CA2966450A1 - Inhibitors of bromodomains - Google Patents
Inhibitors of bromodomains Download PDFInfo
- Publication number
- CA2966450A1 CA2966450A1 CA2966450A CA2966450A CA2966450A1 CA 2966450 A1 CA2966450 A1 CA 2966450A1 CA 2966450 A CA2966450 A CA 2966450A CA 2966450 A CA2966450 A CA 2966450A CA 2966450 A1 CA2966450 A1 CA 2966450A1
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- compound
- disease
- compound according
- alkyl
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| US201462093394P | 2014-12-17 | 2014-12-17 | |
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| PCT/IB2015/002490 WO2016097863A1 (en) | 2014-12-17 | 2015-12-16 | Inhibitors of bromodomains |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2020053660A1 (en) * | 2018-09-13 | 2020-03-19 | Zenith Epigenetics Ltd. | Solid forms of a bet inhibitor |
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| WO2014096965A2 (en) | 2012-12-21 | 2014-06-26 | Rvx Therapeutics Inc. | Novel heterocyclic compounds as bromodomain inhibitors |
| WO2015004533A2 (en) | 2013-06-21 | 2015-01-15 | Zenith Epigenetics Corp. | Novel substituted bicyclic compounds as bromodomain inhibitors |
| SG11201510409QA (en) | 2013-06-21 | 2016-01-28 | Zenith Epigenetics Corp | Novel bicyclic bromodomain inhibitors |
| WO2015015318A2 (en) | 2013-07-31 | 2015-02-05 | Zenith Epigenetics Corp. | Novel quinazolinones as bromodomain inhibitors |
| US10710992B2 (en) | 2014-12-01 | 2020-07-14 | Zenith Epigenetics Ltd. | Substituted pyridinones as bromodomain inhibitors |
| EP3227280B1 (en) | 2014-12-01 | 2019-04-24 | Zenith Epigenetics Ltd. | Substituted pyridines as bromodomain inhibitors |
| JP2017537946A (ja) | 2014-12-11 | 2017-12-21 | ゼニス・エピジェネティクス・リミテッドＺｅｎｉｔｈ Ｅｐｉｇｅｎｅｔｉｃｓ Ｌｔｄ． | ブロモドメイン阻害剤としての置換複素環 |
| HK1245247A1 (zh) | 2014-12-17 | 2018-08-24 | 恒翼生物医药科技(上海)有限公司 | 溴结构域的抑制剂 |
| GB201506660D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201506658D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| JP2018527340A (ja) | 2015-08-11 | 2018-09-20 | ネオメド インスティテュートＮｅｏｍｅｄ Ｉｎｓｔｉｔｕｔｅ | アリール置換ジヒドロキノリノン、その調製及び医薬品としてのその使用 |
| US10836742B2 (en) | 2015-08-11 | 2020-11-17 | Neomed Institute | N-substituted bicyclic lactams, their preparation and their use as pharmaceuticals |
| CA2994478C (en) | 2015-08-12 | 2023-10-03 | Neomed Institute | Substituted benzimidazoles, their preparation and their use as pharmaceuticals |
| US10501459B2 (en) | 2015-10-21 | 2019-12-10 | Neomed Institute | Substituted imidazo[1,2-a]pyridines as bromodomain inhibitors |
| WO2017127930A1 (en) | 2016-01-28 | 2017-08-03 | Neomed Institute | Substituted [1,2,4]triazolo[4,3-a]pyridines, their preparation and their use as pharmaceuticals |
| MX393780B (es) | 2017-01-17 | 2025-03-24 | Heparegenix Gmbh | Inhibidores de proteina cinasa para promover la regeneracion hepatica o reducir o prevenir la muerte de hepatocitos |
| AU2019219678A1 (en) * | 2018-02-08 | 2020-08-27 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Heteroaryl compounds, pharmaceutical compositions thereof, and their therapeutic use |
| TW202003051A (zh) * | 2018-03-23 | 2020-01-16 | 美商白頭生物醫學研究所 | 藉由調節凝聚物來調節基因轉錄之方法及分析 |
| SI3778573T1 (sl) | 2018-03-30 | 2024-08-30 | Kyowa Kirin Co., Ltd., | Spojina s protirakavim delovanjem |
| CN120758591A (zh) | 2018-10-15 | 2025-10-10 | 马克斯·普朗克科学促进协会 | 用于治疗疾病的化合物及其筛选方法 |
| FI3873903T3 (fi) | 2018-10-31 | 2024-03-26 | Gilead Sciences Inc | Substituoituja 6-azabentsiimidatsoliyhdisteitä HPK1-inhibiittoreina |
