ES2549761T3 - Nuevos moduladores de los receptores de esfingosina fosfato - Google Patents
Nuevos moduladores de los receptores de esfingosina fosfato Download PDFInfo
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- ES2549761T3 ES2549761T3 ES09762826.7T ES09762826T ES2549761T3 ES 2549761 T3 ES2549761 T3 ES 2549761T3 ES 09762826 T ES09762826 T ES 09762826T ES 2549761 T3 ES2549761 T3 ES 2549761T3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| US12/465,767 US8796318B2 (en) | 2008-05-14 | 2009-05-14 | Modulators of sphingosine phosphate receptors |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CL2007002593A1 (es) | 2006-09-07 | 2008-06-13 | Actelion Pharmaceuticals Ltd | Compuestos derivados de 4-heteroaril-piridina; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como rechazo de organos transplantados, sindromes autoinmunes y cancer. |
| JP2010521450A (ja) | 2007-03-16 | 2010-06-24 | アクテリオン ファーマシューティカルズ リミテッド | Ｓ１ｐ１／ｅｄｇ１受容体アゴニストとしてのアミノ−ピリジン誘導体 |
| PL2195311T3 (pl) | 2007-08-17 | 2011-08-31 | Actelion Pharmaceuticals Ltd | Pochodne pirydynowe jako modulatory receptora S1P1/EDG1 |
| CN101970430B (zh) | 2007-11-01 | 2013-05-08 | 埃科特莱茵药品有限公司 | 嘧啶衍生物 |
| BRPI0820868A2 (pt) | 2007-12-10 | 2019-09-24 | Actelion Pharmaceuticals Ltd | composto de tiofeno fórmula(i), composição farmacêutica contendo o mesmo e uso deste para a prevenção ou tratamento de doenças ou disturbíos associados a um sistema imune ativado |
| BRPI0910288A2 (pt) | 2008-03-07 | 2019-09-24 | Actelion Pharmaceuticals Ltd | composto de derivados de aminometil benzeno, composição farmacêutica que compreende esse composto e uso do mesmo. |
| HUE025984T2 (hu) | 2008-05-14 | 2016-05-30 | Scripps Research Inst | Szfingozin foszfát receptor új modulátorai |
| WO2010000372A2 (en) | 2008-06-09 | 2010-01-07 | Ludwig-Maximilians-Universität München | New drug for inhibiting aggregation of proteins involved in diseases linked to protein aggregation and/or neurodegenerative diseases |
| US8217028B2 (en) * | 2008-06-20 | 2012-07-10 | Glaxo Group Limited | 1,2,4-oxadiazole indole compounds |
| HRP20161133T1 (hr) | 2008-07-23 | 2016-12-02 | Arena Pharmaceuticals, Inc. | DERIVATI SUSPSTITUIRANE 1,2,3,4-TETRAHIDROCIKLOPENTA[b]INDOL-3-IL-OCTENE KISELINE KORISNI U LIJEČENJU AUTOIMUNIH I UPALNIH POREMEĆAJA |
| CN105816453B (zh) | 2008-08-27 | 2021-03-05 | 艾尼纳制药公司 | 用于治疗自身免疫性病症和炎性病症的作为s1p1受体激动剂的经取代的三环酸衍生物 |
| WO2010085584A1 (en) | 2009-01-23 | 2010-07-29 | Bristol-Myers Squibb Company | Pyrazole-i, 2, 4 -oxad iazole derivatives as s.phing0sine-1-ph0sphate 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 |
| 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 |
| KR101409131B1 (ko) | 2009-07-16 | 2014-06-17 | 액테리온 파마슈티칼 리미티드 | 피리딘-4-일 유도체 |
| US8399451B2 (en) | 2009-08-07 | 2013-03-19 | Bristol-Myers Squibb Company | Heterocyclic compounds |
| KR101781233B1 (ko) * | 2009-11-13 | 2017-09-22 | 셀진 인터내셔널 Ii 에스에이알엘 | 스핑고신 1 포스페이트 수용체 조절자 및 카이랄 합성 방법 |
| SI2498610T2 (sl) * | 2009-11-13 | 2024-10-30 | Receptos Llc | Selektivni modulatorji receptorja sfingozin-1-fosfata in postopki kiralne sinteze |
| PT2498609T (pt) * | 2009-11-13 | 2018-07-06 | Celgene Int Ii Sarl | Moduladores de recetor de esfingosina 1 fosfato heterocíclico seletivo |
| AU2015202660B2 (en) * | 2009-11-13 | 2016-10-27 | Receptos Llc | Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis |
