KR20210010887A - 유비퀴틴-특이적 펩티다제 30 억제제로서 유용한 융합된 비시클릭 화합물 - Google Patents
유비퀴틴-특이적 펩티다제 30 억제제로서 유용한 융합된 비시클릭 화합물 Download PDFInfo
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- KR20210010887A KR20210010887A KR1020207035718A KR20207035718A KR20210010887A KR 20210010887 A KR20210010887 A KR 20210010887A KR 1020207035718 A KR1020207035718 A KR 1020207035718A KR 20207035718 A KR20207035718 A KR 20207035718A KR 20210010887 A KR20210010887 A KR 20210010887A
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- 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
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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| US201862727164P | 2018-09-05 | 2018-09-05 | |
| US62/727,164 | 2018-09-05 | ||
| PCT/US2019/032619 WO2019222468A1 (en) | 2018-05-17 | 2019-05-16 | Fused bicyclic compounds useful as ubiquitin-specific peptidase 30 inhibitors |
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Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2018346597B2 (en) | 2017-10-06 | 2023-07-13 | Forma Therapeutics, Inc. | Inhibiting Ubiquitin Specific Peptidase 30 |
| JP7449242B2 (ja) | 2018-05-17 | 2024-03-13 | フォーマ セラピューティクス,インコーポレイテッド | ユビキチン特異的ペプチダーゼ30(usp30)阻害剤として有用な縮合二環化合物 |
| JP7530889B2 (ja) | 2018-10-05 | 2024-08-08 | フォーマ セラピューティクス,インコーポレイテッド | ユビキチン特異的プロテアーゼ30(usp30)阻害剤として作用する縮合ピロリン |
| GB201905375D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201905371D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201912674D0 (en) | 2019-09-04 | 2019-10-16 | Mission Therapeutics Ltd | Novel compounds |
| JP2023520727A (ja) | 2020-04-08 | 2023-05-18 | ミッション セラピューティクス リミティド | Usp30阻害剤として活性を有するn-シアノピロリジン |
| IL298526A (en) | 2020-05-28 | 2023-01-01 | Mission Therapeutics Ltd | N-(1-cyano-pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)oxazole-2-carboxamide derivatives and the corresponding oxadiazole derivatives as usp30 inhibitors for the treatment of mitochondrial dysfunction |
| US20230303547A1 (en) | 2020-06-04 | 2023-09-28 | Mission Therapeutics Limited | N-cyanopyrrolidines with activity as usp30 inhibitors |
| DK4161929T3 (da) | 2020-06-08 | 2025-08-18 | Mission Therapeutics Ltd | 1-(5-(2-cyanopyridin-4-yl)oxazol-2-carbonyl)-4-methylhexahydropyrrolo[3,4-b]pyrrol-5(1h)-carbonitril som usp30-hæmmer til anvendelse i behandling af mitokondriedysfunktion, cancer og fibrose |
| GB202016800D0 (en) | 2020-10-22 | 2020-12-09 | Mission Therapeutics Ltd | Novel compounds |
| JP2024544660A (ja) | 2021-12-01 | 2024-12-03 | ミッション セラピューティクス リミティド | Usp30阻害剤としての活性を有する置換n-シアノピロリジン |
| EP4488279A1 (en) | 2023-07-03 | 2025-01-08 | Centro Atlantico del Medicamento S.A (Ceamed, S.A) | Substituted hexahydro-2h-pyrazino[1,2-a]pyrazin-1(6h)-one derivatives as activators of human caseinolytic protease p (hsclpp) |
| GB202408928D0 (en) | 2024-06-21 | 2024-08-07 | Mission Therapeutics Ltd | Novel compounds |
| GB202411060D0 (en) | 2024-07-29 | 2024-09-11 | Mission Therapeutics Ltd | Novel compounds |
Family Cites Families (192)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030191279A1 (en) | 1999-08-27 | 2003-10-09 | Goldstein Steven Wayne | Urea derivatives useful as anticancer agents |
