PL195916B1 - Izomery optyczne podstawionej 1-okso-izoindoliny i 1,3-diokso-izoindoliny, kompozycje farmaceutyczne je zawierające oraz ich zastosowanie - Google Patents
Izomery optyczne podstawionej 1-okso-izoindoliny i 1,3-diokso-izoindoliny, kompozycje farmaceutyczne je zawierające oraz ich zastosowanieInfo
- Publication number
- PL195916B1 PL195916B1 PL97373743A PL37374397A PL195916B1 PL 195916 B1 PL195916 B1 PL 195916B1 PL 97373743 A PL97373743 A PL 97373743A PL 37374397 A PL37374397 A PL 37374397A PL 195916 B1 PL195916 B1 PL 195916B1
- Authority
- PL
- Poland
- Prior art keywords
- dioxopiperidin
- disease
- pharmaceutical composition
- oxo
- aminoisoindoline
- Prior art date
Links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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| US08690258 US5635517B1 (en) | 1996-07-24 | 1996-07-24 | Method of reducing TNFalpha levels with amino substituted 2-(2,6-dioxopiperidin-3-YL)-1-oxo-and 1,3-dioxoisoindolines |
| US08/701,494 US5798368A (en) | 1996-08-22 | 1996-08-22 | Tetrasubstituted 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolines and method of reducing TNFα levels |
| US4827897P | 1997-05-30 | 1997-05-30 | |
| PCT/US1997/013375 WO1998003502A1 (en) | 1996-07-24 | 1997-07-24 | Substituted 2(2,6-dioxopiperidin-3-yl)phthalimides and -1-oxoisoindolines and method of reducing tnf-alpha levels |
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| PL332867A PL191566B1 (pl) | 1996-07-24 | 1997-07-24 | Podstawiona 1-oksoizoindolina, kompozycja farmaceutyczna ją zawierająca oraz jej zastosowanie |
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| PL332867A PL191566B1 (pl) | 1996-07-24 | 1997-07-24 | Podstawiona 1-oksoizoindolina, kompozycja farmaceutyczna ją zawierająca oraz jej zastosowanie |
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Families Citing this family (210)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6228879B1 (en) | 1997-10-16 | 2001-05-08 | The Children's Medical Center | Methods and compositions for inhibition of angiogenesis |
| US6429221B1 (en) | 1994-12-30 | 2002-08-06 | Celgene Corporation | Substituted imides |
| HU228769B1 (en) * | 1996-07-24 | 2013-05-28 | Celgene Corp | Substituted 2(2,6-dioxopiperidin-3-yl)phthalimides and -1-oxoisoindolines and their use for production of pharmaceutical compositions for mammals to reduce the level of tnf-alpha |
| DE69739802D1 (de) * | 1996-07-24 | 2010-04-22 | Celgene Corp | Substituierte 2-(2,6-Dioxopiperidine-3-yl)-phthalimide -1-oxoisoindoline und Verfahren zur Reduzierung des TNF-alpha Spiegels |
| US5635517B1 (en) | 1996-07-24 | 1999-06-29 | Celgene Corp | Method of reducing TNFalpha levels with amino substituted 2-(2,6-dioxopiperidin-3-YL)-1-oxo-and 1,3-dioxoisoindolines |
| DE19703763C1 (de) * | 1997-02-01 | 1998-10-01 | Gruenenthal Gmbh | Thalidomidanaloge Verbindungen aus der Klasse der Piperidin-2,6-Dione |
| ES2262753T3 (es) * | 1997-11-18 | 2006-12-01 | Celgene Corporation | 2-(2.6-dioxo-3-fluorpiperidin-3-il)-isoindolinas substituidas y su empleo para reducir los niveles de tnfalfa. |
| US5955476A (en) * | 1997-11-18 | 1999-09-21 | Celgene Corporation | Substituted 2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindolines and method of reducing inflammatory cytokine levels |
| ES2243052T3 (es) * | 1998-03-16 | 2005-11-16 | Celgene Corporation | Derivados de la 2- (2,6-dioxopiperidin-3-il) isoindolina, su preparacion y su empleo como inhibidores de las citocinas inflamatorias. |
| TR200102688T2 (tr) | 1999-03-18 | 2002-01-21 | Celgene Corporation | İkameli 1-okso ve 1,3-dioksoizoindolinler ve enflamatuar sitokin seviyelerinin azaltılması için farmasötik bileşimlerde kullanımları. |
| DE19917195B4 (de) * | 1999-04-16 | 2006-09-28 | Immatics Biotechnologies Gmbh | Peptid zur Auslösung einer Immunreaktion gegen Tumorzellen, diese enthaltende pharmzeutische Zusammensetzungen, dessen Verwendungen, dafür codierende Nukleinsäure und diese Nukleinsäure enthaltender Expressionsvektor |
| US7629360B2 (en) | 1999-05-07 | 2009-12-08 | Celgene Corporation | Methods for the treatment of cachexia and graft v. host disease |
