BR112017027656B1 - Hábito cristalino de placa livre de sal de l-arginina de ácido (r)-2-(7-(4- ciclopentil-3-(trifluorometil)benzilóxi)- 1,2,3,4-tetra-hidrociclo-penta[b]indol-3- il)acético, composição farmacêutica que o compreende, seus usos e método de preparação do mesmo - Google Patents
Hábito cristalino de placa livre de sal de l-arginina de ácido (r)-2-(7-(4- ciclopentil-3-(trifluorometil)benzilóxi)- 1,2,3,4-tetra-hidrociclo-penta[b]indol-3- il)acético, composição farmacêutica que o compreende, seus usos e método de preparação do mesmo Download PDFInfo
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- BR112017027656B1 BR112017027656B1 BR112017027656-9A BR112017027656A BR112017027656B1 BR 112017027656 B1 BR112017027656 B1 BR 112017027656B1 BR 112017027656 A BR112017027656 A BR 112017027656A BR 112017027656 B1 BR112017027656 B1 BR 112017027656B1
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- benzyloxy
- trifluoromethyl
- cyclopentyl
- indol
- acid
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Applications Claiming Priority (5)
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| US201562182841P | 2015-06-22 | 2015-06-22 | |
| US62/182,841 | 2015-06-22 | ||
| US201562207531P | 2015-08-20 | 2015-08-20 | |
| US62/207,531 | 2015-08-20 | ||
| PCT/US2016/038506 WO2016209809A1 (en) | 2015-06-22 | 2016-06-21 | Crystalline l-arginine salt of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid(compound1) for use in sipi receptor-associated disorders |
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| BR112017027656A2 BR112017027656A2 (pt) | 2018-08-28 |
| BR112017027656B1 true BR112017027656B1 (pt) | 2023-12-05 |
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| BR112017027656-9A BR112017027656B1 (pt) | 2015-06-22 | 2016-06-21 | Hábito cristalino de placa livre de sal de l-arginina de ácido (r)-2-(7-(4- ciclopentil-3-(trifluorometil)benzilóxi)- 1,2,3,4-tetra-hidrociclo-penta[b]indol-3- il)acético, composição farmacêutica que o compreende, seus usos e método de preparação do mesmo |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP5856980B2 (ja) | 2010-01-27 | 2016-02-10 | 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 | （Ｒ）−２−（７−（４−シクロペンチル−３−（トリフルオロメチル）ベンジルオキシ）−１，２，３，４−テトラヒドロシクロペンタ［ｂ］インドール−３−イル）酢酸およびその塩の調製のためのプロセス |
| PL3242666T3 (pl) | 2015-01-06 | 2025-02-17 | Arena Pharmaceuticals, Inc. | Związek do zastosowania w leczeniu dolegliwości związanych z receptorem s1p1 |
| BR112017027656B1 (pt) | 2015-06-22 | 2023-12-05 | Arena Pharmaceuticals, Inc. | Hábito cristalino de placa livre de sal de l-arginina de ácido (r)-2-(7-(4- ciclopentil-3-(trifluorometil)benzilóxi)- 1,2,3,4-tetra-hidrociclo-penta[b]indol-3- il)acético, composição farmacêutica que o compreende, seus usos e método de preparação do mesmo |
| MX2019009843A (es) | 2017-02-16 | 2020-01-30 | Arena Pharm Inc | Compuestos y metodos para el tratamiento de la enfermedad inflamatoria intestinal con manifestaciones extraintestinales. |
| MX2019009841A (es) * | 2017-02-16 | 2020-01-30 | Arena Pharm Inc | Compuestos y metodos para el tratamiento de la colangitis biliar primaria. |
| JP7252908B2 (ja) * | 2017-06-14 | 2023-04-05 | トレベナ・インコーポレイテッド | Ｓ１ｐ１活性を調節するための化合物およびその使用法 |
| CA3102136A1 (en) | 2018-06-06 | 2019-12-12 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
| CN112955431A (zh) * | 2018-09-06 | 2021-06-11 | 艾尼纳制药公司 | 可用于治疗自身免疫性病症和炎性病症的化合物 |
| JP7265620B2 (ja) * | 2018-10-03 | 2023-04-26 | 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 | 強皮症の治療のための方法 |
| CN109678715B (zh) * | 2018-11-28 | 2019-11-12 | 中国药科大学 | 2-(1-酰氧正戊基)苯甲酸与碱性氨基酸或氨基胍形成的盐、其制备方法及用途 |
| CN115038438A (zh) * | 2019-10-01 | 2022-09-09 | 艾尼纳制药公司 | 治疗与s1p1受体相关的病症的方法 |
