ES2913929T3 - Compuestos químicos como inhibidores de la ruta de ATF4 - Google Patents
Compuestos químicos como inhibidores de la ruta de ATF4 Download PDFInfo
- Publication number
- ES2913929T3 ES2913929T3 ES17733530T ES17733530T ES2913929T3 ES 2913929 T3 ES2913929 T3 ES 2913929T3 ES 17733530 T ES17733530 T ES 17733530T ES 17733530 T ES17733530 T ES 17733530T ES 2913929 T3 ES2913929 T3 ES 2913929T3
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- Prior art keywords
- chlorophenoxy
- acetamide
- disease
- cancer
- compound
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- 101000905743 Homo sapiens Cyclic AMP-dependent transcription factor ATF-4 Proteins 0.000 title description 70
- 102100023580 Cyclic AMP-dependent transcription factor ATF-4 Human genes 0.000 title description 69
- 230000037361 pathway Effects 0.000 title description 47
- 239000003112 inhibitor Substances 0.000 title description 30
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- 125000000217 alkyl group Chemical group 0.000 claims abstract description 89
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 64
- 239000011737 fluorine Substances 0.000 claims abstract description 64
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 64
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 34
- 125000001424 substituent group Chemical group 0.000 claims abstract description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 22
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 19
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| US6140349A (en) | 1998-02-02 | 2000-10-31 | Merck & Co., Inc. | Cyclic amine modulators of chemokine receptor activity |
| JP2002527477A (ja) * | 1998-10-16 | 2002-08-27 | サントリー株式会社 | 神経細胞保護作用物質としてのアミノフェノキシ酢酸誘導体 |
| EP1031564A1 (en) * | 1999-02-26 | 2000-08-30 | Klinge Pharma GmbH | Inhibitors of cellular nicotinamide mononucleotide formation and their use in cancer therapy |
| SE9902987D0 (sv) * | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
| WO2001014424A2 (en) | 1999-08-24 | 2001-03-01 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| WO2001079170A2 (en) | 2000-04-13 | 2001-10-25 | Suntory Limited | Aminophenoxyacetamide derivatives and pharmaceutical composition containing thereof |
| DK1343782T3 (da) | 2000-12-21 | 2009-08-24 | Smithkline Beecham Corp | Pyrimidinaminer som angiogenesemodulatorer |
| AU2002327534A1 (en) * | 2001-08-17 | 2003-03-03 | Merck And Co., Inc. | Tyrosine kinase inhibitors |
| WO2003049736A1 (en) | 2001-12-11 | 2003-06-19 | Sepracor, Inc. | 4-substituted piperidines, and methods of use thereof |
| MY134200A (en) * | 2002-04-12 | 2007-11-30 | Kowa Co | Method for treating cancer |
| US7595048B2 (en) | 2002-07-03 | 2009-09-29 | Ono Pharmaceutical Co., Ltd. | Method for treatment of cancer by inhibiting the immunosuppressive signal induced by PD-1 |
| WO2004056875A1 (en) | 2002-12-23 | 2004-07-08 | Wyeth | Antibodies against pd-1 and uses therefor |
| EP1591527B1 (en) | 2003-01-23 | 2015-08-26 | Ono Pharmaceutical Co., Ltd. | Substance specific to human pd-1 |
| US7550599B2 (en) | 2003-02-26 | 2009-06-23 | Ciba Specialty Chemicals Corporation | Water compatible sterically hindered alkoxyamines and hydroxy substituted alkoxyamines |
| JP2007513082A (ja) * | 2003-11-10 | 2007-05-24 | シエーリング アクチエンゲゼルシャフト | Ccr−5アンタゴニストとして有用なベンジルエーテルアミン化合物 |
| WO2005058885A2 (en) * | 2003-12-18 | 2005-06-30 | Glaxo Group Limited | Piperidine derivatives and their use as glycine transporter inhibitors |
| DK2161336T4 (en) | 2005-05-09 | 2017-04-24 | Ono Pharmaceutical Co | Human monoclonal antibodies for programmed death 1 (PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapies |
| RS54271B1 (sr) | 2005-07-01 | 2016-02-29 | E. R. Squibb & Sons, L.L.C. | Humana monoklonska antitela za ligand programirane smrti 1 (pd-l1) |
| US7897593B2 (en) | 2006-05-30 | 2011-03-01 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| JP2010503676A (ja) | 2006-09-15 | 2010-02-04 | シェーリング コーポレイション | 疼痛、糖尿病および脂質代謝の障害の治療 |
| NZ582150A (en) | 2007-06-18 | 2012-08-31 | Msd Oss Bv | Antibodies to human programmed death receptor pd-1 |
| TW200938203A (en) | 2007-12-17 | 2009-09-16 | Intervet Int Bv | Anthelmintic agents and their use |