| US6576632B1 (en) | 1999-08-27 | 2003-06-10 | Pfizer Inc | Biaryl compounds useful as anticancer agents |
| US6632815B2 (en) | 1999-09-17 | 2003-10-14 | Millennium Pharmaceuticals, Inc. | Inhibitors of factor Xa |
| CZ2002959A3 (cs) | 1999-09-17 | 2002-07-17 | Millennium Pharmaceuticals, Inc. | Inhibitory faktoru Xa |
| ES2316383T3 (es) | 1999-09-17 | 2009-04-16 | Millennium Pharmaceuticals, Inc. | Benzamidas e inhibidores relacionados del factor xa. |
| CA2387892A1 (en) | 1999-10-18 | 2001-04-26 | University Of Connecticut | Pyrazole derivatives as cannabinoid receptor antagonists |
| WO2001064642A2 (en) | 2000-02-29 | 2001-09-07 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor xa |
| EP1272467A4 (en) | 2000-04-06 | 2003-05-07 | Merck Frosst Canada Inc | Cathepsin cysteine protease inhibitors |
| PL362320A1 (en) | 2000-12-06 | 2004-10-18 | Aventis Pharma Deutschland Gmbh | Guanidine and amidine derivatives as factor xa inhibitors |
| EP1217000A1 (en) | 2000-12-23 | 2002-06-26 | Aventis Pharma Deutschland GmbH | Inhibitors of factor Xa and factor VIIa |
| AU2002317377A1 (en) | 2001-07-20 | 2003-03-03 | Cancer Research Technology Limited | Biphenyl apurinic/apyrimidinic site endonuclease inhibitors to treat cancer |
| CA2457922A1 (en) | 2001-08-31 | 2003-03-13 | University Of Connecticut | Novel pyrazole analogs acting on cannabinoid receptors |
| AU2003243921B2 (en) | 2002-06-27 | 2009-05-07 | Novo Nordisk A/S | Aryl carbonyl derivatives as therapeutic agents |
| US7074809B2 (en) | 2002-08-09 | 2006-07-11 | Astrazeneca Ab | Compounds |
| TW200424183A (en) | 2002-08-09 | 2004-11-16 | Nps Pharma Inc | New compounds |
| RU2366655C2 (ru) | 2003-03-14 | 2009-09-10 | Оно Фармасьютикал Ко., Лтд. | Азотсодержащие гетероциклические производные и лекарственные средства, содержащие их в качестве активного ингредиента |
| TW200505902A (en) | 2003-03-20 | 2005-02-16 | Schering Corp | Cannabinoid receptor ligands |
| WO2004110350A2 (en) | 2003-05-14 | 2004-12-23 | Torreypines Therapeutics, Inc. | Compouds and uses thereof in modulating amyloid beta |
| GB0315111D0 (en) | 2003-06-27 | 2003-07-30 | Cancer Rec Tech Ltd | Substituted 5-membered ring compounds and their use |
| WO2005019200A2 (en) | 2003-08-14 | 2005-03-03 | Icos Corporation | Aryl piperidine derivatives as vla-1 integrin antagonists and uses thereof |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| TWI316955B (en) | 2003-11-19 | 2009-11-11 | Chisso Corp | Photo-polymerization liquid composition,polymer or polymer co mposition and optical compensation device thereof |
| WO2005077345A1 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Compounds for the treatment of gastro-esophageal reflux disease |
| WO2005077373A2 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
| WO2005077368A2 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
| US7585881B2 (en) | 2004-02-18 | 2009-09-08 | Astrazeneca Ab | Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| RU2006127575A (ru) | 2004-02-18 | 2008-03-27 | Астразенека Аб (Se) | Соединение триазола и их применение в качестве антагонистов метаботропного рецептора глутамата |
| WO2005087235A1 (en) | 2004-03-09 | 2005-09-22 | National Health Research Institutes | Pyrrolidine compounds |
