CN102548989A - 1-磷酸-鞘氨醇受体激动剂 - Google Patents
1-磷酸-鞘氨醇受体激动剂 Download PDFInfo
- Publication number
- CN102548989A CN102548989A CN2010800453726A CN201080045372A CN102548989A CN 102548989 A CN102548989 A CN 102548989A CN 2010800453726 A CN2010800453726 A CN 2010800453726A CN 201080045372 A CN201080045372 A CN 201080045372A CN 102548989 A CN102548989 A CN 102548989A
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- China
- Prior art keywords
- phenyl
- oxadiazole
- piperidines
- trifluoromethyl
- ethyl
- 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.)
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- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 title description 6
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 title description 6
- 239000000018 receptor agonist Substances 0.000 title 1
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 340
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- 125000000217 alkyl group Chemical group 0.000 claims description 22
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- GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 claims description 19
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- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
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- DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 77
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| ES2548683T3 (es) * | 2010-04-23 | 2015-10-20 | Bristol-Myers Squibb Company | Amidas del ácido 4-(5-isoxazolil o 5-pirrazolil-1,2,4-oxadiazol-3-il)-mandélico como agonistas de receptor de esfingosina-1-fosfato 1 |
| US8822510B2 (en) | 2010-07-20 | 2014-09-02 | Bristol-Myers Squibb Company | Substituted 3-phenyl-1,2,4-Oxadiazole compounds |
| EP2619190B1 (en) | 2010-09-24 | 2015-08-12 | Bristol-Myers Squibb Company | Substituted oxadiazole compounds and their use as s1p1 agonists |
| EP2635573B1 (en) | 2010-11-03 | 2014-10-01 | Bristol-Myers Squibb Company | Heterocyclic compounds as s1p1 agonists for the treatment of autoimmune and vascular diseases |
| US9115054B2 (en) | 2013-02-21 | 2015-08-25 | Bristol-Myers Squibb Company | Tetrahydronaphthalenyl compounds useful as sipi agonists |
| MA40082B1 (fr) | 2014-08-20 | 2019-09-30 | Bristol Myers Squibb Co | Nouveau compose de substitution sphingosine phosphate utile traitement maladie rhumatisme |
| PY1974248A (es) * | 2018-09-13 | 2020-08-21 | Syngenta Participations Ag | Compuestos de azol-amida pesticidamente activos |
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| WO2003062252A1 (en) * | 2002-01-18 | 2003-07-31 | Merck & Co., Inc. | Edg receptor agonists |
| CN1859908A (zh) * | 2003-10-01 | 2006-11-08 | 默克公司 | 作为s1p受体激动剂的3,5－芳基、杂芳基或环烷基取代的－1,2,4－噁二唑类化合物 |
| WO2008029370A1 (en) * | 2006-09-08 | 2008-03-13 | Actelion Pharmaceuticals Ltd | Pyridin-3-yl derivatives as immunomodulating agents |
| WO2009080663A1 (en) * | 2007-12-21 | 2009-07-02 | Merck Serono S.A. | Triazole oxadiazoles derivatives |
Family Cites Families (69)
| 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 |
| JPS6480026A (en) | 1987-09-21 | 1989-03-24 | Mitsubishi Electric Corp | Resist coater |
| DE4102024A1 (de) * | 1991-01-24 | 1992-07-30 | Thomae Gmbh Dr K | Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| TW432061B (en) | 1994-08-09 | 2001-05-01 | Pfizer Res & Dev | Lactams |