| JP7749552B2 (ja) | 2019-10-31 | 2025-10-06 | イドルシア・ファーマシューティカルズ・リミテッド | Ｃｘｃｒ７アンタゴニストのｓ１ｐ１受容体調節剤との合剤 |
| MX2022005766A (es) | 2019-11-19 | 2022-08-08 | Trevena Inc | Compuestos y métodos para la preparación de compuestos moduladores de esfingosina 1-fosfato tipo 1 (s1p1). |
| AU2020389144A1 (en) | 2019-11-20 | 2022-06-09 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the S1P1 receptor |
| WO2025177319A2 (en) * | 2024-02-22 | 2025-08-28 | Msn Laboratories Private Limited, R&D Center | Solid state forms of L-Arginine, (3R)-7-[[4-cyclopentyl-3-(trifluoromethyl)phenyl]methoxy]-1,2,3,4-tetrahydrocyclopent[b]indole-3-acetate and processes for preparation thereof |
| WO2025243320A1 (en) * | 2024-05-24 | 2025-11-27 | Cipla Limited | Novel etrasimod l-arginine polymorphs and amorphous forms and processes for the same |
| EP4685237A1 (en) | 2024-07-26 | 2026-01-28 | Curia Spain, S.A.U. | Process and intermediates for the preparation of etrasimod and related compounds |
Family Cites Families (518)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH389134A (de) | 1960-03-15 | 1965-03-15 | Ciba Geigy | Verfahren zur Herstellung neuer Anthrachinonküpenfarbstoffe |
| NL293572A (https=) | 1962-06-07 | |||
| CH478816A (de) | 1965-10-22 | 1969-09-30 | Ciba Geigy | Verfahren zur Herstellung neuer N,N'-Di-(pyrimidyl-(4)-aminoalkyl)-diazacycloalkanen |
| CH480410A (de) | 1967-01-09 | 1969-10-31 | Geigy Ag J R | Verfahren zur Herstellung von wasserlöslichen Azopyrimidinfarbstoffen |
| CA961052A (en) | 1967-01-12 | 1975-01-14 | Max Schellenbaum | N-2-ethylhexyl-n'-aryl ureas and preparation containing them |
| FR1593586A (https=) | 1967-10-17 | 1970-06-01 | ||
| US3608087A (en) | 1968-06-21 | 1971-09-21 | Merck & Co Inc | Feed compositions |
| US3887329A (en) | 1969-05-05 | 1975-06-03 | Ciba Geigy Ag | Hexamethyl phosphotriamide-dye compositions |
| BE756953A (fr) | 1969-10-02 | 1971-04-01 | Merck & Co Inc | Potentialisation d'antibiotiques |
| US3686238A (en) | 1970-01-19 | 1972-08-22 | Syntex Corp | Glycerol esterified with 2-naphthyl-acetic acids and fatty acids |
| US3852434A (en) | 1970-09-11 | 1974-12-03 | Merck & Co Inc | Potentiation of ({31 ) cis-1,2-epoxypropyl)phosphonic acid and analogues thereof |
| US3690834A (en) | 1971-01-11 | 1972-09-12 | Syva Co | Ligand determination with spin labeled compounds by receptor displacement |
| US3966744A (en) | 1971-01-11 | 1976-06-29 | Syva Company | Spin labeled compounds |
| DE2106585A1 (de) | 1971-02-11 | 1972-08-24 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Aminothiodiazole und Thiodiazol-Azofarbstoffe |
| CH560197A5 (en) | 1971-05-17 | 1975-03-27 | Ciba Geigy Ag | 2-alkylthio-4,6-bis (subst amino)-5-nitropyrimidines - - herbicides |
| CH558137A (de) | 1971-05-17 | 1975-01-31 | Ciba Geigy Ag | Mittel zur beeinflussung des pflanzenwachstums. |
| DE2226703A1 (de) | 1972-05-25 | 1973-12-13 | Schering Ag | Neue tetrahydrocarbazolderivate und verfahren zu ihrer herstellung |
| US3966764A (en) | 1972-07-10 | 1976-06-29 | Syva Company | Ligand determination of spin labeled compounds by receptor displacement-amphetamine analogs |
| US3849420A (en) | 1972-10-20 | 1974-11-19 | Dow Chemical Co | Bis-(alkylthio-and alkylsulfonyl)-pentachloroquinolines |
| CH574206A5 (https=) | 1972-11-16 | 1976-04-15 | Ciba Geigy Ag | |
| DE2340569C2 (de) | 1973-08-10 | 1982-12-02 | Bayer Ag, 5090 Leverkusen | Azofarbstoffe |
| DE2341925A1 (de) | 1973-08-20 | 1975-03-06 | Thomae Gmbh Dr K | Neue pyrimidinderivate und verfahren zu ihrer herstellung |
| AT340933B (de) | 1973-08-20 | 1978-01-10 | Thomae Gmbh Dr K | Verfahren zur herstellung neuer pyrimidinderivate und ihrer saureadditionssalze |
