
| US11136311B2 (en) | 2016-06-30 | 2021-10-05 | Janssen Pharmaceutica Nv | Heteroaromatic derivatives as NIK inhibitors |
| AU2017289317B2 (en) | 2016-06-30 | 2021-04-01 | Janssen Pharmaceutica Nv | Cyanoindoline derivatives as NIK inhibitors |
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