| CA2786994C (en) | 2010-01-27 | 2018-01-16 | Arena Pharmaceuticals, Inc. | Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof |
| CN105503882B (zh) | 2010-03-03 | 2019-07-05 | 艾尼纳制药公司 | 制备s1p1受体调节剂及其晶体形式的方法 |
| EP2390252A1 (en) * | 2010-05-19 | 2011-11-30 | Almirall, S.A. | New pyrazole derivatives |
| WO2012040532A1 (en) * | 2010-09-24 | 2012-03-29 | Bristol-Myers Squibb Company | Substituted oxadiazole compounds and their use as s1p1 agonists |
| SG191742A1 (en) | 2011-01-19 | 2013-08-30 | Actelion Pharmaceuticals Ltd | 2-methoxy-pyridin-4-yl derivatives |
| US8865754B2 (en) | 2011-03-03 | 2014-10-21 | Proteotech Inc. | Compounds for the treatment of neurodegenerative diseases |
| CN102718726A (zh) * | 2011-03-31 | 2012-10-10 | 上海铂力生物科技有限公司 | 作为免疫调节剂的(z)-5-苯亚甲基噻唑啉-4-酮衍生物 |
| WO2012158550A2 (en) * | 2011-05-13 | 2012-11-22 | Receptos, Inc. | Selective heterocyclic sphingosine 1 phosphate receptor modulators |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US9199975B2 (en) | 2011-09-30 | 2015-12-01 | Asana Biosciences, Llc | Biaryl imidazole derivatives for regulating CYP17 |
| EP2822931B1 (en) | 2012-03-09 | 2017-05-03 | Inception 2, Inc. | Triazolone compounds and uses thereof |
| ES2660249T3 (es) | 2012-12-20 | 2018-03-21 | Inception 2, Inc. | Compuestos de tipo triazolona y sus usos |
| SI2958913T1 (sl) | 2013-02-20 | 2018-12-31 | Lg Chem, Ltd. | Sfingozin-1-fosfat receptor agonisti, postopki za njegovo pripravo in farmacevtski sestavki, ki ga vsebujejo kot aktivno sredstvo |
| CN105189487B (zh) * | 2013-03-15 | 2017-12-26 | 爱杜西亚药品有限公司 | 吡啶‑4‑基衍生物 |
| JP2016529311A (ja) | 2013-09-06 | 2016-09-23 | インセプション ２、 インコーポレイテッド | トリアゾロン化合物類及びそれらの使用 |
| EP2853532B1 (en) * | 2013-09-28 | 2020-12-09 | Instytut Farmakologii Polskiej Akademii Nauk | 1,2,4-oxadiazole derivatives as allosteric modulators of metabotropic glutamate receptors belonging to group III |
| WO2015066515A1 (en) * | 2013-11-01 | 2015-05-07 | Receptos, Inc. | Selective sphingosine 1 phosphate receptor modulators and combination therapy therewith |
| MX2017000184A (es) * | 2014-06-26 | 2017-09-15 | Univ Monash | Agentes de interaccion enzimatica. |
| AU2016205361C1 (en) | 2015-01-06 | 2021-04-08 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the S1P1 receptor |
| WO2016164180A1 (en) | 2015-04-06 | 2016-10-13 | Auspex Pharmaceuticals, Inc. | Deuterium-substituted oxadiazoles |
| MY192358A (en) | 2015-05-20 | 2022-08-17 | Idorsia Pharmaceuticals Ltd | Crystalline form of the compound (s)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol |
| PL3310760T3 (pl) | 2015-06-22 | 2023-03-06 | Arena Pharmaceuticals, Inc. | Krystaliczna sól L-argininy kwasu (R)-2-(7-(4-cyklopentylo-3-(trifluorometylo)benzyloksy)- 1,2,3,4-tetrahydrocyklo-penta[b]indol-3-ilo)octowego do zastosowania w zaburzeniach związanych z receptorem S1P1 |
| FI3470400T3 (fi) | 2016-06-14 | 2025-06-13 | Receptos Llc | Otsanimodin kidemuoto, sen hydrokloridin kidemuoto ja niiden valmistusmenetelmä |
| US11028060B2 (en) | 2016-08-19 | 2021-06-08 | Receptos Llc | Crystalline forms of ozanimod and processes for preparation thereof |
| US10882830B2 (en) | 2016-09-14 | 2021-01-05 | Receptos Llc | Crystal form of ozanimod hydrochloride and processes for preparation therefor |
| EP3518922B1 (en) | 2016-09-29 | 2026-02-11 | Receptos LLC | Compounds and methods for treating lupus |
| CA3051095A1 (en) | 2017-01-23 | 2018-07-26 | Naqi Logics, Llc | Apparatus, methods, and systems for using imagined direction to define actions, functions, or execution |
