ES2337264T3 - Moduladores de interleucina-1 y del factor-alfa de necrosis tumoral, sintesis de dichos moduladores y metodos de utilizacion de dichos moduladores. - Google Patents
Moduladores de interleucina-1 y del factor-alfa de necrosis tumoral, sintesis de dichos moduladores y metodos de utilizacion de dichos moduladores. Download PDFInfo
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- ES2337264T3 ES2337264T3 ES05076500T ES05076500T ES2337264T3 ES 2337264 T3 ES2337264 T3 ES 2337264T3 ES 05076500 T ES05076500 T ES 05076500T ES 05076500 T ES05076500 T ES 05076500T ES 2337264 T3 ES2337264 T3 ES 2337264T3
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- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C69/753—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring of polycyclic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13429599P | 1999-05-14 | 1999-05-14 | |
| US134295 | 1999-05-14 | ||
| US18685300P | 2000-03-03 | 2000-03-03 | |
| US186853 | 2000-03-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2337264T3 true ES2337264T3 (es) | 2010-04-22 |
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| Application Number | Title | Priority Date | Filing Date |
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Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999037600A1 (en) * | 1998-01-26 | 1999-07-29 | Sae Han Pharm. Co., Ltd. | Diterpene derivatives and anti-inflammatory analgesic agents comprising the same |
| US6326507B1 (en) | 1998-06-19 | 2001-12-04 | Trustees Of Dartmouth College | Therapeutic compounds and methods of use |
| CN1361760A (zh) | 1999-05-14 | 2002-07-31 | 尼瑞斯药品公司 | 新的白介素－1和肿瘤坏死因子－α调节剂、所述调节剂的合成以及使用所述调节剂的方法 |
| US7119223B2 (en) * | 1999-05-14 | 2006-10-10 | Nereus Pharmaceuticals, Inc. | Interleukin-1 and tumor necrosis factor-α modulators, synthesis of said modulators and their enantiomers and methods of using said modulators |
| US7435755B2 (en) | 2000-11-28 | 2008-10-14 | The Trustees Of Dartmouth College | CDDO-compounds and combination therapies thereof |
| WO2002079137A1 (en) * | 2001-03-28 | 2002-10-10 | Nereus Pharmaceuticals, Inc. | Interleukin-1 and tumor necrosis factor-alpha modulators and their enantiomers, their synthesis and use |
| US20030087334A1 (en) * | 2001-04-02 | 2003-05-08 | Libraria, Inc. | Method of flexibly generating diverse reaction chemistries |
| AU2003235676A1 (en) | 2002-01-15 | 2003-07-30 | Trustees Of Dartmouth College | Tricyclic-bis-enone derivatives and methods of use thereof |
| WO2003061553A2 (en) * | 2002-01-25 | 2003-07-31 | Korea Research Institute Of Bioscience And Biotechnology | An extract of acanthopanax koreanum for the treatment or prevention of hepatitis or the liver protective drug |
| US7517542B2 (en) * | 2004-03-03 | 2009-04-14 | Korea Research Institute Of Bioscience | Abietane diterpenoid compound, and composition comprising extract of torreya nucifera, or abietane diterpenoid compounds or terpenoid compounds isolated from them for prevention and treatment of cardiovascular disease |
| JP2009505954A (ja) | 2005-07-21 | 2009-02-12 | ネレアス ファーマシューティカルズ インコーポレイテッド | インターロイキン−１及び腫瘍壊死因子−ａ修飾因子、このような修飾因子の合成及びこのような修飾因子の使用方法 |