| KR102658602B1 (ko) | 2018-10-31 | 2024-04-19 | 길리애드 사이언시즈, 인코포레이티드 | Hpk1 억제 활성을 갖는 치환된 6-아자벤즈이미다졸 화합물 |
| US11493519B2 (en) | 2019-02-08 | 2022-11-08 | Dewpoint Therapeutics, Inc. | Methods of characterizing condensate-associated characteristics of compounds and uses thereof |
| TWI826690B (zh) | 2019-05-23 | 2023-12-21 | 美商基利科學股份有限公司 | 經取代之烯吲哚酮化物及其用途 |
| WO2021041801A1 (en) * | 2019-08-29 | 2021-03-04 | University Of Tennessee Research Foundation | Bromodomain inhibitors to target therapy-resistant cancer |
| EP4031876A1 (en) | 2019-09-18 | 2022-07-27 | Dewpoint Therapeutics, Inc. | Methods of screening for condensate-associated specificity and uses thereof |
| US12527741B2 (en) | 2021-06-17 | 2026-01-20 | Wisconsin Alumni Research Foundation | Modular dendron micelles for treatment of pulmonary diseases related to fibrosis and viral infection including COVID-19 |
| CN113712963B (zh) * | 2021-10-15 | 2022-09-23 | 中国科学院昆明动物研究所 | Bet抑制剂bms-986158在制备抗艾滋病的药物中的应用 |
| TW202440098A (zh) * | 2022-12-22 | 2024-10-16 | 美商諾維雪碧歐公司 | 使用bet抑制劑之癌症組合療法 |
| CN117603035B (zh) * | 2023-11-27 | 2025-02-11 | 南开大学 | 一种查尔酮衍生物及其制备方法和应用 |
Family Cites Families (176)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3508258A1 (de) | 1985-03-08 | 1986-09-18 | Bayer Ag, 5090 Leverkusen | Ss-lactamantibiotika, verfahren zur herstellung und ihre verwendung als und in arzneimitteln |
| FR2643903A1 (fr) | 1989-03-03 | 1990-09-07 | Union Pharma Scient Appl | Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux |
| RU1836357C (ru) | 1990-07-23 | 1993-08-23 | Др.Карл Томэ ГмбХ | Производные бензимидазола, их изомеры, смеси изомеров, гидраты или их физиологически переносимые соли, обладающие антагонистическими в отношении ангиотензина свойствами |
| DE4023369A1 (de) | 1990-07-23 | 1992-01-30 | Thomae Gmbh Dr K | Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE4225756A1 (de) | 1992-01-22 | 1994-03-10 | Thomae Gmbh Dr K | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DE4224752A1 (de) | 1992-04-11 | 1994-02-03 | Thomae Gmbh Dr K | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| SI9210098B (sl) | 1991-02-06 | 2000-06-30 | Dr. Karl Thomae | Benzimidazoli, zdravila, ki te spojine vsebujejo, in postopek za njihovo pripravo |
| US5591762A (en) | 1991-02-06 | 1997-01-07 | Dr. Karl Thomae Gmbh | Benzimidazoles useful as angiotensin-11 antagonists |
| US5125961A (en) | 1991-08-12 | 1992-06-30 | Monsanto Company | Substituted pyridine compounds |
| DE4219534A1 (de) | 1992-02-19 | 1993-12-16 | Thomae Gmbh Dr K | Substituierte Biphenylylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DE4408497A1 (de) | 1994-03-14 | 1995-09-21 | Thomae Gmbh Dr K | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| AU699272B2 (en) | 1994-08-02 | 1998-11-26 | Merck Sharp & Dohme Limited | Azetidine, pyrrolidine and piperidine derivatives |
| PL183853B1 (pl) | 1995-04-21 | 2002-07-31 | Neurosearch As | Nowa pochodna benzimidazolu i środek farmaceutyczny |
| JP2000072675A (ja) | 1998-08-26 | 2000-03-07 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| AU760250B2 (en) | 1998-12-04 | 2003-05-08 | Neurosearch A/S | New benzimidazolone-, benzoxazolone-, or benzothiazolone derivatives as ion channel modulating agents |
| US6380235B1 (en) | 1999-05-04 | 2002-04-30 | American Home Products Corporation | Benzimidazolones and analogues |