| US6069143A (en) * | 1994-12-20 | 2000-05-30 | Smithkline Beecham Corporation | Fibrinogen receptor antagonists |
| DE69718194T2 (de) | 1996-08-16 | 2003-10-16 | Bristol-Myers Squibb Pharma Co., Wilmington | Amidinophenyl-pyrrolidine, -pyrroline und -isoxazolidine und ihre derivate |
| WO2003061567A2 (en) | 2002-01-18 | 2003-07-31 | Merck & Co., Inc. | Selective s1p1/edg1 receptor agonists |
| ATE448193T1 (de) | 2002-01-18 | 2009-11-15 | Merck & Co Inc | ßN-(BENZYL)AMINOALKYL CARBOXYLATE, PHOSPHINATE, PHOSPHONATE UND TETRAZOLE ALS EDG REZEPTORAGONISTENß |
| JP2005531506A (ja) | 2002-03-01 | 2005-10-20 | メルク エンド カムパニー インコーポレーテッド | Ｅｄｇ受容体作動薬としてのアミノアルキルホスホネートおよび関連化合物 |
| PT1497019E (pt) * | 2002-04-23 | 2015-09-10 | Bristol Myers Squibb Co | Compostos de pirrolotriazina anilina úteis como inibidores de quinase |
| JP2005533058A (ja) * | 2002-06-17 | 2005-11-04 | メルク エンド カムパニー インコーポレーテッド | Ｅｄｇ受容体アゴニストとしての１−（（５−アリール−１，２，４−オキサジアゾール−３−イル）ベンジル）アゼチジン−３−カルボキシラートおよび１−（（５−アリール−１，２，４−オキサジアゾール−３−イル）ベンジル）ピロリジン−３−カルボキシラート |
| WO2004035538A1 (en) | 2002-10-15 | 2004-04-29 | Merck & Co., Inc. | Process for making azetidine-3-carboxylic acid |
| DE60335827D1 (de) | 2002-12-20 | 2011-03-03 | Merck Sharp & Dohme | 1-(amino)indane als edg-rezeptoragonisten |
| PL378134A1 (pl) | 2003-02-11 | 2006-03-06 | Irm Llc | Nowe pochodne bicykliczne i kompozycje farmaceutyczne zawierające pochodne bicykliczne |
| AU2004240586A1 (en) | 2003-05-15 | 2004-12-02 | Merck & Co., Inc. | 3-(2-amino-1-azacyclyl)-5-aryl-1,2,4-oxadiazoles as S1P receptor agonists |
| CL2004001120A1 (es) | 2003-05-19 | 2005-04-15 | Irm Llc | Compuestos derivados de amina sustituidas con heterociclos, inmunosupresores; composicion farmaceutica; y uso para tratar enfermedades mediadas por interacciones de linfocito, tales como enfermedades autoinmunes, inflamatorias, infecciosas, cancer. |
| MY150088A (en) | 2003-05-19 | 2013-11-29 | Irm Llc | Immunosuppressant compounds and compositions |
| EP1644367B1 (en) | 2003-05-19 | 2015-10-14 | Novartis AG | Immunosuppressant compounds and compositions |
| MXPA05012459A (es) | 2003-05-19 | 2006-02-22 | Irm Llc | Compuestos y composiciones inmunosupresoras. |
| EP1697333A4 (en) | 2003-12-17 | 2009-07-08 | Merck & Co Inc | (3,4-DISUBSTITUTED) PROPANE ACID BOXYLATES AS AGONISTS OF THE S1P (EDG) RECEPTOR |
| TW200538433A (en) * | 2004-02-24 | 2005-12-01 | Irm Llc | Immunosuppressant compounds and compositiions |
| CA2583681A1 (en) | 2004-10-22 | 2006-05-04 | Merck & Co., Inc. | 2-(aryl)azacyclylmethyl carboxylates, sulfonates, phosphonates, phosphinates and heterocycles as s1p receptor agonists |
| US7754703B2 (en) | 2005-02-14 | 2010-07-13 | University Of Virginia Patent Foundation | Cycloalkane-containing sphingosine 1-phosphate agonists |
| US7605269B2 (en) | 2005-03-23 | 2009-10-20 | Actelion Pharmaceuticals Ltd. | Thiophene derivatives as Sphingosine-1-phosphate-1 receptor agonists |
| CA2602474C (en) | 2005-03-23 | 2014-06-10 | Actelion Pharmaceuticals Ltd | Hydrogenated benzo (c) thiophene derivatives as immunomodulators |
| 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 |
| US7951794B2 (en) | 2005-06-24 | 2011-05-31 | Actelion Pharmaceuticals Ltd. | Thiophene derivatives |