| US7182953B2 (en) * | 1999-12-15 | 2007-02-27 | Celgene Corporation | Methods and compositions for the prevention and treatment of atherosclerosis restenosis and related disorders |
| US6458810B1 (en) | 2000-11-14 | 2002-10-01 | George Muller | Pharmaceutically active isoindoline derivatives |
| CA2430669C (en) * | 2000-11-30 | 2011-06-14 | The Children's Medical Center Corporation | Synthesis of 3-amino-thalidomide and its enantiomers |
| CA2431319A1 (en) * | 2000-12-11 | 2002-06-20 | Hiroto Bando | Pharmaceutical composition having an improved water solubility |
| US20030045552A1 (en) * | 2000-12-27 | 2003-03-06 | Robarge Michael J. | Isoindole-imide compounds, compositions, and uses thereof |
| US7091353B2 (en) | 2000-12-27 | 2006-08-15 | Celgene Corporation | Isoindole-imide compounds, compositions, and uses thereof |
| EP1389203B8 (en) * | 2001-02-27 | 2010-03-10 | The Governement of the United States of America, represented by The Secretary Department of Health and Human services | Analogs of thalidomide as angiogenesis inhibitors |
| WO2003014315A2 (en) * | 2001-08-06 | 2003-02-20 | The Children's Medical Center Corporation | Synthesis and anti-tumor activity of nitrogen substituted thalidomide analogs |
| US7498171B2 (en) | 2002-04-12 | 2009-03-03 | Anthrogenesis Corporation | Modulation of stem and progenitor cell differentiation, assays, and uses thereof |
| US7323479B2 (en) | 2002-05-17 | 2008-01-29 | Celgene Corporation | Methods for treatment and management of brain cancer using 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-methylisoindoline |
| US7968569B2 (en) | 2002-05-17 | 2011-06-28 | Celgene Corporation | Methods for treatment of multiple myeloma using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione |
| USRE48890E1 (en) | 2002-05-17 | 2022-01-11 | Celgene Corporation | Methods for treating multiple myeloma with 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione after stem cell transplantation |
| CN1981761B (zh) | 2002-05-17 | 2011-10-12 | 细胞基因公司 | 使用免疫调节性化合物用于制备治疗和控制癌症和其它疾病药物中的应用及组合物 |
| US7393862B2 (en) | 2002-05-17 | 2008-07-01 | Celgene Corporation | Method using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for treatment of certain leukemias |
| US8404717B2 (en) | 2002-10-15 | 2013-03-26 | Celgene Corporation | Methods of treating myelodysplastic syndromes using lenalidomide |
| EP1900369A1 (en) | 2002-10-15 | 2008-03-19 | Celgene Corporation | Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of myelodysplastic syndromes |
| US11116782B2 (en) | 2002-10-15 | 2021-09-14 | Celgene Corporation | Methods of treating myelodysplastic syndromes with a combination therapy using lenalidomide and azacitidine |
| US8404716B2 (en) | 2002-10-15 | 2013-03-26 | Celgene Corporation | Methods of treating myelodysplastic syndromes with a combination therapy using lenalidomide and azacitidine |
| US7189740B2 (en) | 2002-10-15 | 2007-03-13 | Celgene Corporation | Methods of using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myelodysplastic syndromes |
| FR2845994B1 (fr) * | 2002-10-18 | 2006-05-19 | Servier Lab | Nouveaux derives de benzo[e][1,4]oxazino[3,2-g]isoindole substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| EP1556044A2 (en) * | 2002-10-24 | 2005-07-27 | Celgene Corporation | Methods of using and compositions comprising immunomodulatory compounds for treatment, modification and management of pain |
| EP1562597A4 (en) * | 2002-10-31 | 2008-05-14 | Celgene Corp | COMPOSITIONS COMPRISING IMMUNOMODULATORY COMPOUNDS FOR THE TREATMENT AND MANAGEMENT OF MACULAR DEGENERATION AND METHODS OF USE THEREOF |
| US7563810B2 (en) | 2002-11-06 | 2009-07-21 | Celgene Corporation | Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases |
| CH696542A5 (de) * | 2003-07-09 | 2007-07-31 | Siegfried Ltd | Verfahren zur Herstellung von substituierten 2,6-Dioxopiperidin-3-yl-Verbindungen. |
| UA83504C2 (en) | 2003-09-04 | 2008-07-25 | Селджин Корпорейшн | Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione |
| US8952895B2 (en) | 2011-06-03 | 2015-02-10 | Apple Inc. | Motion-based device operations |