| DE112005001070T5 (de) | 2004-05-21 | 2007-04-12 | Merck Patent Gmbh | Flüssigkristallverbindungen, Flüssigkristallmedium und Flüssigkristallanzeige |
| US20090105218A1 (en) | 2004-05-29 | 2009-04-23 | 7Tm Pharma A/S | CRTH2 Receptor Ligands For Therapeutic Use |
| EP1758579A1 (en) | 2004-05-29 | 2007-03-07 | 7TM Pharma A/S | Crth2 receptor ligands for medicinal uses |
| WO2006015279A1 (en) | 2004-07-28 | 2006-02-09 | Neurogen Corporation | Heterocyclic diamine compounds as ligands of the melanin concentrating hormone receptor useful for the treatment of obesity, diabetes, eating and sexual disorders |
| US7652051B2 (en) | 2004-08-25 | 2010-01-26 | Targegen, Inc. | Heterocyclic compounds and methods of use |
| KR101176677B1 (ko) | 2004-09-06 | 2012-08-23 | 메르크 파텐트 게엠베하 | 중합성 액정 물질 |
| DE102004051277A1 (de) | 2004-10-21 | 2006-04-27 | Merck Patent Gmbh | Heterocyclische Carbonylverbindungen |
| DE102004054666A1 (de) | 2004-11-12 | 2006-05-18 | Bayer Cropscience Gmbh | Substituierte Pyrazol-3-carboxamide, Verfahren zur Herstellung und Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| US7678913B2 (en) | 2004-12-07 | 2010-03-16 | Portola Pharmaceuticals, Inc. | Ureas as factor Xa inhibitors |
| JP5123668B2 (ja) | 2005-01-10 | 2013-01-23 | エグゼリクシス, インコーポレイテッド | 医薬品としての複素環カルボキサミド化合物 |
| JP2008526887A (ja) | 2005-01-10 | 2008-07-24 | ユニバーシティ オブ コネチカット | カンナビノイド受容体に作用する新規なヘテロピロール類似体 |
| GB2424881B (en) | 2005-04-07 | 2010-11-24 | Merck Patent Gmbh | Halophenyl derivatives of bisalkylfluorene |
| US20060235028A1 (en) | 2005-04-14 | 2006-10-19 | Li James J | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
| PL1891038T3 (pl) | 2005-05-13 | 2009-04-30 | Lilly Co Eli | Podstawione n-arylopirolidyny jako selektywne modulatory receptora androgenowego |
| GB0510139D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds B1 |
| WO2007024744A2 (en) | 2005-08-21 | 2007-03-01 | Exelixis, Inc. | Heterocyclic carboxamide compounds as steroid nuclear receptor ligands |
| EP1948614A2 (en) | 2005-11-18 | 2008-07-30 | Takeda San Diego, Inc. | Glucokinase activators |
| US20080004273A1 (en) | 2006-05-30 | 2008-01-03 | Stephane Raeppel | Inhibitors of protein tyrosine kinase activity |
| WO2007146838A2 (en) | 2006-06-09 | 2007-12-21 | Icos Corporation | Substituted phenyl acetic acids as dp-2 antagonists |
| TW200815438A (en) | 2006-06-13 | 2008-04-01 | Bayer Schering Pharma Ag | Substituted pyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| TW200815437A (en) | 2006-06-13 | 2008-04-01 | Bayer Schering Pharma Ag | Substituted aminopyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| JP5606736B2 (ja) | 2006-09-02 | 2014-10-15 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 反応性メソゲンを配向するための粒子ビーム法 |
| KR101472765B1 (ko) | 2006-12-08 | 2014-12-15 | 밀레니엄 파머슈티컬스 인코퍼레이티드 | 경구용 Xa 인자 억제제를 포함하는 단위 용량 제형 및 경구용 Xa 인자 억제제를 사용하는 혈전증의 치료 방법 |
| EP2125808A2 (en) | 2006-12-15 | 2009-12-02 | Bayer Schering Pharma Aktiengesellschaft | 3-h-pyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| AU2007338792B2 (en) | 2006-12-20 | 2012-05-31 | Amgen Inc. | Substituted heterocycles and methods of use |
