CA2897200C - Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors - Google Patents
Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors Download PDFInfo
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- CA2897200C CA2897200C CA2897200A CA2897200A CA2897200C CA 2897200 C CA2897200 C CA 2897200C CA 2897200 A CA2897200 A CA 2897200A CA 2897200 A CA2897200 A CA 2897200A CA 2897200 C CA2897200 C CA 2897200C
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- Prior art keywords
- alkyl
- amino
- compound
- pharmaceutically acceptable
- acceptable salt
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- -1 Bicyclic aromatic carboxamide compounds Chemical class 0.000 title claims description 206
- 229940043355 kinase inhibitor Drugs 0.000 title description 6
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 6
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- 239000000203 mixture Substances 0.000 claims abstract description 317
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 63
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- 201000011510 cancer Diseases 0.000 claims abstract description 22
- 230000000694 effects Effects 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 213
- 150000003839 salts Chemical class 0.000 claims description 139
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 105
- 125000001424 substituent group Chemical group 0.000 claims description 102
- 229910052736 halogen Inorganic materials 0.000 claims description 99
- 150000002367 halogens Chemical group 0.000 claims description 94
- ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 claims description 79
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 69
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 64
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 52
- 229910052757 nitrogen Inorganic materials 0.000 claims description 49
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 48
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 125000004432 carbon atom Chemical group C* 0.000 claims description 38
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 35
- 125000005843 halogen group Chemical group 0.000 claims description 35
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 27
- CZWUESRDTYLNDE-UHFFFAOYSA-N (2z)-2-[(2e,4e,6e)-7-[1-(5-carboxypentyl)-3,3-dimethyl-5-sulfoindol-1-ium-2-yl]hepta-2,4,6-trienylidene]-1-ethyl-3,3-dimethylindole-5-sulfonate Chemical compound CC1(C)C2=CC(S([O-])(=O)=O)=CC=C2N(CC)\C1=C/C=C/C=C/C=C/C1=[N+](CCCCCC(O)=O)C2=CC=C(S(O)(=O)=O)C=C2C1(C)C CZWUESRDTYLNDE-UHFFFAOYSA-N 0.000 claims description 24
- 150000001408 amides Chemical class 0.000 claims description 22
- 125000003277 amino group Chemical group 0.000 claims description 21
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- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000006413 ring segment Chemical group 0.000 claims description 14
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 14
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
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- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 7
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- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 4
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- VMWJCFLUSKZZDX-UHFFFAOYSA-N n,n-dimethylmethanamine Chemical compound [CH2]N(C)C VMWJCFLUSKZZDX-UHFFFAOYSA-N 0.000 claims description 2
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| PCT/US2014/011487 WO2014110574A1 (en) | 2013-01-14 | 2014-01-14 | Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors |
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Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9453003B2 (en) * | 2011-08-11 | 2016-09-27 | Jikai Biosciences, Inc. | Pyrimidine derivatives as PIM kinase inhibitors and preparation methods and use in medicinal manufacture thereof |