| CA2808646C (en) | 2003-09-17 | 2016-08-23 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Thalidomide analogs as tnf-alpha modulators |
| US7612096B2 (en) | 2003-10-23 | 2009-11-03 | Celgene Corporation | Methods for treatment, modification and management of radiculopathy using 1-oxo-2-(2,6-dioxopiperidin-3yl)-4-aminoisoindoline |
| US20050100529A1 (en) * | 2003-11-06 | 2005-05-12 | Zeldis Jerome B. | Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of asbestos-related diseases and disorders |
| NZ550026A (en) | 2004-03-22 | 2009-10-30 | Celgene Corp | Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of skin diseases or disorders |
| BRPI0418798A (pt) * | 2004-05-05 | 2007-10-16 | Celgene Corp | métodos de tratamento ou prevenção, e de controle, de uma doença mieloproliferativa, de redução ou prevenção de um efeito adverso, de aumento da eficácia terapêutica de um tratamento de doença mieloproliferativa, composição farmacêutica, e, kit |
| ES2437592T3 (es) | 2004-09-03 | 2014-01-13 | Celgene Corporation | Procedimientos para la preparación de 2-(2,6-dioxopiperidin-3-il)-1-oxoisoindolinas sustituidas |
| RS52704B (sr) | 2005-06-30 | 2013-08-30 | Celgene Corporation | Postupci za dobijanje 4-amino-2-(2,6-dioksopiperidin-3-il) izoindolin-1,3-dionskih jedinjenja |
| EP1919500A2 (en) | 2005-07-13 | 2008-05-14 | Anthrogenesis Corporation | Treatment of leg ulcers using placenta derived collagen biofabric |
| BRPI0614995A2 (pt) | 2005-08-31 | 2010-01-12 | Celgene Corp | composto ou um sal, solvato ou estereoisemero farmaceuticamente aceitável do mesmo, composição farmacêutica, uso de uma quantidade terapêutica ou profilaticamente eficaz de um composto ou um sal, solvato ou estereoisemero farmaceuticamente aceitável do mesmo, e, forma de dosagem unitária única |
| PL1928492T3 (pl) | 2005-09-01 | 2011-09-30 | Celgene Corp | Immunologiczne zastosowania związków immunomodulujących do szczepionki i przeciwzakaźnego leczenia choroby |
| US20070066512A1 (en) | 2005-09-12 | 2007-03-22 | Dominique Verhelle | Methods and compositions using immunomodulatory compounds for the treatment of disorders associated with low plasma leptin levels |
| CN1939922B (zh) * | 2005-09-27 | 2010-10-13 | 天津和美生物技术有限公司 | 可抑制细胞释放肿瘤坏死因子的5H-噻吩[3,4-c]吡咯-4,6-二酮衍生物 |
| EP1974013A2 (en) | 2005-12-29 | 2008-10-01 | Anthrogenesis Corporation | Improved composition for collecting and preserving placental stem cells and methods of using the composition |
| CA2646316C (en) | 2006-03-15 | 2016-05-24 | Theralogics, Inc. | Methods of treating muscular wasting diseases using nf-kb activation inhibitors |
| US20080064876A1 (en) * | 2006-05-16 | 2008-03-13 | Muller George W | Process for the preparation of substituted 2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione |
| CL2007002218A1 (es) | 2006-08-03 | 2008-03-14 | Celgene Corp Soc Organizada Ba | Uso de 3-(4-amino-1-oxo-1,3-dihidro-isoindol-2-il)-piperidina 2,6-diona para la preparacion de un medicamento util para el tratamiento de linfoma de celula de capa. |
| WO2008021391A1 (en) | 2006-08-15 | 2008-02-21 | Anthrogenesis Corporation | Umbilical cord biomaterial for medical use |
| JP5523831B2 (ja) * | 2006-08-30 | 2014-06-18 | セルジーン コーポレイション | 5−置換イソインドリン化合物 |
| US8877780B2 (en) | 2006-08-30 | 2014-11-04 | Celgene Corporation | 5-substituted isoindoline compounds |
| LT2420498T (lt) * | 2006-09-26 | 2017-10-25 | Celgene Corporation | 5-pakeistieji chinazolinono dariniai, kaip priešvėžiniai agentai |
| EP1923053A1 (en) | 2006-09-27 | 2008-05-21 | Novartis AG | Pharmaceutical compositions comprising nilotinib or its salt |
| US8071135B2 (en) | 2006-10-04 | 2011-12-06 | Anthrogenesis Corporation | Placental tissue compositions |
| NZ597223A (en) | 2006-10-06 | 2013-09-27 | Anthrogenesis Corp | Native (telopeptide) placental collagen compositions |
| JP5637852B2 (ja) | 2007-09-26 | 2014-12-10 | セルジーン コーポレイション | 6、7又は8置換キナゾリノン誘導体並びにそれらを含有する組成物及びそれらを使用する方法 |
| RS53841B1 (sr) | 2007-09-28 | 2015-06-30 | Anthrogenesis Corporation | Supresija tumora korišćenjem humanog placentalnog perfuzata i intermedijernih ćelija ubica poreklom iz humane placente |