| US4057559A (en) | 1973-10-01 | 1977-11-08 | American Home Products Corporation | Carbazole acetic acid derivatives |
| CH584739A5 (https=) | 1973-12-21 | 1977-02-15 | Ciba Geigy Ag | |
| US4101541A (en) | 1973-12-21 | 1978-07-18 | Ciba-Geigy Corporation | 3-Cyano-1,2,4-thiadiazolyl-5-czo dyestuffs |
| FR2258841B1 (https=) | 1974-01-29 | 1977-11-04 | Ugine Kuhlmann | |
| AT327605B (de) | 1974-05-06 | 1976-02-10 | Ciba Geigy Ag | Mittel zur hemmung des pflanzenwachstums |
| AU492126B2 (en) | 1974-05-14 | 1975-11-20 | Ciba-Geigy Ag | Nitropyrimidine derivatives |
| FR2306697A1 (fr) | 1975-04-10 | 1976-11-05 | Sogeras | Nouvelles pyrimidines utilisables comme medicaments antidiabetiques et hypocholesterolemiants |
| US4189579A (en) | 1977-05-20 | 1980-02-19 | The Dow Chemical Company | Aminoalkylthiopurines |
| US4139705A (en) | 1977-05-20 | 1979-02-13 | The Dow Chemical Company | Pyrazolopyrimidines |
| DE2731264A1 (de) | 1977-07-11 | 1979-02-01 | Boehringer Mannheim Gmbh | Neue 1-acyl-2-cyanaziridine, verfahren zu deren herstellung und diese verbindungen enthaltende pharmazeutische zubereitungen |
| JPS6038696B2 (ja) | 1977-12-09 | 1985-09-02 | コニカ株式会社 | ハロゲン化銀カラ−写真感光材料 |
| US4242507A (en) | 1978-02-23 | 1980-12-30 | Fujisawa Pharmaceutical Co., Ltd. | Sulfonic acid esters |
| DE2831580C2 (de) | 1978-07-18 | 1980-09-18 | Boehringer Mannheim Gmbh, 6800 Mannheim | Verfahren und Reagens zur Bestimmung von Glycerin |
| DE2831850A1 (de) | 1978-07-20 | 1980-02-07 | Basf Ag | N-arylsulfonylpyrrole, ihre herstellung und diese enthaltende therapeutische mittel |
| DE2906603A1 (de) | 1979-02-21 | 1980-09-04 | Boehringer Mannheim Gmbh | N-substituierte aziridin-2-carbonsaeurederivate, verfahren zu deren herstellung sowie diese substanzen enthaltende arzneimittel |
| US4343804A (en) | 1979-03-26 | 1982-08-10 | A. H. Robins Company, Inc. | 4-Amino-3-quinolinecarboxylic acids and esters-antisecretory anti-ulcer compounds |
| WO1981003174A1 (fr) | 1980-04-28 | 1981-11-12 | Teijin Ltd | Derives de thiazolo (3,2-a) pyrimidine, leur procede de preparation, et medicaments les contenant |
| EP0053678A1 (de) | 1980-12-05 | 1982-06-16 | BASF Aktiengesellschaft | 5-Amino-1-phenyl-4-cyanpyrazole, diese enthaltende herbizide Mittel, Verfahren zu ihrer Herstellung und ihre Anwendung als Herbizide |
| RU938559C (ru) | 1980-12-12 | 1993-11-30 | Всесоюзный научно-исследовательский химико-фармацевтический институт им.Серго Орджоникидзе | S-Производные 5-амино-6-меркаптопиримидина, обладающие противоопухолевым и цитостатическим действием |
| DOP1981004033A (es) | 1980-12-23 | 1990-12-29 | Ciba Geigy Ag | Procedimiento para proteger plantas de cultivo de la accion fitotoxica de herbicidas. |
| US4476248A (en) | 1983-02-28 | 1984-10-09 | The Upjohn Company | Crystallization of ibuprofen |
| DE3334455A1 (de) | 1983-03-04 | 1984-09-06 | Bayer Ag, 5090 Leverkusen | Guanidin - derivate |
| US4612376A (en) | 1983-03-25 | 1986-09-16 | Fujisawa Pharmaceutical Co., Ltd. | Substituted-3,4-dihydro-4-(2,4,6-trimethoxyphenylimino)-2(1H)-pyrimidones useful as cardiotonic, antihypertensive, cerebrovascular vasodilator and anti-platelet agent |
| ZA848275B (en) | 1983-12-28 | 1985-08-28 | Degussa | New piridine-2-ethers or pyridine-2-thioethers having a nitrogen-containing cycloaliphatic ring |
| DE3406329A1 (de) | 1984-02-22 | 1985-08-22 | Merck Patent Gmbh, 6100 Darmstadt | Pyridone |
| JPS6157587A (ja) | 1984-08-29 | 1986-03-24 | Shionogi & Co Ltd | 縮合複素環誘導体および抗潰瘍剤 |
| PH22302A (en) | 1985-02-11 | 1988-07-22 | Fujisawa Pharmaceutical Co | Piperidine compounds |
| IE860511L (en) | 1985-03-01 | 1986-09-01 | Alfa Farmaceutici Spa | "Benzoyl urea derivatives having anti-tumor activity" |