| US9458151B2 (en) * | 2011-08-11 | 2016-10-04 | Jikai Biosciences, Inc. | Isothiazole derivatives as PIM kinase inhibitors and preparation methods and use in medicinal manufacture thereof |
| WO2014110574A1 (en) | 2013-01-14 | 2014-07-17 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors |
| UA121098C2 (uk) | 2013-01-15 | 2020-04-10 | Інсайт Холдинґс Корпорейшн | Тіазолкарбоксаміди і піридинкарбоксаміди, які використовуються як інгібітори рім-кінази |
| WO2015027124A1 (en) | 2013-08-23 | 2015-02-26 | Incyte Corporation | Furo- and thieno-pyridine carboxamide compounds useful as pim kinase inhibitors |
| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
| WO2016010897A1 (en) * | 2014-07-14 | 2016-01-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors |
| WO2016161248A1 (en) * | 2015-04-02 | 2016-10-06 | Tolero Pharmaceuticals, Inc. | Targeting pim kinases in combination with btk inhibition |
| WO2016196244A1 (en) | 2015-05-29 | 2016-12-08 | Incyte Corporation | Pyridineamine compounds useful as pim kinase inhibitors |
| TWI734699B (zh) | 2015-09-09 | 2021-08-01 | 美商英塞特公司 | Ｐｉｍ激酶抑制劑之鹽 |
| WO2017059251A1 (en) * | 2015-10-02 | 2017-04-06 | Incyte Corporation | Heterocyclic compounds useful as pim kinase inhibitors |
| PL3416964T3 (pl) * | 2016-02-19 | 2021-10-18 | Phoenix Molecular Designs | Pochodne 6-okso-n-(1-(benzylo)-1h-pirazol-4-ilo)-6,7,8,9-tetrahydropirydo[3’,2’:4,5]pirolo[1,2-a]pirazyno-2-karboksyamidu jako inhibitory kinazy rybosomalnej s6 p90 (rsk) do leczenia nowotworu złośliwego |
| CN106336371A (zh) * | 2016-08-16 | 2017-01-18 | 成都百事兴科技实业有限公司 | 叔丁氧羰基‑l‑焦谷氨酸甲酯的合成方法 |
| EP3535273A1 (en) * | 2016-11-02 | 2019-09-11 | H. Hoffnabb-La Roche Ag | PYRAZOLO[1,5a]PYRIMIDINE DERIVATIVES AS IRAK4 MODULATORS |
| CN112739345A (zh) | 2017-11-06 | 2021-04-30 | 斯奈普生物公司 | Pim激酶抑制剂组合物，方法和其用途 |
| AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
| AU2018385664B2 (en) | 2017-12-13 | 2022-06-02 | Lupin Limited | Substituted bicyclic heterocyclic compounds as PRMT5 inhibitors |
| WO2024225803A1 (en) * | 2023-04-27 | 2024-10-31 | Daewoong Pharmaceutical Co., Ltd. | Novel heterocyclic compounds and pharmaceutical composition comprising the same as dna polymerase theta inhibitors for the treatment and prophylaxis of cancer |
Family Cites Families (190)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002215608B2 (en) | 2000-06-28 | 2004-12-09 | Smithkline Beecham P.L.C. | Wet milling process |
| AU2002246864A1 (en) | 2000-12-27 | 2002-07-24 | The Trustees Of Columbia University In The City Of New York | Pim kinase-related methods |
| DE10123055A1 (de) | 2001-05-11 | 2003-03-20 | Gruenenthal Gmbh | Screeningverfahren mit PIM1-Kinase oder PIM3-Kinase |
| DE10226702A1 (de) | 2002-06-14 | 2004-09-09 | Grünenthal GmbH | Antisense Oligonukleotide gegen PIM1 |
| US20040142864A1 (en) | 2002-09-16 | 2004-07-22 | Plexxikon, Inc. | Crystal structure of PIM-1 kinase |
| WO2006078228A1 (en) | 2002-09-16 | 2006-07-27 | Plexxikon, Inc. | Methods for the design of molecular scaffolds and ligands |
| WO2004090106A2 (en) | 2003-04-04 | 2004-10-21 | Vertex Pharmaceuticals Incorporated | Crystal structures of human pim-1 kinase protein complexes and binding pockets thereof, and uses thereof in drug design |
| WO2005028624A2 (en) | 2003-09-15 | 2005-03-31 | Plexxikon, Inc. | Molecular scaffolds for kinase ligand development |
| WO2005033310A1 (de) | 2003-10-01 | 2005-04-14 | Grünenthal GmbH | Pim-1-spezifische dsrna-verbindungen |
| WO2006006569A1 (ja) | 2004-07-12 | 2006-01-19 | Nihon Nohyaku Co., Ltd. | フェニルピリジン類又はその塩類、これらを有効成分とする除草剤及びその使用方法 |
| CN103274961B (zh) | 2004-12-28 | 2016-05-18 | 阿西纳斯公司 | 治疗细胞增殖紊乱的化合物和方法 |
| CN102603581B (zh) | 2005-06-22 | 2015-06-24 | 普莱希科公司 | 作为蛋白质激酶抑制剂的吡咯并[2,3-b]吡啶衍生物 |
| WO2007011760A2 (en) | 2005-07-15 | 2007-01-25 | Kalypsys, Inc. | Inhibitors of mitotic kinesin |