| US6664252B2 (en) | 1999-12-02 | 2003-12-16 | Osi Pharmaceuticals, Inc. | 4-aminopyrrolo[2,3-d]pyrimidine compounds specific to adenosine A2a receptor and uses thereof |
| GB0002100D0 (en) | 2000-01-28 | 2000-03-22 | Novartis Ag | Organic compounds |
| EP1263754A1 (en) | 2000-02-01 | 2002-12-11 | Millennium Pharmaceuticals, Inc. | INDALONE AND BENZIMIDAZOLONE INHIBITORS OF FACTOR Xa |
| US20120028912A1 (en) | 2000-02-22 | 2012-02-02 | J.David Gladstone Institute | Methods of modulating bromodomains |
| JP2004519474A (ja) | 2000-10-27 | 2004-07-02 | ダウ アグロサイエンシィズ エルエルシー | 置換４，５−ジヒドロ−１，２，４−トリアジン−６−オン、１，２，４−トリアジン−６−オン、および殺菌・殺カビ剤ならびに殺虫剤としてのその使用 |
| EP1347980A4 (en) | 2000-12-01 | 2005-02-09 | Osi Pharm Inc | RECEPTOR SPECIFIC COMPOUNDS OF ADENOSINE-A1, -A2A, AND-A3 AND USES THEREOF |
| CZ20032332A3 (cs) | 2001-03-01 | 2003-11-12 | Shionogi & Co., Ltd. | Heteroarylové sloučeniny obsahující dusík, které mají inhibiční aktivitu proti HIV integrase |
| ES2251582T3 (es) | 2001-03-09 | 2006-05-01 | Pfizer Products Inc. | Compuestos antiinflamatorios de bencimidazol. |
| ES2290313T3 (es) | 2001-03-15 | 2008-02-16 | Janssen Pharmaceutica N.V. | Derivados de pirazinona que inhiben el vih. |
| TWI261055B (en) | 2001-03-23 | 2006-09-01 | Bayer Corp | Rho-Kinase Inhibitors |
| US7081454B2 (en) | 2001-03-28 | 2006-07-25 | Bristol-Myers Squibb Co. | Tyrosine kinase inhibitors |
| CN1514833A (zh) | 2001-03-28 | 2004-07-21 | ����˹�ж�-����˹˹������˾ | 新型酪氨酸激酶抑制剂 |
| US20050176858A1 (en) | 2002-02-15 | 2005-08-11 | Bridgestone Corporation | Rubber composition and pneumatic tire made therefrom |
| TWI276631B (en) | 2002-09-12 | 2007-03-21 | Avanir Pharmaceuticals | Phenyl-aza-benzimidazole compounds for modulating IgE and inhibiting cellular proliferation |
| AU2003294249A1 (en) | 2002-11-08 | 2004-06-03 | Trimeris, Inc. | Hetero-substituted benzimidazole compounds and antiviral uses thereof |
| AR043063A1 (es) | 2002-12-13 | 2005-07-13 | Altana Pharma Ag | Bencimidazoles 6-sustituidos y su uso como inhibidores de secreciones gastricas |
| AR042956A1 (es) | 2003-01-31 | 2005-07-13 | Vertex Pharma | Inhibidores de girasa y usos de los mismos |
| CL2004000409A1 (es) | 2003-03-03 | 2005-01-07 | Vertex Pharma | Compuestos derivados de 2-(cilo sustituido)-1-(amino u oxi sustituido)-quinazolina, inhibidores de canales ionicos de sodio y calcio dependientes de voltaje; composicion farmaceutica; y uso del compuesto en el tratamiento de dolor agudo, cronico, neu |
| WO2004098494A2 (en) | 2003-04-30 | 2004-11-18 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| AU2003902860A0 (en) | 2003-06-06 | 2003-06-26 | Daicel Chemical Industries, Ltd | Benzimidazole compounds |
| WO2005013950A2 (en) | 2003-08-08 | 2005-02-17 | Avanir Pharmaceuticals | Selective pharmacologic inhibition of protein trafficking and related methods of treating human diseases |
| CL2004002050A1 (es) | 2003-08-13 | 2005-06-03 | Pharmacia Corp Sa Organizada B | Compuestos derivados de piridinonas sustituidas; su uso en el tratamiento de afecciones causadas o exacerbadas por actividad p38 map kinasa y/o tnf no regulada, tales como inflamaciones, tumores, sida y otros. |
| WO2005080380A1 (en) | 2004-02-03 | 2005-09-01 | Eli Lilly And Company | Kinase inhibitors |
| WO2005075432A1 (ja) | 2004-02-06 | 2005-08-18 | Chugai Seiyaku Kabushiki Kaisha | １−（２ｈ）−イソキノロン誘導体およびその抗ガン剤としての使用 |
| CA2559552A1 (en) | 2004-03-23 | 2005-09-29 | F. Hoffmann-La Roche Ag | Benzyl-pyridazinone derivatives as non-nucleoside reverse transcriptase inhibitors |
