CA2699417A1 - S1p receptor modulating compounds and use thereof - Google Patents
S1p receptor modulating compounds and use thereof Download PDFInfo
- Publication number
- CA2699417A1 CA2699417A1 CA2699417A CA2699417A CA2699417A1 CA 2699417 A1 CA2699417 A1 CA 2699417A1 CA 2699417 A CA2699417 A CA 2699417A CA 2699417 A CA2699417 A CA 2699417A CA 2699417 A1 CA2699417 A1 CA 2699417A1
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- Prior art keywords
- 5alk
- 4alk
- phenyl
- 6alk
- heteroaryl
- 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.)
- Abandoned
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US99481207P | 2007-09-20 | 2007-09-20 | |
| US60/994,812 | 2007-09-20 | ||
| PCT/US2008/010887 WO2009038759A2 (en) | 2007-09-20 | 2008-09-19 | 1-(4-(benzylbenzamid0) -benzyl) azetidine-3-carboxylic acid derivatives and related compounds as slp receptor modulators for the treatment of immune disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2699417A1 true CA2699417A1 (en) | 2009-03-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2699417A Abandoned CA2699417A1 (en) | 2007-09-20 | 2008-09-19 | S1p receptor modulating compounds and use thereof |
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| Country | Link |
|---|---|
| US (2) | US8080542B2 (enExample) |
| EP (1) | EP2188252B1 (enExample) |
| JP (1) | JP2010540438A (enExample) |
| AT (1) | ATE505454T1 (enExample) |
| AU (1) | AU2008302746B2 (enExample) |
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| WO (1) | WO2009038759A2 (enExample) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7919519B2 (en) | 2005-11-23 | 2011-04-05 | Epix Pharmaceuticals Inc. | S1P receptor modulating compounds and use thereof |
| CA2630714C (en) | 2005-11-23 | 2014-01-14 | Epix Delaware, Inc. | S1p receptor modulating compounds and use thereof |
| CA2646469A1 (en) | 2006-03-21 | 2007-09-27 | Epix Delaware, Inc. | S1p receptor modulating compounds |
| WO2009011850A2 (en) * | 2007-07-16 | 2009-01-22 | Abbott Laboratories | Novel therapeutic compounds |
| ATE505454T1 (de) | 2007-09-20 | 2011-04-15 | Amgen Inc | 1-(4-(4-benzylbenzamid)-benzyl)-azetidin-3- carboxylsäurederivate und entsprechende verbindungen als s1p-rezeptor-modulatoren zur behandlung von immunerkrankungen |
| TW201000099A (en) * | 2008-06-20 | 2010-01-01 | Amgen Inc | S1P1 receptor agonists and use thereof |
| US8791100B2 (en) * | 2010-02-02 | 2014-07-29 | Novartis Ag | Aryl benzylamine compounds |
| EP2643303A1 (en) | 2010-11-24 | 2013-10-02 | Allergan, Inc. | Modulators of s1p receptors |
| FR3017867A1 (fr) * | 2014-02-21 | 2015-08-28 | Inventiva | Nouveaux composes de type phenylazetidine carboxylate ou carboxamide |
| WO2015129859A1 (ja) * | 2014-02-28 | 2015-09-03 | キッセイ薬品工業株式会社 | 新規なアニリン誘導体、それを含有する医薬組成物およびそれらの用途 |
| US9895324B2 (en) | 2014-03-26 | 2018-02-20 | University Of Kentucky Research Foundation | Halogenated diarylacetylenes and methods of treating cancer |
| EP3365340B1 (en) | 2015-10-19 | 2022-08-10 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| HUE060680T2 (hu) | 2015-11-19 | 2023-04-28 | Incyte Corp | Heterociklusos vegyületek mint immunmodulátorok |
| EP3394033B1 (en) | 2015-12-22 | 2020-11-25 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| WO2017192961A1 (en) | 2016-05-06 | 2017-11-09 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| TW201808902A (zh) | 2016-05-26 | 2018-03-16 | 美商英塞特公司 | 作為免疫調節劑之雜環化合物 |
| MD3472167T2 (ro) | 2016-06-20 | 2023-02-28 | Incyte Corp | Compuși heterociclici ca imunomodulatori |
| WO2018013789A1 (en) | 2016-07-14 | 2018-01-18 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| US20180057486A1 (en) | 2016-08-29 | 2018-03-01 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| PE20200005A1 (es) | 2016-12-22 | 2020-01-06 | Incyte Corp | Derivados de tetrahidro imidazo[4,5-c]piridina como inductores de internalizacion pd-l1 |
| EP3558963B1 (en) | 2016-12-22 | 2022-03-23 | Incyte Corporation | Bicyclic heteroaromatic compounds as immunomodulators |
