AU2003214879B2 - Non-steroidal ligands for the glucocorticoid receptor, compositions and uses thereof - Google Patents
Non-steroidal ligands for the glucocorticoid receptor, compositions and uses thereof Download PDFInfo
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- AU2003214879B2 AU2003214879B2 AU2003214879A AU2003214879A AU2003214879B2 AU 2003214879 B2 AU2003214879 B2 AU 2003214879B2 AU 2003214879 A AU2003214879 A AU 2003214879A AU 2003214879 A AU2003214879 A AU 2003214879A AU 2003214879 B2 AU2003214879 B2 AU 2003214879B2
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- Prior art keywords
- substituted
- compound
- alkyl
- heteroalkyl
- aryl
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Classifications
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- A61P5/46—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of glucocorticosteroids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
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| US35148402P | 2002-01-22 | 2002-01-22 | |
| US60/351,484 | 2002-01-22 | ||
| US37375702P | 2002-04-17 | 2002-04-17 | |
| US60/373,757 | 2002-04-17 | ||
| PCT/US2003/001997 WO2003061651A1 (en) | 2002-01-22 | 2003-01-22 | Non-steroidal ligands for the glucocorticoid receptor, compositions and uses thereof |
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| AU2003214879A1 AU2003214879A1 (en) | 2003-09-18 |
| AU2003214879B2 true AU2003214879B2 (en) | 2008-02-07 |
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| JP (2) | JP4745609B2 (enExample) |
| AU (1) | AU2003214879B2 (enExample) |
| CA (1) | CA2473886C (enExample) |
| WO (1) | WO2003061651A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AU2004232301B2 (en) * | 2003-04-23 | 2009-11-12 | Merck Sharp & Dohme Corp. | Selective spirocyclic glucocorticoid receptor modulators |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP4745609B2 (ja) * | 2002-01-22 | 2011-08-10 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | グルココルチコイドレセプターのための非ステロイド性リガンド、その組成物および使用 |
| ATE496620T1 (de) * | 2002-04-11 | 2011-02-15 | Merck Sharp & Dohme | 1h-benzo(f)indazol-5-yl-derivate als selektive glucocorticoid-rezeptor-modulatoren |
| US20040220153A1 (en) * | 2002-09-24 | 2004-11-04 | Jost-Price Edward Roydon | Methods and reagents for the treatment of diseases and disorders associated with increased levels of proinflammatory cytokines |
| EP1599201B1 (en) * | 2003-02-25 | 2010-04-14 | Merck Sharp & Dohme Corp. | Selective non-steroidal glucocorticoid receptor modulators |
| US20070088042A1 (en) * | 2004-09-09 | 2007-04-19 | Meissner Robert S | Fluorinated 4-azasteroid derivatives as androgen receptor modulators |
| GB0316290D0 (en) | 2003-07-11 | 2003-08-13 | Glaxo Group Ltd | Novel compounds |
| TW200517114A (en) | 2003-10-15 | 2005-06-01 | Combinatorx Inc | Methods and reagents for the treatment of immunoinflammatory disorders |
| NZ547389A (en) | 2003-11-21 | 2009-11-27 | Combinatorx Inc | Combinations of a compound such as ibudilast and a corticosteroid for the treatment of inflammatory disorders |
| PT1735308E (pt) * | 2004-03-09 | 2008-12-02 | Corcept Therapeutics Inc | Moduladores dos receptores de glucocorticóides de azadecalina de anel fundido |
| US20060047855A1 (en) * | 2004-05-13 | 2006-03-02 | Microsoft Corporation | Efficient chunking algorithm |