| BRPI0615133A2 (pt) | 2005-08-23 | 2011-05-03 | Irm Llc | compostos imunossupressores, composições farmacêuticas contendo os mesmos assim como referido uso |
| TW200800911A (en) | 2005-10-20 | 2008-01-01 | Biolipox Ab | Pyrazoles useful in the treatment of inflammation |
| EP1965807A4 (en) * | 2005-11-23 | 2010-10-27 | Epix Delaware Inc | S1P RECEPTOR MODULATING COMPOUNDS AND THEIR USE |
| TWI404706B (zh) | 2006-01-11 | 2013-08-11 | Actelion Pharmaceuticals Ltd | 新穎噻吩衍生物 |
| GB0601744D0 (en) | 2006-01-27 | 2006-03-08 | Novartis Ag | Organic compounds |
| TW200806611A (en) | 2006-02-09 | 2008-02-01 | Daiichi Seiyaku Co | Novel amidopropionic acid derivatives and medicine containing the same |
| AU2007227274A1 (en) | 2006-03-21 | 2007-09-27 | Epix Delaware, Inc. | S1P receptor modulating compounds |
| PL2003132T3 (pl) | 2006-04-03 | 2014-10-31 | Astellas Pharma Inc | Pochodne oksadiazolu jako agoniści S1P1 |
| EP2046766A1 (en) | 2006-08-01 | 2009-04-15 | Praecis Pharmaceuticals Incorporated | Agonists of the sphingosine- 1- phosphate receptor (slp) |
| JP2009269819A (ja) * | 2006-08-25 | 2009-11-19 | Asahi Kasei Pharma Kk | アミン化合物 |
| PT2069336E (pt) | 2006-09-07 | 2013-03-07 | Actelion Pharmaceuticals Ltd | Derivados de piridin-4-ilo como agentes imunomoduladores |
| AR061841A1 (es) | 2006-09-07 | 2008-09-24 | Actelion Pharmaceuticals Ltd | Derivados de tiofen-oxadiazoles, agonistas del receptor s1p1/edg1, composiciones farmaceuticas que los contienen y usos como agentes inmunomoduladores. |
| CA2662852A1 (en) | 2006-09-07 | 2008-03-13 | Allergan, Inc. | Heteroaromatic compounds having sphingosine-1-phosphate (s1p) receptor agonist and/or antagonist biological activity |
| KR20090060333A (ko) | 2006-09-08 | 2009-06-11 | 노파르티스 아게 | 림프구 상호작용에 의해 매개되는 질환의 치료에 유용한 ｎ-바이아릴 (헤테로)아릴술폰아미드 유도체 |
| ES2393412T3 (es) | 2006-09-21 | 2012-12-21 | Actelion Pharmaceuticals Ltd. | Derivados de fenilo y su uso como inmunomoduladores |
| CN101522646A (zh) | 2006-09-29 | 2009-09-02 | 诺瓦提斯公司 | 具有抗炎和免疫抑制特性的二唑衍生物 |
| JP2010510249A (ja) | 2006-11-21 | 2010-04-02 | 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 | スフィンゴシン＝１−燐酸アゴニスト活性を有するテトラリンアナログ |
| EP2109364A4 (en) | 2006-12-15 | 2010-04-14 | Abbott Lab | NOVEL OXADIAZONE COMPOUNDS |
| BRPI0720478A2 (pt) | 2006-12-21 | 2014-01-14 | Abbott Laboratoires | Compostos agonistas e antagonistas do receptor esfingosina-1-fosfato |
| JO2701B1 (en) | 2006-12-21 | 2013-03-03 | جلاكسو جروب ليميتد | Vehicles |
| GB0625648D0 (en) | 2006-12-21 | 2007-01-31 | Glaxo Group Ltd | Compounds |
| WO2008091967A1 (en) | 2007-01-26 | 2008-07-31 | Smithkline Beecham Corporation | Chemical compounds |
| BRPI0808789A2 (pt) | 2007-03-16 | 2014-08-12 | Actelion Pharmaceuticals Ltd | Compostos e composição farmacêutica de derivados aminopiridina e uso destes |
| AU2008240773B2 (en) * | 2007-04-19 | 2013-10-03 | Glaxo Group Limited | Oxadiazole substituted indazole derivatives for use as sphingosine 1-phosphate (S1P) agonists |
| WO2009011850A2 (en) | 2007-07-16 | 2009-01-22 | Abbott Laboratories | Novel therapeutic compounds |
| CN104478821B (zh) | 2007-10-04 | 2016-09-28 | 默克雪兰诺有限公司 | 噁二唑二芳基化合物 |
| MX2010003612A (es) | 2007-10-04 | 2010-04-30 | Merck Serono Sa | Derivados de oxadiazol. |
| KR20100092473A (ko) | 2007-11-01 | 2010-08-20 | 액테리온 파마슈티칼 리미티드 | 신규한 피리미딘 유도체 |