| TW200745123A (en) | 2005-10-06 | 2007-12-16 | Schering Corp | Pyrazolopyrimidines as protein kinase inhibitors |
| EP1940792B1 (en) | 2005-10-06 | 2014-06-04 | Exelixis, Inc. | Aminopyrimidine, aminopyridine and aniline derivatives as inhibitors of pim-1 and/or pim-3 |
| US8372851B2 (en) | 2005-10-21 | 2013-02-12 | Exelixis, Inc. | Pyrazolo pyrimidines as casein kinase II (CK2) modulators |
| WO2007052843A1 (ja) | 2005-11-04 | 2007-05-10 | Takeda Pharmaceutical Company Limited | 複素環アミド化合物およびその用途 |
| US20090182003A1 (en) | 2006-01-13 | 2009-07-16 | President And Fellows Of Harvard College | Methods and Compositions for Treatment Cell Proliferative Disorders |
| US20090253156A1 (en) | 2006-05-05 | 2009-10-08 | Perkinelmer Las, Inc. | Mass spectrometry methods for multiplexed quantification of protein kinases and phosphatases |
| DK2041071T3 (da) | 2006-06-29 | 2014-09-01 | Kinex Pharmaceuticals Llc | Biarylsammensætninger og fremgangsmåder til modulering af en kinasekaskade |
| CA2656564C (en) | 2006-06-29 | 2015-06-16 | Kinex Pharmaceuticals, Llc | Biaryl compositions and methods for modulating a kinase cascade |
| ATE517868T1 (de) | 2006-08-16 | 2011-08-15 | Boehringer Ingelheim Int | Pyrazinverbindungen, ihre verwendung und herstellungsverfahren |
| WO2008045252A2 (en) | 2006-10-04 | 2008-04-17 | The Board Of Trustees Of The Leland Stanford Junior University | Engineered integrin binding peptides |
| AU2007314305B2 (en) | 2006-10-31 | 2013-01-24 | Merck Sharp & Dohme Corp. | 2-aminothiazole-4-carboxylic amides as protein kinase inhibitors |
| MX2009004700A (es) | 2006-11-06 | 2009-05-15 | Supergen Inc | Derivados de imidazo[1,2-b]piridazin y pirazolo[1,5-a] pirimidina y su uso como inhibidores de proteina cinasa. |
| WO2008082839A2 (en) | 2006-12-29 | 2008-07-10 | Abbott Laboratories | Pim kinase inhibitors as cancer chemotherapeutics |
| WO2008082840A1 (en) | 2006-12-29 | 2008-07-10 | Abbott Laboratories | Pim kinase inhibitors as cancer chemotherapeutics |
| CA2679659C (en) * | 2007-03-01 | 2016-01-19 | Novartis Ag | Pim kinase inhibitors and methods of their use |
| CA2682231A1 (en) | 2007-03-28 | 2008-10-09 | Array Biopharma Inc. | Imidazo[1,2-a]pyridine compounds as receptor tyrosine kinase inhibitors |
| MX2009010728A (es) | 2007-04-03 | 2009-10-26 | Array Biopharma Inc | Compuestos de imidazo[1,2-a]piridina como inhibidores de la tirosina-cinasa repectora. |
| WO2008143759A1 (en) | 2007-04-25 | 2008-11-27 | Exelixis, Inc. | Pyrimidinones as casein kinase ii (ck2) modulators |
| WO2008133955A1 (en) | 2007-04-25 | 2008-11-06 | Exelixis, Inc. | 6-phenylpyrimidinones as pim modulators |
| MY150032A (en) * | 2007-07-19 | 2013-11-29 | Merck Sharp & Dohme | Heterocyclic amide compounds as protein kinase inhibitors |
| AU2008282885A1 (en) | 2007-07-31 | 2009-02-05 | Schering Corporation | Anti-mitotic agent and aurora kinase inhibitor combination as anti-cancer treatment |
| EP2217235A4 (en) | 2007-11-15 | 2011-01-12 | Musc Found For Res Dev | INHIBITORS OF PIM PROTEIN KINASES, COMPOSITIONS AND METHOD FOR THE TREATMENT OF CANCER |
| JP2011503207A (ja) | 2007-11-16 | 2011-01-27 | サン ディエゴ ステート ユニバーシティ リサーチ ファウンデーション | 循環系細胞におけるｐｉｍ−１活性を操作するための組成物および方法 |
| AU2009219154A1 (en) | 2008-02-29 | 2009-09-03 | Cylene Pharmaceuticals, Inc. | Protein kinase modulators |
| UY31679A1 (es) | 2008-03-03 | 2009-09-30 | Inhibidores de cinasa pim y metodos para su uso | |
| US8168794B2 (en) * | 2008-03-03 | 2012-05-01 | Novartis Ag | Pim kinase inhibitors and methods of their use |
| EP2285217A4 (en) | 2008-05-12 | 2011-06-08 | Amnestix Inc | CONNECTIONS TO IMPROVE LEARNING AND MEMORY |
| MX2011000150A (es) | 2008-06-30 | 2011-04-05 | Cylene Pharmaceuticals Inc | Compuestos de oxoindol. |
| UY31952A (es) | 2008-07-02 | 2010-01-29 | Astrazeneca Ab | 5-metilideno-1,3-tiazolidina-2,4-dionas sustituidas como inhibidores de quinasa pim |
