NO323515B1 - Substituerte acylhydroksamsyrer samt fremgangsmate for a redusere tnftalfa-nivaet - Google Patents
Substituerte acylhydroksamsyrer samt fremgangsmate for a redusere tnftalfa-nivaet Download PDFInfo
- Publication number
- NO323515B1 NO323515B1 NO20022936A NO20022936A NO323515B1 NO 323515 B1 NO323515 B1 NO 323515B1 NO 20022936 A NO20022936 A NO 20022936A NO 20022936 A NO20022936 A NO 20022936A NO 323515 B1 NO323515 B1 NO 323515B1
- Authority
- NO
- Norway
- Prior art keywords
- methoxyphenyl
- propanoylamino
- isomer
- dioxoisoindolin
- ethoxy
- Prior art date
Links
- -1 acyl hydroxamic acids Chemical class 0.000 title description 41
- 238000000034 method Methods 0.000 title description 37
- 150000001875 compounds Chemical class 0.000 claims description 55
- 239000001257 hydrogen Substances 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
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- 239000000203 mixture Substances 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 28
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
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- RKUKMEJKLRORIR-UHFFFAOYSA-N [[3-(1,3-dioxoisoindol-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoyl]amino] propanoate Chemical group C1=C(OC)C(OCC)=CC(C(CC(=O)NOC(=O)CC)N2C(C3=CC=CC=C3C2=O)=O)=C1 RKUKMEJKLRORIR-UHFFFAOYSA-N 0.000 claims description 10
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- C—CHEMISTRY; METALLURGY
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- 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
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- C07D401/12—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 linked by a chain containing hetero atoms as chain links
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
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US09/468,529 US6699899B1 (en) | 1999-12-21 | 1999-12-21 | Substituted acylhydroxamic acids and method of reducing TNFα levels |
PCT/US2000/034455 WO2001045702A1 (en) | 1999-12-21 | 2000-12-19 | SUBSTITUTED ACYLHYDROXAMIC ACIDS AND METHOD OF REDUCING TNFα LEVELS |
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NO20022936A NO323515B1 (no) | 1999-12-21 | 2002-06-18 | Substituerte acylhydroksamsyrer samt fremgangsmate for a redusere tnftalfa-nivaet |
NO20071498A NO20071498L (no) | 1999-12-21 | 2007-03-21 | Substituerte acylhydroksamsyrer samt fremgangsmate for a redusere TNFa-nivaet |
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NO20071498A NO20071498L (no) | 1999-12-21 | 2007-03-21 | Substituerte acylhydroksamsyrer samt fremgangsmate for a redusere TNFa-nivaet |
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EP (1) | EP1246620A4 (ja) |
JP (1) | JP2003518060A (ja) |
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CN (1) | CN1413109A (ja) |
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FI (1) | FI20021193A (ja) |
HK (1) | HK1050625A1 (ja) |
MX (1) | MXPA02005840A (ja) |
NO (2) | NO323515B1 (ja) |
NZ (1) | NZ519638A (ja) |
TW (2) | TWI295925B (ja) |
WO (1) | WO2001045702A1 (ja) |
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Publication number | Priority date | Publication date | Assignee | Title |
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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 |
CZ299810B6 (cs) * | 1996-08-12 | 2008-12-03 | Celgene Corporation | Substituovaná aromatická sloucenina a její použití pro snížení hladiny cytokinu |
US6699899B1 (en) * | 1999-12-21 | 2004-03-02 | Celgene Corporation | Substituted acylhydroxamic acids and method of reducing TNFα levels |
US8030343B2 (en) * | 2000-06-08 | 2011-10-04 | Celgene Corporation | Pharmaceutically active isoindoline derivatives |
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 |