| EP1734820A4 (en) | 2004-04-16 | 2008-01-23 | Neurogen Corp | Imidazopyrrazine, imidazopyridine, and imidazo-pyrimidine as CRF1 receptor ligands |
| NZ551775A (en) | 2004-06-01 | 2010-12-24 | Univ Virginia | Dual small molecule inhibitors of cancer and angiogenesis |
| WO2005121132A1 (ja) | 2004-06-11 | 2005-12-22 | Shionogi & Co., Ltd. | 抗ｈｃｖ作用を有する縮合ヘテロ環化合物 |
| WO2006021886A1 (en) | 2004-08-26 | 2006-03-02 | Pfizer Inc. | Aminoheteroaryl compounds as protein tyrosine kinase inhibitors |
| GB0420719D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| GB0420722D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| WO2006038734A1 (en) | 2004-10-08 | 2006-04-13 | Astellas Pharma Inc. | Pyridazinone derivatives cytokines inhibitors |
| US7846915B2 (en) | 2004-10-20 | 2010-12-07 | Resverlogix Corporation | Stilbenes and chalcones for the prevention and treatment of cardiovascular diseases |
| AU2006210422B2 (en) | 2005-02-04 | 2012-09-13 | Takeda Pharmaceutical Company Limited | Inhibitors of E1 activating enzymes |
| CA2600570C (en) | 2005-03-14 | 2011-12-06 | Transtech Pharma, Inc. | Benzazole derivatives, compositions, and methods of use as .beta.-secretase inhibitors |
| CN101189214A (zh) | 2005-05-03 | 2008-05-28 | 美国陶氏益农公司 | 取代的4，5-二氢-1，2，4-三嗪-6-酮、1，2，4-三嗪-6-酮及其作为杀菌剂的用途 |
| US8410109B2 (en) | 2005-07-29 | 2013-04-02 | Resverlogix Corp. | Pharmaceutical compositions for the prevention and treatment of complex diseases and their delivery by insertable medical devices |
| AU2006298132A1 (en) | 2005-10-03 | 2007-04-12 | Ono Pharmaceutical Co., Ltd. | Nitrogen-containing heterocyclic compound and pharmaceutical application thereof |
| WO2007061923A2 (en) | 2005-11-18 | 2007-05-31 | Takeda San Diego, Inc. | Glucokinase activators |
| CN101321525B (zh) | 2005-12-01 | 2013-01-30 | 霍夫曼-拉罗奇有限公司 | 作为l-cpt1抑制剂的杂芳基取代的哌啶衍生物 |
| CN101384593A (zh) | 2006-02-17 | 2009-03-11 | 辉瑞有限公司 | 用作tlr7调节剂的3-脱氮嘌呤衍生物 |
| JP2009528989A (ja) | 2006-02-17 | 2009-08-13 | ファイザー・リミテッド | Ｔｌｒ７変調剤としての３−デアザプリン誘導体 |
| AR060237A1 (es) | 2006-04-03 | 2008-06-04 | Glaxo Group Ltd | Compuesto de 3-azabiciclo[3.1.0]hexano como moduladores del receptor de dopamina d3, su uso para la preparacion de un medicamento para el tratamiento de afecciones psicoticas y composicion farmaceutica que lo comprende. |
| CA2700988A1 (en) | 2006-09-27 | 2008-05-08 | Surface Logix, Inc. | Rho kinase inhibitors |
| WO2008072784A1 (en) | 2006-12-14 | 2008-06-19 | Astellas Pharma Inc. | Polycyclic acid compounds useful as crth2 antagonists and antiallergic agents |
| SG144809A1 (en) | 2007-01-11 | 2008-08-28 | Millipore U K Ltd | Benzimidazole compounds and their use as chromatographic ligands |
| MX2009008099A (es) | 2007-02-01 | 2009-12-14 | Resverlogix Corp | Compuestos para la prevencion y tratamiento de enfermedades cardiovasculares. |
| WO2008153701A1 (en) | 2007-05-24 | 2008-12-18 | Schering Corporation | Compounds for inhibiting ksp kinesin activity |
| KR20100023907A (ko) | 2007-06-26 | 2010-03-04 | 사노피-아벤티스 | 벤즈이미다졸 및 아자벤즈이미다졸의 위치선택적 구리 촉매화 합성 |
| DE102007032507A1 (de) | 2007-07-12 | 2009-04-02 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102007038957A1 (de) | 2007-08-17 | 2009-02-19 | Merck Patent Gmbh | 6-Thioxo-pyridazinderivate |
| GB0719235D0 (en) | 2007-10-02 | 2007-11-14 | Glaxo Group Ltd | Novel compounds |