| US8642660B2 (en) * | 2007-12-21 | 2014-02-04 | The University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| WO2009114335A2 (en) | 2008-03-12 | 2009-09-17 | Merck & Co., Inc. | Pd-1 binding proteins |
| WO2009151152A1 (en) * | 2008-06-11 | 2009-12-17 | Shionogi & Co., Ltd. | Oxycarbamoyl compounds and the use thereof |
| EP2307440A4 (en) * | 2008-07-01 | 2012-12-19 | Zacharon Pharmaceuticals Inc | HEPARAN SULFATE INHIBITORS |
| CN102203125A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂及其使用方法 |
| MX2011003195A (es) | 2008-09-26 | 2011-08-12 | Dana Farber Cancer Inst Inc | Anticuerpos anti-pd-1, pd-l1 y pd-l2 humanos y usos de los mismos. |
| CN101712679B (zh) | 2008-10-08 | 2013-04-10 | 中国科学院上海药物研究所 | 一种酰胺类化合物、其药物组合物及其制备方法和用途 |
| HRP20170908T1 (hr) | 2008-12-09 | 2017-09-22 | F. Hoffmann - La Roche Ag | Protutijela anti-pd-l1 i njihova uporaba za poboljšanje funkcije t-stanice |
| JP2013028538A (ja) * | 2009-11-13 | 2013-02-07 | Dainippon Sumitomo Pharma Co Ltd | 新規アミド誘導体 |
| PT2504364T (pt) | 2009-11-24 | 2017-11-14 | Medimmune Ltd | Agentes de ligação direcionados contra b7-h1 |
| JP2013512251A (ja) | 2009-11-24 | 2013-04-11 | アンプリミューン、インコーポレーテッド | Pd−l1/pd−l2の同時阻害 |
| US20110280877A1 (en) | 2010-05-11 | 2011-11-17 | Koji Tamada | Inhibition of B7-H1/CD80 interaction and uses thereof |
| WO2013019621A1 (en) | 2011-07-29 | 2013-02-07 | Tempero Pharmaceuticals, Inc. | Compounds and methods |
| AU2012290121B2 (en) | 2011-08-01 | 2015-11-26 | Genentech, Inc. | Methods of treating cancer using PD-1 axis binding antagonists and MEK inhibitors |
| RS61033B1 (sr) | 2011-11-28 | 2020-12-31 | Merck Patent Gmbh | Antitela na pd-l1 i njihova upotreba |
| SG10201701649YA (en) * | 2012-02-21 | 2017-04-27 | Acraf | 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors |
| AU2013224313B2 (en) * | 2012-02-21 | 2017-03-30 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Use of 1H-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors |
| WO2013170072A2 (en) | 2012-05-09 | 2013-11-14 | Neurop, Inc. | Compounds for the treatment of neurological disorders |
| CA2873402C (en) | 2012-05-15 | 2023-10-24 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
| KR101947702B1 (ko) | 2012-10-04 | 2019-02-14 | 다나-파버 캔서 인스티튜트 인크. | 인간 단클론 항-pd-l1 항체 및 사용 방법 |
| CN105263910A (zh) | 2013-02-18 | 2016-01-20 | 斯克利普斯研究所 | 具有治疗潜力的血管加压素受体调节剂 |
| AU2014233520B2 (en) | 2013-03-15 | 2019-02-21 | The Regents Of The University Of California | Modulators of the eIF2alpha pathway |
| EP3116877A1 (en) * | 2014-03-11 | 2017-01-18 | Glaxosmithkline Intellectual Property (No. 2) Limited | Chemical compounds acting as perk inhibitors |
| WO2016055935A1 (en) * | 2014-10-06 | 2016-04-14 | Glaxosmithkline Intellectual Property (No.2) Limited | Combination of lysine-specific demethylase 1 inhibitor and thrombopoietin agonist |
-
2017
- 2017-06-07 CN CN201780048778.1A patent/CN109563071B/zh active Active
- 2017-06-07 JP JP2018564345A patent/JP2019521111A/ja active Pending
- 2017-06-07 US US16/307,507 patent/US20190298705A1/en not_active Abandoned
- 2017-06-07 ES ES17733530T patent/ES2913929T3/es active Active
- 2017-06-07 RU RU2018145734A patent/RU2018145734A/ru not_active Application Discontinuation
- 2017-06-07 EP EP17733530.4A patent/EP3468960B1/en active Active
- 2017-06-07 WO PCT/IB2017/053372 patent/WO2017212425A1/en not_active Ceased
- 2017-06-07 KR KR1020197000186A patent/KR20190015748A/ko not_active Withdrawn
- 2017-06-07 CA CA3026982A patent/CA3026982A1/en active Pending
- 2017-06-07 BR BR112018075598-2A patent/BR112018075598A2/pt not_active IP Right Cessation
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2022
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Also Published As
| Publication number | Publication date |
|---|---|
| JP2019521111A (ja) | 2019-07-25 |
| KR20190015748A (ko) | 2019-02-14 |
| EP3468960A1 (en) | 2019-04-17 |
| CN109563071A (zh) | 2019-04-02 |
| US20190298705A1 (en) | 2019-10-03 |
| WO2017212425A1 (en) | 2017-12-14 |
| US11547704B2 (en) | 2023-01-10 |
| AU2017279029A1 (en) | 2018-12-20 |
| CA3026982A1 (en) | 2017-12-14 |
| CN109563071B (zh) | 2021-08-03 |
| BR112018075598A2 (pt) | 2019-03-26 |
| US20200297710A1 (en) | 2020-09-24 |
| EP3468960B1 (en) | 2022-03-23 |
| US20230165848A1 (en) | 2023-06-01 |
| RU2018145734A (ru) | 2020-07-14 |
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