| FR2933409B1 (fr) | 2008-07-03 | 2010-08-27 | Centre Nat Rech Scient | NOUVEAUX PYRROLO °2,3-a! CARBAZOLES ET LEUR UTILISATION COMME INHIBITEURS DES KINASES PIM |
| WO2010022081A1 (en) | 2008-08-19 | 2010-02-25 | Array Biopharma Inc. | Triazolopyridine compounds as pim kinase inhibitors |
| TWI496779B (zh) | 2008-08-19 | 2015-08-21 | Array Biopharma Inc | 作為ｐｉｍ激酶抑制劑之三唑吡啶化合物 |
| MX2011002362A (es) | 2008-09-02 | 2011-04-04 | Novartis Ag | Inhibidores heterociclicos de cinasa pim. |
| BRPI0918268B1 (pt) * | 2008-09-02 | 2021-08-03 | Novartis Ag | Derivados de picolinamida, seu uso, e composição farmacêutica |
| CA2735779A1 (en) | 2008-09-02 | 2010-03-11 | Matthew Burger | Bicyclic kinase inhibitors |
| LT3106463T (lt) | 2008-10-22 | 2018-06-25 | Array Biopharma, Inc. | Pakeistieji pirazolo[1,5-]pirimidino junginiai kaip trk kinazės slopikliai |
| GB0821307D0 (en) | 2008-11-21 | 2008-12-31 | Summit Corp Plc | Compounds for treatment of duchenne muscular dystrophy |
| ES2539620T3 (es) | 2008-12-19 | 2015-07-02 | Cephalon, Inc. | Pirrolotriazina como inhibidor de ALK y de JAK2 |
| US20120128631A1 (en) | 2009-05-19 | 2012-05-24 | San Diego State University (SDSU) Foundation, dba San Diego State University (SDSU) Research | Compositions and methods for kinase-mediated cytoprotection and enhanced cellular engraftment and persistence |
| AU2010249493A1 (en) | 2009-05-20 | 2011-12-08 | Cylene Pharmaceuticals, Inc. | Pyrazolopyrimidines and related heterocycles as kinase inhibitors |
| WO2010135571A1 (en) | 2009-05-20 | 2010-11-25 | Cylene Pharmaceuticals, Inc. | Novel protein kinase modulators |
| EP2432555B1 (en) | 2009-05-22 | 2014-04-30 | Incyte Corporation | N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| WO2010148351A1 (en) | 2009-06-18 | 2010-12-23 | Cylene Pharmaceuticals, Inc. | Rhodanines and related heterocycles as kinase inhibitors |
| PL2448938T3 (pl) | 2009-06-29 | 2014-11-28 | Incyte Holdings Corp | Pirymidynony jako inhibitory PI3K |
| WO2011025859A1 (en) | 2009-08-26 | 2011-03-03 | Cylene Pharmaceuticals, Inc. | Condensed quinolines as protein kinase modulators |
| TW201113285A (en) | 2009-09-01 | 2011-04-16 | Incyte Corp | Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| US8435976B2 (en) | 2009-09-08 | 2013-05-07 | F. Hoffmann-La Roche | 4-substituted pyridin-3-yl-carboxamide compounds and methods of use |
| SG10201405568UA (en) | 2009-09-08 | 2014-11-27 | Hoffmann La Roche | 4-substituted pyridin-3-yl-carboxamide compounds and methods of use |
| AU2010292116A1 (en) | 2009-09-11 | 2012-05-03 | Cylene Pharmaceuticals Inc. | Pharmaceutically useful heterocycle-substituted lactams |
| CA2774148A1 (en) | 2009-09-16 | 2011-03-24 | Cylene Pharmaceuticals, Inc. | Tricyclic compounds and pharmaceutical uses thereof |
| IN2012DN03217A (OSRAM) | 2009-09-16 | 2015-10-23 | Cylene Pharmaceuticals Inc | |
| WO2011053861A1 (en) | 2009-10-29 | 2011-05-05 | Genosco | Kinase inhibitors |
| EP2332917B1 (en) | 2009-11-11 | 2012-08-01 | Sygnis Bioscience GmbH & Co. KG | Compounds for PIM kinase inhibition and for treating malignancy |
| US8304172B2 (en) | 2009-11-12 | 2012-11-06 | Advanced Micro Devices, Inc. | Semiconductor device fabrication using a multiple exposure and block mask approach to reduce design rule violations |
| EP2499117B1 (en) | 2009-11-12 | 2015-10-21 | Selvita S.A. | A compound, a process for its preparation, a pharmaceutical composition, use of a compound, a method for modulating or regulating serine/threonine kinases and a serine/threonine kinases modulating agent |
| EP2498607B1 (en) | 2009-11-13 | 2016-02-17 | Genosco | Kinase inhibitors |
| US8853235B2 (en) | 2009-11-23 | 2014-10-07 | Senhwa Biosciences, Inc. | Polymorphs and salts of a kinase inhibitor |
| PL2509602T3 (pl) | 2009-12-04 | 2017-08-31 | Senhwa Biosciences, Inc. | Pirazolopirymidyny i podobne heterocykle jako inhibitory ck2 |