| KR20190116416A (ko) | 2017-02-16 | 2019-10-14 | 아레나 파마슈티칼스, 인크. | 원발 담즙성 담관염을 치료하기 위한 화합물 및 방법 |
| JP2020507610A (ja) | 2017-02-16 | 2020-03-12 | アリーナ ファーマシューティカルズ， インコーポレイテッド | 腸管外症状を伴う炎症性腸疾患の治療のための化合物および方法 |
| EP3590929B1 (en) * | 2017-02-28 | 2021-09-15 | Medshine Discovery Inc. | Spiro compound and use thereof |
| WO2018211323A1 (en) * | 2017-05-17 | 2018-11-22 | Oppilan Pharma Ltd. | Hetercyclic compounds for the treatment of disease |
| CN110944982A (zh) | 2017-08-31 | 2020-03-31 | 苏州科睿思制药有限公司 | 奥扎莫德盐酸盐的晶型及其制备方法 |
| WO2019094409A1 (en) | 2017-11-07 | 2019-05-16 | Teva Pharmaceuticals International Gmbh | Salts and solid state forms of ozanimod |
| AU2019280822A1 (en) | 2018-06-06 | 2021-01-07 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the S1P1 receptor |
| EP3847158A1 (en) | 2018-09-06 | 2021-07-14 | Arena Pharmaceuticals, Inc. | Compounds useful in the treatment of autoimmune and inflammatory disorders |
| AR116479A1 (es) | 2018-09-25 | 2021-05-12 | Quim Sintetica S A | Intermediarios para la síntesis de ozanimod y procedimiento para la preparación del mencionado agonista del receptor de esfingosina-1-fosfato y de dichos intermediarios |
| WO2020152718A1 (en) | 2019-01-25 | 2020-07-30 | Mylan Laboratories Limited | Polymorphic forms 5-[3-[(1s)-2,3-dihydro-1-[(2-hydroxyethyl) amino]-1h-inden-4-yl]-1,2,4-oxadiazol-5-yl]-2-(1-methylethoxy)benzonitrile |
| CN114008034A (zh) * | 2019-04-26 | 2022-02-01 | 瑞塞普托斯公司 | 1-磷酸鞘氨醇受体调节剂 |
| CN112062785B (zh) * | 2019-06-11 | 2023-06-27 | 广东东阳光药业有限公司 | 奥扎莫德及其中间体的制备方法 |
| WO2021026479A1 (en) * | 2019-08-07 | 2021-02-11 | Stamford, Andrew | Small molecule inhibitors of s1p2 receptor and uses thereof |
| CN114980887A (zh) | 2019-12-20 | 2022-08-30 | 特纳亚治疗股份有限公司 | 氟代烷基-噁二唑及其用途 |
| US12428386B2 (en) | 2020-03-27 | 2025-09-30 | Receptos Llc | Sphingosine 1 phosphate receptor modulators |
| ES3003657T3 (en) | 2020-03-27 | 2025-03-10 | Receptos Llc | Sphingosine 1 phosphate receptor modulators |
| JP7653447B2 (ja) * | 2020-03-27 | 2025-03-28 | レセプトス・リミテッド・ライアビリティ・カンパニー | スフィンゴシン１ホスフェート受容体モジュレーター |
| WO2021207051A1 (en) * | 2020-04-06 | 2021-10-14 | Bristol-Myers Squibb Company | Methods of treating acute respiratory disorders |
| US20230233532A1 (en) * | 2020-06-26 | 2023-07-27 | The Penn State Research Foundation | Sphingosine-1-phosphate receptor 1 agonist and liposomal formulations thereof |
| WO2022035805A1 (en) * | 2020-08-10 | 2022-02-17 | Dana-Farber Cancer Institute, Inc. | Substituted 1,2,4-oxadiazoles as small molecule inhibitors of ubiquitin-specific protease 28 |
| WO2022235842A1 (en) | 2021-05-04 | 2022-11-10 | Tenaya Therapeutics, Inc. | 2-fluoroalkyl-1,3,4-oxadiazol-5-yl-thiazol, hdac6 inhibitors for use in the treatment of metabolic disease and hfpef |
| WO2023152767A1 (en) | 2022-02-11 | 2023-08-17 | Mylan Laboratories Limited | Polymorphic forms of ozanimod hydrochloride |
| CN120302973A (zh) | 2022-11-30 | 2025-07-11 | 花王株式会社 | 发痒的预防或改善剂 |
| WO2024246174A1 (en) | 2023-05-31 | 2024-12-05 | Química Sintética, S.A. | Amorphous and crystalline form of ozanimod hydrochloride |
| CN119320366B (zh) * | 2023-07-17 | 2025-11-18 | 中国医学科学院药物研究所 | 取代萘甲基噁二唑-苯胺类化合物及其用途 |
| US11905265B1 (en) * | 2023-10-13 | 2024-02-20 | King Faisal University | 3,4-dimethoxy-n′-(2-(5-phenyl-1,3,4-oxadiazol-2ylthio)acetoxy)benzimidamide as an antimicrobial compound |
| 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 |