| EP2094651A1 (en) | 2006-11-17 | 2009-09-02 | Trustees Of Dartmouth College | Synthesis and biological activities of new tricyclic-bis-enones (tbes) |
| US8921340B2 (en) | 2006-11-17 | 2014-12-30 | Trustees Of Dartmouth College | Methods for using synthetic triterpenoids in the treatment of bone or cartilage diseases or conditions |
| US8299046B2 (en) | 2006-11-17 | 2012-10-30 | Trustees Of Dartmouth College | Synthetic triterpenoids and tricyclic-bis-enones for use in stimulating bone and cartilage growth |
| EP1925301A1 (en) * | 2006-11-24 | 2008-05-28 | DSMIP Assets B.V. | Use of tricyclic diterpenes and their derivatives for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders |
| US7875853B2 (en) * | 2007-07-23 | 2011-01-25 | Honeywell International Inc. | Low-cost PIR scanning mechanism |
| ME03529B (me) | 2008-01-11 | 2020-04-20 | Reata Pharmaceuticals Inc | Sintetički triterpenoidi i metode njihove upotrebe u tretmanu bolesti |
| EP2279197B1 (en) | 2008-04-18 | 2014-11-05 | Reata Pharmaceuticals, Inc. | Antioxidant inflammation modulators: oleanolic acid derivatives with saturation in the c-ring |
| CN102083442B (zh) | 2008-04-18 | 2014-08-13 | 里亚塔医药公司 | 抗氧化剂炎症调节剂：在c-17具有氨基和其它修饰的齐墩果酸衍生物 |
| SI2271658T1 (sl) | 2008-04-18 | 2017-03-31 | Reata Pharmaceuticals, Inc. | Antioksidantni modulatorji vnetja: C-17 homologirani derivati oleanolne kisline |
| WO2009146216A2 (en) | 2008-04-18 | 2009-12-03 | Reata Pharmaceuticals. Inc. | Antioxidant inflammation modulators: novel derivatives of oleanolic acid |
| CA2721665C (en) | 2008-04-18 | 2017-01-24 | Reata Pharmaceuticals, Inc. | Compounds including an anti-inflammatory pharmacore and methods of use |
| ES2449396T3 (es) | 2008-07-22 | 2014-03-19 | Trustees Of Dartmouth College | Cianoenonas monocíclicas y métodos de uso de las mismas |
| US20110293653A1 (en) * | 2010-03-11 | 2011-12-01 | University Of Massachusetts | Antagonists of mir-155 for the treatment of inflammatory liver disease |
| EP2558105B1 (en) | 2010-04-12 | 2019-11-20 | Reata Pharmaceuticals, Inc. | Bardoxolone methyl for the treatment of obesity |
| MY158661A (en) * | 2010-10-27 | 2016-10-31 | Sigma Tau Ind Farmaceutieche Riunite S P A | Diterpenoid derivatives endowed of biological properties |
| EP2648706A4 (en) | 2010-12-06 | 2014-07-23 | Penn State Res Found | COMPOSITIONS AND METHODS RELATING TO PROLIFERATIVE DISEASES |
| CA2822071C (en) | 2010-12-17 | 2019-07-16 | Reata Pharmaceuticals, Inc. | Pyrazolyl and pyrimidinyl tricyclic enones as antioxidant inflammation modulators |
| HUE044081T2 (hu) | 2011-03-11 | 2019-09-30 | Reata Pharmaceuticals Inc | C4 Monometil-triterpenoid-származékok, és módszerek azok alkalmazására |
| BR112014026640B1 (pt) | 2012-04-27 | 2021-05-18 | Reata Pharmaceuticals, Inc | compostos derivados de 2,2-difluoropropionamida de metil bardoxolona, formas polimórficas, composição farmacêutica, e uso dos mesmos |
| US8921419B2 (en) | 2012-05-08 | 2014-12-30 | Trustees Of Dartmouth College | Triterpenoids and compositions containing the same |
| US9556222B2 (en) | 2012-06-15 | 2017-01-31 | Reata Pharmaceuticals, Inc. | A-ring epoxidized triterpenoid-based anti-inflammation modulators and methods of use thereof |