| DE3601196A1 (de) | 1986-01-17 | 1987-07-23 | Merck Patent Gmbh | 1,4-dihydropyridine |
| US4810699A (en) | 1987-02-20 | 1989-03-07 | American Home Products Corporation | Substituted 1,3,4,9-tetrahydropyrano[3,4,-b]indole-1-acetic acids, pharmaceutical compositions containing them, and methods for treating inflammatory conditions and for analgesic purposes using them |
| CA1340284C (en) | 1987-03-19 | 1998-12-22 | Zeneca Inc. | Herbicidal substituted cyclic diones |
| EP0324426B1 (en) | 1988-01-11 | 1996-06-19 | Fuji Photo Film Co., Ltd. | Process for forming super high contrast negative images |
| US4782076A (en) | 1988-03-01 | 1988-11-01 | American Home Products Corporation | Substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid derivatives, composition and use |
| PT95692A (pt) | 1989-10-27 | 1991-09-13 | American Home Prod | Processo para a preparacao de derivados de acidos indole-,indeno-,piranoindole- e tetra-hidrocarbazole-alcanoicos, ou quais sao uteis como inibidores de pla2 e da lipoxigenase |
| NZ238863A (en) | 1990-07-19 | 1993-03-26 | Janssen Pharmaceutica Nv | Substituted thiazolyl and pyridinyl derivatives |
| US5221678A (en) | 1990-07-26 | 1993-06-22 | Merck Frosst Canada, Inc. | (quinolin-2-ylmethoxy)tetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes |
| WO1992012976A1 (fr) | 1991-01-16 | 1992-08-06 | Yoshitomi Pharmaceutical Industries, Ltd. | Compose de pyridine utilise comme medicament selectif et nouveau compose de pyridine |
| CA2070978A1 (en) | 1991-06-11 | 1992-12-12 | William J. Greenlee | Cyclic renin inhibitors |
| GB9114760D0 (en) | 1991-07-09 | 1991-08-28 | Pfizer Ltd | Therapeutic agents |
| JPH0533359A (ja) | 1991-08-02 | 1993-02-09 | Kubota Corp | 全旋回型の小型バツクホウ |
| EP0556889A1 (en) | 1992-02-18 | 1993-08-25 | Duphar International Research B.V | Method of preparing aryl(homo)piperazines |
| DE4208254A1 (de) | 1992-03-14 | 1993-09-16 | Hoechst Ag | Substituierte pyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel und fungizid |
| TW237456B (https=) | 1992-04-09 | 1995-01-01 | Ciba Geigy | |
| FR2692575B1 (fr) | 1992-06-23 | 1995-06-30 | Sanofi Elf | Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| NZ314207A (en) | 1992-09-28 | 2000-12-22 | Vertex Pharma | 1-(2-Oxoacetyl)-piperidine-2-carboxylic acid derivatives as multi drug resistant cancer cell sensitizers |
| DE4241632A1 (de) | 1992-12-10 | 1994-06-16 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| TW370529B (en) | 1992-12-17 | 1999-09-21 | Pfizer | Pyrazolopyrimidines |
| US5998499A (en) | 1994-03-25 | 1999-12-07 | Dentsply G.M.B.H. | Liquid crystalline (meth)acrylate compounds, composition and method |
| JPH0753546A (ja) | 1993-08-09 | 1995-02-28 | Kuraray Co Ltd | ジアリール置換複素環化合物およびその医薬用途 |
| BR9407799A (pt) | 1993-10-12 | 1997-05-06 | Du Pont Merck Pharma | Composição de matéria método de tratamento e composição farmaceutica |
| GB9400889D0 (en) | 1994-01-18 | 1994-03-16 | Sandoz Ltd | Novel compounds |
| TW530047B (en) | 1994-06-08 | 2003-05-01 | Pfizer | Corticotropin releasing factor antagonists |
| PT781766E (pt) | 1994-09-09 | 2004-07-30 | Nippon Shinyaku Co Ltd | Derivado heterociclico e medicamento |
| DE69521529T2 (de) | 1994-11-29 | 2001-10-11 | Dainippon Pharmaceutical Co., Ltd. | Indolderivat |
| DE69630214T2 (de) | 1995-03-10 | 2004-07-15 | Berlex Laboratories, Inc., Richmond | Benzamidin-derivate, deren herstellung und deren verwendung als anti-koagulantien |
| US5691364A (en) | 1995-03-10 | 1997-11-25 | Berlex Laboratories, Inc. | Benzamidine derivatives and their use as anti-coagulants |