| PE20060272A1 (es) | 2004-05-24 | 2006-05-22 | Glaxo Group Ltd | (2r,3r,4s,5r,2'r,3'r,4's,5's)-2,2'-{trans-1,4-ciclohexanodiilbis-[imino(2-{[2-(1-metil-1h-imidazol-4-il)etil]amino}-9h-purin-6,9-diil)]}bis[5-(2-etil-2h-tetrazol-5-il)tetrahidro-3,4-furanodiol] como agonista a2a |
| TWI307630B (en) | 2004-07-01 | 2009-03-21 | Glaxo Group Ltd | Immunoglobulins |
| ATE517908T1 (de) | 2005-01-10 | 2011-08-15 | Glaxo Group Ltd | Androstan-17-alpha-carbonat-derivate zur verwendung bei der behandlung allergischer und entzündlicher zustände |
| PE20061351A1 (es) | 2005-03-25 | 2007-01-14 | Glaxo Group Ltd | COMPUESTOS 8H-PIRIDO[2,3-d]PIRIMIDIN-7-ONA 2,4,8-TRISUSTITUIDOS COMO INHIBIDORES DE LA QUINASA CSBP/RK/p38 |
| AR053450A1 (es) | 2005-03-25 | 2007-05-09 | Glaxo Group Ltd | Derivados de 3,4-dihidro-pirimido(4,5-d)pirimidin-2-(1h)-ona 1,5,7 trisustituidos como inhibidores de la quinasa p38 |
| US7888381B2 (en) | 2005-06-14 | 2011-02-15 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity, and use thereof |
| GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| US7645885B2 (en) * | 2005-08-26 | 2010-01-12 | The Regents Of The University Of California | Non-steroidal antiandrogens |
| US20070225217A1 (en) | 2005-11-09 | 2007-09-27 | Combinatorx, Incorporated | Methods, compositions, and kits for the treatment of medical conditions |
| PE20071068A1 (es) | 2005-12-20 | 2007-12-13 | Glaxo Group Ltd | Acido 3-(4-{[4-(4-{[3-(3,3-dimetil-1-piperidinil)propil]oxi}fenil)-1-piperidinil]carbonil}-1-naftalenil)propanoico o propenoico, sales de los mismos, como antagonistas de los receptores h1 y h3 |
| TW200811111A (en) | 2006-04-20 | 2008-03-01 | Glaxo Group Ltd | Novel compounds |
| GB0611587D0 (en) | 2006-06-12 | 2006-07-19 | Glaxo Group Ltd | Novel compounds |
| EP2091922B1 (en) * | 2006-10-23 | 2011-12-21 | Merck Sharp & Dohme Corp. | 2-[1-phenyl-5-hydroxy-4alpha-methyl-hexahydrocyclopenta[f]indazol-5-yl]ethyl phenyl derivatives as glucocorticoid receptor ligands |
| AR065804A1 (es) | 2007-03-23 | 2009-07-01 | Smithkline Beecham Corp | Compuesto de indol carboxamida, composicion farmaceutica que lo comprende y uso de dicho compuesto para preparar un medicamento |
| SG190667A1 (en) | 2008-05-23 | 2013-06-28 | Panmira Pharmaceuticals Llc | 5-lipoxygenase-activating protein inhibitor |
| JP5502077B2 (ja) | 2008-06-05 | 2014-05-28 | グラクソ グループ リミテッド | 新規な化合物 |
| ES2566339T3 (es) | 2008-06-05 | 2016-04-12 | Glaxo Group Limited | Derivados de 4-carboxamida indazol útiles como inhibidores de PI3-quinasas |
| US20100092479A1 (en) * | 2008-08-18 | 2010-04-15 | Combinatorx (Singapore) Pte. Ltd. | Compositions and methods for treatment of viral diseases |
| US7741350B1 (en) | 2009-01-28 | 2010-06-22 | Cara Therapeutics, Inc. | Bicyclic pyrazolo-heterocycles |
| WO2010094643A1 (en) | 2009-02-17 | 2010-08-26 | Glaxo Group Limited | Quinoline derivatives and their uses for rhinitis and urticaria |
| US8524751B2 (en) | 2009-03-09 | 2013-09-03 | GlaxoSmithKline Intellecutual Property Development | 4-oxadiazol-2-YL-indazoles as inhibitors of P13 kinases |
| EP2406249A1 (en) | 2009-03-10 | 2012-01-18 | Glaxo Group Limited | Indole derivatives as ikk2 inhibitors |
| EP2408769A1 (en) | 2009-03-17 | 2012-01-25 | Glaxo Group Limited | Pyrimidine derivatives used as itk inhibitors |
