DK2958888T3 - BICYCLIC RELATIONS - Google Patents
BICYCLIC RELATIONS Download PDFInfo
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- DK2958888T3 DK2958888T3 DK14709822.2T DK14709822T DK2958888T3 DK 2958888 T3 DK2958888 T3 DK 2958888T3 DK 14709822 T DK14709822 T DK 14709822T DK 2958888 T3 DK2958888 T3 DK 2958888T3
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| US201361767531P | 2013-02-21 | 2013-02-21 | |
| PCT/US2014/017534 WO2014130752A2 (en) | 2013-02-21 | 2014-02-21 | Bicyclic compounds |
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| EP3022176B8 (en) | 2013-07-15 | 2019-12-25 | The Regents of the University of California | Azacyclic constrained analogs of fty720 |
| UY36274A (es) | 2014-08-20 | 2016-02-29 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Compuestos bicíclicos sustituidos como agonistas selectivos de la actividad del receptor s1p1 acoplado a la proteína g |
| CA2999177A1 (en) | 2015-09-24 | 2017-03-30 | The Regents Of The University Of California | Synthetic sphingolipid-like molecules, drugs, methods of their synthesis and methods of treatment |
| CN110234633A (zh) | 2016-09-02 | 2019-09-13 | 百时美施贵宝公司 | 取代的三环杂环化合物 |
| WO2019032631A1 (en) | 2017-08-09 | 2019-02-14 | Bristol-Myers Squibb Company | Oxime ether compounds |
| WO2019032632A1 (en) | 2017-08-09 | 2019-02-14 | Bristol-Myers Squibb Company | ALKYLPHENYL COMPOUNDS |
| WO2021062168A1 (en) * | 2019-09-25 | 2021-04-01 | The Regents Of The University Of California | Synthetic sphingolipid inspired molecules with heteroaromatic appendages, methods of their synthesis and methods of treatment |
| WO2025083549A1 (en) | 2023-10-16 | 2025-04-24 | Sun Pharma Advanced Research Company Limited | Methods and combinations of inhibitors of il-23 pathway and modulators of s1p signaling pathway for the treatment of autoimmune disorders |
Family Cites Families (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4200750A (en) | 1977-01-07 | 1980-04-29 | Westwood Pharmaceuticals Inc. | 4-Substituted imidazo [1,2-a]quinoxalines |
| US6069143A (en) | 1994-12-20 | 2000-05-30 | Smithkline Beecham Corporation | Fibrinogen receptor antagonists |
| ATE448193T1 (de) | 2002-01-18 | 2009-11-15 | Merck & Co Inc | ßN-(BENZYL)AMINOALKYL CARBOXYLATE, PHOSPHINATE, PHOSPHONATE UND TETRAZOLE ALS EDG REZEPTORAGONISTENß |
| ATE441654T1 (de) | 2002-01-18 | 2009-09-15 | Merck & Co Inc | Edg-rezeptoragonisten |
| CA2472680A1 (en) | 2002-01-18 | 2003-07-31 | Merck & Co., Inc. | Selective s1p1/edg1 receptor agonists |
| WO2003073986A2 (en) | 2002-03-01 | 2003-09-12 | Merck & Co., Inc. | Aminoalkylphosphonates and related compounds as edg receptor agonists |
| CA2488117A1 (en) | 2002-06-17 | 2003-12-24 | Merck & Co., Inc. | 1-((5-aryl-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylates and 1-((5-aryl-1,2,4-oxadiazol-3-yl)benzyl)pyrrolidine-3-carboxylates as edg receptor agonists |
| BRPI0410439A (pt) | 2003-05-19 | 2006-06-06 | Irm Llc | compostos e composições imunossupressoras |