| WO2009054790A1 (en) | 2007-10-26 | 2009-04-30 | Astrazeneca Ab | Amide linked heteroaromatic derivatives as modulators of mglur5 |
| WO2009079001A1 (en) | 2007-12-18 | 2009-06-25 | Janssen Pharmaceutica N.V. | Bicyclic heteroaryl-substituted imidazoles as modulators of the histamine h4 receptor |
| EP2239264A4 (en) | 2007-12-28 | 2012-01-11 | Mitsubishi Tanabe Pharma Corp | ANTITUMORAL MEDIUM |
| TW200938542A (en) | 2008-02-01 | 2009-09-16 | Irm Llc | Compounds and compositions as kinase inhibitors |
| WO2009158258A1 (en) | 2008-06-25 | 2009-12-30 | E. I. Du Pont De Nemours And Company | Herbicidal dihydro oxo six-membered azinyl isoxazolines |
| US9643922B2 (en) | 2008-08-18 | 2017-05-09 | Yale University | MIF modulators |
| US9540322B2 (en) | 2008-08-18 | 2017-01-10 | Yale University | MIF modulators |
| CA2733554A1 (en) | 2008-08-18 | 2010-02-25 | Yale University | Mif modulators |
| CN102264743B (zh) | 2008-11-25 | 2015-02-11 | 罗彻斯特大学 | Mlk抑制剂及其使用方法 |
| PT2370413E (pt) | 2008-12-08 | 2015-10-23 | Arena Pharm Inc | Moduladores do recetor da prostaciclina (pgi2) úteis para o tratamento de distúrbios relacionados com o mesmo |
| EP2196465A1 (en) | 2008-12-15 | 2010-06-16 | Almirall, S.A. | (3-oxo)pyridazin-4-ylurea derivatives as PDE4 inhibitors |
| DE102008062826A1 (de) | 2008-12-23 | 2010-07-01 | Merck Patent Gmbh | Pyridazinonderivate |
| US8389550B2 (en) | 2009-02-25 | 2013-03-05 | Hoffmann-La Roche Inc. | Isoxazoles / O-pyridines with ethyl and ethenyl linker |
| JP2012519732A (ja) | 2009-03-09 | 2012-08-30 | サーフェイス ロジックス，インコーポレイティド | Ｒｈｏキナーゼ阻害剤 |
| US8975247B2 (en) | 2009-03-18 | 2015-03-10 | The Board Of Trustees Of The Leland Stanford Junion University | Methods and compositions of treating a flaviviridae family viral infection |
| KR101913109B1 (ko) | 2009-03-18 | 2018-10-31 | 리스버로직스 코퍼레이션 | 신규한 소염제 |
| DK2421533T3 (en) | 2009-04-22 | 2019-01-07 | Resverlogix Corp | Hitherto unknown anti-inflammatory agents |
| SG175867A1 (en) | 2009-05-05 | 2011-12-29 | Hoffmann La Roche | Isoxazole-pyridine derivatives |
| GB0919431D0 (en) | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| GB0919423D0 (en) | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| KR20120097508A (ko) | 2009-11-05 | 2012-09-04 | 글락소스미스클라인 엘엘씨 | 벤조디아제핀 브로모도메인 억제제 |
| MY160456A (en) | 2009-11-05 | 2017-03-15 | Glaxosmithkline Llc | Benzodiazepine bromodomain inhibitor |
| GB0919434D0 (en) | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| GB0919432D0 (en) | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Use |
| EP2390250B1 (en) | 2009-11-20 | 2015-08-12 | Sk Chemicals Co., Ltd. | Gonadotropin releasing hormone receptor antagonists, manufacturing method thereof, and pharmaceutical composition containing same |
| US20130085133A1 (en) | 2010-02-08 | 2013-04-04 | Sourthern Research Institute Office of Commercialization and Intellectual Prop. | Anti-viral treatment and assay to screenfor anti-viral agent |
| KR101165996B1 (ko) | 2010-04-23 | 2012-07-18 | 주식회사 녹십자 | 프탈라지논 유도체, 이의 제조방법 및 이를 함유하는 약학적 조성물 |
| US8981083B2 (en) | 2010-05-14 | 2015-03-17 | Dana Farber Cancer Institute, Inc. | Compositions and methods for treating neoplasia, inflammatory disease and other disorders |
| US8933096B2 (en) | 2010-06-09 | 2015-01-13 | Rugers, The State University of New Jersey | Antimicrobial agents |
| WO2011159926A1 (en) | 2010-06-16 | 2011-12-22 | Rutgers, The State University Of New Jersey | Antimicrobial agents |
