NO319790B1 - Substituerte fenyletylsulfoner og fremgangsmate for reduksjon av TNF<alfa>-nivaene - Google Patents
Substituerte fenyletylsulfoner og fremgangsmate for reduksjon av TNF<alfa>-nivaene Download PDFInfo
- Publication number
- NO319790B1 NO319790B1 NO20012021A NO20012021A NO319790B1 NO 319790 B1 NO319790 B1 NO 319790B1 NO 20012021 A NO20012021 A NO 20012021A NO 20012021 A NO20012021 A NO 20012021A NO 319790 B1 NO319790 B1 NO 319790B1
- Authority
- NO
- Norway
- Prior art keywords
- ethoxy
- methoxyphenyl
- methylsulfonylethyl
- dione
- isoindoline
- Prior art date
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- 238000000034 method Methods 0.000 title description 15
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Classifications
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- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- C07D209/46—Iso-indoles; Hydrogenated iso-indoles with an oxygen atom in position 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Treatment Of Water By Oxidation Or Reduction (AREA)
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US09/183,049 US6020358A (en) | 1998-10-30 | 1998-10-30 | Substituted phenethylsulfones and method of reducing TNFα levels |
PCT/US1999/024376 WO2000025777A1 (en) | 1998-10-30 | 1999-10-19 | SUBSTITUTED PHENETHYLSULFONES AND METHOD OF REDUCING TNFαLEVELS |
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NO20012021A NO319790B1 (no) | 1998-10-30 | 2001-04-24 | Substituerte fenyletylsulfoner og fremgangsmate for reduksjon av TNF<alfa>-nivaene |
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US (2) | US6020358A (de) |
EP (3) | EP1752148B1 (de) |
JP (1) | JP4530543B2 (de) |
AT (2) | ATE471718T1 (de) |
AU (1) | AU756308B2 (de) |
BR (2) | BR9915201A (de) |
CA (1) | CA2348993C (de) |
CY (3) | CY1107499T1 (de) |
DE (2) | DE69942532D1 (de) |
DK (3) | DK1752148T3 (de) |
ES (3) | ES2343744T3 (de) |
HK (2) | HK1038696B (de) |
NO (1) | NO319790B1 (de) |
NZ (1) | NZ511253A (de) |
PT (3) | PT1126839E (de) |
WO (1) | WO2000025777A1 (de) |
Families Citing this family (141)
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---|---|---|---|---|
US6429221B1 (en) * | 1994-12-30 | 2002-08-06 | Celgene Corporation | Substituted imides |
US6518281B2 (en) * | 1995-08-29 | 2003-02-11 | Celgene Corporation | Immunotherapeutic agents |
TW432073B (en) * | 1995-12-28 | 2001-05-01 | Pfizer | Pyrazolopyridine compounds |
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 |
US6281230B1 (en) | 1996-07-24 | 2001-08-28 | Celgene Corporation | Isoindolines, method of use, and pharmaceutical compositions |
CZ299810B6 (cs) * | 1996-08-12 | 2008-12-03 | Celgene Corporation | Substituovaná aromatická sloucenina a její použití pro snížení hladiny cytokinu |
US6673828B1 (en) * | 1998-05-11 | 2004-01-06 | Children's Medical Center Corporation | Analogs of 2-Phthalimidinoglutaric acid |
US7629360B2 (en) * | 1999-05-07 | 2009-12-08 | Celgene Corporation | Methods for the treatment of cachexia and graft v. host disease |
US6667316B1 (en) * | 1999-11-12 | 2003-12-23 | Celgene Corporation | Pharmaceutically active isoindoline derivatives |
US7182953B2 (en) | 1999-12-15 | 2007-02-27 | Celgene Corporation | Methods and compositions for the prevention and treatment of atherosclerosis restenosis and related disorders |