| RS59194B1 (sr) | 2012-09-10 | 2019-10-31 | Reata Pharmaceuticals Inc | C17-alkandiilni i alkendiilni derivati oleanolne kiseline i metode za njihovu upotrebu |
| US9512094B2 (en) | 2012-09-10 | 2016-12-06 | Reata Pharmaceuticals, Inc. | C17-heteroaryl derivatives of oleanolic acid and methods of use thereof |
| WO2014040073A1 (en) | 2012-09-10 | 2014-03-13 | Reata Pharmaceuticals, Inc. | C13-hydroxy derivatives of oleanolic acid and methods of use thereof |
| BR112018005861B1 (pt) | 2015-09-23 | 2022-11-22 | Reata Pharmaceuticals, Inc | Compostos derivados de ácido oleanólico modificado com c4 para a inibição de il-17, composição farmacêutica e usos terapêuticos dos ditos compostos |
| CA3042123A1 (en) | 2016-11-08 | 2018-05-17 | Reata Pharmaceuticals, Inc. | Methods of treating alport syndrome using bardoxolone methyl or analogs thereof |
| CN106928095A (zh) * | 2017-03-14 | 2017-07-07 | 华东师范大学 | 氰基烯酮类三环二萜类似物及其制备方法和应用 |
| US10463631B2 (en) * | 2017-06-12 | 2019-11-05 | University Of South Carolina | Pimarane diterpenoids for use in wound healing and angiogenesis |
| WO2019246461A1 (en) | 2018-06-20 | 2019-12-26 | Reata Pharmaceuticals, Inc. | Cysteine-dependent inverse agonists of nuclear receptors ror-gamma/ror-gamma-t and methods of treating diseases or disorders therewith |
| CN120248001A (zh) | 2019-07-19 | 2025-07-04 | 里亚塔医药公司 | C17极性的-取代的杂芳族合成三萜类化合物及其使用方法 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5212708B2 (enExample) | 1974-05-14 | 1977-04-08 | ||
| JPS522910B2 (enExample) | 1974-05-17 | 1977-01-25 | ||
| GB1452053A (en) | 1974-08-28 | 1976-10-06 | Nippon Shinyaku Co Ltd | Abietamide derivatives and a method for the preparation thereof |
| US4874891A (en) | 1986-05-01 | 1989-10-17 | Washington University | Open "D" ring hormone analogs |
| US5133974A (en) | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| EP0472733B1 (en) | 1990-03-06 | 1994-12-28 | Otsuka Pharmaceutical Co., Ltd. | Phenanthrene derivative |
| US5276182A (en) | 1990-07-09 | 1994-01-04 | The Dow Chemical Company | Process for preparing polyurea oligomers |
| DE4039602A1 (de) | 1990-12-12 | 1992-06-17 | Bauer Kurt Heinz Prof Dr | Pharmazeutische formulierungen |
| KR100221695B1 (ko) | 1991-08-12 | 1999-09-15 | 그린 마틴, 브라이언 쥐 테슬리 | 약학적 구상 제형 |
| US5683676A (en) | 1991-12-12 | 1997-11-04 | Glaxo Group Limited | Canister containing aerosol formulations containing P134a and particulate medicaments |
| DK0674510T3 (da) | 1992-11-27 | 1999-05-10 | Napro Biotherapeutics Inc | Injicerbart præparat omfattende paclitaxel |
| US5654286A (en) | 1993-05-12 | 1997-08-05 | Hostetler; Karl Y. | Nucleotides for topical treatment of psoriasis, and methods for using same |
| CZ301771B6 (cs) | 1993-10-01 | 2010-06-16 | Syntex (U.S.A.) Llc. | Farmaceutický prostredek ve forme suchého granulátu obsahující mofetil mykofenolát nebo kyselinu mykofenolovou a zpusob jeho prípravy |
| KR0145941B1 (ko) * | 1994-06-13 | 1998-08-17 | 김은영 | 인터루킨-1과 종양 괴사 인자-알파의 생산 억제에 유용한 아칸토산을 포함하는 약학적 조성물 |
| US5707641A (en) | 1994-10-13 | 1998-01-13 | Pharmaderm Research & Development Ltd. | Formulations comprising therapeutically-active proteins or polypeptides |