| US20090088393A1 (en) * | 2007-09-28 | 2009-04-02 | Zomanex, Llc | Methods and formulations for converting intravenous and injectable drugs into oral dosage forms |
| AU2008325140A1 (en) * | 2007-11-08 | 2009-05-14 | Celgene Corporation | Use of immunomodulatory compounds for the treatment of disorders associated with endothelial dysfunction |
| US7964354B2 (en) | 2007-12-20 | 2011-06-21 | Celgene Corporation | Use of micro-RNA as a biomarker of immunomodulatory drug activity |
| WO2009114601A2 (en) * | 2008-03-11 | 2009-09-17 | Dr. Reddy's Laboratories Ltd. | Preparation of lenalidomide |
| US20110060010A1 (en) * | 2008-03-13 | 2011-03-10 | Tianjin Hemay Bio-Tech Co., Ltd | Salts of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)piperidine-2,6-dione and derivatives thereof, or polymorphs of salts, process for preparing same and use thereof |
| WO2009111948A1 (zh) * | 2008-03-13 | 2009-09-17 | 天津和美生物技术有限公司 | 3-(4-氨基-1-氧代-1,3-二氢异吲哚-2-基)哌啶-2,6-二酮及其衍生物的盐或盐的多晶型物及其制备和应用 |
| WO2009139880A1 (en) * | 2008-05-13 | 2009-11-19 | Celgene Corporation | Thioxoisoindoline compounds and compositions and methods of using the same |
| MX361467B (es) | 2008-10-29 | 2018-12-06 | Celgene Corp | Compuestos de isoindolina para uso en el tratamiento de cancer. |
| US9045453B2 (en) | 2008-11-14 | 2015-06-02 | Concert Pharmaceuticals, Inc. | Substituted dioxopiperidinyl phthalimide derivatives |
| ES2444433T3 (es) * | 2008-11-14 | 2014-02-25 | Concert Pharmaceuticals, Inc. | Derivados de dioxopiperidinil-ftalimida sustituidos |
| DE102008057335A1 (de) | 2008-11-14 | 2010-05-20 | Ratiopharm Gmbh | Amorphes Lenalidomid |
| DE102008057285A1 (de) | 2008-11-14 | 2010-05-20 | Ratiopharm Gmbh | 3-(4-Amino-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-2,6-piperidindion in Form einer festen Lösung |
| DE102008057284A1 (de) | 2008-11-14 | 2010-05-20 | Ratiopharm Gmbh | Tabletten enthaltend Lenalidomid und Adhäsionsverstärker |
| WO2010093434A1 (en) | 2009-02-11 | 2010-08-19 | Celgene Corporation | Isotopologues of lenalidomide |
| CA3110964A1 (en) | 2009-03-25 | 2010-09-30 | Xiaokui Zhang | Preventing a symptom of graft-versus-host disease using human placenta-derived intermediate natural killer cells |
| EP3199149A1 (en) | 2009-05-19 | 2017-08-02 | Celgene Corporation | Formulations of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione |
| EP2436387B1 (en) | 2009-05-25 | 2018-07-25 | Celgene Corporation | Pharmaceutical composition comprising crbn for use in treating a disease of the cerebral cortex |
| CN101580501B (zh) | 2009-06-01 | 2011-03-09 | 南京卡文迪许生物工程技术有限公司 | 3-(取代二氢异吲哚酮-2-基)-2,6-哌啶二酮的合成方法及其中间体 |
| CA2773012A1 (en) | 2009-09-03 | 2011-03-10 | Ranbaxy Laboratories Limited | Process for the preparation of lenalidomide |
| WO2011050962A1 (en) * | 2009-10-29 | 2011-05-05 | Ratiopharm Gmbh | Acid addition salts of lenalidomide |
| CN101696205B (zh) | 2009-11-02 | 2011-10-19 | 南京卡文迪许生物工程技术有限公司 | 3-(取代二氢异吲哚-2-基)-2,6-哌啶二酮多晶型物和药用组合物 |
| CN102127054B (zh) * | 2009-11-02 | 2013-04-03 | 南京卡文迪许生物工程技术有限公司 | 3-(取代二氢异吲哚-2-基)-2,6-哌啶二酮多晶型物和药用组合物 |
| WO2011069608A1 (en) * | 2009-12-09 | 2011-06-16 | Ratiopharm Gmbh | S-lenalidomide, polymorphic forms thereof and blend comprising s- und r-lenalidomide |
| AU2010333767A1 (en) | 2009-12-22 | 2012-07-05 | Celgene Corporation | (Methylsulfonyl) ethyl benzene isoindoline derivatives and their therapeutical uses |
| CA2786266A1 (en) | 2010-01-05 | 2011-07-14 | Celgene Corporation | A combination of an immunomodulatory compound and an artemisinin or a derivative thereof for treating cancer |
| PL2536706T3 (pl) | 2010-02-11 | 2017-10-31 | Celgene Corp | Pochodne arylometoksyizoindoliny i zawierające je kompozycje oraz sposoby ich zastosowania |
| JP5937060B2 (ja) | 2010-04-07 | 2016-06-22 | セルジーン コーポレイション | 呼吸器ウイルス感染症の治療方法 |
| WO2012078492A1 (en) | 2010-12-06 | 2012-06-14 | Celgene Corporation | A combination therapy with lenalidomide and a cdk inhibitor for treating multiple myeloma |
| MX347928B (es) | 2011-01-10 | 2017-05-19 | Celgene Corp | Derivados de fenetilsulfona isoindolina y su uso. |
