CN102361867A - 在治疗自身免疫疾病和炎性疾病中作为s1p激动剂的取代的噁二唑衍生物 - Google Patents
在治疗自身免疫疾病和炎性疾病中作为s1p激动剂的取代的噁二唑衍生物 Download PDFInfo
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- CN102361867A CN102361867A CN2010800132551A CN201080013255A CN102361867A CN 102361867 A CN102361867 A CN 102361867A CN 2010800132551 A CN2010800132551 A CN 2010800132551A CN 201080013255 A CN201080013255 A CN 201080013255A CN 102361867 A CN102361867 A CN 102361867A
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- Prior art keywords
- phenyl
- carboxylic acid
- isoxazole
- benzyl
- azetidine
- Prior art date
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Classifications
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
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- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US61/146,827 | 2009-01-23 | ||
| PCT/US2010/021693 WO2010085581A1 (en) | 2009-01-23 | 2010-01-22 | Substituted oxadiazole derivatives as s1p agonists in the treatment of autoimmune and inflammatory diseases |
Publications (1)
| Publication Number | Publication Date |
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| CN102361867A true CN102361867A (zh) | 2012-02-22 |
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| CN2010800132551A Pending CN102361867A (zh) | 2009-01-23 | 2010-01-22 | 在治疗自身免疫疾病和炎性疾病中作为s1p激动剂的取代的噁二唑衍生物 |
Country Status (5)
| Country | Link |
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| US (1) | US8354398B2 (https=) |
| EP (1) | EP2382212B1 (https=) |
| JP (1) | JP2012515787A (https=) |
| CN (1) | CN102361867A (https=) |
| WO (1) | WO2010085581A1 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108463460A (zh) * | 2016-01-08 | 2018-08-28 | 先正达参股股份有限公司 | 杀微生物的噁二唑衍生物 |
| CN112079791A (zh) * | 2020-08-21 | 2020-12-15 | 宁夏农林科学院农业资源与环境研究所(宁夏土壤与植物营养重点实验室) | 单环β-内酰胺类抗生素侧链酸及其酯、其制备方法和应用 |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| EP2389377B1 (en) | 2009-01-23 | 2014-07-16 | Bristol-Myers Squibb Company | Substituted oxadiazole derivatives as s1p agonists in the treatment of autoimmune and inflammatory diseases |
| US8399451B2 (en) | 2009-08-07 | 2013-03-19 | Bristol-Myers Squibb Company | Heterocyclic compounds |
| 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 |
| JP5788507B2 (ja) | 2010-07-20 | 2015-09-30 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 置換3−フェニル−1,2,4−オキサジアゾール化合物 |
| EP2619190B1 (en) | 2010-09-24 | 2015-08-12 | Bristol-Myers Squibb Company | Substituted oxadiazole compounds and their use as s1p1 agonists |
| WO2012061459A1 (en) | 2010-11-03 | 2012-05-10 | Bristol-Myers Squibb Company | Heterocyclic compounds as s1p1 agonists for the treatment of autoimmune and vascular diseases |
| RU2013130019A (ru) * | 2010-12-03 | 2015-01-10 | Аллерган, Инк. | Новые производные азетидина в качестве модуляторов рецептора сфингозин 1-фосфата (s1p) |
| HUE036027T2 (hu) * | 2011-01-28 | 2018-08-28 | Immunic Ag | IL17 és IFN-gamma inhibitorok autoimmun gyulladás kezelésére |
| US8859598B2 (en) * | 2012-10-04 | 2014-10-14 | Allergan, Inc. | 1, 2, 4-oxadiazoles azetidine derivatives as sphingosine-1 phosphate receptors modulators |
| CN102977046B (zh) * | 2012-11-30 | 2016-01-20 | 石家庄诚志永华显示材料有限公司 | 1,2,4-噁二唑类化合物及其制备方法与应用 |
| TWI613182B (zh) | 2013-02-21 | 2018-02-01 | 必治妥美雅史谷比公司 | 雙環化合物 |
| CN103450171B (zh) * | 2013-09-22 | 2015-07-08 | 苏州康乃德生物医药有限公司 | 一种免疫调节化合物、其用途和包含其的药物组合物 |
