JP2010540438A - 免疫障害を処置するためのｓ１ｐ受容体調節剤としての１−（４−ベンジルベンズアミド）−ベンジル）アゼチジン−３−カルボン酸誘導体および関連化合物 - Google Patents
免疫障害を処置するためのｓ１ｐ受容体調節剤としての１−（４−ベンジルベンズアミド）−ベンジル）アゼチジン−３−カルボン酸誘導体および関連化合物 Download PDFInfo
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- JP2010540438A JP2010540438A JP2010525834A JP2010525834A JP2010540438A JP 2010540438 A JP2010540438 A JP 2010540438A JP 2010525834 A JP2010525834 A JP 2010525834A JP 2010525834 A JP2010525834 A JP 2010525834A JP 2010540438 A JP2010540438 A JP 2010540438A
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Landscapes
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| 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 |
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| JP2010540438A true JP2010540438A (ja) | 2010-12-24 |
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| EP (1) | EP2188252B1 (enExample) |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
Families Citing this family (33)
| 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 |
| 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 |
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Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0632784A (ja) * | 1992-05-15 | 1994-02-08 | Hoechst Ag | ４−アルキル−置換ピリミジン−５−カルボキシアニリド、それらの製造方法、それらを含有する組成物およびそれらの殺菌剤としての用途 |
| JPH07228571A (ja) * | 1993-11-02 | 1995-08-29 | Hoechst Ag | 置換された複素環式カルボキサミド、それらの製法および医薬としてのそれらの使用 |
| JPH10265452A (ja) * | 1996-05-24 | 1998-10-06 | Ono Pharmaceut Co Ltd | フェニルスルホンアミド誘導体 |
| JP2002520309A (ja) * | 1998-07-08 | 2002-07-09 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 硫黄置換スルホニルアミノカルボン酸ｎ−アリールアミド、それらの製造、それらの使用、及びそれらを含む医薬製剤 |
| WO2005020882A2 (ja) * | 2003-08-29 | 2005-03-10 | Ono Pharmaceutical Co | Ｓ１ｐ受容体結合能を有する化合物およびその医薬用途 |
| JP2005515259A (ja) * | 2002-01-18 | 2005-05-26 | 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 |
| JP2006500371A (ja) * | 2002-08-12 | 2006-01-05 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | アポリポタンパク質ｂ分泌阻害剤としてのｎ−アリールピペリジン置換ビフェニルカルボキサミド類 |
| WO2006020951A1 (en) * | 2004-08-13 | 2006-02-23 | Praecis Pharmaceuticals, Inc. | Methods and compositions for modulating sphingosine-1-phosphate (s1p) receptor activity |
| WO2006043149A2 (en) * | 2004-10-22 | 2006-04-27 | Bioprojet | Novel dicarboxylic acid derivatives |
| 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 |
| WO2007061458A2 (en) * | 2005-11-23 | 2007-05-31 | Epix Delaware, Inc. | S1p receptor modulating compounds and use thereof |
| WO2007092190A2 (en) * | 2006-02-06 | 2007-08-16 | Praecis Pharmaceuticals, Inc. | Methods and compositions for modulating sphingosine-1-phosphate (s1p) receptor activity |
Family Cites Families (28)
| 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 |
| 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 |
| DE4405378A1 (de) | 1994-02-19 | 1995-08-24 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| 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 |
| 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 |
| 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 |
| 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 |
| EP2371811B1 (en) | 2004-12-13 | 2014-10-08 | Ono Pharmaceutical Co., Ltd. | Azetidinecarboxylic acid derivative and medicinal 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
- 2008-09-19 DE DE602008006209T patent/DE602008006209D1/de active Active
- 2008-09-19 MX MX2010002885A patent/MX2010002885A/es active IP Right Grant
- 2008-09-19 US US12/234,514 patent/US8080542B2/en not_active Expired - Fee Related
- 2008-09-19 CA CA2699417A patent/CA2699417A1/en not_active Abandoned
- 2008-09-19 JP JP2010525834A patent/JP2010540438A/ja active Pending
- 2008-09-19 EP EP08831946A patent/EP2188252B1/en active Active
-
2011
- 2011-12-16 US US13/327,951 patent/US20120088749A1/en not_active Abandoned
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0632784A (ja) * | 1992-05-15 | 1994-02-08 | Hoechst Ag | ４−アルキル−置換ピリミジン−５−カルボキシアニリド、それらの製造方法、それらを含有する組成物およびそれらの殺菌剤としての用途 |
| JPH07228571A (ja) * | 1993-11-02 | 1995-08-29 | Hoechst Ag | 置換された複素環式カルボキサミド、それらの製法および医薬としてのそれらの使用 |
| JPH10265452A (ja) * | 1996-05-24 | 1998-10-06 | Ono Pharmaceut Co Ltd | フェニルスルホンアミド誘導体 |
| JP2002520309A (ja) * | 1998-07-08 | 2002-07-09 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 硫黄置換スルホニルアミノカルボン酸ｎ−アリールアミド、それらの製造、それらの使用、及びそれらを含む医薬製剤 |
| JP2005515259A (ja) * | 2002-01-18 | 2005-05-26 | 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 |
| JP2006500371A (ja) * | 2002-08-12 | 2006-01-05 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | アポリポタンパク質ｂ分泌阻害剤としてのｎ−アリールピペリジン置換ビフェニルカルボキサミド類 |
| WO2005020882A2 (ja) * | 2003-08-29 | 2005-03-10 | Ono Pharmaceutical Co | Ｓ１ｐ受容体結合能を有する化合物およびその医薬用途 |
| WO2006020951A1 (en) * | 2004-08-13 | 2006-02-23 | Praecis Pharmaceuticals, Inc. | Methods and compositions for modulating sphingosine-1-phosphate (s1p) receptor activity |
| WO2006043149A2 (en) * | 2004-10-22 | 2006-04-27 | Bioprojet | Novel dicarboxylic acid derivatives |
| 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 |
| WO2007061458A2 (en) * | 2005-11-23 | 2007-05-31 | Epix Delaware, Inc. | S1p receptor modulating compounds and use thereof |
| WO2007092190A2 (en) * | 2006-02-06 | 2007-08-16 | Praecis Pharmaceuticals, Inc. | Methods and compositions for modulating sphingosine-1-phosphate (s1p) receptor activity |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JPWO2015129859A1 (ja) * | 2014-02-28 | 2017-03-30 | 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 |
| US9718771B2 (en) | 2014-02-28 | 2017-08-01 | Kissei Pharmaceutical Co., Ltd. | Aniline derivative, pharmaceutical composition containing same, and use thereof |
| US9988350B2 (en) | 2014-02-28 | 2018-06-05 | Kissei Pharmaceutical Co., Ltd. | Aniline derivative, pharmaceutical composition containing same, and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2188252A2 (en) | 2010-05-26 |
| WO2009038759A3 (en) | 2009-07-23 |
| US8080542B2 (en) | 2011-12-20 |
| CA2699417A1 (en) | 2009-03-26 |
| 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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