| IL117659A (en) | 1995-04-13 | 2000-12-06 | Dainippon Pharmaceutical Co | Substituted 2-phenyl pyrimidino amino acetamide derivative process for preparing the same and a pharmaceutical composition containing same |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| WO1996033994A1 (en) | 1995-04-28 | 1996-10-31 | Nippon Soda Co., Ltd. | Amino-substituted derivatives, process for the preparation thereof, and herbicide |
| EP0770080B1 (en) | 1995-05-12 | 1999-07-14 | Neurogen Corporation | Novel deazapurine derivatives; a new class of crf1 specific ligands |
| WO1996036613A1 (en) | 1995-05-19 | 1996-11-21 | Nippon Soda Co., Ltd. | Substituted benzoic acid derivatives, process for the production thereof, and herbicides |
| US6956047B1 (en) | 1995-06-06 | 2005-10-18 | Pfizer Inc. | Corticotropin releasing factor antagonists |
| US6403599B1 (en) | 1995-11-08 | 2002-06-11 | Pfizer Inc | Corticotropin releasing factor antagonists |
| TWI238064B (en) | 1995-06-20 | 2005-08-21 | Takeda Chemical Industries Ltd | A pharmaceutical composition for prophylaxis and treatment of diabetes |
| KR0169813B1 (ko) | 1995-07-12 | 1999-01-15 | 김종인 | 4-아미노-3-아실나프티리딘 유도체 |
| DE59606057D1 (de) | 1995-08-31 | 2000-11-30 | Lonza Ag | Verfahren zur herstellung von dihydroxypyrimidin-derivaten |
| WO1997015549A1 (en) | 1995-10-26 | 1997-05-01 | Tokyo Tanabe Company Limited | PHENYLETHANOLAMINE COMPOUNDS USEFUL AS β3 AGONIST, PROCESS FOR PRODUCING THE SAME, AND INTERMEDIATES IN THE PRODUCTION OF THE SAME |
| US5849759A (en) | 1995-12-08 | 1998-12-15 | Berlex Laboratories, Inc. | Naphthyl-substituted benzimidazole derivatives as anti-coagulants |
| USH2007H1 (en) | 1996-01-19 | 2001-12-04 | Fmc Corporation | Insecticidal N-heterocyclylalkyl-or N-[(polycyclyl)alkyl]-N′substituted piperazines |
| DE19602095A1 (de) | 1996-01-22 | 1997-07-24 | Bayer Ag | Halogenpyrimidine |
| WO1997028137A1 (en) | 1996-02-02 | 1997-08-07 | Merck & Co., Inc. | Heterocyclic derivatives as antidiabetic and antiobesity agents |
| AU713673B2 (en) | 1996-02-07 | 1999-12-09 | Neurocrine Biosciences Inc. | Pyrazolopyrimidines as crf receptor antagonists |
| US5948786A (en) | 1996-04-12 | 1999-09-07 | Sumitomo Pharmaceuticals Company, Limited | Piperidinylpyrimidine derivatives |
| DE122010000020I1 (de) | 1996-04-25 | 2010-07-08 | Prosidion Ltd | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
| DE19624659A1 (de) | 1996-06-20 | 1998-01-08 | Klinge Co Chem Pharm Fab | Neue Pyridylalken- und Pyridylalkinsäureamide |
| AU3176297A (en) | 1996-06-25 | 1998-01-14 | Novartis Ag | Substituted 7-amino-pyrrolo{3,2-d}pyrimidines and the use thereof |
| US6060478A (en) | 1996-07-24 | 2000-05-09 | Dupont Pharmaceuticals | Azolo triazines and pyrimidines |
| US5776967A (en) | 1996-07-26 | 1998-07-07 | American Home Products Corporation | Pyranoindole inhibitors of COX--2 |
| AR008789A1 (es) | 1996-07-31 | 2000-02-23 | Bayer Corp | Piridinas y bifenilos substituidos |
| US5830911A (en) | 1996-08-14 | 1998-11-03 | American Home Products Corporation | Pyranoindole and tetrahydrocarbazole inhibitors of COX-2 |
| TW477787B (en) | 1996-08-27 | 2002-03-01 | Pfizer | Pyrido six-membered nitrogen-containing cyclic ring derivatives having corticotropin releasing factor antagonist activity and pharmaceutical composition containing same |
| JP3621706B2 (ja) | 1996-08-28 | 2005-02-16 | ファイザー・インク | 置換された６，５―ヘテロ―二環式誘導体 |
| EP0929547B1 (en) | 1996-09-12 | 2002-11-27 | Schering Aktiengesellschaft | Benzamidine derivatives substituted by cyclic amino acid or cycl ic hydroxy acid derivatives and their use as anti-coagulants |
| US6008234A (en) | 1996-09-12 | 1999-12-28 | Berlex Laboratories, Inc. | Benzamidine derivatives substituted by cyclic amino acid and cyclic hydroxy acid derivatives and their use as anti-coagulants |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| TW492957B (en) | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