| WO2012003576A1 (en) | 2010-07-06 | 2012-01-12 | Université de Montréal | Imidazopyridine, imidazopyrimidine and imidazopyrazine derivatives as melanocortin-4 receptor modulators |
| WO2012009258A2 (en) | 2010-07-13 | 2012-01-19 | Edward Roberts | Peptidomimetic galanin receptor modulators |
| WO2012021382A1 (en) | 2010-08-12 | 2012-02-16 | Merck Sharp & Dohme Corp. | Positive allosteric modulators of mglur2 |
| WO2012040499A2 (en) | 2010-09-22 | 2012-03-29 | Surface Logix, Inc. | Metabolic inhibitors |
| KR101242572B1 (ko) | 2010-10-12 | 2013-03-19 | 한국화학연구원 | 5-환 헤테로 아릴로 치환된 프탈라지논 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 약학적 조성물 |
| GB201018147D0 (en) | 2010-10-27 | 2010-12-08 | Glaxo Group Ltd | Method of treatment |
| AR084070A1 (es) | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
| US9249161B2 (en) | 2010-12-02 | 2016-02-02 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| CN102731409A (zh) | 2011-04-08 | 2012-10-17 | 中国科学院上海药物研究所 | 一类哒嗪酮类化合物，其药物组合物、制备方法及用途 |
| GB201106743D0 (en) | 2011-04-21 | 2011-06-01 | Glaxosmithkline Llc | Novel compounds |
| GB201106799D0 (en) | 2011-04-21 | 2011-06-01 | Glaxosmithkline Llc | Novel compounds |
| GB201106750D0 (en) | 2011-04-21 | 2011-06-01 | Glaxosmithkline Llc | Novel compounds |
| GB201107325D0 (en) | 2011-05-04 | 2011-06-15 | Glaxosmithkline Llc | Novel compounds |
| US9328117B2 (en) | 2011-06-17 | 2016-05-03 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| GB201114103D0 (en) | 2011-08-17 | 2011-09-28 | Glaxosmithkline Llc | Novel compounds |
| WO2013027168A1 (en) | 2011-08-22 | 2013-02-28 | Pfizer Inc. | Novel heterocyclic compounds as bromodomain inhibitors |
| LT2773354T (lt) | 2011-11-01 | 2019-08-12 | Resverlogix Corp. | Geriamosios greitai atsipalaiduojančios pakeistų chinozolinų vaisto formos |
| AU2012345779B2 (en) | 2011-12-01 | 2017-04-06 | Chemocentryx, Inc. | Substituted benzimidazoles and benzopyrazoles as CCR(4) antagonists |
| WO2013097052A1 (en) | 2011-12-30 | 2013-07-04 | Abbott Laboratories | Bromodomain inhibitors |
| US20130281397A1 (en) | 2012-04-19 | 2013-10-24 | Rvx Therapeutics Inc. | Treatment of diseases by epigenetic regulation |
| US20130281396A1 (en) | 2012-04-19 | 2013-10-24 | Rvx Therapeutics Inc. | Treatment of diseases by epigenetic regulation |
| US20130281399A1 (en) | 2012-04-19 | 2013-10-24 | Rvx Therapeutics Inc. | Treatment of diseases by epigenetic regulation |
| US20130281398A1 (en) | 2012-04-19 | 2013-10-24 | Rvx Therapeutics Inc. | Treatment of diseases by epigenetic regulation |
| CA2870931A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Isoindolone derivatives |
| US9624244B2 (en) | 2012-06-06 | 2017-04-18 | Constellation Pharmaceuticals, Inc. | Benzo [B] isoxazoloazepine bromodomain inhibitors and uses thereof |
| US9550737B2 (en) | 2012-06-11 | 2017-01-24 | Ucb Biopharma Sprl | TNF -α modulating benzimidazoles |
| WO2014031928A2 (en) | 2012-08-24 | 2014-02-27 | Philip Jones | Heterocyclic modulators of hif activity for treatment of disease |
| AU2013311826A1 (en) | 2012-09-05 | 2015-03-26 | Bayer Cropscience Ag | Use of substituted 2-amidobenzimidazoles, 2-amidobenzoxazoles and 2-amidobenzothiazoles or salts thereof as active substances against abiotic plant stress |
| US20150246888A1 (en) | 2012-09-11 | 2015-09-03 | Michael Johnson | Enoyl reductase inhibitors with antibacterial activity |
| WO2014078257A1 (en) | 2012-11-14 | 2014-05-22 | Glaxosmithkline Llc | Thieno[3,2-c]pyridin-4(5h)-ones as bet inhibitors |