US6326388B1 (en) | 1999-12-21 | 2001-12-04 | Celgene Corporation | Substituted 1,3,4-oxadiazoles and a method of reducing TNF-alpha level |
US6699899B1 (en) * | 1999-12-21 | 2004-03-02 | Celgene Corporation | Substituted acylhydroxamic acids and method of reducing TNFα levels |
US20020022627A1 (en) * | 2000-03-31 | 2002-02-21 | Dannenberg Andrew J. | Inhibition of cyclooxygenase-2activity |
US8030343B2 (en) | 2000-06-08 | 2011-10-04 | Celgene Corporation | Pharmaceutically active isoindoline derivatives |
US7812169B2 (en) * | 2000-11-30 | 2010-10-12 | The Children's Medical Center Corporation | Method of synthesis of 4-amino-thalidomide enantiomers |
US7091353B2 (en) * | 2000-12-27 | 2006-08-15 | Celgene Corporation | Isoindole-imide compounds, compositions, and uses thereof |
US7491634B2 (en) * | 2006-04-28 | 2009-02-17 | Asm International N.V. | Methods for forming roughened surfaces and applications thereof |
US7208516B2 (en) * | 2002-03-20 | 2007-04-24 | Celgene Corporation | Methods of the treatment of psoriatic arthritis using (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione |
US7893101B2 (en) | 2002-03-20 | 2011-02-22 | Celgene Corporation | Solid forms comprising (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, compositions thereof, and uses thereof |
CN1965823B (zh) * | 2002-03-20 | 2010-05-12 | 细胞基因公司 | (+)-2-[1-(3-乙氧基-4-甲氧基苯基)-2-甲磺酰基乙基]-4-乙酰氨基异吲哚啉-1,3-二酮、其合成方法及其组合物 |
US7276529B2 (en) * | 2002-03-20 | 2007-10-02 | Celgene Corporation | Methods of the treatment or prevention of exercise-induced asthma using (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione |
US6962940B2 (en) | 2002-03-20 | 2005-11-08 | Celgene Corporation | (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof |
WO2003080048A1 (en) * | 2002-03-20 | 2003-10-02 | Celgene Corporation | (-)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof |
US7498171B2 (en) * | 2002-04-12 | 2009-03-03 | Anthrogenesis Corporation | Modulation of stem and progenitor cell differentiation, assays, and uses thereof |
US20050148034A1 (en) * | 2002-04-12 | 2005-07-07 | Hariri Robert J. | Methods for identification of modulators of angiogenesis, compounds discovered thereby, and methods of treatment using the compounds |
AU2003262187A1 (en) * | 2002-04-12 | 2003-10-27 | Celgene Corporation | Modulation of stem and progenitor cell differentiation, assays, and uses thereof |
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 |
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 |
US20100129363A1 (en) * | 2002-05-17 | 2010-05-27 | Zeldis Jerome B | Methods and compositions using pde4 inhibitors for the treatment and management of cancers |
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 |
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 |
EP1556033A4 (de) * | 2002-05-17 | 2006-05-31 | Celgene Corp | Verfahren und zusammensetzungen mit selektiven cytokin-hemmenden arzneimitteln zur behandlung und versorgung von krebs und anderen erkrankungen |
DE60331537D1 (de) * | 2002-05-17 | 2010-04-15 | Celgene Corp | Kombinationen zur behandlung von multiplem myelom |
AU2003281245A1 (en) * | 2002-07-02 | 2004-01-23 | Qlt Inc. | Compounds and methods for treating cancer and inflammation |
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 |
