ES2233488T3 - 1,2,3-oxadisazoles sustituidos y un metodo para reducir los niveles de tnf-alfa. - Google Patents
1,2,3-oxadisazoles sustituidos y un metodo para reducir los niveles de tnf-alfa.Info
- Publication number
- ES2233488T3 ES2233488T3 ES00986568T ES00986568T ES2233488T3 ES 2233488 T3 ES2233488 T3 ES 2233488T3 ES 00986568 T ES00986568 T ES 00986568T ES 00986568 T ES00986568 T ES 00986568T ES 2233488 T3 ES2233488 T3 ES 2233488T3
- Authority
- ES
- Spain
- Prior art keywords
- hydrogen
- ethyl
- methoxyphenyl
- oxadiazole
- oxadiazol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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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Landscapes
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Photoreceptors In Electrophotography (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Electrochromic Elements, Electrophoresis, Or Variable Reflection Or Absorption Elements (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
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| US09/470,203 US6326388B1 (en) | 1999-12-21 | 1999-12-21 | Substituted 1,3,4-oxadiazoles and a method of reducing TNF-alpha level |
| US470203 | 1999-12-21 |
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| ES2233488T3 true ES2233488T3 (es) | 2005-06-16 |
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| ES04003830T Expired - Lifetime ES2333011T3 (es) | 1999-12-21 | 2000-12-19 | 1,3,4-oxadiazoles sustituidos y un metodo para reducir los niveles de tnf-alfa. |
| ES04020108T Expired - Lifetime ES2356238T3 (es) | 1999-12-21 | 2000-12-19 | 1,3,4-oxadiazoles sustituidos para uso en el tratamiento o la profilaxis de enfermedades. |
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| Application Number | Title | Priority Date | Filing Date |
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| ES04003830T Expired - Lifetime ES2333011T3 (es) | 1999-12-21 | 2000-12-19 | 1,3,4-oxadiazoles sustituidos y un metodo para reducir los niveles de tnf-alfa. |
| ES04020108T Expired - Lifetime ES2356238T3 (es) | 1999-12-21 | 2000-12-19 | 1,3,4-oxadiazoles sustituidos para uso en el tratamiento o la profilaxis de enfermedades. |
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| US6429221B1 (en) * | 1994-12-30 | 2002-08-06 | Celgene Corporation | Substituted imides |
| RU2188819C2 (ru) * | 1996-08-12 | 2002-09-10 | Селджин Корпорейшн | НОВЫЕ ИММУНОТЕРАПЕВТИЧЕСКИЕ СОЕДИНЕНИЯ, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ СНИЖЕНИЯ УРОВНЕЙ ФДЭ, TNFα И NFκB |
| AU2002253795B2 (en) | 2000-11-30 | 2007-02-01 | The Children's Medical Center Corporation | Synthesis of 4-Amino-Thalidomide enantiomers |
| EP1556033A4 (en) | 2002-05-17 | 2006-05-31 | Celgene Corp | METHODS AND COMPOSITIONS USING CYTOKINE INHIBITOR SELECTIVE MEDICAMENTS FOR THE TREATMENT AND MANAGEMENT OF CANCERS AND OTHER DISEASES |
| 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 |
| 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 |
| KR20050043923A (ko) * | 2002-09-16 | 2005-05-11 | 알콘 매뉴팩츄어링, 리미티드 | 혈관신생 치료를 위한 ｐｄｅ-ⅳ 저해제의 용도 |
| JP2006510606A (ja) * | 2002-10-15 | 2006-03-30 | セルジーン・コーポレーション | 骨髄異形成症候群を治療および管理するための選択的サイトカイン阻害剤の使用方法およびそれを含む組成物 |
| 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 |
| NZ540384A (en) * | 2002-11-06 | 2008-06-30 | Celgene Corp | Methods of using and compositions comprising selective cytokine inhibitory drugs for the treatment and management of myeloproliferative diseases |
| EP1567154A4 (en) | 2002-11-06 | 2006-05-31 | Celgene Corp | METHODS AND COMPOSITIONS USING CYTOKINE SELECTIVE INHIBITION DRUGS FOR TREATING AND CONTROLLING CANCERS AND OTHER DISEASES |
| WO2004054501A2 (en) * | 2002-11-18 | 2004-07-01 | Celgene Corporation | Methods of usig and compositions comprising (-)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide |
| JP2006510617A (ja) * | 2002-11-18 | 2006-03-30 | セルジーン・コーポレーション | （＋）−３−（３，４−ジメトキシ−フェニル）−３−（１−オキソ−１，３−ジヒドロ−イソインドール−２−イル）−プロピオンアミドの使用方法およびそれを含む組成物 |