| US20250230251A1 (en) | 2023-12-20 | 2025-07-17 | Bristol-Myers Squibb Company | Antibodies targeting il-18 receptor beta (il-18rb) and related methods |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3647809A (en) * | 1968-04-26 | 1972-03-07 | Chinoin Gyogyszer Es Vegyeszet | Certain pyridyl-1 2 4-oxadiazole derivatives |
| ES2203061T3 (es) * | 1998-01-23 | 2004-04-01 | Sankyo Company Limited | Derivados de espiropiperadina. |
| DE10240818A1 (de) | 2002-08-30 | 2004-05-13 | Grünenthal GmbH | Substituierte 2-Pyrrolidin-2-yl-[1,3,4]-oxadiazol-Derivate |
| 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 |
| JP2006524638A (ja) | 2003-04-30 | 2006-11-02 | メルク フロスト カナダ リミテツド | ８−（３−ビアリール）フェニルキノリン系ホスホジエステラーゼ−４阻害薬 |
| WO2004110351A2 (en) * | 2003-05-14 | 2004-12-23 | Anadys Pharmaceuticals, Inc. | Heterocyclic compounds for treating hepatitis c virus |
| 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 |
| AU2004299456B2 (en) * | 2003-12-17 | 2010-10-07 | Merck Sharp & Dohme Corp. | (3,4-disubstituted)propanoic carboxylates as S1P (Edg) receptor agonists |
| WO2005058845A2 (en) * | 2003-12-19 | 2005-06-30 | Novo Nordisk A/S | Novel glucagon antagonists/inverse agonists |
| US7585881B2 (en) * | 2004-02-18 | 2009-09-08 | Astrazeneca Ab | Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| EP1650186B1 (en) * | 2004-10-22 | 2008-06-04 | Bioprojet | Novel dicarboxylic acid derivatives |
| CA2600008A1 (en) | 2005-02-22 | 2006-11-16 | Teva Pharmaceutical Industries Ltd. | Improved process for the synthesis of enantiomeric indanylamine derivatives |
| JP2008545767A (ja) | 2005-06-08 | 2008-12-18 | ノバルティス アクチエンゲゼルシャフト | 多環式オキサジアゾールまたはイソキサゾールおよびｓｉｐ受容体リガンドとしてのそれらの使用 |
| EP2386554A1 (en) | 2005-07-04 | 2011-11-16 | High Point Pharmaceuticals, LLC | Compounds active at the histamine H3 receptor |
| BRPI0620146A2 (pt) * | 2005-12-23 | 2011-11-01 | Hoffmann La Roche | derivados de aril-isoxazolo-4-il-oxadiazol, processo para a preparação dos referidos derivados, medicamento que os contém e usos de um desses derivados |
| MX2008012738A (es) | 2006-04-03 | 2009-02-06 | Astellas Pharma Inc | Heterocompuesto. |
| US20080015193A1 (en) | 2006-06-20 | 2008-01-17 | Mendoza Jose S | Certain azoles exhibiting ATP-utilizing enzyme inhibitory activity, compositions, and uses thereof |
| US20080009534A1 (en) * | 2006-07-07 | 2008-01-10 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as antidiabetic and antiobesity agents and method |
| US20100087491A1 (en) | 2006-09-29 | 2010-04-08 | Rainer Albert | Polycyclic compounds |
| EP2099741A2 (en) * | 2006-11-21 | 2009-09-16 | University Of Virginia Patent Foundation | Hydrindane analogs having sphingosine 1-phosphate receptor agonist activity |
| CN101562977A (zh) | 2006-12-15 | 2009-10-21 | 艾博特公司 | 新的二唑化合物 |
| JO2701B1 (en) | 2006-12-21 | 2013-03-03 | جلاكسو جروب ليميتد | Vehicles |
| US20090188269A1 (en) | 2008-01-25 | 2009-07-30 | Henkel Corporation | High pressure connection systems and methods for their manufacture |
| BRPI0912545B1 (pt) | 2008-05-14 | 2022-02-01 | The Scripps Research Institute | Compostos moduladores de receptores de esfingosina fosfato, uso dos mesmos e composição e combinação farmacêutica compreendendo os ditos compostos |
| HUE025984T2 (hu) | 2008-05-14 | 2016-05-30 | Scripps Research Inst | Szfingozin foszfát receptor új modulátorai |
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