| TW201130842A (en) | 2009-12-18 | 2011-09-16 | Incyte Corp | Substituted fused aryl and heteroaryl derivatives as PI3K inhibitors |
| WO2011075643A1 (en) | 2009-12-18 | 2011-06-23 | Incyte Corporation | Substituted heteroaryl fused derivatives as pi3k inhibitors |
| WO2011075613A1 (en) | 2009-12-18 | 2011-06-23 | Sanofi | Azaindole derivatives, their preparation and their therapeutic application |
| WO2011079274A1 (en) | 2009-12-23 | 2011-06-30 | Jasco Pharmaceuticals, LLC | Aminopyrimidine kinase inhibitors |
| GB201002861D0 (en) | 2010-02-19 | 2010-04-07 | Cxr Biosciences Ltd | Compositions |
| DK3354652T3 (da) | 2010-03-10 | 2020-05-18 | Incyte Holdings Corp | Piperidin-4-yl azetidinderivativer som jak1-inhibitorer |
| KR101464060B1 (ko) | 2010-04-07 | 2014-11-20 | 에프. 호프만-라 로슈 아게 | 피라졸-4-일-헤테로사이클릴-카복사마이드 화합물 및 사용 방법 |
| CA2796311A1 (en) | 2010-04-14 | 2011-10-20 | Incyte Corporation | Fused derivatives as pi3k.delta. inhibitors |
| US9062055B2 (en) | 2010-06-21 | 2015-06-23 | Incyte Corporation | Fused pyrrole derivatives as PI3K inhibitors |
| US20130109682A1 (en) | 2010-07-06 | 2013-05-02 | Novartis Ag | Cyclic ether compounds useful as kinase inhibitors |
| MX358682B (es) | 2010-07-13 | 2018-08-31 | Hoffmann La Roche | Derivados de pirazolo [1,5a]pirimidina y de tieno[3,2b] pirimidina como moduladores de la cinasa asociada al receptor de la interleucina 4 (irak4). |
| ES2823350T3 (es) | 2010-07-29 | 2021-05-06 | Rigel Pharmaceuticals Inc | Compuestos heterocíclicos que activan AMPK y métodos de uso de los mismos |
| US8227773B2 (en) | 2010-07-29 | 2012-07-24 | Axcelis Technologies, Inc. | Versatile beam glitch detection system |
| EP2637650A2 (en) | 2010-11-10 | 2013-09-18 | National Jewish Health | Methods to test allergic conditions |
| WO2012065297A1 (en) | 2010-11-16 | 2012-05-24 | Impact Therapeutics, Inc. | 3-ARYL-6-ARYL-[1,2,4]TRIAZOLO[4,3-a]PYRIDINES AS INHIBITORS OF CELL PROLIFERATION AND THE USE THEREOF |
| PH12013501001A1 (en) | 2010-11-19 | 2019-09-02 | Incyte Holdings Corp | Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
| EP2640725B1 (en) | 2010-11-19 | 2015-01-07 | Incyte Corporation | Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors |
| MX2013006467A (es) | 2010-12-09 | 2013-10-01 | Amgen Inc | Compuestos biciclicos como inhibidores pim. |
| MX342873B (es) | 2010-12-17 | 2016-10-17 | Nerviano Medical Sciences S R L * | Derivados de pirazolo-quinazolina sustituidos como inhibidores de cinasa. |
| CA2822070C (en) | 2010-12-20 | 2019-09-17 | Incyte Corporation | N-(1-(substituted-phenyl)ethyl)-9h-purin-6-amines as pi3k inhibitors |
| EP2668190B1 (en) | 2011-01-26 | 2016-08-17 | Nerviano Medical Sciences S.r.l. | Tricyclic pyrrolo derivatives, process for their preparation and their use as kinase inhibitors |
| US8916577B2 (en) | 2011-01-26 | 2014-12-23 | Nerviano Medical Sciences S.R.L. | Tricyclic derivatives, process for their preparation and their use as kinase inhibitors |
| DK2678329T3 (da) | 2011-02-25 | 2016-02-22 | Array Biopharma Inc | Triazolopyridinforbindelser som pim-kinase-hæmmere |
| EP2681197A1 (en) * | 2011-03-04 | 2014-01-08 | Novartis AG | Tetrasubstituted cyclohexyl compounds as kinase inhibitors |
| UY33930A (es) | 2011-03-04 | 2012-10-31 | Novartis Ag | Inhibidores novedosos de quinasas |
| WO2012125629A1 (en) | 2011-03-14 | 2012-09-20 | Incyte Corporation | Substituted diamino-pyrimidine and diamino-pyridine derivatives as pi3k inhibitors |
| AU2012230890A1 (en) | 2011-03-22 | 2013-09-26 | Amgen Inc. | Azole compounds as Pim inhibitors |
| WO2012135009A1 (en) | 2011-03-25 | 2012-10-04 | Incyte Corporation | Pyrimidine-4,6-diamine derivatives as pi3k inhibitors |
| AU2012238369A1 (en) | 2011-04-05 | 2013-10-03 | Pfizer Limited | Pyrrolo (2, 3 -d) pyrimidine derivatives as inhibitors of tropomyosin- related kinases |
| JP5976778B2 (ja) | 2011-04-11 | 2016-08-24 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | キナーゼ阻害剤としてのピラゾリル−ピリミジン誘導体 |