| DE60330187D1 (de) * | 2002-12-30 | 2009-12-31 | Celgene Corp | Fluoralkoxy-substituierte 1, 3-dihydro-isoindolyl-verbindungen und ihre pharmazeutischen verwendungen |
| 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 |
| 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 |
| 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 |
| WO2005046593A2 (en) * | 2003-11-06 | 2005-05-26 | Celgene Corporation | Methods and compositions using thalidomide for the treatment and management of cancers and other diseases. |
| AU2004293443A1 (en) | 2003-11-19 | 2005-06-09 | Signal Pharmaceuticals, Llc. | Indazole Compounds and methods of use thereof as protein kinase inhibitors |
| EP1744748A4 (en) * | 2004-04-14 | 2009-08-12 | Celgene Corp | METHOD FOR USE OF SELECTIVE CYTOKINE-INHIBITORY MEDICAMENTS AND COMPOSITIONS CONTAINING THEREOF FOR THE TREATMENT AND SUPPLY OF MYELODYSPLASTIC SYNDROMES |
| US20050239867A1 (en) * | 2004-04-23 | 2005-10-27 | Zeldis Jerome B | Methods of using and compositions comprising PDE4 modulators for the treatment and management of pulmonary hypertension |
| US7405237B2 (en) * | 2004-07-28 | 2008-07-29 | Celgene Corporation | Isoindoline compounds and methods of their use |
| 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 |
| ZA200704251B (en) * | 2004-10-28 | 2008-11-26 | Celgene Corp | Methods and compositions using PDE4 modulators for treatment and management of central nervous injury |
| 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 |
| 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. |
| WO2009020590A1 (en) * | 2007-08-07 | 2009-02-12 | Celgene Corporation | Methods for treating lymphomas in certain patient populations and screening patients for said therapy |
| EP2296683B1 (en) * | 2008-06-03 | 2017-01-25 | University Of Rochester | AvrA PROTEIN FOR TREATING INFLAMMATORY INTESTINAL DISEASE AND MANAGING SYMPTOMS THEREOF |
| US8563580B2 (en) | 2008-09-23 | 2013-10-22 | Georgetown University | Flavivirus inhibitors and methods for their use |
| WO2010039545A2 (en) * | 2008-09-23 | 2010-04-08 | Georgetown University | 1,2-benzisothiazolinone and isoindolinone derivatives |
| PE20120580A1 (es) | 2009-02-10 | 2012-05-23 | Celgene Corp | Metodos para utilizar y composiciones que comprenden moduladores pde4 para tratamiento, prevencion y control de tuberculosis |
| ES2739973T3 (es) * | 2009-05-29 | 2020-02-05 | Merck Sharp & Dohme | Inhibidores de PDE10 radiomarcados |
| MX341050B (es) | 2010-04-07 | 2016-08-05 | Celgene Corp * | Metodos para tratar infeccion viral respiratoria. |
| US20110318741A1 (en) | 2010-06-15 | 2011-12-29 | Schafer Peter H | Biomarkers for the treatment of psoriasis |
| US9428472B2 (en) | 2011-08-16 | 2016-08-30 | Georgetown University | Methods of treating bacterial infections with 1,2-benzisothiazolinone and isoindolinone derivatives |
| US20170087129A1 (en) | 2014-05-16 | 2017-03-30 | Celgene Corporation | Compositions and methods for the treatment of atherosclerotic cardiovascular diseases with pde4 modulators |
| KR20170042598A (ko) | 2014-08-22 | 2017-04-19 | 셀진 코포레이션 | 항체와 조합된 면역조절 화합물을 이용하여 다발성 골수종을 치료하는 방법 |
| JP2018527302A (ja) | 2015-06-26 | 2018-09-20 | セルジーン コーポレイション | 免疫調節化合物を用いたカポジ肉腫またはｋｓｈｖ誘発性リンパ腫の治療方法、及びバイオマーカーの使用 |
| WO2017070291A1 (en) | 2015-10-21 | 2017-04-27 | Celgene Corporation | Pde4 modulators for treating and preventing immune reconstitution inflammatory syndrome (iris) |
| CN107698484B (zh) * | 2017-11-13 | 2020-05-19 | 广东中科药物研究有限公司 | 一种来那度胺的衍生物的制备方法与应用 |
| CN110386893B (zh) | 2018-04-17 | 2025-07-11 | 天津合美医药科技有限公司 | 异吲哚衍生物 |
| WO2020060963A1 (en) * | 2018-09-18 | 2020-03-26 | Alxerion Biotech Corp. | 1, 3, 4-oxadiazole derivatives and uses thereof |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
| SK280193B6 (sk) * | 1992-04-07 | 1999-09-10 | Pfizer Inc. | Indolové deriváty predstavujúce 5-ht1 agonisty, fa |
| 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 |