| EP3558973B1 (en) | 2016-12-22 | 2021-09-15 | Incyte Corporation | Pyridine derivatives as immunomodulators |
| EP3558989B1 (en) | 2016-12-22 | 2021-04-14 | Incyte Corporation | Triazolo[1,5-a]pyridine derivatives as immunomodulators |
| MA47123A (fr) | 2016-12-22 | 2021-03-17 | Incyte Corp | Dérivés de benzooxazole en tant qu'mmunomodulateurs |
| PL4212529T3 (pl) | 2018-03-30 | 2025-07-07 | Incyte Corporation | Związki heterocykliczne jako immunomodulatory |
| HRP20230306T1 (hr) | 2018-05-11 | 2023-05-12 | Incyte Corporation | Derivati tetrahidro-imidazo[4,5-c]piridina kao pd-l1 imunomodulatori |
| WO2021030162A1 (en) | 2019-08-09 | 2021-02-18 | Incyte Corporation | Salts of a pd-1/pd-l1 inhibitor |
| IL291471B2 (en) | 2019-09-30 | 2025-04-01 | Incyte Corp | Pyrimido[3,2–D]pyrimidine compounds as immunomodulators |
| CR20220237A (es) | 2019-11-11 | 2022-08-05 | Incyte Corp | Sales y formas cristalinas de un inhibidor de pd-1/pd-l1 |
| AR124001A1 (es) | 2020-11-06 | 2023-02-01 | Incyte Corp | Proceso para fabricar un inhibidor pd-1 / pd-l1 y sales y formas cristalinas del mismo |
| WO2022099075A1 (en) | 2020-11-06 | 2022-05-12 | Incyte Corporation | Crystalline form of a pd-1/pd-l1 inhibitor |
| US11780836B2 (en) | 2020-11-06 | 2023-10-10 | Incyte Corporation | Process of preparing a PD-1/PD-L1 inhibitor |
| CN113332435B (zh) * | 2021-06-18 | 2022-10-18 | 广州中医药大学(广州中医药研究院) | 鞘氨醇-1-磷酸4受体激动剂及其与真武汤联合在制备治疗慢性肾小球肾炎药物中的应用 |
| AU2022328136A1 (en) | 2021-08-10 | 2023-11-30 | Abbvie Inc. | Nicotinamide ripk1 inhibitors |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3329781A (en) | 1965-07-06 | 1967-07-04 | Mallory & Co Inc P R | Sequential timing device |
| US4767896A (en) | 1985-09-03 | 1988-08-30 | Molex Incorporated | Stamped circuitry assembly |
| DK0393607T3 (da) * | 1989-04-19 | 1996-03-18 | Otsuka Pharma Co Ltd | Phenylcarboxylsyrederivater med en heteroring |
| HUT63941A (en) * | 1992-05-15 | 1993-11-29 | Hoechst Ag | Process for producing 4-alkyl-substituted pyrimidine-5-carboxanilide derivatives, and fungicidal compositions comprising same |
| SK94393A3 (en) | 1992-09-11 | 1994-08-10 | Thomae Gmbh Dr K | Cyclic derivatives of urea, process for their production and their pharmaceutical agents with the content of those |
| EP0650961B1 (de) * | 1993-11-02 | 1997-03-05 | Hoechst Aktiengesellschaft | Substituierte heterocyclische Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE4405378A1 (de) | 1994-02-19 | 1995-08-24 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| WO1997045402A1 (fr) * | 1996-05-24 | 1997-12-04 | Ono Pharmaceutical Co., Ltd. | Derives de phenylsulfonamide |
| JPH10204059A (ja) | 1997-01-22 | 1998-08-04 | Ono Pharmaceut Co Ltd | フェニルスルホンアミド誘導体 |
| JP3802653B2 (ja) | 1997-05-21 | 2006-07-26 | オリンパス株式会社 | 立体画像表示装置 |
| US6384061B1 (en) | 1997-07-26 | 2002-05-07 | Lg Chemical Ltd. | Hydantoin compounds and methods related thereto |
| WO2000002851A1 (en) * | 1998-07-08 | 2000-01-20 | Aventis Pharma Deutschland Gmbh | Sulfur substituted sulfonylaminocarboxylic acid n-arylamides, their preparation, their use and pharmaceutical preparations comprising them |
| WO2000031536A2 (en) * | 1998-11-23 | 2000-06-02 | President And Fellows Of Harvard College | Detecting structural or synthetic information about chemical compounds |
| AU2002237988B2 (en) | 2001-01-30 | 2008-01-03 | University Of Virginia Patent Foundation | Agonists and antagonists of sphingosine-1-phosphate receptors |
| MXPA01013326A (es) | 2001-02-14 | 2002-08-26 | Warner Lambert Co | Bifenil sulfonamidas utiles como inhibisdores de metaloproteinasa de matriz. |
| US20020183519A1 (en) | 2001-03-13 | 2002-12-05 | Herbert Nar | Antithrombotic carboxylic acid amides |
| US20050113283A1 (en) | 2002-01-18 | 2005-05-26 | David Solow-Cordero | Methods of treating conditions associated with an EDG-4 receptor |
| AU2003216054B2 (en) | 2002-01-18 | 2007-01-04 | Merck & Co., Inc. | Selective S1P1/Edg1 receptor agonists |
| AU2003207567B2 (en) | 2002-01-18 | 2008-01-24 | Merck Sharp & Dohme Corp. | Edg receptor agonists |