| US9073878B2 (en) | 2012-11-21 | 2015-07-07 | Zenith Epigenetics Corp. | Cyclic amines as bromodomain inhibitors |
| WO2014080291A2 (en) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Biaryl derivatives as bromodomain inhibitors |
| JP2016509576A (ja) | 2012-12-20 | 2016-03-31 | バイエル ファーマ アクチエンゲゼルシャフト | Ｂｅｔタンパク質阻害性ジヒドロキノキザリノン類 |
| WO2014096965A2 (en) * | 2012-12-21 | 2014-06-26 | Rvx Therapeutics Inc. | Novel heterocyclic compounds as bromodomain inhibitors |
| HK1212345A1 (en) | 2013-02-22 | 2016-06-10 | Bayer Pharma Aktiengesellschaft | 4-substituted pyrrolo- and pyrazolo-diazepines |
| CN105189514A (zh) | 2013-02-22 | 2015-12-23 | 拜耳医药股份有限公司 | 作为bet-蛋白抑制剂用于治疗过度增殖性疾病的吡咯并-和吡唑并-三唑并二氮杂卓 |
| WO2014128655A1 (en) | 2013-02-25 | 2014-08-28 | Aurigene Discovery Technologies Limited | Substituted imidazo[4,5-c]quinoline derivatives as bromodomain inhibitors |
| JP6404838B2 (ja) | 2013-02-27 | 2018-10-17 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | ブロモドメイン阻害剤として有用なカルバゾール化合物 |
| US9492460B2 (en) | 2013-02-27 | 2016-11-15 | Bristol-Myers Squibb Company | Carbazole compounds useful as bromodomain inhibitors |
| EP2970312B1 (en) | 2013-03-11 | 2017-11-15 | The Regents of The University of Michigan | Bet bromodomain inhibitors and therapeutic methods using the same |
| MX2015012158A (es) | 2013-03-11 | 2015-12-01 | Abbvie Inc | Inhibidores de bomodominio tetraciclicos fusionados. |
| BR112015022861A8 (pt) | 2013-03-11 | 2019-11-26 | Abbvie Inc | inibidores de bromodomínio |
| KR20150126696A (ko) | 2013-03-12 | 2015-11-12 | 애브비 인코포레이티드 | 디하이드로-피롤로피리디논 브로모도메인 억제제 |
| US9493411B2 (en) | 2013-03-12 | 2016-11-15 | Abbvie Inc. | Pyrrole-3-carboxamide bromodomain inhibitors |
| KR20150128842A (ko) | 2013-03-14 | 2015-11-18 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 브로모도메인 억제제로서의 퓨로피리딘 |
| WO2014140076A1 (en) | 2013-03-14 | 2014-09-18 | Glaxosmithkline Intellectual Property (No.2) Limited | 2,3-disubstituted 1 -acyl-4-amino-1,2,3,4-tetrahydroquinoline derivatives and their use as bromodomain inhibitors |
| CN105407894A (zh) | 2013-03-14 | 2016-03-16 | 康威基内有限公司 | 用于抑制含布罗莫结构域的蛋白质的方法和组合物 |
| AU2014236606A1 (en) | 2013-03-15 | 2015-09-24 | Epigenetix, Inc. | Oxazolo(5,4-c)quinolin-2-one compounds as bromodomain inhibitors |
| MX366703B (es) | 2013-03-15 | 2019-07-22 | Incyte Holdings Corp | Heterociclos tricíclicos como inhibidores de la proteína bet. |
| US20140303121A1 (en) | 2013-03-15 | 2014-10-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| JP6325078B2 (ja) * | 2013-03-15 | 2018-05-16 | プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． | ヘテロ環式化合物およびその使用 |
| EP2978757B1 (en) | 2013-03-27 | 2017-02-08 | Boehringer Ingelheim International GmbH | Indolinone analogues as brd4 inhibitors |
| US9199988B2 (en) | 2013-03-27 | 2015-12-01 | Boehringer Ingelheim International Gmbh | Dihydroquinazolinone analogues |
| TWI530499B (zh) | 2013-03-28 | 2016-04-21 | 吉李德科學股份有限公司 | 作為溴結構域（ｂｒｏｍｏｄｏｍａｉｎ）抑制劑之苯並咪唑酮衍生物類 |
| EP2792355A1 (en) | 2013-04-17 | 2014-10-22 | Albert-Ludwigs-Universität Freiburg | Compounds for use as bromodomain inhibitors |
| EP2996689A1 (en) | 2013-04-17 | 2016-03-23 | Albert-Ludwigs-Universität Freiburg | Compounds for use as bromodomain inhibitors |
| CA2901083A1 (en) | 2013-04-26 | 2014-10-30 | Beigene, Ltd. | Substituted 5-(3,5-dimethylisoxazol-4-yl)indoline-2-ones |