US20100129363A1 (en) * | 2002-05-17 | 2010-05-27 | Zeldis Jerome B | Methods and compositions using pde4 inhibitors for the treatment and management of cancers |
CA2501936A1 (en) * | 2002-10-15 | 2004-04-29 | Celgene Corporation | Selective cytokine inhibitory drugs for treating myelodysplastic syndrome |
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 |
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 |
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 |
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 |
CA2511843C (en) * | 2002-12-30 | 2012-04-24 | Celgene Corporation | Fluoroalkoxy-substituted 1,3-dihydro-isoindolyl compounds and their pharmaceutical uses |
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 |
WO2004080422A2 (en) * | 2003-03-12 | 2004-09-23 | Celgene Corporation | N-alkyl-hydroxamic acid-isoindolyl compounds and their pharmaceutical uses |
NZ542671A (en) * | 2003-03-12 | 2008-12-24 | Celgene Corp | 7-Amido-isoindolyl compounds and their pharmaceutical uses |
CN100427465C (zh) * | 2003-03-12 | 2008-10-22 | 细胞基因公司 | N-烷基-异羟肟酸-异吲哚基化合物及其药物用途 |
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 |
CN101010298A (zh) * | 2004-04-05 | 2007-08-01 | 默克Hdac研究有限责任公司 | 组蛋白脱乙酰酶抑制剂前药 |
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 |
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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 |
WO2007134169A2 (en) * | 2006-05-10 | 2007-11-22 | Nuada, Llc | Indole, benzimidazole, and benzolactam boronic acid compounds, analogs thereof and methods of use thereof |
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 |
US20080138295A1 (en) * | 2005-09-12 | 2008-06-12 | Celgene Coporation | Bechet's disease using cyclopropyl-N-carboxamide |
KR100608487B1 (ko) * | 2006-05-08 | 2006-08-02 | (주)거산기계 | 웨어 임펙트 플레이트가 장착된 외벽 함몰형 로터 |
WO2008074132A1 (en) * | 2006-12-19 | 2008-06-26 | Methylgene Inc. | Inhibitors of histone deacetylase and prodrugs thereof |
US8796330B2 (en) * | 2006-12-19 | 2014-08-05 | Methylgene Inc. | Inhibitors of histone deacetylase and prodrugs thereof |
CN107021895A (zh) * | 2007-06-12 | 2017-08-08 | 尔察祯有限公司 | 抗菌剂 |
WO2009110947A2 (en) * | 2007-12-19 | 2009-09-11 | Alba Therapeutics Corporation | Compositions and methods for inhibiting cytokine production |
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CN101654427B (zh) * | 2008-08-19 | 2012-12-05 | 信谊药厂 | 抗凝化合物、组合物及其用途 |
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 |
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. |
US20170087129A1 (en) | 2014-05-16 | 2017-03-30 | Celgene Corporation | Compositions and methods for the treatment of atherosclerotic cardiovascular diseases with pde4 modulators |
US10682336B2 (en) | 2015-10-21 | 2020-06-16 | Amgen Inc. | PDE4 modulators for treating and preventing immune reconstitution inflammatory syndrome (IRIS) |
CN105294533A (zh) * | 2015-12-02 | 2016-02-03 | 宋彤云 | 一种治疗骨病的药物组合物 |
Family Cites Families (23)
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 |
JPH01153658A (ja) * | 1987-12-08 | 1989-06-15 | E R Squibb & Sons Inc | ヘテロ含有置換基を有するフェニルヒドロキサム酸類 |
US5629327A (en) * | 1993-03-01 | 1997-05-13 | Childrens Hospital Medical Center Corp. | Methods and compositions for inhibition of angiogenesis |
JPH0881443A (ja) * | 1994-09-12 | 1996-03-26 | Otsuka Pharmaceut Co Ltd | 細胞外マトリックス金属プロテアーゼ阻害剤 |
US5605914A (en) | 1993-07-02 | 1997-02-25 | Celgene Corporation | Imides |
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 |
US5801195A (en) | 1994-12-30 | 1998-09-01 | Celgene Corporation | Immunotherapeutic aryl amides |
US5719144A (en) * | 1995-02-22 | 1998-02-17 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