| 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 |
| UA79300C2 (en) * | 2002-08-12 | 2007-06-11 | Janssen Pharmaceutica Nv | N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b secretion |
| US7820682B2 (en) | 2002-10-03 | 2010-10-26 | Ono Pharmaceutical Co., Ltd. | LPA receptor antagonist |
| CA2506799A1 (en) | 2002-11-21 | 2004-06-10 | Eli Lilly And Company | Mixed lineage kinase modulators |
| DE10300398A1 (de) | 2003-01-09 | 2004-07-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von substituierten 2-Phenylbenzimidazolen als Arzneimittel |
| WO2004113330A1 (en) | 2003-05-19 | 2004-12-29 | Irm Llc | Immunosuppressant compounds and compositions |
| AU2004251146A1 (en) | 2003-05-19 | 2005-01-06 | Irm, Llc | Immunosuppressant compounds and compositions |
| US7723376B2 (en) * | 2003-07-15 | 2010-05-25 | Korea Research Institute Of Bioscience And Biotechnology | 2-oxo-heterocyclic compounds and pharmaceutical compositions |
| ES2754221T3 (es) | 2003-08-29 | 2020-04-16 | Ono Pharmaceutical Co | Compuesto capaz de unirse al receptor de S1P y uso farmacéutico del mismo |
| BRPI0514316A (pt) * | 2004-08-13 | 2008-06-10 | Praecis Pharm Inc | métodos e composições para modulação de atividade de receptor de esfingosina-1-fosfato (s1p) |
| US20060223866A1 (en) * | 2004-08-13 | 2006-10-05 | Praecis Pharmaceuticals, Inc. | Methods and compositions for modulating sphingosine-1-phosphate (S1P) receptor activity |
| SI1650186T1 (sl) * | 2004-10-22 | 2008-12-31 | Bioprojet Soc Civ | Novi derivati dikarboksilne kisline |
| EP2371811B1 (en) | 2004-12-13 | 2014-10-08 | Ono Pharmaceutical Co., Ltd. | Azetidinecarboxylic acid derivative and medicinal use thereof |
| JP2007051121A (ja) * | 2005-07-22 | 2007-03-01 | Taiho Yakuhin Kogyo Kk | プロスタグランジンｄ合成酵素を阻害するピリミジン化合物 |
| CA2630714C (en) * | 2005-11-23 | 2014-01-14 | Epix Delaware, Inc. | S1p receptor modulating compounds and use thereof |
| US7919519B2 (en) * | 2005-11-23 | 2011-04-05 | Epix Pharmaceuticals Inc. | S1P receptor modulating compounds and use thereof |
| CA2646469A1 (en) | 2006-03-21 | 2007-09-27 | Epix Delaware, Inc. | S1p receptor modulating compounds |
| CA2679980A1 (en) | 2007-03-21 | 2007-09-27 | Epix Pharmaceuticals, Inc. | S1p receptor modulating compounds and use thereof |
| BRPI0814975A2 (pt) * | 2007-08-08 | 2015-02-03 | Merck Serono Sa | Derivados de 6-amino-pirimidina-4-carboxamida e compostos relacionados que se ligam ao receptor de 1-fosfato de esfingosina (s1p) para o tratamento de esclerose múltipla |
| ATE505454T1 (de) | 2007-09-20 | 2011-04-15 | Amgen Inc | 1-(4-(4-benzylbenzamid)-benzyl)-azetidin-3- carboxylsäurederivate und entsprechende verbindungen als s1p-rezeptor-modulatoren zur behandlung von immunerkrankungen |
| US7939546B2 (en) * | 2007-10-12 | 2011-05-10 | Supergen, Inc. | Quinoline derivatives for modulating DNA methylation |
-
2008
- 2008-09-19 AT AT08831946T patent/ATE505454T1/de not_active IP Right Cessation
- 2008-09-19 ES ES08831946T patent/ES2360929T3/es active Active
- 2008-09-19 AU AU2008302746A patent/AU2008302746B2/en not_active Ceased
- 2008-09-19 WO PCT/US2008/010887 patent/WO2009038759A2/en not_active Ceased
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- 2008-09-19 US US12/234,514 patent/US8080542B2/en not_active Expired - Fee Related
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- 2008-09-19 EP EP08831946A patent/EP2188252B1/en active Active
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| EP2188252A2 (en) | 2010-05-26 |
| WO2009038759A3 (en) | 2009-07-23 |
| US8080542B2 (en) | 2011-12-20 |
| JP2010540438A (ja) | 2010-12-24 |
| MX2010002885A (es) | 2010-04-01 |
| ATE505454T1 (de) | 2011-04-15 |
| US20120088749A1 (en) | 2012-04-12 |
| AU2008302746B2 (en) | 2014-07-03 |
| AU2008302746A1 (en) | 2009-03-26 |
| EP2188252B1 (en) | 2011-04-13 |
| DE602008006209D1 (de) | 2011-05-26 |
| ES2360929T3 (es) | 2011-06-10 |
| US20090082331A1 (en) | 2009-03-26 |
| WO2009038759A2 (en) | 2009-03-26 |
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