| US20120035247A1 (en) | 2009-03-19 | 2012-02-09 | Merck Sharp & Dohme Corp. | RNA Interference Mediated Inhibition of Signal Transducer and Activator of Transcription 6 (STAT6) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
| KR20110137799A (ko) | 2009-03-19 | 2011-12-23 | 머크 샤프 앤드 돔 코포레이션 | 짧은 간섭 핵산 (siNA) 서열 목록을 사용한 BTB 및 CNC 상동체 1, 염기성 류신 지퍼 전사 인자 1 (BACH1) 유전자 발현의 RNA 간섭 매개 억제 |
| EP2408916A2 (en) | 2009-03-19 | 2012-01-25 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF CONNECTIVE TISSUE GROWTH FACTOR (CTGF) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| EP2408915A2 (en) | 2009-03-19 | 2012-01-25 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF GATA BINDING PROTEIN 3 (GATA3) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| WO2010111468A2 (en) | 2009-03-27 | 2010-09-30 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF THE NERVE GROWTH FACTOR BETA CHAIN (NGFß) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (SINA) |
| US20120010272A1 (en) | 2009-03-27 | 2012-01-12 | Merck Sharp & Dohme Corp. | RNA Interference Mediated Inhibition of Apoptosis Signal-Regulating Kinase 1 (ASK1) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
| JP2012521764A (ja) | 2009-03-27 | 2012-09-20 | メルク・シャープ・エンド・ドーム・コーポレイション | 低分子干渉核酸(siNA)を用いた胸腺間質性リンパ球新生因子(TSLP)遺伝子発現のRNA干渉媒介性阻害 |
| AU2010229847A1 (en) | 2009-03-27 | 2011-10-13 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of the intercellular adhesion molecule 1 (ICAM-1)gene expression using short interfering nucleic acid (siNA) |
| EP2411019A2 (en) | 2009-03-27 | 2012-02-01 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 1 (STAT1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| WO2010122088A1 (en) | 2009-04-24 | 2010-10-28 | Glaxo Group Limited | Pyrazole and triazole carboxamides as crac channel inhibitors |
| TW201103892A (en) | 2009-04-24 | 2011-02-01 | Glaxo Group Ltd | Compounds |
| ES2644724T3 (es) | 2009-04-30 | 2017-11-30 | Glaxo Group Limited | Indazoles sustituidos con oxazol como inhibidores de PI3-cinasas |
| US20120238571A1 (en) | 2009-12-03 | 2012-09-20 | Glaxo Group Limited | Indazole derivatives as pi 3-kinase |
| EP2507226A1 (en) | 2009-12-03 | 2012-10-10 | Glaxo Group Limited | Novel compounds |
| JP2013512879A (ja) | 2009-12-03 | 2013-04-18 | グラクソ グループ リミテッド | Pi3キナーゼの阻害剤としてのベンズピラゾール誘導体 |
| EP2512438B1 (en) | 2009-12-16 | 2017-01-25 | 3M Innovative Properties Company | Formulations and methods for controlling mdi particle size delivery |
| CN101768608B (zh) * | 2009-12-31 | 2012-02-08 | 杭州师范大学 | 一种一锅法合成维兰德-米歇尔酮类化合物的方法 |
| EP2524057B1 (en) * | 2010-01-15 | 2016-03-30 | Rigel Pharmaceuticals, Inc. | Screening assay employing dex and gdf8 |
| WO2011110575A1 (en) | 2010-03-11 | 2011-09-15 | Glaxo Group Limited | Derivatives of 2-[2-(benzo- or pyrido-) thiazolylamino]-6-aminopyridine, useful in the treatment of respiratoric, allergic or inflammatory diseases |
| GB201007203D0 (en) | 2010-04-29 | 2010-06-16 | Glaxo Group Ltd | Novel compounds |
| JP5876051B2 (ja) | 2010-09-08 | 2016-03-02 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | インフルエンザウィルス感染の治療に使用するためのインダゾール誘導体 |
| HUE026059T2 (en) | 2010-09-08 | 2016-05-30 | Glaxosmithkline Ip Dev Ltd | N- [5- [4- (5 - {[(2R, 6S) -2,6-dimethyl-4-morpholinyl] methyl} -1,3-oxazol-2-yl) -1H-indazol-6-yl ] Polymorphs and salts of 2 - (methyloxy) -3-pyridinyl] methanesulfonamide |
