ES2956642T3 - Compuestos y métodos para la inhibición de JAK - Google Patents
Compuestos y métodos para la inhibición de JAK Download PDFInfo
- Publication number
- ES2956642T3 ES2956642T3 ES16770031T ES16770031T ES2956642T3 ES 2956642 T3 ES2956642 T3 ES 2956642T3 ES 16770031 T ES16770031 T ES 16770031T ES 16770031 T ES16770031 T ES 16770031T ES 2956642 T3 ES2956642 T3 ES 2956642T3
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- Prior art keywords
- methyl
- amino
- methoxy
- indol
- pyrazol
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 138
- 238000000034 method Methods 0.000 title claims abstract description 64
- 230000005764 inhibitory process Effects 0.000 title description 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 603
- 239000001257 hydrogen Substances 0.000 claims abstract description 301
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 301
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 150
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 148
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 143
- 150000003839 salts Chemical class 0.000 claims abstract description 110
- 239000011737 fluorine Chemical group 0.000 claims abstract description 83
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 83
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims abstract description 76
- 239000000460 chlorine Chemical group 0.000 claims abstract description 36
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 36
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 30
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 29
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 29
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 28
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract 4
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 108
- 239000007787 solid Substances 0.000 claims description 104
- CVCVOSPZEVINRM-MRXNPFEDSA-N COC1=NN(C=C1NC1=NC=CC(=N1)C1=CNC2=C(C=CC=C12)NC([C@@H](C)N1CCN(CC1)C)=O)C Chemical compound COC1=NN(C=C1NC1=NC=CC(=N1)C1=CNC2=C(C=CC=C12)NC([C@@H](C)N1CCN(CC1)C)=O)C CVCVOSPZEVINRM-MRXNPFEDSA-N 0.000 claims description 97
- 238000011282 treatment Methods 0.000 claims description 92
- -1 3-ethoxy-1-methyl-1H-pyrazol-4-yl Chemical group 0.000 claims description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 68
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 62
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 51
- 229940125216 golidocitinib Drugs 0.000 claims description 41
- 239000003814 drug Substances 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 11
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 6
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Landscapes
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| US201562232629P | 2015-09-25 | 2015-09-25 | |
| PCT/EP2016/072616 WO2017050938A1 (en) | 2015-09-25 | 2016-09-22 | Compounds and methods for inhibiting jak |
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| ES2956642T3 true ES2956642T3 (es) | 2023-12-26 |
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| ES (1) | ES2956642T3 (enExample) |
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| KR20250035597A (ko) * | 2015-09-25 | 2025-03-12 | 디잘 (지앙수) 파마슈티칼 씨오., 리미티드 | Jak를 억제하기 위한 화합물 및 방법 |
| US10513509B2 (en) | 2016-05-26 | 2019-12-24 | Recurium Ip Holdings, Llc | EGFR inhibitor compounds |