US8404717B2 (en) * | 2002-10-15 | 2013-03-26 | Celgene Corporation | Methods of treating myelodysplastic syndromes using lenalidomide |
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 |
CA2501936A1 (en) * | 2002-10-15 | 2004-04-29 | Celgene Corporation | Selective cytokine inhibitory drugs for treating myelodysplastic syndrome |
US20050203142A1 (en) * | 2002-10-24 | 2005-09-15 | Zeldis Jerome B. | Methods of using and compositions comprising immunomodulatory compounds for treatment, modification and management of pain |
US20040087558A1 (en) | 2002-10-24 | 2004-05-06 | Zeldis Jerome B. | Methods of using and compositions comprising selective cytokine inhibitory drugs for treatment, modification and management of pain |
US7776907B2 (en) * | 2002-10-31 | 2010-08-17 | Celgene Corporation | Methods for the treatment and management of macular degeneration using cyclopropyl-N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-3-oxoisoindoline-4-yl}carboxamide |
WO2004041181A2 (en) * | 2002-10-31 | 2004-05-21 | Celgene Corporation | Methods of using and compositions comprising selective cytokine inhibitory drugs for treatment and management of macular degeneration |
MXPA05004777A (es) * | 2002-11-06 | 2005-07-22 | Celgene Corp | Metodos de uso y composiciones que comprenden farmacos inhibidores selectivos de citocina para el tratamiento y el manejo de padecimientos mieloproliferativos. |
CN1735412A (zh) | 2002-11-06 | 2006-02-15 | 细胞基因公司 | 利用选择性细胞因子抑制药物治疗和控制癌症和其它疾病的方法和组合物 |
BR0316256A (pt) * | 2002-11-18 | 2005-10-04 | Celgene Corp | Métodos de inibir a produção de tnf-alfa e a atividade de pde4, de tratar ou prevenir uma doença ou um distúrbio, de controlar os nìveis de camp em uma célula e de produzir um composto, composição farmacêutica e composto |
AU2003294311B8 (en) * | 2002-11-18 | 2008-06-05 | Celgene Corporation | Method of using and compositions comprising (+)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide |
CA2511843C (en) * | 2002-12-30 | 2012-04-24 | Celgene Corporation | Fluoroalkoxy-substituted 1,3-dihydro-isoindolyl compounds and their pharmaceutical uses |
CA2517146A1 (en) * | 2003-03-03 | 2004-09-16 | F. Hoffmann-La Roche Ag | 2,5- and 2,6-substituted tetrahydroisoquinolines for use as 5-ht6 modulators |
US20040175382A1 (en) * | 2003-03-06 | 2004-09-09 | Schafer Peter H. | Methods of using and compositions comprising selective cytokine inhibitory drugs for the treatment and management of disorders of the central nervous system |
KR100831545B1 (ko) * | 2003-03-06 | 2008-05-21 | 셀진 코포레이션 | 중추 신경계 장애의 치료 또는 관리를 위한 선택적사이토카인 억제 약물의 사용 방법 및 그를 포함하는조성물 |
NZ542671A (en) * | 2003-03-12 | 2008-12-24 | Celgene Corp | 7-Amido-isoindolyl compounds and their pharmaceutical uses |
NZ544687A (en) * | 2003-06-23 | 2009-06-26 | Bellus Health Int Ltd | Treatment of amyloid- and epileptogenesis-associated diseases |
US7320992B2 (en) * | 2003-08-25 | 2008-01-22 | Amgen Inc. | Substituted 2,3-dihydro-1h-isoindol-1-one derivatives and methods of use |
US20050187278A1 (en) * | 2003-08-28 | 2005-08-25 | Pharmacia Corporation | Treatment or prevention of vascular disorders with Cox-2 inhibitors in combination with cyclic AMP-specific phosphodiesterase inhibitors |
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 |
JP2007524656A (ja) * | 2003-10-23 | 2007-08-30 | セルジーン・コーポレーション | 疼痛を治療、改変および管理するための選択的サイトカイン阻害薬を含む組成物ならびにその使用方法 |