| BRPI0811947A2 (pt) | 2007-05-22 | 2014-11-11 | Via Pharmaceuticals Inc | Composto, processo para a preparação de um composto, composição farmacêutica, uso de um composto e método de tratamento de obesidade, diabetes do tipo ii, dislipidemia ou síndrome metabólica |
| KR101077417B1 (ko) | 2007-06-12 | 2011-10-26 | 주식회사 엘지화학 | 위상차 필름, 이를 포함하는 편광판 및 액정 표시 장치 |
| WO2009011850A2 (en) | 2007-07-16 | 2009-01-22 | Abbott Laboratories | Novel therapeutic compounds |
| EP2017264A1 (de) | 2007-07-16 | 2009-01-21 | Bayer Cropscience Ag | Substituierte Phenylpropargylverbindungen, Verfahren zu deren Herstellung und deren Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| JP5057056B2 (ja) | 2007-08-03 | 2012-10-24 | Jsr株式会社 | 液晶配向剤、液晶配向膜の製造方法、ポリアミック酸およびポリイミドならびにジアミン化合物 |
| EP2197869B1 (en) | 2007-10-10 | 2013-04-24 | Basf Se | Sulphonium salt initiators |
| JP2009108152A (ja) | 2007-10-29 | 2009-05-21 | Sumitomo Chemical Co Ltd | 重合性化合物および光学フィルム |
| WO2009078992A1 (en) | 2007-12-17 | 2009-06-25 | Amgen Inc. | Linear tricyclic compounds as p38 kinase inhibitors |
| JP2009149754A (ja) | 2007-12-20 | 2009-07-09 | Sumitomo Chemical Co Ltd | 重合性化合物および該重合性化合物を重合してなる光学フィルム |
| US20090270418A1 (en) | 2008-01-09 | 2009-10-29 | Marianne Sloss | Pyrazole pyrazine amine compounds as kinase inhibitors, compositions thereof and methods of treatment therewith |
| JP5219583B2 (ja) | 2008-03-31 | 2013-06-26 | 住友化学株式会社 | 組成物、光学フィルムとその製造方法、光学部材及び表示装置 |
| WO2009129371A1 (en) | 2008-04-18 | 2009-10-22 | Glaxo Group Limited | Cathepsin c inhibitors |
| NZ603525A (en) | 2008-06-27 | 2015-02-27 | Celgene Avilomics Res Inc | Pyrimidine based compound and uses thereof |
| JP5443720B2 (ja) | 2008-09-05 | 2014-03-19 | 住友化学株式会社 | 組成物、光学フィルム及びその製造方法、光学部材ならびに表示装置 |
| JP2010066630A (ja) | 2008-09-12 | 2010-03-25 | Sumitomo Chemical Co Ltd | 光学フィルムの製造方法及び光学フィルム |
| WO2010048149A2 (en) | 2008-10-20 | 2010-04-29 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| SG172352A1 (en) | 2008-12-23 | 2011-07-28 | Abbott Lab | Anti-viral compounds |
| CN104592219B (zh) | 2009-03-16 | 2017-04-12 | 住友化学株式会社 | 化合物、光学膜和光学膜的制造方法 |
| JP5899607B2 (ja) | 2009-03-16 | 2016-04-06 | 住友化学株式会社 | 化合物、光学フィルム及び光学フィルムの製造方法 |
| JP2011006360A (ja) | 2009-06-26 | 2011-01-13 | Sumitomo Chemical Co Ltd | 化合物、光学フィルム及び光学フィルムの製造方法 |
| JP2011042606A (ja) | 2009-08-20 | 2011-03-03 | Sumitomo Chemical Co Ltd | 化合物、光学フィルム及び光学フィルムの製造方法 |
| KR101256018B1 (ko) | 2009-08-20 | 2013-04-18 | 한국과학기술연구원 | 단백질 키나아제 저해활성을 갖는 1,3,6-치환된 인돌 화합물 |
| US8669259B2 (en) | 2009-08-26 | 2014-03-11 | Merck Sharp & Dohme Corp. | Heterocyclic amide compounds as protein kinase inhibitors |
| WO2011031934A1 (en) | 2009-09-11 | 2011-03-17 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| WO2011053825A2 (en) | 2009-10-30 | 2011-05-05 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Compositions and methods for the treatment or prevention of mitochondrial diseases |
| WO2011103091A1 (en) | 2010-02-18 | 2011-08-25 | Transtech Pharma, Inc. | Phenyl-heteroaryl derivatives and methods of use thereof |
| CN102918034B (zh) | 2010-03-30 | 2015-06-03 | 维颂公司 | 多取代芳族化合物作为凝血酶的抑制剂 |
| JP2013526546A (ja) | 2010-05-13 | 2013-06-24 | アムジエン・インコーポレーテツド | Pde10阻害剤としてのヘテロアリ−ルオキシヘテロシクリル化合物 |
| GB201010359D0 (en) | 2010-06-21 | 2010-08-04 | Univ Nottingham | Compounds for treating proliferative disorders |