| EA026100B1 (ru) | 2011-03-11 | 2017-03-31 | Селджин Корпорейшн | Твердые формы 3-(5-амино-2-метил-4-оксо-4н-хиназолин-3-ил)пиперидин-2,6-диона и их фармацевтические композиции и применение |
| WO2012135299A1 (en) | 2011-03-28 | 2012-10-04 | Deuteria Pharmaceuticals Inc | 2',6'-dioxo-3'-deutero-piperdin-3-yl-isoindoline compounds |
| EP2699909A1 (en) | 2011-04-18 | 2014-02-26 | Celgene Corporation | Biomarkers for the treatment of multiple myeloma |
| MX353482B (es) | 2011-04-29 | 2018-01-16 | Celgene Corp | Metodos para el tratamiento del cancer y enfermedades inflamatorias utilizando cereblon como predictor. |
| US20140221427A1 (en) | 2011-06-22 | 2014-08-07 | Celgene Corporation | Isotopologues of pomalidomide |
| JP2014526508A (ja) | 2011-09-14 | 2014-10-06 | セルジーン コーポレイション | シクロプロパンカルボン酸{2−[(1s)−1−(3−エトキシ−4−メトキシ−フェニル)−2−メタンスルホニル−エチル]−3−オキソ−2,3−ジヒドロ−1h−イソインドール−4−イル}−アミドの製剤 |
| US8927725B2 (en) | 2011-12-02 | 2015-01-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Thio compounds |
| BR112014015923B1 (pt) | 2011-12-27 | 2022-02-01 | Amgen (Europe) GmbH | Comprimidos revestidos de (+)-2-[1-(3-etoxi-4-metoxi-fenil)-2-metano-sulfoniletil]-4 - acetilaminoisoindolina-1,3-diona |
| ES2671608T3 (es) * | 2012-02-21 | 2018-06-07 | Celgene Corporation | Formas sólidas de 3-(4-nitro-1-oxoisoindolin-2-il)piperidina-2,6-diona |
| US20150174235A1 (en) | 2012-06-06 | 2015-06-25 | Bionor Immuno As | Vaccine |
| CA3136093C (en) | 2012-06-29 | 2025-07-08 | Celgene Corporation | METHODS FOR DETERMINING THE EFFICACY OF A DRUG USING PROTEINS ASSOCIATED WITH CEREBLON |
| RS58548B1 (sr) | 2012-08-09 | 2019-05-31 | Celgene Corp | Čvrsta forma (s)-3-(4-((4-(morfolinometil)benzil)oksi)-1-oksoizoindolin-2-il)piperidin-2,6-dion hidrohlorida |
| US9587281B2 (en) | 2012-08-14 | 2017-03-07 | Celgene Corporation | Cereblon isoforms and their use as biomarkers for therapeutic treatment |
| EP2922838B1 (en) | 2012-10-22 | 2018-03-14 | Concert Pharmaceuticals Inc. | Solid forms of {s-3-(4-amino-1-oxo-isoindolin-2-yl)(piperidine-3,4,4,5,5-d5)-2,6-dione} . |
| AU2013204922B2 (en) | 2012-12-20 | 2015-05-14 | Celgene Corporation | Chimeric antigen receptors |
| FR2999915B1 (fr) * | 2012-12-21 | 2017-08-11 | Oreal | Utilisation de derives de l'acide imidocarboxylique en tant qu'agent apaisant |
| FR2999914B1 (fr) * | 2012-12-21 | 2015-08-07 | Oreal | Utilisation de derives de l'acide imidocarboxylique pour traiter les alterations de la peau liees a l'age ou au photovieillissement |
| WO2014110322A2 (en) | 2013-01-11 | 2014-07-17 | Concert Pharmaceuticals, Inc. | Substituted dioxopiperidinyl phthalimide derivatives |
| US9540340B2 (en) | 2013-01-14 | 2017-01-10 | Deuterx, Llc | 3-(5-substituted-4-oxoquinazolin-3(4H)-yl)-3-deutero-piperidine-2,6-dione derivatives and compositions comprising and methods of using the same |
| AU2014215458A1 (en) | 2013-02-05 | 2015-08-13 | Anthrogenesis Corporation | Natural killer cells from placenta |
| EP2764866A1 (en) | 2013-02-07 | 2014-08-13 | IP Gesellschaft für Management mbH | Inhibitors of nedd8-activating enzyme |
| JP6493692B2 (ja) | 2013-03-15 | 2019-04-10 | セルジーン コーポレイション | 修飾されたtリンパ球 |
| CN104072476B (zh) * | 2013-03-27 | 2018-08-21 | 江苏豪森药业集团有限公司 | 泊马度胺晶型及其制备方法和用途 |
| AU2014254056B2 (en) | 2013-04-17 | 2019-06-06 | Signal Pharmaceuticals, Llc | Combination therapy comprising a TOR kinase inhibitor and an IMiD compound for treating cancer |
| EP2815749A1 (en) * | 2013-06-20 | 2014-12-24 | IP Gesellschaft für Management mbH | Solid form of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione having specified X-ray diffraction pattern |
| WO2015007337A1 (en) | 2013-07-19 | 2015-01-22 | Bionor Immuno As | Method for the vaccination against hiv |
| CN103497174B (zh) * | 2013-07-29 | 2015-10-28 | 杭州派臣医药科技有限公司 | 泊利度胺的制备和精制方法 |
| CN104557857A (zh) * | 2013-10-29 | 2015-04-29 | 上海医药工业研究院 | 一种泊利度胺的纯化方法 |
| CN104557858B (zh) * | 2013-10-29 | 2018-06-01 | 上海医药工业研究院 | 一种泊利度胺的制备方法 |
| PE20161030A1 (es) | 2013-12-03 | 2016-11-06 | Acetylon Pharmaceuticals Inc | Combinaciones de inhibidores de histona deacetilasa y farmacos inmunomoduladores |