| TWI689487B (zh) | 2014-08-20 | 2020-04-01 | 美商必治妥美雅史谷比公司 | 經取代雙環化合物 |
| AR109304A1 (es) | 2016-08-10 | 2018-11-21 | Sumitomo Chemical Co | Compuesto de oxadiazol y su uso |
| CN115233243B (zh) * | 2022-06-27 | 2025-05-16 | 台州学院 | 一种电催化下2,4,5-三取代噁唑衍生物的制备方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003062252A1 (en) * | 2002-01-18 | 2003-07-31 | Merck & Co., Inc. | Edg receptor agonists |
| US20050245575A1 (en) * | 2002-06-17 | 2005-11-03 | Weirong Chen | 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 |
| CN1788008A (zh) * | 2003-05-15 | 2006-06-14 | 麦克公司 | 作为s1p受体激动剂的3-(2-氨基-1-氮杂环基)-5-芳基-1,2,4-噁二唑 |
| CN101184739A (zh) * | 2005-06-08 | 2008-05-21 | 诺瓦提斯公司 | 多环二唑类和异唑类化合物及其作为s1p受体的配体的用途 |
| WO2009011850A2 (en) * | 2007-07-16 | 2009-01-22 | Abbott Laboratories | Novel therapeutic compounds |
Family Cites Families (38)
| 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 |
| US20050070506A1 (en) | 2002-01-18 | 2005-03-31 | Doherty George A. | 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 |
| US7309721B2 (en) | 2002-03-01 | 2007-12-18 | Merck + Co., Inc. | Aminoalkylphosphonates and related compounds as Edg receptor agonists |
| JP2006508145A (ja) | 2002-11-15 | 2006-03-09 | テイボテク・フアーマシユーチカルズ・リミテツド | 抗感染化合物としての置換インドールピリジニウム |
| JP4516430B2 (ja) | 2002-12-20 | 2010-08-04 | メルク・シャープ・エンド・ドーム・コーポレイション | 1−(アミノ)インダン並びに(1,2−ジヒドロ−3−アミノ)−ベンゾフラン、ベンゾチオフェン及びインドール |
| BRPI0410439A (pt) | 2003-05-19 | 2006-06-06 | Irm Llc | compostos e composições imunossupressoras |
| US7605171B2 (en) | 2003-12-17 | 2009-10-20 | Merck & Co., Inc. | (3,4-disubstituted)propanoic carboxylates as S1P (Edg) receptor agonists |
| TW200538433A (en) | 2004-02-24 | 2005-12-01 | Irm Llc | Immunosuppressant compounds and compositiions |
| AU2005299851B2 (en) | 2004-10-22 | 2011-03-17 | Merck Sharp & Dohme Corp. | 2-(aryl)azacyclylmethyl carboxylates, sulfonates, phosphonates, phosphinates and heterocycles as S1P receptor agonists |
| AU2006214314B2 (en) | 2005-02-14 | 2012-02-09 | University Of Virginia Patent Foundation | Sphingosine 1- phos phate agonists comprising cycloalkanes and 5 -membered heterocycles substituted by amino and phenyl groups |
| US7723378B2 (en) | 2005-03-23 | 2010-05-25 | Actelion Pharmaceuticals Ltd. | Hydrogenated benzo (C) thiophene derivatives as immunomodulators |
| BRPI0609668A2 (pt) | 2005-03-23 | 2011-10-18 | Actelion Pharmaceuticals Ltd | composto, composição farmacêutica, e, uso de um composto |
| CN101203512A (zh) | 2005-04-22 | 2008-06-18 | 第一三共株式会社 | 杂环化合物 |
| BRPI0612028A2 (pt) | 2005-06-08 | 2010-10-13 | Novartis Ag | oxadiazóis ou isodiazóis policìclicos e uso dos mesmos como ligantes de receptor s1p |
| WO2007024922A1 (en) | 2005-08-23 | 2007-03-01 | Irm Llc | Immunosuppressant compounds and compositions |
| EP1965807A4 (en) | 2005-11-23 | 2010-10-27 | Epix Delaware Inc | S1P RECEPTOR MODULATING COMPOUNDS AND THEIR USE |
| GB0601744D0 (en) | 2006-01-27 | 2006-03-08 | Novartis Ag | Organic compounds |
| MX2008012738A (es) | 2006-04-03 | 2009-02-06 | Astellas Pharma Inc | Heterocompuesto. |
| JP2009269819A (ja) | 2006-08-25 | 2009-11-19 | Asahi Kasei Pharma Kk | アミン化合物 |
| TWI392671B (zh) | 2006-09-07 | 2013-04-11 | Actelion Pharmaceuticals Ltd | 吡啶-4-基衍生物 |
| TWI408139B (zh) | 2006-09-07 | 2013-09-11 | Actelion Pharmaceuticals Ltd | 新穎噻吩衍生物 |
| MX2009002915A (es) | 2006-09-21 | 2009-03-31 | Actelion Pharmaceuticals Ltd | Derivados de fenilo y su uso como inmunomoduladores. |