| MX390625B (es) * | 2017-01-17 | 2025-03-19 | Astrazeneca Ab | Inhibidores selectivos de jak1. |
| JOP20180094A1 (ar) | 2017-10-18 | 2019-04-18 | Hk Inno N Corp | مركب حلقي غير متجانس كمثبط بروتين كيناز |
| CN118580223A (zh) * | 2018-07-18 | 2024-09-03 | 阿斯利康(瑞典)有限公司 | 抑制jak的化合物的昔萘酸盐 |
| CN112823159B (zh) * | 2018-09-21 | 2024-03-01 | 上海轶诺药业有限公司 | 一类具有激酶抑制活性的芳香杂环类化合物 |
| KR102195348B1 (ko) * | 2018-11-15 | 2020-12-24 | 에이치케이이노엔 주식회사 | 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 |
| MX2021012749A (es) * | 2019-04-19 | 2021-11-18 | Dizal Jiangsu Pharmaceutical Co Ltd | Inhibidor selectivo de la jak1 cinasa. |
| CN110627775A (zh) * | 2019-10-24 | 2019-12-31 | 嘉兴特科罗生物科技有限公司 | 一种小分子化合物 |
| CN111961037B (zh) * | 2020-09-17 | 2021-09-21 | 嘉兴特科罗生物科技有限公司 | 一种作为jak激酶抑制剂的药物化合物 |
| CN114269736B (zh) * | 2020-11-26 | 2024-02-02 | 科辉智药(深圳)新药研究中心有限公司 | 一种酰胺化合物、药物组合物及其应用 |
| MX2023010642A (es) | 2021-03-11 | 2023-11-28 | Janssen Pharmaceutica Nv | Lorpucitinib para uso en el tratamiento de trastornos mediados por jak. |
| CN115260128B (zh) * | 2022-09-21 | 2022-12-09 | 苏州凯瑞医药科技有限公司 | 一种新型jak抑制剂关键中间体的制备方法 |
| WO2025230951A1 (en) * | 2024-04-29 | 2025-11-06 | Icahn School Of Medicine At Mount Sinai | Method of treating adenoid cystic carcinoma |
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| CA2560454C (en) * | 2004-03-30 | 2013-05-21 | Vertex Pharmaceuticals Incorporated | Azaindoles useful as inhibitors of jak and other protein kinases |
| GB0500492D0 (en) * | 2005-01-11 | 2005-02-16 | Cyclacel Ltd | Compound |
| EP2388259A1 (en) | 2005-10-28 | 2011-11-23 | AstraZeneca AB | 4- (3-aminopyrazole) pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer |
| WO2007089768A2 (en) * | 2006-01-30 | 2007-08-09 | Exelixis, Inc. | 4-aryl-2-amino-pyrimidines or 4-aryl-2-aminoalkyl-pyrimidines as jak-2 modulators and pharmaceutical compositions containing them |
| ME00811B (me) * | 2006-12-08 | 2012-03-20 | Novartis Ag | JEDINJENJA l KOMPOZICIJE KAO INHIBITORI PROTEIN KINAZE |
| US9908884B2 (en) * | 2009-05-05 | 2018-03-06 | Dana-Farber Cancer Institute, Inc. | EGFR inhibitors and methods of treating disorders |
| ES2487542T3 (es) | 2009-05-22 | 2014-08-21 | Incyte Corporation | Derivados de N-(hetero)aril-pirrolidina de pirazol-4-il-pirrolo[2,3-d]pirimidinas y pirrol-3-il-pirrolo[2,3-d]pirimidinas como inhibidores de cinasas Janus |
| TWI466885B (zh) * | 2009-07-31 | 2015-01-01 | Japan Tobacco Inc | 含氮螺環化合物及其醫藥用途 |
| US20130225615A1 (en) * | 2010-09-01 | 2013-08-29 | Ambit Biosciences Corporation | 2-cycloquinazoline derivatives and methods of use thereof |
| US9198911B2 (en) | 2010-11-02 | 2015-12-01 | The Trustees Of Columbia University In The City Of New York | Methods for treating hair loss disorders |
| JP2014500254A (ja) * | 2010-11-09 | 2014-01-09 | セルゾーム リミティッド | Ｔｙｋ２阻害剤としてのピリジン化合物およびそのアザ類似体 |
| SG190839A1 (en) * | 2010-11-19 | 2013-07-31 | Incyte Corp | Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
| WO2012116247A1 (en) * | 2011-02-25 | 2012-08-30 | Synta Pharmaceuticals Corp. | Hsp90 inhibitory compounds in treating jak/stat signaling-mediated cancers |
| WO2012177606A1 (en) * | 2011-06-20 | 2012-12-27 | Incyte Corporation | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors |
| CN104334191A (zh) | 2012-03-29 | 2015-02-04 | 纽约市哥伦比亚大学托管会 | 治疗毛发脱落疾病的方法 |
| KR20250035597A (ko) * | 2015-09-25 | 2025-03-12 | 디잘 (지앙수) 파마슈티칼 씨오., 리미티드 | Jak를 억제하기 위한 화합물 및 방법 |
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