| CN104016967A (zh) * | 2014-04-04 | 2014-09-03 | 南京工业大学 | 一种泊利度胺的合成方法 |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| JP6778114B2 (ja) * | 2014-04-14 | 2020-10-28 | アルビナス・オペレーションズ・インコーポレイテッドArvinas Operations, Inc. | イミド系タンパク質分解モジュレーター及び関連する使用方法 |
| WO2015200795A1 (en) | 2014-06-27 | 2015-12-30 | Celgene Corporation | Compositions and methods for inducing conformational changes in cereblon other e3 ubiquitin ligases |
| CN109678840B (zh) * | 2014-08-20 | 2023-12-01 | 河北菲尼斯生物技术有限公司 | 泊马度胺的制备方法 |
| SMT202300081T1 (it) | 2014-08-22 | 2023-05-12 | Celgene Corp | Metodi di trattamento di mieloma multiplo con composti immunomodulatori in combinazione con anticorpi |
| CN105440013B (zh) * | 2014-08-29 | 2018-10-09 | 杭州和泽医药科技有限公司 | 一种泊马度胺的制备方法 |
| NZ731789A (en) | 2014-10-30 | 2019-04-26 | Kangpu Biopharmaceuticals Ltd | Isoindoline derivative, intermediate, preparation method, pharmaceutical composition and use thereof |
| EP3233059A1 (en) | 2014-12-19 | 2017-10-25 | Synthon B.V. | Pharmaceutical composition comprising amorphous lenalidomide |
| US10471156B2 (en) | 2014-12-19 | 2019-11-12 | Synthon B.V. | Pharmaceutical composition comprising amorphous lenalidomide |
| CN104447689B (zh) * | 2014-12-22 | 2016-07-20 | 上海迈柏医药科技有限公司 | 来那度胺的晶型及其制备方法 |
| US12312316B2 (en) | 2015-01-20 | 2025-05-27 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| MX390189B (es) | 2015-01-20 | 2025-03-20 | Arvinas Operations Inc | COMPUESTOS Y METODOS PARA LA DEGRADACION DIRIGIDA DE RECEPTOR DE ANDROGENOs. |
| RU2694895C2 (ru) * | 2015-05-22 | 2019-07-18 | Биотерикс, Инк. | Нацеленные на белки соединения, их композиции, способы и применения |
| WO2016197114A1 (en) | 2015-06-05 | 2016-12-08 | Arvinas, Inc. | Tank-binding kinase-1 protacs and associated methods of use |
| WO2016210262A1 (en) | 2015-06-26 | 2016-12-29 | Celgene Corporation | Methods for the treatment of kaposi's sarcoma or kshv-induced lymphoma using immunomodulatory compounds, and uses of biomarkers |
| WO2017030814A1 (en) | 2015-08-19 | 2017-02-23 | Arvinas, Inc. | Compounds and methods for the targeted degradation of bromodomain-containing proteins |
| WO2017109041A1 (en) | 2015-12-22 | 2017-06-29 | Synthon B.V. | Pharmaceutical composition comprising amorphous lenalidomide and an antioxidant |
| US10830762B2 (en) | 2015-12-28 | 2020-11-10 | Celgene Corporation | Compositions and methods for inducing conformational changes in cereblon and other E3 ubiquitin ligases |
| US20170281784A1 (en) | 2016-04-05 | 2017-10-05 | Arvinas, Inc. | Protein-protein interaction inducing technology |
| WO2017201069A1 (en) | 2016-05-18 | 2017-11-23 | Biotheryx, Inc. | Oxoindoline derivatives as protein function modulators |
| IL318681A (en) | 2016-10-11 | 2025-03-01 | Arvinas Operations Inc | Compounds and methods for targeted reduction of androgen receptor |
| AU2017367872B2 (en) | 2016-11-01 | 2022-03-31 | Arvinas, Inc. | Tau-protein targeting protacs and associated methods of use |
| CN118834201A (zh) | 2016-12-01 | 2024-10-25 | 阿尔维纳斯运营股份有限公司 | 作为雌激素受体降解剂的四氢萘和四氢异喹啉衍生物 |
| WO2018102786A1 (en) | 2016-12-03 | 2018-06-07 | Juno Therapeutics, Inc. | Methods for modulation of car-t cells |
| KR20220028178A (ko) | 2016-12-16 | 2022-03-08 | 강푸 바이오파마슈티칼즈 리미티드 | 조성물, 이의 적용 및 치료 방법 |
| WO2018118598A1 (en) | 2016-12-23 | 2018-06-28 | Arvinas, Inc. | Compounds and methods for the targeted degradation of fetal liver kinase polypeptides |
| KR102839545B1 (ko) | 2016-12-23 | 2025-07-29 | 아비나스 오퍼레이션스, 인코포레이티드 | 급속 진행성 섬유육종 폴리펩티드의 표적화 분해를 위한 화합물 및 방법 |
| KR20190101406A (ko) | 2016-12-23 | 2019-08-30 | 아비나스 오퍼레이션스, 인코포레이티드 | Egfr 단백질분해 표적화 키메라 분자 및 관련 사용 방법 |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| US11191741B2 (en) | 2016-12-24 | 2021-12-07 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide |
| CA3049912A1 (en) | 2017-01-26 | 2018-08-02 | Arvinas Operations, Inc. | Modulators of estrogen receptor proteolysis and associated methods of use |
| JP2020506922A (ja) | 2017-01-31 | 2020-03-05 | アルビナス・オペレーションズ・インコーポレイテッドArvinas Operations, Inc. | セレブロンリガンド、およびセレブロンリガンドを含有する二官能性化合物 |
| CA3053805C (en) | 2017-02-13 | 2020-06-30 | Kangpu Biopharmaceuticals, Ltd. | Combination treating prostate cancer, pharmaceutical composition and treatment method |