| PE20130774A1 (es) | 2010-07-29 | 2013-06-26 | Rigel Pharmaceuticals Inc | Compuestos heterociclicos activadores de ampk y metodos para emplearlos |
| EP3366688B1 (en) | 2010-12-08 | 2022-02-09 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Substituted pyrazolopyrimidines as glucocerebrosidase activators |
| JP5728921B2 (ja) | 2010-12-10 | 2015-06-03 | コニカミノルタ株式会社 | 光学フィルム、及びそれを用いた偏光板、液晶表示装置 |
| WO2012083048A2 (en) | 2010-12-15 | 2012-06-21 | Abbott Laboratories | Anti-viral compounds |
| US20150232455A1 (en) | 2010-12-15 | 2015-08-20 | Allan C. Krueger | Anti-viral compounds |
| US9464065B2 (en) | 2011-03-24 | 2016-10-11 | The Scripps Research Institute | Compounds and methods for inducing chondrogenesis |
| BR112013026341A2 (pt) | 2011-04-13 | 2019-09-24 | Merck Sharp & Dohe Corp | composto, composição farmacêutica, e, método para tratar, prevenir e/ou atrasar o início de uma doença ou patologia |
| SG194625A1 (en) | 2011-05-23 | 2013-12-30 | Sanofi Sa | Process for the preparation of deuterated compounds containing n-alkyl groups |
| JP6007417B2 (ja) | 2011-05-31 | 2016-10-12 | レセプトス エルエルシー | 新規glp−1受容体安定剤および調節剤 |
| EP2739144A4 (en) | 2011-06-20 | 2015-04-01 | Alzheimer S Inst Of America Inc | COMPOUNDS AND ITS THERAPEUTIC USE |
| CA2840224C (en) | 2011-06-22 | 2019-08-13 | The General Hospital Corporation | Treatment of proteinopathies |
| BR112014007310A2 (pt) | 2011-09-27 | 2017-04-04 | Novartis Ag | 3-pirimidin-4-il-oxazolidin-2-onas como inibidores de idh mutante |
| WO2013052845A1 (en) | 2011-10-05 | 2013-04-11 | The Board Of Trustees Of The Leland Stanford Junior University | Pi-kinase inhibitors with broad spectrum anti-infective activity |
| US9012443B2 (en) | 2011-12-07 | 2015-04-21 | Amgen Inc. | Bicyclic aryl and heteroaryl sodium channel inhibitors |
| WO2013106678A1 (en) | 2012-01-12 | 2013-07-18 | Envivo Pharmaceuticals, Inc. | Tetrasubstituted benzenes |
| TW201348231A (zh) | 2012-02-29 | 2013-12-01 | Amgen Inc | 雜雙環化合物 |
| JP5798066B2 (ja) | 2012-03-08 | 2015-10-21 | 富士フイルム株式会社 | 化合物、液晶組成物、高分子材料およびフィルム |
| US9013997B2 (en) | 2012-06-01 | 2015-04-21 | Broadcom Corporation | System for performing distributed data cut-through |
| EP2671885A1 (en) | 2012-06-05 | 2013-12-11 | Ares Trading S.A. | Imidazo-oxadiazole and Imidazo-thiadiazole derivatives |
| FR2992317B1 (fr) | 2012-06-22 | 2016-05-13 | Diverchim | Procede de preparation de peptides chiraux |
| JP6285924B2 (ja) | 2012-06-26 | 2018-02-28 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | 複屈折ポリマーフィルムの製造方法 |
| CN104640556B (zh) | 2012-09-17 | 2019-08-06 | 霍夫曼-拉罗奇有限公司 | Usp30抑制剂及其使用方法 |
| KR101668574B1 (ko) | 2012-11-02 | 2016-10-24 | 화이자 인코포레이티드 | 브루톤 티로신 키나제 억제제 |
| CN104768554B (zh) | 2012-11-07 | 2018-04-17 | 霍夫曼-拉罗奇有限公司 | 三唑并化合物 |
| CN103012428A (zh) | 2013-01-08 | 2013-04-03 | 中国药科大学 | 4-(五元杂环并嘧啶/吡啶取代)氨基-1H-3-吡唑甲酰胺类CDK/Aurora双重抑制剂及其用途 |
| CN105142641A (zh) | 2013-03-12 | 2015-12-09 | 广州源生医药科技有限公司 | 用于治疗癌症的化合物 |
| CN104045552B (zh) | 2013-03-13 | 2019-06-11 | 江苏先声药业有限公司 | 作为神经保护剂的药用化合物 |
| EP2968321A4 (en) | 2013-03-14 | 2016-11-09 | Curegenix Inc | COMPOUNDS FOR THE TREATMENT OF FIBROSIS DISEASES |
| US9393244B2 (en) | 2013-03-15 | 2016-07-19 | Georgetown University | Increasing parkin activity by administering a deubiquitinating enzyme inhibitor |