AU2004288714A1 (en) * | 2003-11-06 | 2005-05-26 | Celgene Corporation | Methods and compositions using thalidomide for the treatment and management of cancers and other diseases. |
US20050142104A1 (en) * | 2003-11-06 | 2005-06-30 | Zeldis Jerome B. | Methods of using and compositions comprising PDE4 modulators for the treatment and management of asbestos-related diseases and disorders |
EP2065383A1 (de) | 2003-11-19 | 2009-06-03 | Signal Pharmaceuticals, Inc. | Indazolverbindungen und Verwendungsverfahren davon als Proteinkinasehemmer |
EP1694328A4 (de) * | 2003-12-02 | 2010-02-17 | Celgene Corp | Verfahren und zusammensetzungen zur behandlung und versorgung von hämoglobinopathie und anämie |
BRPI0418743A (pt) * | 2004-04-14 | 2007-09-18 | Celgene Corp | métodos de tratamento, prevenção ou controle de uma sìndrome mielodisplásica, de redução ou evitação de um efeito adverso associado com a administração de um segundo ingrediente ativo em um paciente sofrendo de uma sìndrome mielodisplásica, composição farmacêutica, forma de dosagem unitária única, e, kit |
EP1744749A4 (de) * | 2004-04-14 | 2009-04-22 | Celgene Corp | Verfahren zur verwendung von und zusammensetzungen mit immunomodulatorischen verbindungen zur behandlung und versorgung von myelodysplastischen syndromen |
CA2563377A1 (en) * | 2004-04-23 | 2005-11-03 | Celgene Corporation | Methods of using and compositions comprising pde4 modulators for the treatment and management of pulmonary hypertension |
CN1984652A (zh) * | 2004-05-05 | 2007-06-20 | 细胞基因公司 | 使用选择性细胞因子抑制药治疗和控制骨髓增生性疾病的方法和组合物 |
US7244759B2 (en) * | 2004-07-28 | 2007-07-17 | Celgene Corporation | Isoindoline compounds and methods of making and using the same |
US20070190070A1 (en) * | 2004-09-03 | 2007-08-16 | Zeldis Jerome B | Methods of using and compositions comprising selective cytokine inhibitory drugs for the treatment and management of disorders of the central nervous system |
JP2008518924A (ja) | 2004-10-28 | 2008-06-05 | セルジーン・コーポレーション | 中枢神経系損傷の治療及び管理のためのpde4モジュレータを使用する方法及び組成物 |
JP2008523102A (ja) * | 2004-12-13 | 2008-07-03 | セルジーン・コーポレーション | Pde4モジュレーターを含有する組成物及び気道炎症の治療又は予防のためのそれらの使用 |
US20060270707A1 (en) * | 2005-05-24 | 2006-11-30 | Zeldis Jerome B | Methods and compositions using 4-[(cyclopropanecarbonylamino)methyl]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione for the treatment or prevention of cutaneous lupus |
US20080138295A1 (en) * | 2005-09-12 | 2008-06-12 | Celgene Coporation | Bechet's disease using cyclopropyl-N-carboxamide |
US20070155791A1 (en) * | 2005-12-29 | 2007-07-05 | Zeldis Jerome B | Methods for treating cutaneous lupus using aminoisoindoline compounds |
TW200804347A (en) * | 2006-01-10 | 2008-01-16 | Janssen Pharmaceutica Nv | Urotensin II receptor antagonists |
AU2007281591A1 (en) | 2006-07-31 | 2008-02-07 | Janssen Pharmaceutica, N.V. | Urotensin II receptor antagonists |
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. |
PA8782701A1 (es) | 2007-06-07 | 2009-01-23 | Janssen Pharmaceutica Nv | Antagonistas del receptor de urotensina ii |
US7893045B2 (en) | 2007-08-07 | 2011-02-22 | Celgene Corporation | Methods for treating lymphomas in certain patient populations and screening patients for said therapy |
CN102036663A (zh) * | 2008-03-24 | 2011-04-27 | 细胞基因公司 | 用环丙基-n-{2-[(1s)-1-(3-乙氧基-4-甲氧基苯基)-2-(甲磺酰基)乙基]-3-氧代异吲哚啉-4基}甲酰胺治疗银屑病或者银屑病关节炎 |