| DZ2376A1 (fr) | 1996-12-19 | 2002-12-28 | Smithkline Beecham Plc | Dérivés de sulfonamides nouveaux procédé pour leurpréparation et compositions pharmaceutiques les c ontenant. |
| IL123232A0 (en) | 1997-02-11 | 1999-11-30 | Lilly Co Eli | Medicament for inhibiting glucose metabolism deterioration |
| AU6279598A (en) | 1997-02-18 | 1998-09-08 | Neurocrine Biosciences, Inc. | Biazacyclic CRF antagonists |
| NZ335823A (en) | 1997-04-22 | 2001-06-29 | Neurocrine Biosciences Inc | Thiophenopyridines, preparation as CRF receptor antagonists |
| DE69818248T2 (de) | 1997-04-22 | 2004-06-17 | Janssen Pharmaceutica N.V. | Chinolin- und chinazolin-derivate als crf antagonisten |
| JPH11193277A (ja) | 1997-05-14 | 1999-07-21 | Nippon Soda Co Ltd | ピリミジン誘導体、その製法および有害生物防除剤 |
| DE19737723A1 (de) | 1997-08-14 | 1999-02-18 | Bayer Ag | Methoximinomethyloxadiazine |
| BR9811939A (pt) | 1997-08-14 | 2000-09-05 | Bayer Ag | Metoximinometiloxadiazinas como pesticidas |
| NL1010018C2 (nl) | 1997-09-09 | 1999-03-10 | Duphar Int Res | Chinoline en chinazoline derivaten met corticotropine releasing factor (CRF) antagonistische werking. |
| US6861448B2 (en) | 1998-01-14 | 2005-03-01 | Virtual Drug Development, Inc. | NAD synthetase inhibitors and uses thereof |
| US6187777B1 (en) | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
| AU3378799A (en) | 1998-04-02 | 1999-10-25 | Neurogen Corporation | Aminoalkyl substituted pyrrolo(2,3-b)pyridine and pyrrolo(2,3-d)pyrimidine derivatives: modulators of crf1 receptors |
| JP2000038350A (ja) | 1998-05-18 | 2000-02-08 | Yoshitomi Pharmaceut Ind Ltd | 糖尿病治療薬 |
| EP1105394A1 (en) | 1998-08-21 | 2001-06-13 | Du Pont Pharmaceuticals Company | ISOXAZOLO 4,5-d]PYRIMIDINES AS CRF ANTAGONISTS |
| SK287270B6 (sk) | 1998-11-10 | 2010-05-07 | Janssen Pharmaceutica N. V. | Derivát pyrimidínu |
| US6262088B1 (en) | 1998-11-19 | 2001-07-17 | Berlex Laboratories, Inc. | Polyhydroxylated monocyclic N-heterocyclic derivatives as anti-coagulants |
| DK1584683T3 (da) | 1998-11-20 | 2007-10-29 | Arena Pharm Inc | Human G-protein-koblet orphan receptor RUP3 |
| CO5150173A1 (es) | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
| EP1140831A1 (en) | 1998-12-17 | 2001-10-10 | American Home Products Corporation | Arylpiperidine and aryl-1,2,5,6-tetrahydropyridine urea derivatives having 5ht1a receptor activity |
| US6239126B1 (en) | 1998-12-17 | 2001-05-29 | American Home Products Corporation | Arylpiperidine and aryl-1,2,5,6-tetra-hydropyridine urea derivatives |
| HUP0104987A3 (en) | 1998-12-18 | 2002-09-30 | Axys Pharmaceuticals Inc South | Benzimidazole or indole derivatives protease inhibitors, and pharmaceutical compositions containing them |
| CZ27399A3 (cs) | 1999-01-26 | 2000-08-16 | Ústav Experimentální Botaniky Av Čr | Substituované dusíkaté heterocyklické deriváty, způsob jejich přípravy, tyto deriváty pro použití jako léčiva, farmaceutická kompozice a kombinovaný farmaceutický přípravek tyto deriváty obsahující a použití těchto derivátů pro výrobu léčiv |
| US6267985B1 (en) | 1999-06-30 | 2001-07-31 | Lipocine Inc. | Clear oil-containing pharmaceutical compositions |
| AU761453B2 (en) | 1999-03-17 | 2003-06-05 | Astrazeneca Ab | Amide derivatives |
| EP1040831A3 (en) | 1999-04-02 | 2003-05-02 | Pfizer Products Inc. | Use of corticotropin releasing factor (CRF) antagonists to prevent sudden death |
| YU72201A (sh) | 1999-04-28 | 2005-07-19 | Aventis Pharma Deutschland Gmbh. | Derivati di-aril kiseline kao ppar receptorski ligandi |
| WO2001003739A1 (fr) | 1999-07-12 | 2001-01-18 | Ono Pharmaceutical Co., Ltd. | Inhibiteurs de fibrose contenant comme ingredient actif l'agoniste du recepteur de sphingosine-1-phosphate ou la sphingosine-1-phosphate |