| WO2012035055A1 (en) | 2010-09-17 | 2012-03-22 | Glaxo Group Limited | Novel compounds |
| EP2630127A1 (en) | 2010-10-21 | 2013-08-28 | Glaxo Group Limited | Pyrazole compounds acting against allergic, inflammatory and immune disorders |
| JP5795643B2 (ja) | 2010-10-21 | 2015-10-14 | グラクソ グループ リミテッドGlaxo Group Limited | アレルギー性状態、免疫性状態及び炎症性状態に作用するピラゾール化合物 |
| GB201018124D0 (en) | 2010-10-27 | 2010-12-08 | Glaxo Group Ltd | Polymorphs and salts |
| AU2012204232A1 (en) | 2011-01-07 | 2013-06-27 | Corcept Therapeutics, Inc. | Combination steroid and glucocorticoid receptor antagonist therapy |
| WO2012123312A1 (en) | 2011-03-11 | 2012-09-20 | Glaxo Group Limited | Pyrido[3,4-b]pyrazine derivatives as syk inhibitors |
| GB201104153D0 (en) | 2011-03-11 | 2011-04-27 | Glaxo Group Ltd | Novel compounds |
| US12226412B2 (en) | 2012-05-25 | 2025-02-18 | Corcept Therapeutics, Inc. | Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators |
| US8859774B2 (en) | 2012-05-25 | 2014-10-14 | Corcept Therapeutics, Inc. | Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators |
| CA2920059A1 (en) | 2013-09-22 | 2015-03-26 | Calitor Sciences, Llc | Substituted aminopyrimidine compounds and methods of use |
| AU2014336250A1 (en) | 2013-10-17 | 2016-04-14 | Glaxosmithkline Intellectual Property Development Limited | PI3K inhibitor for treatment of respiratory disease |
| US20160263109A1 (en) | 2013-10-17 | 2016-09-15 | Glaxosmithkline Intellectual Property Development Limited | P13k inhibitor for treatment of respiratory disease |
| ES2743620T3 (es) | 2013-11-25 | 2020-02-20 | Corcept Therapeutics Inc | Moduladores del receptor de glucocorticoides de azadecalina condensada con octahidro |
| JP6517319B2 (ja) | 2014-03-28 | 2019-05-22 | キャリター・サイエンシーズ・リミテッド・ライアビリティ・カンパニーCalitor Sciences, Llc | 置換されたヘテロアリール化合物および使用方法 |
| JP2017515840A (ja) | 2014-05-12 | 2017-06-15 | グラクソスミスクライン、インテレクチュアル、プロパティー、(ナンバー2)、リミテッドGlaxosmithkline Intellectual Property (No.2) Limited | 感染症を治療するためのダニリキシンを含む医薬組成物 |
| US9938257B2 (en) | 2015-09-11 | 2018-04-10 | Calitor Sciences, Llc | Substituted heteroaryl compounds and methods of use |
| GB201602527D0 (en) | 2016-02-12 | 2016-03-30 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| EP3497100A1 (en) | 2016-08-08 | 2019-06-19 | GlaxoSmithKline Intellectual Property Development Limited | Chemical compounds |
| SG11201908790PA (en) | 2017-03-31 | 2019-10-30 | Corcept Therapeutics Inc | Glucocorticoid receptor modulators to treat cervical cancer |
| JP2020516633A (ja) * | 2017-04-11 | 2020-06-11 | オリック ファーマシューティカルズ,インク. | グルココルチコイド受容体モジュレーター |
| GB201706102D0 (en) | 2017-04-18 | 2017-05-31 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| GB201712081D0 (en) | 2017-07-27 | 2017-09-13 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| WO2019099311A1 (en) | 2017-11-19 | 2019-05-23 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
| AU2019209960B2 (en) | 2018-01-20 | 2023-11-23 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine compounds and methods of use |
| WO2020132046A1 (en) | 2018-12-19 | 2020-06-25 | Corcept Therapeutics Incorporated | Methods of treating cancer comprising administration of a glucocorticoid receptor modulator and a cancer chemotherapy agent |
| CN117281790A (zh) | 2018-12-19 | 2023-12-26 | 科塞普特治疗公司 | 含有瑞拉可兰、杂芳基-酮稠合的氮杂十氢化萘化合物的药物制剂 |