EP2687213B1 (de) | 2008-03-27 | 2019-01-23 | Celgene Corporation | (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindolin-1,3-dion umfassende feste Formen, Zusammensetzungen daraus und ihre Verwendungszwecke |
EP2695616A1 (de) | 2008-03-27 | 2014-02-12 | Celgene Corporation | (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindolin-1,3-dion umfassende feste Formen, Zusammensetzungen daraus und ihre Verwendungszwecke |
US9079896B2 (en) * | 2008-08-02 | 2015-07-14 | Janssen Pharmaceutica Nv | Urotensin II receptor antagonists |
JP5513508B2 (ja) * | 2008-09-10 | 2014-06-04 | セルジーン コーポレイション | アミノスルホン化合物を調製するためのプロセス |
MY160002A (en) | 2009-02-10 | 2017-02-15 | Celgene Corp | Methods of using and compositions comprising pde4 modulators for treatment, prevention and management of tuberculosis |
CN107964016B (zh) | 2009-05-14 | 2021-10-01 | 天津合美医药科技有限公司 | 噻吩衍生物 |
ES2469849T3 (es) | 2009-06-18 | 2014-06-20 | Concert Pharmaceuticals Inc. | Derivados deuterados de isoindolin-1,3-diona como inhibidores de PDE4 y TNF-alfa |
CA2775581A1 (en) | 2009-10-09 | 2011-04-14 | Celgene Corporation | Processes for the preparation of 2-(1-phenylethyl)isoindolin-1-one compounds |
MX341050B (es) | 2010-04-07 | 2016-08-05 | Celgene Corp * | Metodos para tratar infeccion viral respiratoria. |
MX341896B (es) | 2010-06-15 | 2016-09-07 | Celgene Corp * | Biomarcadores para el tratamiento de psoriasis. |
WO2012083153A1 (en) * | 2010-12-16 | 2012-06-21 | Nektar Therapeutics | Oligomer-containing apremilast moiety compounds |
CN102558022B (zh) * | 2010-12-22 | 2016-06-15 | 康塞特医药品有限公司 | 取代的异吲哚啉-1,3二酮衍生物 |
MX347928B (es) * | 2011-01-10 | 2017-05-19 | Celgene Corp | Derivados de fenetilsulfona isoindolina y su uso. |
US9045417B2 (en) | 2011-01-14 | 2015-06-02 | Celgene Corporation | Isotopologues of isoindole derivatives |
US9387195B2 (en) | 2011-03-07 | 2016-07-12 | Celgene Corporation | Methods for treating diseases using isoindoline compounds |
US9272035B2 (en) | 2011-04-28 | 2016-03-01 | Celgene Corporation | Methods and compositions using PDE4 inhibitors for the treatment and management of autoimmune and inflammatory diseases |
PT2797581T (pt) | 2011-12-27 | 2020-06-18 | Amgen Europe Gmbh | Formulações de (+)-2-[1-(3-etoxi-4-metoxi-fenil)-2-metanossulfonil-etil]-4-acetilaminoisoindolino-1,3-diona |
AR090100A1 (es) | 2012-02-21 | 2014-10-22 | Celgene Corp | Procesos para la preparacion de la (s)-1-(3-etoxi-4-metoxifenil)-2-metanosulfoniletilamina |
EP2730278A1 (de) | 2012-11-08 | 2014-05-14 | Ratiopharm GmbH | Zusammensetzungsschmelze |
WO2014151180A1 (en) | 2013-03-14 | 2014-09-25 | Celgene Corporation | Treatment of psoriatic arthritis using apremilast |
WO2014204825A1 (en) | 2013-06-17 | 2014-12-24 | Celgene Corporation | Tablet formulations of (+)-2-[1 -(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione |
IN2014MU01283A (de) | 2014-04-04 | 2015-10-09 | Cadila Healthcare Ltd | |
WO2015173792A1 (en) | 2014-05-11 | 2015-11-19 | Mapi Pharma Ltd. | Amorphous form of apremilast |
WO2015175773A1 (en) | 2014-05-15 | 2015-11-19 | Celgene Corporation | Use of pde4 inhibitors and combinations thereof for the treatment of cystic fibrosis |
US20170087129A1 (en) | 2014-05-16 | 2017-03-30 | Celgene Corporation | Compositions and methods for the treatment of atherosclerotic cardiovascular diseases with pde4 modulators |