| EP1074549B1 (en) | 1999-08-06 | 2003-11-19 | F. Hoffmann-La Roche Ag | Tetrahydro-benzo(d)azepines and their use as antagonists at metabotropic glutamate receptors |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| JP2003509428A (ja) | 1999-09-17 | 2003-03-11 | アボツト・ゲー・エム・ベー・ハー・ウント・コンパニー・カーゲー | 治療薬としてのピラゾロピリミジン |
| US6414002B1 (en) | 1999-09-22 | 2002-07-02 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as antidiabetic and antiobesity agents and method |
| JP2001089452A (ja) | 1999-09-22 | 2001-04-03 | Sankyo Co Ltd | ピリミジン誘導体 |
| TR200200763T2 (tr) | 1999-09-24 | 2003-09-22 | Janssen Pharmaceutica N.V. | Antiviral bileşimler |
| CA2379585C (en) | 1999-09-30 | 2006-06-20 | James W. Darrow | Certain alkylene diamine-substituted pyrazolo[1,5,-a]-1,5-pyrimidines and pyrazolo[1,5-a]-1,3,5-triazines |
| PL354784A1 (en) | 1999-09-30 | 2004-02-23 | Neurogen Corporation | Certain alkylene diamine-substituted heterocycles |
| ES2277855T3 (es) | 1999-09-30 | 2007-08-01 | Neurogen Corporation | Pirazolo-(1,5-a)-1,5-pirimidinas y pirazolo-(1,5-a)-1,3,5-triazinas amino sustituidas. |
| DE19947154A1 (de) | 1999-10-01 | 2001-10-04 | Bayer Ag | Substituierte 2-Thio-3,5-dicyano-4-aryl-6-aminopyridine und ihre Verwendung |
| US6887870B1 (en) | 1999-10-12 | 2005-05-03 | Bristol-Myers Squibb Company | Heterocyclic sodium/proton exchange inhibitors and method |
| CO5271670A1 (es) | 1999-10-29 | 2003-04-30 | Pfizer Prod Inc | Antagonistas del factor de liberacion de corticitropina y composiciones relacionadas |
| GR990100388A (el) | 1999-11-09 | 2001-07-31 | Φαρμακευτικος συνδυασμος αποτελουμενος απο χωριστες δοσολογικες μορφες σε συσκευασια συμμορφωσης (compliance package) ενος αναστολεα της αναγωγασης του υδροξυ-μεθυλο-γλουταρυλο συνενζυμου α (στατινης, statin) και ενος παραγωγου του φιμπρικου οξεος.... | |
| JP2003518128A (ja) | 1999-12-22 | 2003-06-03 | メルク フロスト カナダ アンド カンパニー | タンパク質チロシンホスファターゼ１ｂ（ｐｔｐ−１ｂ）のインヒビターとなる芳香族ホスホネート |
| DE19962936A1 (de) | 1999-12-24 | 2001-06-28 | Bayer Ag | Neue beta-Aminosäureverbindungen als Integrinantagonisten |
| IL150337A0 (en) | 1999-12-30 | 2002-12-01 | Lundbeck & Co As H | Phenylpiperazinyl derivatives |
| HUP0204272A3 (en) | 2000-01-18 | 2005-03-29 | Pfizer Prod Inc | Corticotropin releasing factor antagonists, pharmaceutical compositions containing them and their use |
| CA2399136A1 (en) | 2000-02-09 | 2001-08-16 | Hideo Kato | 1h-imidazopyridine derivatives |
| JP2003523418A (ja) | 2000-02-15 | 2003-08-05 | フオスター・ミラー・インコーポレイテツド | 揮発性有機成分を含まない放射硬化性樹脂組成物 |
| US6569879B2 (en) | 2000-02-18 | 2003-05-27 | Merck & Co., Inc. | Aryloxyacetic acids for diabetes and lipid disorders |
| JP2003523336A (ja) | 2000-02-18 | 2003-08-05 | メルク エンド カムパニー インコーポレーテッド | 糖尿病及び脂質障害のためのアリールオキシ酢酸 |
| WO2001062233A2 (en) | 2000-02-25 | 2001-08-30 | F. Hoffmann La Roche Ag | Adenosine receptor modulators |
| CN1440283A (zh) | 2000-04-12 | 2003-09-03 | 诺瓦提斯公司 | 有机化合物的联合形式 |
| AU782948B2 (en) | 2000-05-08 | 2005-09-15 | Janssen Pharmaceutica N.V. | Prodrugs of HIV replication inhibiting pyrimidines |
| DE10024319A1 (de) | 2000-05-17 | 2001-11-22 | Merck Patent Gmbh | Bisacylguanidine |
| EP1287133B1 (en) | 2000-05-18 | 2006-12-13 | Bayer HealthCare AG | Regulation of human dopamine-like g protein-coupled receptor |
| US6440960B1 (en) | 2000-05-18 | 2002-08-27 | Neurocrine Biosciences, Inc. | CRF receptor antagonists and methods relating thereto |
| EP1289964B1 (en) | 2000-05-25 | 2004-10-20 | F. Hoffmann-La Roche Ag | Substituted 1-aminoalkyl-lactams and their use as muscarinic receptor antagonists |
| US6620821B2 (en) | 2000-06-15 | 2003-09-16 | Bristol-Myers Squibb Company | HMG-CoA reductase inhibitors and method |