| SG177221A1 (en) | 2006-12-15 | 2012-01-30 | Abbott Lab | Novel oxadiazole 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 |
| GB0625648D0 (en) | 2006-12-21 | 2007-01-31 | Glaxo Group Ltd | Compounds |
| MX2009010060A (es) | 2007-03-21 | 2010-01-20 | Epix Pharm Inc | Compuestos moduladores del receptor de esfingosin-1-fosfato y uso de los mismos. |
| CA2687306A1 (en) | 2007-05-18 | 2008-11-27 | Bayer Schering Pharma Aktiengesellschaft | Heteroaryl substituted pyrazole derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis |
| ES2622423T3 (es) | 2007-10-04 | 2017-07-06 | Merck Serono S.A. | Derivados de oxadiazol |
| AU2008306886B2 (en) | 2007-10-04 | 2014-01-16 | Merck Serono S.A. | Oxadiazole diaryl compounds |
| RU2010121969A (ru) | 2007-11-01 | 2011-12-10 | Актелион Фармасьютиклз Лтд (Ch) | Новые производные пиримидина |
| US20090298894A1 (en) | 2008-04-21 | 2009-12-03 | Asahi Kasei Pharma Corporation | Amino acid compounds |
| SI2291080T1 (sl) | 2008-05-14 | 2015-11-30 | The Scripps Research Institute | Novi modulatorji sfingosinskih fosfatnih receptorjev |
| EP2350006A1 (en) | 2008-10-01 | 2011-08-03 | Synta Pharmaceuticals Corp. | Compounds for inflammation and immune-related uses |
| EP2350064A1 (en) | 2008-10-01 | 2011-08-03 | Synta Pharmaceuticals Corp. | Compounds for inflammation and immune-related uses |
| US20100160369A1 (en) | 2008-12-04 | 2010-06-24 | Exelixis, Inc. | S1P1 Agonists and Methods of Making And Using |
| EP2389377B1 (en) | 2009-01-23 | 2014-07-16 | Bristol-Myers Squibb Company | Substituted oxadiazole derivatives as s1p agonists in the treatment of autoimmune and inflammatory diseases |
| 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 |
-
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- 2010-01-22 JP JP2011548107A patent/JP2012515787A/ja not_active Ceased
- 2010-01-22 CN CN2010800132551A patent/CN102361867A/zh active Pending
- 2010-01-22 US US13/145,730 patent/US8354398B2/en active Active
- 2010-01-22 EP EP10701297.3A patent/EP2382212B1/en not_active Not-in-force
- 2010-01-22 WO PCT/US2010/021693 patent/WO2010085581A1/en not_active Ceased
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003062252A1 (en) * | 2002-01-18 | 2003-07-31 | Merck & Co., Inc. | Edg receptor agonists |
| US20050245575A1 (en) * | 2002-06-17 | 2005-11-03 | Weirong Chen | 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 |
| CN1788008A (zh) * | 2003-05-15 | 2006-06-14 | 麦克公司 | 作为s1p受体激动剂的3-(2-氨基-1-氮杂环基)-5-芳基-1,2,4-噁二唑 |
| CN101184739A (zh) * | 2005-06-08 | 2008-05-21 | 诺瓦提斯公司 | 多环二唑类和异唑类化合物及其作为s1p受体的配体的用途 |
| WO2009011850A2 (en) * | 2007-07-16 | 2009-01-22 | Abbott Laboratories | Novel therapeutic compounds |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108463460A (zh) * | 2016-01-08 | 2018-08-28 | 先正达参股股份有限公司 | 杀微生物的噁二唑衍生物 |
| US11259524B2 (en) | 2016-01-08 | 2022-03-01 | Syngenta Participations Ag | Microbiocidal oxadiazole derivatives |
| CN108463460B (zh) * | 2016-01-08 | 2022-10-28 | 先正达参股股份有限公司 | 杀微生物的噁二唑衍生物 |
| CN112079791A (zh) * | 2020-08-21 | 2020-12-15 | 宁夏农林科学院农业资源与环境研究所(宁夏土壤与植物营养重点实验室) | 单环β-内酰胺类抗生素侧链酸及其酯、其制备方法和应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20110300165A1 (en) | 2011-12-08 |
| JP2012515787A (ja) | 2012-07-12 |
| EP2382212A1 (en) | 2011-11-02 |
| EP2382212B1 (en) | 2014-07-16 |
| WO2010085581A1 (en) | 2010-07-29 |
| US8354398B2 (en) | 2013-01-15 |
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