| AU2004299456B2 (en) | 2003-12-17 | 2010-10-07 | Merck Sharp & Dohme Corp. | (3,4-disubstituted)propanoic carboxylates as S1P (Edg) receptor agonists |
| TW200538433A (en) | 2004-02-24 | 2005-12-01 | Irm Llc | Immunosuppressant compounds and compositiions |
| JP2008517915A (ja) | 2004-10-22 | 2008-05-29 | メルク エンド カムパニー インコーポレーテッド | Ｓ１ｐ受容体アゴニストとしての２−（アリール）アザシクリルメチルカルボキシレート、スルホネート、ホスホネート、ホスフィネート及びヘテロ環 |
| BRPI0607435A2 (pt) | 2005-02-14 | 2010-04-06 | Univ Virginia | composto ou um sal ou éster farmaceuticamente aceitável do mesmo, e, uso de um composto |
| CN101193852A (zh) | 2005-02-18 | 2008-06-04 | 因诺迪亚有限公司 | 4-羟基异亮氨酸类似物及其用途 |
| CA2600886A1 (en) | 2005-03-08 | 2006-09-14 | Biota Scientific Management Pty Ltd. | Bicyclic nucleosides and nucleotides as therapeutic agents |
| ATE413874T1 (de) | 2005-03-23 | 2008-11-15 | Actelion Pharmaceuticals Ltd | Neue thiophen-derivate als sphingosin-1-phosphat- 1-rezeptorantagonisten |
| WO2006115188A1 (ja) | 2005-04-22 | 2006-11-02 | Daiichi Sankyo Company, Limited | ヘテロ環化合物 |
| WO2006131336A1 (en) | 2005-06-08 | 2006-12-14 | Novartis Ag | POLYCYCLIC OXADIAZOLES OR I SOXAZOLES AND THEIR USE AS SlP RECEPTOR LIGANDS |
| MX2008002540A (es) | 2005-08-23 | 2008-03-14 | Irm Llc | Compuestos inmunosupresores y composiciones. |
| KR101294014B1 (ko) | 2006-01-06 | 2013-08-09 | 선오비온 파마슈티컬스 인코포레이티드 | 모노아민 재흡수 저해제로서의 시클로알킬아민 |
| JP2009528274A (ja) | 2006-01-27 | 2009-08-06 | ユニバーシティ オブ バージニア パテント ファンデーション | 神経因性疼痛の治療法 |
| WO2007088450A2 (en) | 2006-02-01 | 2007-08-09 | Pfizer Products Inc. | Chromane antagonist of the h-3 receptor |
| US7790707B2 (en) | 2006-03-21 | 2010-09-07 | Epix Pharmaceuticals Inc. | S1P receptor modulating compounds and use thereof |
| WO2007111864A2 (en) | 2006-03-23 | 2007-10-04 | Merck & Co., Inc. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| JP5099005B2 (ja) | 2006-04-03 | 2012-12-12 | アステラス製薬株式会社 | ヘテロ化合物 |
| JP2009269819A (ja) | 2006-08-25 | 2009-11-19 | Asahi Kasei Pharma Kk | アミン化合物 |
| AU2007292992B2 (en) | 2006-09-08 | 2013-01-10 | Actelion Pharmaceuticals Ltd | Pyridin-3-yl derivatives as immunomodulating agents |
| US8217027B2 (en) | 2006-12-21 | 2012-07-10 | Abbott Laboratories | Sphingosine-1-phosphate receptor agonist and antagonist compounds |
| CL2007003784A1 (es) * | 2006-12-21 | 2008-06-27 | Abbott Lab | Compuestos derivados de 1-amino-3-fenilciclopentano, que son agonistas o antagonistas de uno o mas receptores de la familia s1p; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar la esclerosis multiple, artritis reumato |
| CN101610674A (zh) * | 2006-12-21 | 2009-12-23 | 艾博特公司 | 鞘氨醇-1-磷酸酯受体激动剂和拮抗剂化合物 |
| GB0625648D0 (en) | 2006-12-21 | 2007-01-31 | Glaxo Group Ltd | Compounds |
| NZ578260A (en) | 2007-02-02 | 2012-02-24 | Hoffmann La Roche | Novel 2-aminooxazolines as taar1 ligands for cns disorders |
| SI2125797T1 (sl) | 2007-03-16 | 2014-03-31 | Actelion Pharmaceuticals Ltd. | Derivati amino-piridina kot agonisti receptorja s1p1/edg1 |
| EP2193125B1 (en) | 2007-10-04 | 2017-01-11 | Merck Serono S.A. | Oxadiazole derivatives |