| TWI527811B (zh) | 2013-05-09 | 2016-04-01 | 吉李德科學股份有限公司 | 作爲溴結構域抑制劑的苯並咪唑衍生物 |
| US8975417B2 (en) | 2013-05-27 | 2015-03-10 | Novartis Ag | Pyrazolopyrrolidine derivatives and their use in the treatment of disease |
| CN105209467B (zh) | 2013-05-27 | 2018-06-08 | 诺华股份有限公司 | 咪唑并吡咯烷酮衍生物及其在治疗疾病中的用途 |
| EP3010909A1 (de) | 2013-06-17 | 2016-04-27 | Bayer Pharma Aktiengesellschaft | Substituierte phenyl-2,3-benzodiazepine |
| SG11201510409QA (en) | 2013-06-21 | 2016-01-28 | Zenith Epigenetics Corp | Novel bicyclic bromodomain inhibitors |
| WO2015004533A2 (en) | 2013-06-21 | 2015-01-15 | Zenith Epigenetics Corp. | Novel substituted bicyclic compounds as bromodomain inhibitors |
| AR096758A1 (es) | 2013-06-28 | 2016-02-03 | Abbvie Inc | Inhibidores cristalinos de bromodominios |
| WO2015006193A1 (en) | 2013-07-08 | 2015-01-15 | Incyte Corporation | Tricyclic heterocycles as bet protein inhibitors |
| HK1221952A1 (zh) | 2013-07-23 | 2017-06-16 | Bayer Pharma Aktiengesellschaft | 作为bet蛋白和极体样激酶的双重抑制剂的取代的二氢吡啶并[3，4-b]吡嗪酮 |
| BR112016001457A2 (pt) | 2013-07-25 | 2017-08-29 | Dana Farber Cancer Inst Inc | Inibidores de fatores de transcrição e usos dos mesmos |
| WO2015015318A2 (en) | 2013-07-31 | 2015-02-05 | Zenith Epigenetics Corp. | Novel quinazolinones as bromodomain inhibitors |
| US20150051208A1 (en) | 2013-08-14 | 2015-02-19 | Boehringer Ingelheim International Gmbh | Pyridinones |
| US9422281B2 (en) | 2013-11-18 | 2016-08-23 | Forma Therapeutics, Inc. | Benzopiperazine compositions as BET bromodomain inhibitors |
| WO2015074064A2 (en) | 2013-11-18 | 2015-05-21 | Bair Kenneth W | Tetrahydroquinoline compositions as bet bromodomain inhibitors |
| GB201321739D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| US9458156B2 (en) | 2014-12-23 | 2016-10-04 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
| EP3227280B1 (en) | 2014-12-01 | 2019-04-24 | Zenith Epigenetics Ltd. | Substituted pyridines as bromodomain inhibitors |
| US10710992B2 (en) | 2014-12-01 | 2020-07-14 | Zenith Epigenetics Ltd. | Substituted pyridinones as bromodomain inhibitors |
| JP2017537946A (ja) | 2014-12-11 | 2017-12-21 | ゼニス・エピジェネティクス・リミテッドＺｅｎｉｔｈ Ｅｐｉｇｅｎｅｔｉｃｓ Ｌｔｄ． | ブロモドメイン阻害剤としての置換複素環 |
| HK1245247A1 (zh) | 2014-12-17 | 2018-08-24 | 恒翼生物医药科技(上海)有限公司 | 溴结构域的抑制剂 |
| CA2966452A1 (en) | 2014-12-17 | 2016-06-23 | Samuel David Brown | Substituted bicyclic compounds as bromodomain inhibitors |
-
2015
- 2015-12-16 HK HK18104393.5A patent/HK1245247A1/zh unknown
- 2015-12-16 WO PCT/IB2015/002490 patent/WO2016097863A1/en not_active Ceased
- 2015-12-16 CA CA2966450A patent/CA2966450A1/en not_active Abandoned
- 2015-12-16 EP EP15869419.0A patent/EP3233846A4/en not_active Withdrawn
- 2015-12-16 US US15/534,166 patent/US10231953B2/en not_active Expired - Fee Related
- 2015-12-16 CN CN201580066751.6A patent/CN107406438B/zh active Active
- 2015-12-16 JP JP2017532157A patent/JP2017538721A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020053660A1 (en) * | 2018-09-13 | 2020-03-19 | Zenith Epigenetics Ltd. | Solid forms of a bet inhibitor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107406438B (zh) | 2021-05-14 |
| JP2017538721A (ja) | 2017-12-28 |
| US10231953B2 (en) | 2019-03-19 |
| EP3233846A1 (en) | 2017-10-25 |
| EP3233846A4 (en) | 2018-07-18 |
| HK1245247A1 (zh) | 2018-08-24 |
| WO2016097863A1 (en) | 2016-06-23 |
| CN107406438A (zh) | 2017-11-28 |
| US20170360760A1 (en) | 2017-12-21 |
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