EP2949645A1 (de) | 2014-05-28 | 2015-12-02 | LEK Pharmaceuticals d.d. | Verfahren zur Herstellung von ß-Aminosulfonverbindungen |
US10300042B2 (en) | 2014-06-23 | 2019-05-28 | Celgene Corporation | Apremilast for the treatment of a liver disease or a liver function abnormality |
US10092541B2 (en) | 2014-08-15 | 2018-10-09 | Celgene Corporation | Methods for the treatment of diseases ameliorated by PDE4 inhibition using dosage titration of apremilast |
ES2940302T3 (es) | 2014-08-22 | 2023-05-05 | Celgene Corp | Métodos para tratar el mieloma múltiple con compuestos inmunomoduladores en combinación con anticuerpos |
CN105461610B (zh) * | 2014-09-10 | 2018-04-13 | 杭州普晒医药科技有限公司 | 一种阿普斯特的晶型及其制备方法、药物组合物和用途 |
CN104761484B (zh) * | 2014-11-24 | 2018-03-27 | 上海优拓医药科技有限公司 | 一种稳定的不含溶剂化物的阿普司特晶型ii及其制备方法 |
CN104496886A (zh) * | 2014-12-11 | 2015-04-08 | 杭州新博思生物医药有限公司 | 一种高纯度阿普斯特b晶型的制备方法 |
CN107635962A (zh) | 2015-03-19 | 2018-01-26 | 印度商西伯拉有限公司 | 用于制备阿普斯特的改进工艺 |
EP3280701B1 (de) | 2015-04-09 | 2019-10-16 | Zentiva K.S. | Verfahren zur chiralen auflösung des schlüsselintermediats der synthese von apremilast und dessen verwendung zur herstellung von reinem apremilast |
EP3286168A1 (de) | 2015-04-24 | 2018-02-28 | Zentiva K.S. | Feste form von apremilast und verfahren zu ihrer herstellung |
WO2016174685A1 (en) | 2015-04-27 | 2016-11-03 | Mylan Laboratories Limited | Process for the enantiomeric resolution of apremilast intermediates |
CN104945306B (zh) * | 2015-05-25 | 2017-07-21 | 山东铭康医药技术有限公司 | 制备光学纯阿普斯特的方法 |
CZ2015383A3 (cs) | 2015-06-05 | 2016-12-14 | Zentiva, K.S. | Způsob přípravy klíčového intermediátu apremilastu, využívající enzymatické štěpení racemických aminů |
EP3106457A1 (de) | 2015-06-15 | 2016-12-21 | LEK Pharmaceuticals d.d. | Neuartiger synthetischer pfad zu apremilast |
ES2970117T3 (es) | 2015-06-26 | 2024-05-27 | Celgene Corp | Métodos para el tratamiento de sarcoma de Kaposi o linfoma inducido por KSHV usando compuestos inmunomoduladores, y usos de biomarcadores |
EP3144393A1 (de) | 2015-09-18 | 2017-03-22 | LEK Pharmaceuticals d.d. | Synthetischer pfad zu apremilast |
WO2017059040A1 (en) | 2015-09-29 | 2017-04-06 | Pliva Hrvatska D.O.O. | Processes for the preparation of apremilast and intermediates thereof |
US10682336B2 (en) | 2015-10-21 | 2020-06-16 | Amgen Inc. | PDE4 modulators for treating and preventing immune reconstitution inflammatory syndrome (IRIS) |
WO2017085568A1 (en) * | 2015-11-19 | 2017-05-26 | Alembic Pharmaceuticals Limited | An improved process and novel polymorphic form of apremilast |
CN105294533A (zh) * | 2015-12-02 | 2016-02-03 | 宋彤云 | 一种治疗骨病的药物组合物 |
WO2017179065A1 (en) | 2016-04-15 | 2017-10-19 | Davuluri Ramamohan Rao | Improved process for the preparation of apremilast |
WO2017216738A1 (en) | 2016-06-15 | 2017-12-21 | Torrent Pharmaceuticals Limited | Topical compositions of apremilast |
US10196355B2 (en) | 2016-06-20 | 2019-02-05 | Johnson Matthey Public Limited Company | Forms of apremilast |
CN106543050B (zh) * | 2016-09-28 | 2018-04-10 | 中南大学湘雅医院 | 一种阿普斯特中间体的合成工艺 |
KR102318401B1 (ko) * | 2017-02-28 | 2021-10-29 | 강푸 바이오파마슈티칼즈 리미티드 | 신규한 이소인돌린 유도체, 이의 약학 조성물 및 용도 |
ES2866476T3 (es) | 2017-04-04 | 2021-10-19 | Quim Sintetica S A | Compuestos de beta-aminosulfona racémicos |