| EP2699569B1 (en) | 2011-04-22 | 2017-08-30 | Jasco Pharmaceuticals, LLC | Aminopyrimidine kinase inhibitors |
| GB201107176D0 (en) | 2011-04-28 | 2011-06-15 | Cxr Biosciences Ltd | Pyrrolnitrin derivatives |
| GB201107197D0 (en) | 2011-04-28 | 2011-06-15 | Cxr Biosciences Ltd | Compounds |
| CA2834166A1 (en) | 2011-04-29 | 2012-11-01 | Amgen Inc. | Bicyclic pyridazine compounds as pim inhibitors |
| WO2012156367A1 (en) | 2011-05-17 | 2012-11-22 | Bayer Intellectual Property Gmbh | Amino-substituted imidazopyridazines as mknk1 kinase inhibitors |
| PL2710018T3 (pl) | 2011-05-19 | 2022-04-04 | Fundación Del Sector Público Estatal Centro Nacional De Investigaciones Oncológicas Carlos III (F.S.P. CNIO) | Związki makrocykliczne jako inhibitory kinaz białkowych |
| RU2013157898A (ru) | 2011-05-27 | 2015-07-10 | Темпл Юниверсити-Оф Дзе Коммонвелт Систем Оф Хайер Эдьюкейшн | ЗАМЕЩЕННЫЕ 2-БЕНЗИЛИДЕН-2H-БЕНЗО[b][1,4]ТИАЗИН-3(4H)-ОНЫ, ИХ ПРОИЗВОДНЫЕ И ИХ ПРИМЕНЕНИЕ В ТЕРАПЕВТИЧЕСКИХ ЦЕЛЯХ |
| CA2837630A1 (en) | 2011-06-01 | 2012-12-06 | Knut Eis | Substituted aminoimidazopyridazines |
| WO2012170827A2 (en) | 2011-06-08 | 2012-12-13 | Cylene Pharmaceuticals, Inc. | Pyrazolopyrimidines and related heterocycles as ck2 inhibitors |
| AR086983A1 (es) | 2011-06-20 | 2014-02-05 | Incyte Corp | Derivados de azetidinil fenil, piridil o pirazinil carboxamida como inhibidores de jak |
| CN103764656A (zh) | 2011-06-22 | 2014-04-30 | 拜耳知识产权有限责任公司 | 杂环基氨基咪唑并哒嗪 |
| PT3409278T (pt) | 2011-07-21 | 2020-12-18 | Sumitomo Dainippon Pharma Oncology Inc | Inibidores de proteína cinase heterocíclicos |
| CN102924445B (zh) | 2011-08-11 | 2015-07-08 | 上海吉铠医药科技有限公司 | Pim激酶抑制剂及其制备方法与在制药中的应用 |
| KR20140071361A (ko) | 2011-08-12 | 2014-06-11 | 에프. 호프만-라 로슈 아게 | 피라졸로[3,4-c]피리딘 화합물 및 사용 방법 |
| TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物 |
| JP5843524B2 (ja) | 2011-09-02 | 2016-01-13 | キヤノン株式会社 | 有機無機複合組成物、有機無機複合材料、光学素子および積層型回折光学素子 |
| PH12021552978A1 (en) | 2011-09-02 | 2022-08-22 | Incyte Holdings Corp | Heterocyclylamines as pi3k inhibitors |
| UA117092C2 (uk) | 2011-09-06 | 2018-06-25 | Байєр Інтеллектуал Проперті Гмбх | Амінозаміщені імідазопіридазини |
| UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
| WO2013041634A1 (en) | 2011-09-23 | 2013-03-28 | Bayer Intellectual Property Gmbh | Substituted imidazopyridazines |
| WO2013045461A1 (en) | 2011-09-27 | 2013-04-04 | F. Hoffmann-La Roche Ag | Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use |
| EP2788350B1 (en) | 2011-10-07 | 2017-12-06 | Nerviano Medical Sciences S.r.l. | 4-ALKYL SUBSTITUTED 3,4-DIHYDROPYRROLO[1,2-a]PYRAZIN-1(2H)-ONE DERIVATIVES AS KINASES INHIBITORS |
| EP2788351B1 (en) | 2011-10-07 | 2017-06-28 | Nerviano Medical Sciences S.r.l. | SUBSTITUTED 3,4-DIHYDROPYRROLO[1,2-a]PYRAZIN-1(2H)-ONE DERIVATIVES AS KINASE INHIBITORS |
| BR112014010563B1 (pt) | 2011-11-04 | 2021-01-12 | Jasco Pharmaceuticals, LLC | compostos inibidores da aminopirimidina quinase |
| TW201348226A (zh) | 2012-02-28 | 2013-12-01 | Amgen Inc | 作為ｐｉｍ抑制劑之醯胺 |
| EP2822944A1 (en) | 2012-03-05 | 2015-01-14 | Amgen, Inc. | Oxazolidinone compounds and derivatives thereof |
| CA2868673A1 (en) | 2012-03-29 | 2013-10-03 | Bayer Intellectual Property Gmbh | Amino-substituted imidazopyridazines |
| AR090548A1 (es) | 2012-04-02 | 2014-11-19 | Incyte Corp | Azaheterociclobencilaminas biciclicas como inhibidores de pi3k |
| EP2834245B1 (en) | 2012-04-04 | 2017-12-13 | Bayer Pharma Aktiengesellschaft | Amino-substituted imidazopyridazines |
| RS56395B1 (sr) | 2012-04-26 | 2017-12-29 | Bristol Myers Squibb Co | Derivati imidazotiadiazola i imidazopirazina kao inhibitori proteazom aktiviranog receptora 4 (par4) za lečenje agregacije trombocita |
| PE20160802A1 (es) | 2012-04-27 | 2016-09-03 | Novartis Ag | Inhibidores de dgat1 de eter ciclico de cabeza de puente |
| KR102163377B1 (ko) | 2012-05-09 | 2020-10-08 | 바이오젠 엠에이 인코포레이티드 | 핵 수송 조절인자 및 이의 용도 |