JPH0967331A (ja) * | 1995-06-21 | 1997-03-11 | Takeda Chem Ind Ltd | 芳香族ヒドロキサム酸誘導体、その製造法および剤 |
CA2227237C (en) | 1995-07-26 | 2005-12-13 | Pfizer Inc. | N-(aroyl)glycine hydroxamic acid derivatives and related compounds |
US5728845A (en) | 1995-08-29 | 1998-03-17 | Celgene Corporation | Immunotherapeutic nitriles |
US5728844A (en) | 1995-08-29 | 1998-03-17 | Celgene Corporation | Immunotherapeutic agents |
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) |
CZ299810B6 (cs) | 1996-08-12 | 2008-12-03 | Celgene Corporation | Substituovaná aromatická sloucenina a její použití pro snížení hladiny cytokinu |
CZ299873B6 (cs) * | 1997-07-31 | 2008-12-17 | Celgene Corporation | Derivát hydroxamové kyseliny a farmaceutický prostredek s jeho obsahem |
DE69828638T2 (de) * | 1997-11-12 | 2005-12-01 | Darwin Discovery Ltd., Slough | Hydroxam- und carbonsäurederivate mit mmp- und tnf-hemmender aktivität |
US6020358A (en) * | 1998-10-30 | 2000-02-01 | Celgene Corporation | Substituted phenethylsulfones and method of reducing TNFα levels |
US6699899B1 (en) * | 1999-12-21 | 2004-03-02 | Celgene Corporation | Substituted acylhydroxamic acids and method of reducing TNFα levels |
NZ542671A (en) * | 2003-03-12 | 2008-12-24 | Celgene Corp | 7-Amido-isoindolyl compounds and their pharmaceutical uses |
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1999
- 1999-12-21 US US09/468,529 patent/US6699899B1/en not_active Expired - Fee Related
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2000
- 2000-12-12 TW TW095124062A patent/TWI295925B/zh not_active IP Right Cessation
- 2000-12-12 TW TW089125922A patent/TWI282788B/zh active
- 2000-12-19 NZ NZ519638A patent/NZ519638A/en unknown
- 2000-12-19 KR KR1020077015292A patent/KR20070086919A/ko active Search and Examination
- 2000-12-19 CN CN00817538A patent/CN1413109A/zh active Pending
- 2000-12-19 MX MXPA02005840A patent/MXPA02005840A/es active IP Right Grant
- 2000-12-19 KR KR1020027007915A patent/KR100831339B1/ko not_active IP Right Cessation
- 2000-12-19 CA CA002394604A patent/CA2394604A1/en not_active Abandoned
- 2000-12-19 WO PCT/US2000/034455 patent/WO2001045702A1/en active IP Right Grant
- 2000-12-19 EP EP00988151A patent/EP1246620A4/en not_active Withdrawn
- 2000-12-19 JP JP2001546641A patent/JP2003518060A/ja active Pending
- 2000-12-19 AU AU24389/01A patent/AU782634B2/en not_active Ceased
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2002
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- 2002-06-19 FI FI20021193A patent/FI20021193A/fi not_active Application Discontinuation
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2003
- 2003-02-19 HK HK03101278.8A patent/HK1050625A1/zh unknown
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2007
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2008
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Also Published As
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CN1413109A (zh) | 2003-04-23 |
US20040167174A1 (en) | 2004-08-26 |
NO20071498L (no) | 2002-08-14 |
JP2003518060A (ja) | 2003-06-03 |
MXPA02005840A (es) | 2005-09-08 |
TWI295925B (en) | 2008-04-21 |
CA2394604A1 (en) | 2001-06-28 |
US7345062B2 (en) | 2008-03-18 |
HK1050625A1 (zh) | 2003-07-04 |
TW200727895A (en) | 2007-08-01 |
FI20021193A (fi) | 2002-07-31 |
NO20022936L (no) | 2002-08-14 |
KR100831339B1 (ko) | 2008-05-22 |
TWI282788B (en) | 2007-06-21 |
US6699899B1 (en) | 2004-03-02 |
EP1246620A4 (en) | 2003-06-18 |
KR20070086919A (ko) | 2007-08-27 |
NZ519638A (en) | 2003-09-26 |
WO2001045702A1 (en) | 2001-06-28 |
EP1246620A1 (en) | 2002-10-09 |
KR20020073145A (ko) | 2002-09-19 |
AU2438901A (en) | 2001-07-03 |
US20080280967A1 (en) | 2008-11-13 |
NO20022936D0 (no) | 2002-06-18 |
AU782634B2 (en) | 2005-08-18 |
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