| EP3782991A1 (en) | 2008-05-14 | 2021-02-24 | The Scripps Research Institute | Novel modulators of sphingosine phosphate receptors |
| JP5537433B2 (ja) | 2008-10-06 | 2014-07-02 | 昭和電工株式会社 | 触媒およびその製造方法ならびにその用途 |
| US20100160369A1 (en) * | 2008-12-04 | 2010-06-24 | Exelixis, Inc. | S1P1 Agonists and Methods of Making And Using |
| MX2011005954A (es) | 2008-12-05 | 2011-10-11 | Astellas Pharma Inc | Compuesto de 2h-cromeno y su derivado. |
| US8741923B2 (en) | 2008-12-18 | 2014-06-03 | Merck Serono Sa | Oxadiazole fused heterocyclic derivatives useful for the treatment of multiple sclerosis |
| UY32349A (es) | 2008-12-23 | 2010-07-30 | Novartis Ag | Derivados de biaril-bencil-amina |
| 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 |
| WO2010085582A1 (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 |
| JP2012515787A (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 |
| JP5669363B2 (ja) | 2009-03-31 | 2015-02-12 | 昭和電工株式会社 | 樹脂組成物及びこれで処理された紙又は繊維加工品 |
| CN102369747A (zh) | 2009-04-03 | 2012-03-07 | 松下电器产业株式会社 | 移动通信方法、移动通信系统和对应设备 |
-
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- 2010-08-06 PE PE2012000174A patent/PE20120732A1/es not_active Application Discontinuation
- 2010-08-06 EP EP10742067.1A patent/EP2462139B1/en not_active Not-in-force
- 2010-08-06 BR BR112012002824A patent/BR112012002824A2/pt not_active IP Right Cessation
- 2010-08-06 TW TW099126390A patent/TW201109323A/zh unknown
- 2010-08-06 CN CN2010800453726A patent/CN102548989A/zh active Pending
- 2010-08-06 EA EA201270266A patent/EA201270266A1/ru unknown
- 2010-08-06 CA CA2770194A patent/CA2770194A1/en not_active Abandoned
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- 2012-02-07 CL CL2012000326A patent/CL2012000326A1/es unknown
- 2012-02-16 CO CO12027713A patent/CO6430439A2/es not_active Application Discontinuation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003062252A1 (en) * | 2002-01-18 | 2003-07-31 | Merck & Co., Inc. | Edg receptor agonists |
| CN1859908A (zh) * | 2003-10-01 | 2006-11-08 | 默克公司 | 作为s1p受体激动剂的3,5－芳基、杂芳基或环烷基取代的－1,2,4－噁二唑类化合物 |
| WO2008029370A1 (en) * | 2006-09-08 | 2008-03-13 | Actelion Pharmaceuticals Ltd | Pyridin-3-yl derivatives as immunomodulating agents |
| WO2009080663A1 (en) * | 2007-12-21 | 2009-07-02 | Merck Serono S.A. | Triazole oxadiazoles derivatives |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114181276A (zh) * | 2021-12-17 | 2022-03-15 | 安徽大学 | 硫酯肽合成方法 |
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| CL2012000326A1 (es) | 2012-10-19 |
| BR112012002824A2 (pt) | 2019-09-24 |
| EA201270266A1 (ru) | 2012-07-30 |
| CO6430439A2 (es) | 2012-04-30 |
| PE20120732A1 (es) | 2012-06-20 |
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| JP2013501729A (ja) | 2013-01-17 |
| EP2462139B1 (en) | 2015-01-14 |
| EP2462139A1 (en) | 2012-06-13 |
| MX2012001160A (es) | 2012-02-13 |
| SG177691A1 (en) | 2012-02-28 |
| JP5602230B2 (ja) | 2014-10-08 |
| ZA201200641B (en) | 2013-06-26 |
| KR20120108963A (ko) | 2012-10-05 |
| US20110190255A1 (en) | 2011-08-04 |
| TW201109323A (en) | 2011-03-16 |
| AU2010279354A1 (en) | 2012-02-09 |
| AR077819A1 (es) | 2011-09-28 |
| US8399451B2 (en) | 2013-03-19 |
| WO2011017578A1 (en) | 2011-02-10 |
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