| CN105121404A (zh) | 2013-03-15 | 2015-12-02 | 豪夫迈·罗氏有限公司 | 作为RORc调节剂的芳基磺酰胺和氨基磺酸衍生物 |
| JP2014232188A (ja) | 2013-05-29 | 2014-12-11 | コニカミノルタ株式会社 | セルロースアシレートフィルム、円偏光板及び画像表示装置 |
| CN105793424B (zh) | 2013-07-12 | 2021-02-19 | 亥姆霍兹感染研究中心有限公司 | 孢囊菌酰胺 |
| WO2015010297A1 (en) | 2013-07-25 | 2015-01-29 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and their methods of use |
| WO2015011284A2 (en) | 2013-07-25 | 2015-01-29 | Fondazione Telethon | Inhibitors of fapp2 and uses thereof |
| KR101715090B1 (ko) | 2013-08-28 | 2017-03-13 | 한국화학연구원 | 신규한 화합물 또는 이의 약학적으로 허용가능한 염, 및 이를 유효성분으로 함유하는 인플루엔자 바이러스 감염으로 인한 질환의 예방 또는 치료용 약학적 조성물 |
| US20150087673A1 (en) | 2013-09-26 | 2015-03-26 | Rigel Pharmaceuticals, Inc. | Methods for using and biomarkers for ampk-activating compounds |
| KR102272792B1 (ko) | 2013-09-30 | 2021-07-05 | 광저우 이노케어 파마 테크 씨오., 엘티디. | Btk의 치환된 니코틴이미드 저해제 및 그의 제조 방법 및 암, 염증 및 자가면역 질환에의 용도 |
| BR112016008632A8 (pt) | 2013-10-21 | 2020-03-17 | Merck Patent Gmbh | compostos de heteroarila como inibidores de btk, seus usos, e composição farmacêutica |
| KR102243116B1 (ko) | 2013-10-21 | 2021-04-22 | 메르크 파텐트 게엠베하 | 복굴절성 중합체 필름의 제조 방법 |
| WO2015085238A1 (en) | 2013-12-05 | 2015-06-11 | The Regents Of The University Of California, A California Corporation | Inhibitors of lpxc |
| WO2015095104A1 (en) | 2013-12-18 | 2015-06-25 | Merck Sharp & Dohme Corp. | Iminothiadiazepane dioxide compounds as bace inhibitors, compositions, and their use |
| WO2015106292A1 (en) | 2014-01-13 | 2015-07-16 | Coferon, Inc. | Bcr-abl tyrosine-kinase ligands capable of dimerizing in an aqueous solution, and methods of using same |
| US9663504B2 (en) | 2014-02-25 | 2017-05-30 | Board Of Regents, The University Of Texas System | Salts of heterocyclic modulators of HIF activity for treatment of disease |
| HUE053939T2 (hu) | 2014-05-13 | 2021-08-30 | Hoffmann La Roche | Deuterált heterociklikus vegyületek és képalkotó kontrasztanyagként való használatuk |
| KR102412045B1 (ko) | 2014-05-22 | 2022-06-22 | 놀스 차이나 파마수티칼 컴퍼니., 엘티디. | 혈액응고인자 Xa 억제제로서의 히드라지드 화합물 |
| US9511142B2 (en) | 2014-06-11 | 2016-12-06 | VenatoRx Pharmaceuticals, Inc. | Beta-lactamase inhibitors |
| GB201410653D0 (en) | 2014-06-14 | 2014-07-30 | Mission Therapeutics Ltd | Methodologies for measuring isopeptidase activity in biological samples in a high throughput manner |
| WO2015197028A1 (en) | 2014-06-28 | 2015-12-30 | Sunshine Lake Pharma Co., Ltd. | Compounds as hepatitis c virus (hcv) inhibitors and uses thereof in medicine |
| CN106715418A (zh) | 2014-07-07 | 2017-05-24 | 基因泰克公司 | 治疗化合物及其使用方法 |
| US20170152226A1 (en) | 2014-07-16 | 2017-06-01 | Novogen Ltd. | Functionalised and substituted indoles as anti-cancer agents |
| US9290457B2 (en) | 2014-07-31 | 2016-03-22 | Boehringer Ingelheim International Gmbh | Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| WO2016019237A2 (en) | 2014-07-31 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| EP3189551B1 (de) | 2014-09-05 | 2021-01-27 | Merck Patent GmbH | Formulierungen und verfahren zur herstellung einer organischen elektrolumineszenzvorrichtung |
| WO2016040449A1 (en) | 2014-09-10 | 2016-03-17 | Raze Therapeutics, Inc. | 3-phosphoglycerate dehydrogenase inhibitors and uses thereof |