| CA3061945A1 (en) | 2017-05-01 | 2018-11-08 | Juno Therapeutics, Inc. | Combination of a cell therapy and an immunomodulatory compound |
| US10093647B1 (en) | 2017-05-26 | 2018-10-09 | Celgene Corporation | Crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione dihydrate, compositions and methods of use thereof |
| KR20200054160A (ko) | 2017-06-02 | 2020-05-19 | 주노 쎄러퓨티크스 인코퍼레이티드 | 입양 세포 요법을 사용한 치료를 위한 물품 제조 및 방법 |
| WO2019006427A1 (en) | 2017-06-29 | 2019-01-03 | Juno Therapeutics, Inc. | WALL MODEL FOR ASSESSING TOXICITIES ASSOCIATED WITH IMMUNOTHERAPIES |
| TWI793151B (zh) * | 2017-08-23 | 2023-02-21 | 瑞士商諾華公司 | 3-(1-氧異吲哚啉-2-基)之氫吡啶-2,6-二酮衍生物及其用途 |
| US10093649B1 (en) | 2017-09-22 | 2018-10-09 | Celgene Corporation | Crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione monohydrate, compositions and methods of use thereof |
| US10093648B1 (en) | 2017-09-22 | 2018-10-09 | Celgene Corporation | Crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione hemihydrate, compositions and methods of use thereof |
| US20200246393A1 (en) | 2017-09-28 | 2020-08-06 | Celularity, Inc. | Tumor suppression using human placenta-derived intermediate natural killer (pink) cells in combination with an antibody |
| KR20200074997A (ko) | 2017-11-01 | 2020-06-25 | 주노 쎄러퓨티크스 인코퍼레이티드 | B-세포 성숙 항원에 특이적인 항체 및 키메릭 항원 수용체 |
| WO2019089858A2 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
| US11065231B2 (en) | 2017-11-17 | 2021-07-20 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of interleukin-1 receptor- associated kinase 4 polypeptides |
| WO2019118937A1 (en) | 2017-12-15 | 2019-06-20 | Juno Therapeutics, Inc. | Anti-cct5 binding molecules and methods of use thereof |
| EP3505158A1 (en) | 2017-12-27 | 2019-07-03 | KRKA, d.d., Novo mesto | Pharmaceutical composition of lenalidomide pharmaceutically acceptable acid addition salt |
| WO2019138424A1 (en) | 2018-01-11 | 2019-07-18 | Natco Pharma Limited | Stable pharmaceutical compositions comprising lenalidomide |
| WO2019148055A1 (en) | 2018-01-26 | 2019-08-01 | Yale University | Imide-based modulators of proteolysis and methods of use |
| US11401336B2 (en) | 2018-02-21 | 2022-08-02 | Celgene Corporation | BCMA-binding antibodies and uses thereof |
| EP3545949A1 (en) | 2018-03-29 | 2019-10-02 | Midas Pharma GmbH | Oral dosage forms comprising pomalidomide crystalline form a |
| BR112020020307A2 (pt) | 2018-04-04 | 2021-01-12 | Arvinas Operations, Inc. | Moduladores de proteólise e métodos de uso associados |
| KR102286497B1 (ko) | 2018-04-13 | 2021-08-05 | 주식회사 삼양홀딩스 | 다양한 용량의 레날리도마이드의 경구용 정제 조성물 |
| KR102286500B1 (ko) | 2018-04-13 | 2021-08-05 | 주식회사 삼양홀딩스 | 레날리도마이드를 포함하는 경구용 고형제제의 제조방법 |
| KR102259798B1 (ko) | 2018-04-13 | 2021-06-02 | 주식회사 삼양홀딩스 | 붕해가 개선된 레날리도마이드의 경구용 정제 조성물 |
| JP7581052B2 (ja) | 2018-04-13 | 2024-11-12 | サムヤン ホールディングス コーポレイション | レナリドミドの経口用コーティング錠剤組成物 |
| JP7585043B2 (ja) | 2018-04-13 | 2024-11-18 | サムヤン ホールディングス コーポレイション | レナリドミドを含む医薬組成物 |
| JP7297053B2 (ja) | 2018-08-20 | 2023-06-23 | アルビナス・オペレーションズ・インコーポレイテッド | 神経変性疾患を治療するためのe3ユビキチンリガーゼ結合活性を有するキメラ(protac)化合物を標的とし、アルファ-シヌクレインタンパク質を標的とするタンパク質分解 |
| WO2020097403A1 (en) | 2018-11-08 | 2020-05-14 | Juno Therapeutics, Inc. | Methods and combinations for treatment and t cell modulation |
| SG11202105084VA (en) | 2018-11-16 | 2021-06-29 | Juno Therapeutics Inc | Methods of dosing engineered t cells for the treatment of b cell malignancies |
| FI3886875T3 (fi) | 2018-11-30 | 2024-07-23 | Juno Therapeutics Inc | Adoptiivista soluterapiaa käyttäviä hoitomenetelmiä |
| EP3891128A4 (en) * | 2018-12-05 | 2022-08-17 | Vividion Therapeutics, Inc. | SUBSTITUTED ISOINDOLINONES AS MODULATORS OF CEREBLON-MEDIATED NEOSUBSTRATE RECRUITMENT |
| CN113365660A (zh) | 2019-01-29 | 2021-09-07 | 朱诺治疗学股份有限公司 | 对受体酪氨酸激酶样孤儿受体1(ror1)具特异性的抗体及嵌合抗原受体 |
| WO2020227183A1 (en) * | 2019-05-03 | 2020-11-12 | Dynamic Biologics Inc. | Lenalidomide prodrugs, polymeric conjugates, and formulations thereof, and their uses for the treatment of multiple myeloma |
| CN110343063A (zh) * | 2019-08-09 | 2019-10-18 | 新乡双鹭药业有限公司 | 一种泊马度胺合成中杂质的制备方法 |