WO2018184936A1 (en) | 2017-04-04 | 2018-10-11 | Quimica Sintetica, S. A. | Resolution of racemic beta-aminosulfone compounds |
EP3619195A4 (de) | 2017-05-04 | 2020-12-02 | Unichem Laboratories Ltd | Neues verfahren zur herstellung von n-[2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1h-isoindol-4-yl]acetamid |
CN109422671B (zh) * | 2017-08-31 | 2022-06-07 | 重庆医药工业研究院有限责任公司 | 一种阿普斯特中间体的制备方法 |
US20200254093A1 (en) | 2017-09-14 | 2020-08-13 | Glaxosmithkline Intellectual Property Development Limited | Combination treatment for cancer |
AU2018357775B2 (en) | 2017-10-23 | 2024-02-15 | Boehringer Ingelheim International Gmbh | New combination of active agents for the treatment of progressive fibrosing interstitial lung diseases (PF-ILD) |
WO2019142124A1 (en) | 2018-01-17 | 2019-07-25 | Cadila Healthcare Limited | Pharmaceutical compositions for treatment of vitiligo |
EP3789387B1 (de) * | 2018-05-02 | 2024-02-28 | Tianjin Hemay Pharmaceutical Co., Ltd. | Kristallformen von (s)-n-[5-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4,6-dioxo-5,6-dihydro-4h-thieno[3,4-c]pyrrole-1-yl]acetamide |
WO2020020101A1 (zh) * | 2018-07-22 | 2020-01-30 | 上海星叶医药科技有限公司 | 苯并异硒唑酮胺类化合物及其制备方法和用途 |
CN110423213B (zh) * | 2019-08-22 | 2021-06-04 | 上海英诺富成生物科技有限公司 | 一种阿普斯特衍生物及其制备方法与应用 |
EP3929179A1 (de) | 2020-06-22 | 2021-12-29 | Biohorm, S.L. | Entzündungshemmende verbindungen und verfahren zu deren herstellung |
CA3187693A1 (en) * | 2020-07-30 | 2022-02-03 | Zheng Huang | Drug conjugates comprising apremilast, and a nitric oxide-releasing moiety and uses thereof |
CN114790164B (zh) | 2021-08-13 | 2022-12-27 | 苏州璞正医药有限公司 | 一种取代的异吲哚啉-1,3-二酮类pde4抑制剂及其药物用途 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4173652A (en) * | 1976-12-18 | 1979-11-06 | Akzona Incorporated | Pharmaceutical hydroxamic acid compositions and uses thereof |
SE434638B (sv) * | 1980-06-06 | 1984-08-06 | Lekemedelsfabriken Medica Ab | Nya terapeutiska verdefulla taurinderivat och deras framstellning |
US4820828A (en) * | 1987-03-04 | 1989-04-11 | Ortho Pharmaceutical Corporation | Cinnamohydroxamic acids |
US5236917A (en) * | 1989-05-04 | 1993-08-17 | Sterling Winthrop Inc. | Saccharin derivatives useful as proteolytic enzyme inhibitors and compositions and method of use thereof |
US5463063A (en) * | 1993-07-02 | 1995-10-31 | Celgene Corporation | Ring closure of N-phthaloylglutamines |
US5698579A (en) * | 1993-07-02 | 1997-12-16 | Celgene Corporation | Cyclic amides |
US5703098A (en) * | 1994-12-30 | 1997-12-30 | Celgene Corporation | Immunotherapeutic imides/amides |
CA2227237C (en) * | 1995-07-26 | 2005-12-13 | Pfizer Inc. | N-(aroyl)glycine hydroxamic acid derivatives and related compounds |
US5728844A (en) * | 1995-08-29 | 1998-03-17 | Celgene Corporation | Immunotherapeutic agents |
US5728845A (en) * | 1995-08-29 | 1998-03-17 | Celgene Corporation | Immunotherapeutic nitriles |
US5658940A (en) * | 1995-10-06 | 1997-08-19 | Celgene Corporation | Succinimide and maleimide cytokine inhibitors |
PT871439E (pt) * | 1996-01-02 | 2004-08-31 | Aventis Pharma Inc | Compostos do acido hidroxamico substituidos (arilo heteroarilo arilmetilo ou heteroarilmetilo) |
-
1998
- 1998-10-30 US US09/183,049 patent/US6020358A/en not_active Expired - Lifetime
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