| PE20210667A1 (es) | 2012-05-15 | 2021-04-05 | Novartis Ag | Derivados de benzamida para la inhibicion de la actividad abl1, abl2 y bcr-abl1 |
| AR091079A1 (es) | 2012-05-18 | 2014-12-30 | Incyte Corp | Derivados de pirrolopirimidina y pirrolopiridina sustituida con piperidinilciclobutilo como inhibidores de jak |
| HK1206021A1 (en) | 2012-05-21 | 2015-12-31 | Novartis Ag | Novel ring-substituted n-pyridinyl amides as kinase inhibitors |
| JP6165848B2 (ja) | 2012-05-22 | 2017-07-19 | イデニク ファーマシューティカルズ エルエルシー | 肝疾患のためのｄ−アミノ酸化合物 |
| TWI568722B (zh) | 2012-06-15 | 2017-02-01 | 葛蘭馬克製藥公司 | 作爲ｍＰＧＥＳ－１抑制劑之三唑酮化合物 |
| RU2665462C2 (ru) | 2012-06-27 | 2018-08-30 | Ф. Хоффманн-Ля Рош Аг | Соединения 5-азаиндазола и способы их применения |
| AR092348A1 (es) | 2012-07-11 | 2015-04-15 | Hoffmann La Roche | DERIVADOS DE ARIL-SULTAMO COMO MODULADORES DE RORc |
| TW201414737A (zh) | 2012-07-13 | 2014-04-16 | 必治妥美雅史谷比公司 | 作爲激酶抑制劑之咪唑并三□甲腈 |
| WO2014022752A1 (en) | 2012-08-03 | 2014-02-06 | Amgen Inc. | Macrocycles as pim inhibitors |
| WO2014033630A1 (en) | 2012-08-31 | 2014-03-06 | Novartis Ag | Novel aminothiazole carboxamides as kinase inhibitors |
| WO2014033631A1 (en) | 2012-08-31 | 2014-03-06 | Novartis Ag | N-(3-pyridyl) biarylamides as kinase inhibitors |
| CN103664878A (zh) | 2012-09-12 | 2014-03-26 | 山东亨利医药科技有限责任公司 | 杂芳环及其衍生物类酪氨酸激酶抑制剂 |
| HK1212684A1 (zh) | 2012-09-14 | 2016-06-17 | AbbVie Deutschland GmbH & Co. KG | 三環喹啉和喹喔啉衍生物 |
| US9328106B2 (en) | 2012-09-26 | 2016-05-03 | Genentech, Inc. | Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use |
| WO2014053568A1 (en) | 2012-10-02 | 2014-04-10 | Sanofi | Indolyldihydroimidazopyrimidinone derivatives, preparation thereof and therapeutic use thereof |
| EP2909195B1 (en) | 2012-10-16 | 2017-06-14 | Janssen Sciences Ireland UC | Rsv antiviral compounds |
| AR093308A1 (es) | 2012-11-01 | 2015-05-27 | Incyte Corp | Derivados triciclicos fusionados de tiofeno como inhibidores de jak |
| US9783543B2 (en) | 2012-11-19 | 2017-10-10 | Bayer Pharma Aktiengesellschaft | Aminoimidazopyridazines |
| WO2014079011A1 (en) | 2012-11-22 | 2014-05-30 | Agios Pharmaceuticals, Inc. | Heterocyclic compounds for inhibiting glutaminase and their methods of use |
| EP2930068B1 (en) | 2012-12-07 | 2017-10-18 | Toyota Jidosha Kabushiki Kaisha | Vehicle body end structure |
| EP3418281B1 (en) | 2012-12-07 | 2020-09-30 | Vertex Pharmaceuticals Inc. | Pyrazolo[1,5-a]pyrimidines useful as inhibitors of atr kinase for the treatment of cancer diseases |
| ES2685975T3 (es) | 2012-12-18 | 2018-10-15 | Vertex Pharmaceuticals Incorporated | Derivados de manosa para tratar las infecciones bacterianas |
| US20150336960A1 (en) | 2012-12-19 | 2015-11-26 | Novartis Ag | Aryl-substituted fused bicyclic pyridazine compounds |
| US9630945B2 (en) | 2012-12-19 | 2017-04-25 | Novartis Ag | Autotaxin inhibitors |
| AU2013361401C1 (en) | 2012-12-21 | 2018-08-09 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
| HUE040323T2 (hu) | 2012-12-21 | 2019-02-28 | Epizyme Inc | PRMT5-inhibitorok és alkalmazásaik |
| FR3000569B1 (fr) | 2013-01-03 | 2015-02-13 | Peugeot Citroen Automobiles Sa | Dispositif d'eclairage a ecran a bord(s) lumineux |
| WO2014110574A1 (en) | 2013-01-14 | 2014-07-17 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors |
| UA121098C2 (uk) | 2013-01-15 | 2020-04-10 | Інсайт Холдинґс Корпорейшн | Тіазолкарбоксаміди і піридинкарбоксаміди, які використовуються як інгібітори рім-кінази |
| TW202214254A (zh) | 2013-03-01 | 2022-04-16 | 美商英塞特控股公司 | 吡唑并嘧啶衍生物治療PI3Kδ相關病症之用途 |
| SMT201900081T1 (it) | 2013-03-06 | 2019-05-10 | Incyte Holdings Corp | Procedimenti e intermedi per produrre un inibitore di jak |
| JO3383B1 (ar) | 2013-03-14 | 2019-03-13 | Lilly Co Eli | مثبطات cdc7 |
| ES2663789T3 (es) | 2013-03-15 | 2018-04-17 | Japan Tobacco, Inc. | Compuesto de pirazol-amida y usos medicinales del mismo |