| US11234971B2 (en) | 2018-12-19 | 2022-02-01 | Corcept Therapeutics Incorporated | Methods of treating cancer comprising administration of a glucocorticoid receptor modulator and a cancer chemotherapy agent |
| CN113490496A (zh) | 2019-02-22 | 2021-10-08 | 科赛普特治疗学股份有限公司 | 一种杂芳基-酮稠合氮杂萘烷糖皮质激素受体调节剂瑞拉可兰的治疗用途 |
| KR20220113767A (ko) | 2019-12-11 | 2022-08-16 | 코어셉트 쎄라퓨틱스 인코포레이티드 | 미리코릴란트로 항정신병약-유도 체중 증가를 치료하는 방법 |
| CA3173172A1 (en) | 2020-03-26 | 2021-09-30 | Christopher D. Kane | Cathepsin inhibitors for preventing or treating viral infections |
| WO2022134033A1 (en) | 2020-12-25 | 2022-06-30 | Corcept Therapeutics Incorporated | Methods of preparing heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators |
| CN113563163A (zh) * | 2021-07-07 | 2021-10-29 | 南京伊派森化学科技有限公司 | 一种5-溴-1,2,3-三甲氧基苯的合成方法 |
| KR20250073629A (ko) | 2022-10-06 | 2025-05-27 | 코어셉트 쎄라퓨틱스 인코포레이티드 | 글루코코르티코이드 수용체 조절제의 제형 |
| AU2023367284A1 (en) | 2022-10-28 | 2025-05-29 | Corcept Therapeutics Incorporated | Treatments for amyotrophic lateral sclerosis using dazucorilant |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6462036B1 (en) * | 1998-11-06 | 2002-10-08 | Basf Aktiengesellschaft | Tricyclic pyrazole derivatives |
| US6518294B2 (en) * | 2001-01-24 | 2003-02-11 | Yung Shin Pharmaceutical Ind. Co. | Fused pyrazolyl compounds |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3135743A (en) * | 1960-06-29 | 1964-06-02 | Sterling Drug Inc | Steroido[2. 3-d]isoxazoles and preparation thereof |
| NL273722A (enExample) * | 1961-01-18 | |||
| DE1169442B (de) * | 1962-05-05 | 1964-05-06 | Schering Ag | Verfahren zur Herstellung von Steroidthioaethern bzw. Aminothiazolosteroiden |
| GB1071124A (en) * | 1965-05-11 | 1967-06-07 | Biorex Laboratories Ltd | Derivatives of pyrazolo-[4',5'-b]-11-oxo-18ª‡- and 18ª‰-olean-12-en-30-oic acid |
| US4412995A (en) | 1981-02-19 | 1983-11-01 | Sterling Drug Inc. | Pentacyclic phenylpyrazole compounds as anti-inflammatory agents |
| EP0102404A1 (en) * | 1982-09-02 | 1984-03-14 | Sterling Drug Inc. | Novel polycyclic fused pyrazole compounds useful as antiinflammatory agents and preparation thereof |
| CA1178965A (en) | 1982-09-13 | 1984-12-04 | Sterling Drug Inc. | Polycyclic fused pyrazole compounds useful as anti- inflammatory agents and preparation thereof |
| US6139873A (en) * | 1996-07-10 | 2000-10-31 | Cedars-Sinai Medical Center | Combined pharmaceutical estrogen-androgen-progestin |
| DK1023063T3 (da) * | 1997-10-06 | 2004-01-26 | Abbott Gmbh & Co Kg | Indeno[1,2-c]-,naphtho[1,2-c]- og benzo[6,7]cyclohepta[1,2-c]pyrazolderivater |
| ZA9811898B (en) | 1997-12-29 | 2000-06-28 | Ortho Mcneil Pharm Inc | Anti-Inflammatory Compounds. |
| US6380207B2 (en) | 1998-02-13 | 2002-04-30 | Abbott Laboratories | Glucocortiocoid-selective antiinflammatory agents |
| PT1100483E (pt) | 1998-07-30 | 2005-02-28 | Abbott Lab | Agentes anti-inflamatorios selectivos para glicocorticoide |
| GB9816935D0 (en) | 1998-08-05 | 1998-09-30 | Karobio Ab | Novel glucocortoid and thyroid receptor ligands for the treatment of metabolic disorders |
| US7026484B2 (en) * | 2001-02-23 | 2006-04-11 | Ligand Pharmaceuticals Incorporated | Tricyclic androgen receptor modulator compounds and methods |
| HUP0402310A2 (hu) * | 2001-09-26 | 2005-02-28 | Bayer Pharmaceuticals Corporation | 1,6-Naftiridin-származékok mint antidiabetikumok és ezeket tartalmazó gyógyszerkészítmények |