| GB201416754D0 (en) | 2014-09-23 | 2014-11-05 | Mission Therapeutics Ltd | Novel compounds |
| US9997717B2 (en) | 2014-12-12 | 2018-06-12 | Idemitsu Kosan Co., Ltd. | Organic electroluminescence device and electronic device |
| CN104557862B (zh) | 2014-12-15 | 2017-05-17 | 苏州云轩医药科技有限公司 | 具有Wnt信号通路抑制活性的杂环化合物 |
| US10351532B2 (en) | 2014-12-29 | 2019-07-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Small molecule inhibitors of lactate dehydrogenase and methods of use thereof |
| CA2976741C (en) * | 2015-03-30 | 2023-01-17 | Mission Therapeutics Limited | 1-cyano-pyrrolidine compounds as usp30 inhibitors |
| WO2016172631A2 (en) | 2015-04-24 | 2016-10-27 | President And Fellows Of Harvard College | Substrate selective inhibitors of insulin-degrading enzyme (ide) and uses thereof |
| WO2017002120A1 (en) | 2015-07-02 | 2017-01-05 | Yeda Research And Development Co. Ltd. | Selective inhibitors of senescent cells and uses thereof |
| WO2017010399A1 (ja) | 2015-07-10 | 2017-01-19 | 塩野義製薬株式会社 | RORγt阻害作用を有する化合物およびそれらを含有する医薬組成物 |
| WO2017009650A1 (en) | 2015-07-14 | 2017-01-19 | Mission Therapeutics Limited | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
| WO2017019822A1 (en) | 2015-07-29 | 2017-02-02 | Medivation Technologies, Inc. | Pellet composition containing repair cells |
| WO2017019817A1 (en) | 2015-07-29 | 2017-02-02 | Medivation Technologies, Inc. | Methods and compositions for targeted therapeutics |
| WO2017019830A1 (en) | 2015-07-29 | 2017-02-02 | Medivation Technologies, Inc. | Methods and compositions for targeted therapeutics |
| EP3350181B1 (en) | 2015-09-02 | 2023-11-01 | The Regents of The University of California | Her3 ligands and uses thereof |
| BR112018003622B8 (pt) | 2015-09-04 | 2022-08-23 | Dow Agrosciences Llc | Moléculas apresentando utilidade pesticida, e composição pesticida |
| WO2017066705A1 (en) | 2015-10-14 | 2017-04-20 | Aquinnah Pharmaceuticals, Inc. | Compounds, compositions and methods of use against stress granules |
| GB201521109D0 (en) | 2015-11-30 | 2016-01-13 | Mission Therapeutics Ltd | Novel compounds |
| WO2017100558A1 (en) | 2015-12-09 | 2017-06-15 | Research Triangle Institute | Improved apelin receptor (apj) agonists and uses thereof |
| JO3793B1 (ar) | 2015-12-10 | 2021-01-31 | Janssen Pharmaceutica Nv | مثبطات تيروزين كاينيز بروتون وأساليب استخدامها |
| GB201522267D0 (en) * | 2015-12-17 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201522768D0 (en) | 2015-12-23 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| CN106986859B (zh) | 2016-01-20 | 2020-02-11 | 广东东阳光药业有限公司 | 吲哚衍生物及其用途 |
| GB201602854D0 (en) | 2016-02-18 | 2016-04-06 | Mission Therapeutics Ltd | Novel compounds |
| GB201603779D0 (en) | 2016-03-04 | 2016-04-20 | Mission Therapeutics Ltd | Novel compounds |
| PL3429591T3 (pl) | 2016-03-16 | 2023-07-17 | Kura Oncology, Inc. | Podstawione pochodne tieno[2,3-d]pirymidyny jako inhibitory meniny-mll i metody ich zastosowania |
| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| CN108884068B (zh) | 2016-03-24 | 2021-02-26 | 特殊治疗有限公司 | 作为dub抑制剂的1-氰基-吡咯烷衍生物 |
| CN107226805A (zh) | 2016-03-24 | 2017-10-03 | 北京天诚医药科技有限公司 | 芳香族酰胺类衍生物、其制备方法及其在医药上的应用 |