| EP2217594B1 (en) | 2007-11-01 | 2014-01-08 | Actelion Pharmaceuticals Ltd. | Novel pyrimidine derivatives |
| GB0725105D0 (en) | 2007-12-21 | 2008-01-30 | Glaxo Group Ltd | Compounds |
| EP2280933B1 (en) | 2008-04-01 | 2013-07-24 | Theravance, Inc. | 2 -aminotetralin derivatives as mu opioid receptor antagonists |
| WO2010042998A1 (en) | 2008-10-17 | 2010-04-22 | Akaal Pharma Pty Ltd | S1p receptors modulators |
| US8741923B2 (en) | 2008-12-18 | 2014-06-03 | Merck Serono Sa | Oxadiazole fused heterocyclic derivatives useful for the treatment of multiple sclerosis |
| EP2202232A1 (en) | 2008-12-26 | 2010-06-30 | Laboratorios Almirall, S.A. | 1,2,4-oxadiazole derivatives and their therapeutic use |
| EP2210890A1 (en) | 2009-01-19 | 2010-07-28 | Almirall, S.A. | Oxadiazole derivatives as S1P1 receptor agonists |
| WO2010085581A1 (en) | 2009-01-23 | 2010-07-29 | Bristol-Myers Squibb Company | Substituted oxadiazole derivatives as s1p agonists in the treatment of autoimmune and inflammatory diseases |
| JP2012515788A (ja) | 2009-01-23 | 2012-07-12 | ブリストル−マイヤーズ スクイブ カンパニー | 自己免疫疾患および炎症性疾患の処置における、ｓ１ｐアゴニストとしての置換オキサジアゾール誘導体 |
| ES2405054T3 (es) | 2009-01-23 | 2013-05-30 | Bristol-Myers Squibb Company | Derivados de pirazol-1,2,4-oxadiazol como agonistas de esfingosina-1-fosfato |
| WO2010093616A1 (en) | 2009-02-10 | 2010-08-19 | Abbott Laboratories | Methods for preparing s1p receptor agonists and antagonists |
| US8399451B2 (en) | 2009-08-07 | 2013-03-19 | Bristol-Myers Squibb Company | Heterocyclic compounds |
| JP5728487B2 (ja) | 2009-10-29 | 2015-06-03 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 三環式ヘテロ環化合物 |
| WO2011133734A1 (en) | 2010-04-23 | 2011-10-27 | Bristol-Myers Squibb Company | 4 - (5 - isoxazolyl or 5 - pyrrazolyl -1,2,4- oxadiazol - 3 - yl) -mandelic acid amides as sphingosin- 1 - phosphate 1 rreceptor agonists |
| CN102260177A (zh) | 2010-05-25 | 2011-11-30 | 中国医学科学院药物研究所 | 丙二醇类衍生物、其制备方法和其药物组合物与用途 |
| CN102260178A (zh) | 2010-05-25 | 2011-11-30 | 中国医学科学院药物研究所 | 羟基丙二醇类衍生物、其制备方法和其药物组合物与用途 |
| ES2539256T3 (es) | 2010-07-20 | 2015-06-29 | Bristol-Myers Squibb Company | Compuestos de 3-fenil-1,2,4-oxadiazol sustituidos |
| US9187437B2 (en) | 2010-09-24 | 2015-11-17 | Bristol-Myers Squibb Company | Substituted oxadiazole compounds |
| ES2525298T3 (es) | 2010-11-03 | 2014-12-19 | Bristol-Myers Squibb Company | Compuestos heterocíclicos como agonistas del S1P1 para el tratamiento de enfermedades autoinmunes y vasculares |
| WO2012129073A2 (en) | 2011-03-18 | 2012-09-27 | University Of Virginia Patent Foundation | Compositions and methods for tissue engineering and cell based therapies |
| JP5090580B1 (ja) | 2011-04-26 | 2012-12-05 | パナソニック株式会社 | 暖房システム及び暖房システム制御方法 |
| GB201107325D0 (en) * | 2011-05-04 | 2011-06-15 | Glaxosmithkline Llc | Novel compounds |
| ES2758841T3 (es) | 2011-05-13 | 2020-05-06 | Celgene Int Ii Sarl | Moduladores heterocíclicos selectivos del receptor de la esfingosina-1-fosfato |
| TWI631097B (zh) | 2012-07-27 | 2018-08-01 | 百健Ｍａ公司 | 作爲ｓ１ｐ調節劑及／或ａｔｘ調節劑之化合物 |
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