| DE10164564B4 (de) * | 2001-12-14 | 2007-05-16 | Zentaris Gmbh | Tetrahydrocarbazolderivate als Liganden für G-Protein gekoppelte Rezeptoren (GPCR) |
| JP4745609B2 (ja) * | 2002-01-22 | 2011-08-10 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | グルココルチコイドレセプターのための非ステロイド性リガンド、その組成物および使用 |
| ATE496620T1 (de) | 2002-04-11 | 2011-02-15 | Merck Sharp & Dohme | 1h-benzo(f)indazol-5-yl-derivate als selektive glucocorticoid-rezeptor-modulatoren |
| ES2309484T3 (es) * | 2003-01-09 | 2008-12-16 | Pfizer Inc. | Derivados de diazepinoindol como inhibidores de quinasa. |
| WO2004066920A2 (en) | 2003-01-21 | 2004-08-12 | Merck & Co. Inc. | 17-carbamoyloxy cortisol derivatives as selective glucocorticoid receptor modulators |
| EP1599201B1 (en) * | 2003-02-25 | 2010-04-14 | Merck Sharp & Dohme Corp. | Selective non-steroidal glucocorticoid receptor modulators |
| CN1809347A (zh) | 2003-04-23 | 2006-07-26 | 麦克公司 | 选择性螺环糖皮质激素受体调节剂 |
| US7071333B2 (en) * | 2003-07-30 | 2006-07-04 | Bristol-Myers Squibb Company | Triazolopurine-based tricyclic compounds and pharmaceutical compositions comprising same |
| ATE463479T1 (de) | 2005-05-18 | 2010-04-15 | Merck Sharp & Dohme | D-homoandrosta-17-yl-carbamat-derivate als selektive glucocorticoid-rezeptor-liganden |
| US7645885B2 (en) * | 2005-08-26 | 2010-01-12 | The Regents Of The University Of California | Non-steroidal antiandrogens |
-
2003
- 2003-01-22 JP JP2003561595A patent/JP4745609B2/ja not_active Expired - Fee Related
- 2003-01-22 CA CA2473886A patent/CA2473886C/en not_active Expired - Fee Related
- 2003-01-22 EP EP03710722A patent/EP1467730A4/en not_active Withdrawn
- 2003-01-22 AU AU2003214879A patent/AU2003214879B2/en not_active Ceased
- 2003-01-22 WO PCT/US2003/001997 patent/WO2003061651A1/en not_active Ceased
- 2003-01-22 US US10/350,260 patent/US6831093B2/en not_active Expired - Fee Related
-
2004
- 2004-10-22 US US10/972,250 patent/US7485660B2/en not_active Expired - Fee Related
-
2009
- 2009-02-03 US US12/365,106 patent/US7947726B2/en not_active Expired - Fee Related
-
2010
- 2010-01-14 JP JP2010006117A patent/JP2010132672A/ja active Pending
-
2011
- 2011-05-11 US US13/105,349 patent/US20110218225A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6462036B1 (en) * | 1998-11-06 | 2002-10-08 | Basf Aktiengesellschaft | Tricyclic pyrazole derivatives |
| US6518294B2 (en) * | 2001-01-24 | 2003-02-11 | Yung Shin Pharmaceutical Ind. Co. | Fused pyrazolyl compounds |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004232301B2 (en) * | 2003-04-23 | 2009-11-12 | Merck Sharp & Dohme Corp. | Selective spirocyclic glucocorticoid receptor modulators |
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| EP1467730A4 (en) | 2010-03-10 |
| US7485660B2 (en) | 2009-02-03 |
| US20030176478A1 (en) | 2003-09-18 |
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| EP1467730A1 (en) | 2004-10-20 |
| US20110218225A1 (en) | 2011-09-08 |
| US6831093B2 (en) | 2004-12-14 |
| JP2005523254A (ja) | 2005-08-04 |
| US20090137655A1 (en) | 2009-05-28 |
| JP2010132672A (ja) | 2010-06-17 |
| JP4745609B2 (ja) | 2011-08-10 |
| US7947726B2 (en) | 2011-05-24 |
| CA2473886A1 (en) | 2003-07-31 |
| CA2473886C (en) | 2012-08-21 |
| WO2003061651A1 (en) | 2003-07-31 |
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