| US5605914A (en) | 1993-07-02 | 1997-02-25 | Celgene Corporation | Imides |
| FR2712886B1 (fr) * | 1993-11-26 | 1996-01-05 | Synthelabo | Dérivés de 1,3,4-oxadiazol-2(3H)-one, leur préparation et leur application en thérapeutique. |
| JPH07278125A (ja) * | 1994-03-31 | 1995-10-24 | Nippon Chemiphar Co Ltd | アルキレンジアミン誘導体 |
| US5703098A (en) | 1994-12-30 | 1997-12-30 | Celgene Corporation | Immunotherapeutic imides/amides |
| US6429221B1 (en) * | 1994-12-30 | 2002-08-06 | Celgene Corporation | Substituted imides |
| US5801195A (en) | 1994-12-30 | 1998-09-01 | Celgene Corporation | Immunotherapeutic aryl amides |
| NZ305940A (en) | 1995-07-26 | 1999-05-28 | Pfizer | N-(aroyl)glycine hydroxamic acid derivatives and related compounds that inhibit the production of tnf and are useful in treating asthma |
| 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 |
| US5670526A (en) * | 1995-12-21 | 1997-09-23 | Otsuka Pharmaceutical Co., Ltd. | 1,3,4-oxadiazoles |
| JP4358908B2 (ja) | 1996-01-02 | 2009-11-04 | アヴェンティス ファーマシューティカルズ インコーポレイテッド | 置換（アリール、ヘテロアリール、アリールメチル又はヘテロアリールメチル）ヒドロキサム酸化合物 |
| RU2188819C2 (ru) | 1996-08-12 | 2002-09-10 | Селджин Корпорейшн | НОВЫЕ ИММУНОТЕРАПЕВТИЧЕСКИЕ СОЕДИНЕНИЯ, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ СНИЖЕНИЯ УРОВНЕЙ ФДЭ, TNFα И NFκB |
| JP2921760B2 (ja) * | 1997-05-21 | 1999-07-19 | 日本たばこ産業株式会社 | フタルイミド誘導体及びそれら誘導体を含んでなる医薬 |
| EP1049693A1 (en) * | 1997-11-26 | 2000-11-08 | Du Pont Pharmaceuticals Company | 1,3,4-THIADIAZOLES AND 1,3,4-OXADIAZOLES AS $g(a) v?$g(b) 3? ANTAGONISTS |
| US6034113A (en) * | 1998-01-29 | 2000-03-07 | Bristol-Myers Squibb Company | Derivatives of 1,3,4-oxadiazolone |
| US6020358A (en) | 1998-10-30 | 2000-02-01 | Celgene Corporation | Substituted phenethylsulfones and method of reducing TNFα levels |
-
1999
- 1999-12-21 US US09/470,203 patent/US6326388B1/en not_active Expired - Lifetime
-
2000
- 2000-12-11 TW TW095138294A patent/TW200733960A/zh unknown
- 2000-12-11 TW TW089125923A patent/TWI280961B/zh not_active IP Right Cessation
- 2000-12-19 DE DE60042902T patent/DE60042902D1/de not_active Expired - Lifetime
- 2000-12-19 NZ NZ529009A patent/NZ529009A/en not_active IP Right Cessation
- 2000-12-19 ES ES00986568T patent/ES2233488T3/es not_active Expired - Lifetime
- 2000-12-19 DE DE60016029T patent/DE60016029T2/de not_active Expired - Lifetime
- 2000-12-19 EP EP04003830A patent/EP1462449B9/en not_active Expired - Lifetime
- 2000-12-19 KR KR1020027007983A patent/KR100832499B1/ko not_active Expired - Fee Related
- 2000-12-19 WO PCT/US2000/034457 patent/WO2001046183A1/en not_active Ceased
- 2000-12-19 CA CA002394615A patent/CA2394615C/en not_active Expired - Fee Related
- 2000-12-19 AT AT04020108T patent/ATE489996T1/de not_active IP Right Cessation
- 2000-12-19 ES ES04003830T patent/ES2333011T3/es not_active Expired - Lifetime
- 2000-12-19 MX MXPA02006084A patent/MXPA02006084A/es active IP Right Grant
- 2000-12-19 EP EP00986568A patent/EP1242413B1/en not_active Expired - Lifetime
- 2000-12-19 EP EP04020108A patent/EP1510518B1/en not_active Expired - Lifetime
- 2000-12-19 JP JP2001547093A patent/JP4806151B2/ja not_active Expired - Fee Related
- 2000-12-19 KR KR1020077008998A patent/KR20070049688A/ko not_active Ceased
- 2000-12-19 AT AT04003830T patent/ATE441644T1/de not_active IP Right Cessation
- 2000-12-19 PT PT00986568T patent/PT1242413E/pt unknown
- 2000-12-19 CN CN00817536A patent/CN1413211A/zh active Pending
- 2000-12-19 ES ES04020108T patent/ES2356238T3/es not_active Expired - Lifetime
- 2000-12-19 DE DE60045320T patent/DE60045320D1/de not_active Expired - Lifetime
- 2000-12-19 HK HK03101117.3A patent/HK1050522B/en not_active IP Right Cessation
- 2000-12-19 AT AT00986568T patent/ATE282612T1/de active
- 2000-12-19 AU AU22785/01A patent/AU782168B2/en not_active Ceased
-
2002
- 2002-06-18 NO NO20022937A patent/NO323449B1/no not_active IP Right Cessation
- 2002-06-19 FI FI20021192A patent/FI121708B/fi not_active IP Right Cessation
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