| ES2984389T3 (es) | 2016-06-29 | 2024-10-29 | Univ Montreal | Heterociclos de biarilmetilo |
| CN107619384B (zh) | 2016-07-13 | 2020-07-28 | 江苏恒瑞医药股份有限公司 | 苯并杂环衍生物、其制备方法及其在医药上的应用 |
| CN107619388A (zh) | 2016-07-13 | 2018-01-23 | 南京天印健华医药科技有限公司 | 作为fgfr抑制剂的杂环化合物 |
| CN107674013B (zh) | 2016-08-02 | 2022-05-24 | 上海迪诺医药科技有限公司 | 多环化合物、其制备方法、药物组合物及应用 |
| US11124628B2 (en) | 2016-08-30 | 2021-09-21 | Dow Global Technologies Llc | Method of attenuating concerntration of acrolein |
| US11014912B2 (en) | 2016-09-27 | 2021-05-25 | Mission Therapeutics Limited | Cyanopyrrolidine derivatives with activity as inhibitors of USP30 |
| GB201616511D0 (en) | 2016-09-29 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| GB201616627D0 (en) * | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) * | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
| WO2018106818A1 (en) | 2016-12-07 | 2018-06-14 | Kura Oncology, Inc. | Methods of promoting beta cell proliferation |
| WO2018106820A1 (en) | 2016-12-07 | 2018-06-14 | Kura Oncology, Inc. | Methods of promoting beta cell proliferation |
| WO2018134352A1 (en) | 2017-01-20 | 2018-07-26 | Leo Pharma A/S | Bicyclic amines as novel jak kinase inhibitors |
| US20190367537A1 (en) | 2017-02-08 | 2019-12-05 | Helmholtz-Zentrum Dresden - Rossendorf E.V. | In vivo stable hg-197(m) compounds, method for the production thereof and use thereof in nuclear medical diagnostics and endoradionuclide therapy (theranostics) |
| US10744213B2 (en) | 2017-02-14 | 2020-08-18 | Colossus Biopharma Consultants Company, Limited | Fluorescent compounds for imaging of blood vessels and blood flow, and an in vivo screen for pro- and anti-angiogenic agents |
| WO2018160891A1 (en) | 2017-03-01 | 2018-09-07 | Achillion Pharmaceutical, Inc. | Pharmaceutical compounds for treatment of medical disorders |
| US11136324B2 (en) | 2017-03-03 | 2021-10-05 | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | Substituted imidazoles as apoptosis signal regulating kinase 1 inhibitors |
| US10968172B2 (en) | 2017-05-15 | 2021-04-06 | Mitobridge, Inc. | USP30 inhibitors |
| GB201708652D0 (en) | 2017-05-31 | 2017-07-12 | Mission Therapeutics Ltd | Novel compounds and uses |
| CN110831936B (zh) | 2017-06-20 | 2023-03-28 | 特殊治疗有限公司 | 具有dub抑制剂活性的取代氰基吡咯烷 |
| AU2018346597B2 (en) | 2017-10-06 | 2023-07-13 | Forma Therapeutics, Inc. | Inhibiting Ubiquitin Specific Peptidase 30 |
| GB2571731A (en) | 2018-03-06 | 2019-09-11 | Mission Therapeutics Ltd | Novel compounds and uses |
| JP7449242B2 (ja) | 2018-05-17 | 2024-03-13 | フォーマ セラピューティクス,インコーポレイテッド | ユビキチン特異的ペプチダーゼ30(usp30)阻害剤として有用な縮合二環化合物 |
| US11572374B2 (en) | 2018-08-14 | 2023-02-07 | Amgen Inc. | N-cyano-7-azanorbornane derivatives and uses thereof |
| JP7530889B2 (ja) | 2018-10-05 | 2024-08-08 | フォーマ セラピューティクス,インコーポレイテッド | ユビキチン特異的プロテアーゼ30(usp30)阻害剤として作用する縮合ピロリン |
| GB201905371D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201905375D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201912674D0 (en) | 2019-09-04 | 2019-10-16 | Mission Therapeutics Ltd | Novel compounds |
| US11845724B2 (en) | 2019-09-11 | 2023-12-19 | Vincere Biosciences, Inc. | USP30 inhibitors and uses thereof |
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