| IL290789B2 (en) | 2019-08-26 | 2025-09-01 | Arvinas Operations Inc | Methods for treating breast cancer with a history of tetrahydronaphthalene as estrogen receptor-disrupting agents |
| WO2021061644A1 (en) * | 2019-09-23 | 2021-04-01 | Accutar Biotechnology Inc. | Novel substituted quinoline-8-carbonitrile derivatives with androgen receptor degradation activity and uses thereof |
| EP4034114A4 (en) * | 2019-09-23 | 2023-07-26 | Accutar Biotechnology Inc. | NEW UREAES HAVING ANDROGEN RECEPTOR DEGRADING ACTIVITY AND THEIR USES |
| CN119019369A (zh) | 2019-10-17 | 2024-11-26 | 阿尔维纳斯运营股份有限公司 | 含有与bcl6靶向部分连接的e3泛素连接酶结合部分的双官能分子 |
| AR120481A1 (es) | 2019-11-19 | 2022-02-16 | Bristol Myers Squibb Co | Compuestos útiles como inhibidores de la proteína helios |
| CN119039273A (zh) * | 2019-12-17 | 2024-11-29 | 奥里尼斯生物科学股份有限公司 | 调节蛋白质募集和/或降解的化合物 |
| PE20221582A1 (es) | 2019-12-19 | 2022-10-06 | Arvinas Operations Inc | Compuestos y metodos para la degradacion dirigida de receptor de androgenos |
| TW202140441A (zh) | 2020-03-23 | 2021-11-01 | 美商必治妥美雅史谷比公司 | 經取代之側氧基異吲哚啉化合物 |
| MX2022012964A (es) | 2020-04-15 | 2022-11-09 | Tecnimede Sociedade Tecnico Medicinal Sa | Forma de dosificacion oral solida que comprende pomalidomida. |
| TW202208345A (zh) | 2020-05-09 | 2022-03-01 | 美商亞文納營運公司 | 雙官能性化合物的製造方法、該雙官能性化合物的超純形式、及含彼之劑型 |
| US12180193B2 (en) | 2020-08-28 | 2024-12-31 | Arvinas Operations, Inc. | Accelerating fibrosarcoma protein degrading compounds and associated methods of use |
| KR20230069144A (ko) | 2020-09-14 | 2023-05-18 | 아비나스 오퍼레이션스, 인코포레이티드 | 에스트로겐 수용체의 표적화된 분해를 위한 화합물의 결정질 형태 |
| MX2023008296A (es) | 2021-01-13 | 2023-09-29 | Monte Rosa Therapeutics Inc | Compuestos de isoindolinona. |
| SI4320112T1 (sl) | 2021-04-06 | 2025-09-30 | Bristol-Myers Squibb Company | Oksoizoindolin spojine, substituirane s piridinilom |
| CN118388454A (zh) | 2021-04-16 | 2024-07-26 | 阿尔维纳斯运营股份有限公司 | Bcl6蛋白水解的调节剂和其相关使用方法 |
| US20250073220A1 (en) | 2021-12-31 | 2025-03-06 | A Fine House S.A. | Oral solution comprising lenalidomide |
| WO2023126531A1 (en) | 2021-12-31 | 2023-07-06 | A Fine House S.A. | Lenalidomide oral solution |
| US20250381272A1 (en) | 2022-06-22 | 2025-12-18 | Juno Therapeutics, Inc. | Treatment methods for second line therapy of cd19-targeted car t cells |
| EP4584258A1 (en) | 2022-09-07 | 2025-07-16 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
| EP4611798A1 (en) | 2022-11-02 | 2025-09-10 | Celgene Corporation | Methods of treatment with t cell therapy and immunomodulatory agent maintenance therapy |
| AU2024212035A1 (en) | 2023-01-26 | 2025-08-14 | Arvinas Operations, Inc. | Cereblon-based kras degrading protacs ans uses related thereto |
| US12496301B2 (en) | 2023-12-08 | 2025-12-16 | Arvinas Operations, Inc. | Use of androgen receptor degrader for the treatment of spinal and bulbar muscular atrophy |
| WO2026006247A1 (en) * | 2024-06-26 | 2026-01-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | 2-(piperidin-3-yl)isoindole-1,3-dione analogs and uses thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9109645D0 (en) | 1991-05-03 | 1991-06-26 | Celltech Ltd | Recombinant antibodies |
| AU1531492A (en) * | 1991-02-14 | 1992-09-15 | Rockefeller University, The | Method for controlling abnormal concentration tnf alpha in human tissues |
| US5629327A (en) * | 1993-03-01 | 1997-05-13 | Childrens Hospital Medical Center Corp. | Methods and compositions for inhibition of angiogenesis |
| US5463063A (en) * | 1993-07-02 | 1995-10-31 | Celgene Corporation | Ring closure of N-phthaloylglutamines |
| DE4422237A1 (de) * | 1994-06-24 | 1996-01-04 | Gruenenthal Gmbh | Verwendung von Lactamverbindungen als pharmazeutische Wirkstoffe |
| DE69739802D1 (de) * | 1996-07-24 | 2010-04-22 | Celgene Corp | Substituierte 2-(2,6-Dioxopiperidine-3-yl)-phthalimide -1-oxoisoindoline und Verfahren zur Reduzierung des TNF-alpha Spiegels |
| US5635517B1 (en) * | 1996-07-24 | 1999-06-29 | Celgene Corp | Method of reducing TNFalpha levels with amino substituted 2-(2,6-dioxopiperidin-3-YL)-1-oxo-and 1,3-dioxoisoindolines |
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