| IE80468B1 (en) | 1995-04-04 | 1998-07-29 | Elan Corp Plc | Controlled release biodegradable nanoparticles containing insulin |
| US5653987A (en) | 1995-05-16 | 1997-08-05 | Modi; Pankaj | Liquid formulations for proteinic pharmaceuticals |
| US5726181A (en) | 1995-06-05 | 1998-03-10 | Bionumerik Pharmaceuticals, Inc. | Formulations and compositions of poorly water soluble camptothecin derivatives |
| US5667809A (en) | 1995-06-07 | 1997-09-16 | Alliance Pharmaceutical Corp. | Continuous fluorochemical microdispersions for the delivery of lipophilic pharmaceutical agents |
| FR2741262B1 (fr) | 1995-11-20 | 1999-03-05 | Oreal | Utilisation d'un antagoniste de tnf-alpha pour le traitement des rougeurs cutanees d'origine neurogene |
| WO1999037600A1 (en) * | 1998-01-26 | 1999-07-29 | Sae Han Pharm. Co., Ltd. | Diterpene derivatives and anti-inflammatory analgesic agents comprising the same |
| US6051590A (en) | 1999-05-13 | 2000-04-18 | Merck & Co., Inc. | Immunosuppressant tricyclic compounds |
| CN1361760A (zh) * | 1999-05-14 | 2002-07-31 | 尼瑞斯药品公司 | 新的白介素－1和肿瘤坏死因子－α调节剂、所述调节剂的合成以及使用所述调节剂的方法 |
| WO2002079137A1 (en) | 2001-03-28 | 2002-10-10 | Nereus Pharmaceuticals, Inc. | Interleukin-1 and tumor necrosis factor-alpha modulators and their enantiomers, their synthesis and use |
-
2000
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- 2000-05-12 WO PCT/US2000/013202 patent/WO2000073253A1/en not_active Ceased
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- 2000-05-12 JP JP2000621320A patent/JP5059996B2/ja not_active Expired - Lifetime
- 2000-05-12 EP EP05076500A patent/EP1591437B1/en not_active Expired - Lifetime
- 2000-05-12 BR BR0011522-3A patent/BR0011522A/pt not_active Application Discontinuation
- 2000-05-12 DE DE60043400T patent/DE60043400D1/de not_active Expired - Lifetime
- 2000-05-12 DE DE60036101T patent/DE60036101T2/de not_active Expired - Lifetime
- 2000-05-12 NZ NZ529505A patent/NZ529505A/en not_active IP Right Cessation
- 2000-05-12 ES ES05076500T patent/ES2337264T3/es not_active Expired - Lifetime
- 2000-05-12 US US09/570,202 patent/US6365768B1/en not_active Expired - Fee Related
- 2000-05-12 MX MXPA01011613A patent/MXPA01011613A/es active IP Right Grant
- 2000-05-12 NZ NZ515675A patent/NZ515675A/en not_active IP Right Cessation
- 2000-05-12 IL IL14622100A patent/IL146221A0/xx active IP Right Grant
- 2000-05-12 KR KR1020067020613A patent/KR20060110013A/ko not_active Withdrawn
- 2000-05-12 ES ES00932408T patent/ES2295031T3/es not_active Expired - Lifetime
- 2000-05-12 CA CA002372962A patent/CA2372962C/en not_active Expired - Fee Related
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- 2000-05-12 EP EP00932408A patent/EP1178952B1/en not_active Expired - Lifetime
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- 2000-05-12 KR KR1020067025785A patent/KR100840925B1/ko not_active Expired - Fee Related
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2001
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2002
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2006
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2007
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