| JO3279B1 (ar) | 2013-03-15 | 2018-09-16 | Respivert Ltd | مشتقات 2-((4- امينو -3- (3- فلورو-5- هيدروكسي فينيل)-h1- بيرازولو [d-3,4] بيرمدين-1-يل )ميثيل )- 3- (2- تراي فلورو ميثيل ) بينزيل ) كوينازولين -4 (h3)- واحد واستخدامها كمثبطات فوسفواينوسيتايد 3- كاينيز |
| MX2015012947A (es) | 2013-03-15 | 2016-06-02 | Dow Agrosciences Llc | 4-amino-6-(heterociclico) picolinatos y 6-amino-2-(heterociclico) pirimidina-4-carboxilatos y su uso como herbicidas. |
| EP2970282B1 (en) | 2013-03-15 | 2019-08-21 | Incyte Holdings Corporation | Tricyclic heterocycles as bet protein inhibitors |
| US20140275108A1 (en) | 2013-03-15 | 2014-09-18 | Galderma Research & Development | Novel benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine as well as in cosmetics |
| ES2864707T3 (es) | 2013-03-15 | 2021-10-14 | Global Blood Therapeutics Inc | Compuestos y usos de los mismos para la modulación de la hemoglobina |
| US9308236B2 (en) | 2013-03-15 | 2016-04-12 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions |
| TWI742541B (zh) | 2013-03-15 | 2021-10-11 | 英商邊緣生物科技有限公司 | 用於治療肺纖維化、肝纖維化、皮膚纖維化及心臟纖維化之經取代之芳族化合物 |
| UY35421A (es) | 2013-03-15 | 2014-10-31 | Nihon Nohyaku Co Ltd | Compuesto heterocíclico condensado o su sal, insecticida agrícola u hortícola que comprende el comp uesto y método de uso del insecticida |
| EA029309B1 (ru) | 2013-03-15 | 2018-03-30 | Идорсиа Фармасьютиклз Лтд | Производные пиридин-4-ила в качестве агонистов s1p/edg1 |
| BR112015021982B1 (pt) | 2013-03-15 | 2022-12-13 | Global Blood Therapeutics, Inc | Compostos e seus usos para a modulação de hemoglobina |
| AR095443A1 (es) | 2013-03-15 | 2015-10-14 | Fundación Centro Nac De Investig Oncológicas Carlos Iii | Heterociclos condensados con acción sobre atr |
| TWI689490B (zh) | 2013-03-15 | 2020-04-01 | 英商邊緣生物科技有限公司 | 用於治療纖維化之經取代之芳族化合物及相關方法 |
| RU2680100C9 (ru) | 2013-03-15 | 2019-04-18 | Плексксикон Инк. | Гетероциклические соединения и их применения |
| WO2014139145A1 (en) | 2013-03-15 | 2014-09-18 | Hutchison Medipharma Limited | Novel pyrimidine and pyridine compounds and usage thereof |
| HRP20200955T1 (hr) | 2013-08-07 | 2020-10-02 | Incyte Corporation | Dozni oblici s produženim oslobađanjem za jak1 inhibitor |
| WO2015027124A1 (en) | 2013-08-23 | 2015-02-26 | Incyte Corporation | Furo- and thieno-pyridine carboxamide compounds useful as pim kinase inhibitors |
| KR20160136323A (ko) | 2014-02-28 | 2016-11-29 | 인사이트 코포레이션 | 골수형성이상증후군 치료용 jak1 억제제 |
| NZ763326A (en) | 2014-04-08 | 2023-04-28 | Incyte Holdings Corp | Treatment of b-cell malignancies by a combination jak and pi3k inhibitor |
| PE20170300A1 (es) | 2014-04-30 | 2017-04-19 | Incyte Corp | Procesos para preparar un inhibidor de jak 1 y nuevas formas de este |
| WO2015184305A1 (en) | 2014-05-30 | 2015-12-03 | Incyte Corporation | TREATMENT OF CHRONIC NEUTROPHILIC LEUKEMIA (CNL) AND ATYPICAL CHRONIC MYELOID LEUKEMIA (aCML) BY INHIBITORS OF JAK1 |
| US10077277B2 (en) | 2014-06-11 | 2018-09-18 | Incyte Corporation | Bicyclic heteroarylaminoalkyl phenyl derivatives as PI3K inhibitors |
| WO2016010897A1 (en) | 2014-07-14 | 2016-01-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors |
| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
| WO2016196244A1 (en) | 2015-05-29 | 2016-12-08 | Incyte Corporation | Pyridineamine compounds useful as pim kinase inhibitors |
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| ES2649156T3 (es) | 2018-01-10 |
| EP2943485B1 (en) | 2017-09-20 |
| JP6437452B2 (ja) | 2018-12-12 |
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| US20140200216A1 (en) | 2014-07-17 |
| HK1216316A1 (en) | 2016-11-11 |
| EP2943485A1 (en) | 2015-11-18 |
| CA2897200A1 (en) | 2014-07-17 |
| US20160137626A1 (en) | 2016-05-19 |
| JP2016505021A (ja) | 2016-02-18 |
| US9676750B2 (en) | 2017-06-13 |
| US9278950B2 (en) | 2016-03-08 |
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