| JP2004501191A (ja) | 2000-06-28 | 2004-01-15 | テバ ファーマシューティカル インダストリーズ リミティド | カルベジロール |
| EP1294704A1 (en) | 2000-06-29 | 2003-03-26 | Abbott Laboratories | Aryl phenylheterocyclyl sulfide derivatives and their use as cell adhesion-inhibiting anti-inflammatory and immune-suppressive agents |
| AR028782A1 (es) | 2000-07-05 | 2003-05-21 | Taisho Pharmaceutical Co Ltd | Derivados heterociclicos tetrahidropiridino o piperidino |
| US6444685B1 (en) | 2000-07-17 | 2002-09-03 | Wyeth | N-(4-sulfonylaryl)Cyclylamine 2-hydroxyethylamines as beta-3 adrenergic receptor agonists |
| CA2415899A1 (en) | 2000-07-18 | 2003-01-13 | Chikashi Saitoh | Medicine comprising dicyanopyridine derivative |
| US6410583B1 (en) | 2000-07-25 | 2002-06-25 | Merck Frosst Canada & Co. | Cyclopentanoindoles, compositions containing such compounds and methods of treatment |
| AU7705601A (en) | 2000-07-25 | 2002-02-05 | Merck & Co Inc | N-substituted indoles useful in the treatment of diabetes |
| AU2001284417A1 (en) | 2000-09-05 | 2002-03-22 | Taisho Pharmaceutical Co. Ltd. | Hair growth stimulants |
| ATE367802T1 (de) | 2000-09-20 | 2007-08-15 | Jagotec Ag | Verfahren zur sprühtrocknung von zusammensetzungen enthaltend fenofibrat |
| US20030224058A1 (en) | 2002-05-24 | 2003-12-04 | Elan Pharma International, Ltd. | Nanoparticulate fibrate formulations |
| US7276249B2 (en) | 2002-05-24 | 2007-10-02 | Elan Pharma International, Ltd. | Nanoparticulate fibrate formulations |
| PE20020507A1 (es) | 2000-10-17 | 2002-06-25 | Schering Corp | Compuestos no-imidazoles como antagonistas del receptor histamina h3 |
| AU2002223626A1 (en) | 2000-10-20 | 2002-04-29 | Novartis Ag | Combinations of a thyromimetic compound and a statin |
| CN100525768C (zh) | 2000-10-23 | 2009-08-12 | 史密丝克莱恩比彻姆公司 | 新化合物 |
| AU2002248221B2 (en) | 2000-10-31 | 2006-08-17 | Merck & Co., Inc. | Benzopyrancarboxylic acid derivatives for the treatment of diabetes and lipid disorders |
| DE60126134T2 (de) | 2000-11-03 | 2007-10-18 | Neurocrine Biosciences, Inc., San Diego | CRF-Rezeptorantagonisten und Verfahren, die damit in Beziehung stehen |
| US20020058026A1 (en) | 2000-11-13 | 2002-05-16 | Milton Hammerly | HMG CoA reductase inhibitor medications combined wih CoEnzyme Q-10 |
| WO2002039987A2 (en) | 2000-11-14 | 2002-05-23 | Neurosearch A/S | Use of malaria parasite anion channel blockers for treating malaria |
| UA77165C2 (en) | 2000-11-17 | 2006-11-15 | Lilly Co Eli | (n)-((s)-2-hydroxy-3-methyl-butyryl)-1-(l-alaninyl)-(s)-1-amino-3-methyl-4,5,6,7-tetrahydro-2h-3-benzazepin-2-one dihydrate, processes for manufacturing and pharmaceutical composition |
| EP1340749A4 (en) | 2000-11-17 | 2007-09-05 | Takeda Pharmaceutical | ISOXAZOLE DERIVATIVES |
| CA2448729A1 (en) | 2000-11-20 | 2002-05-23 | Biovitrum Ab | Piperazinyl and piperidyl substituted heterocyclic compounds |
| EP1338651B9 (en) | 2000-12-01 | 2007-05-09 | Astellas Pharma Inc. | Method of screening remedy for diabetes |
| US20020137755A1 (en) | 2000-12-04 | 2002-09-26 | Bilodeau Mark T. | Tyrosine kinase inhibitors |
| US6545017B1 (en) | 2000-12-08 | 2003-04-08 | 3M Innovative Properties Company | Urea substituted imidazopyridines |
| US6525064B1 (en) | 2000-12-08 | 2003-02-25 | 3M Innovative Properties Company | Sulfonamido substituted imidazopyridines |
| US6545016B1 (en) | 2000-12-08 | 2003-04-08 | 3M Innovative Properties Company | Amide substituted imidazopyridines |
| US20020107262A1 (en) | 2000-12-08 | 2002-08-08 | 3M Innovative Properties Company | Substituted imidazopyridines |
| WO2002050071A1 (en) | 2000-12-21 | 2002-06-27 | Bristol-Myers Squibb Company | Thiazolyl inhibitors of tec family tyrosine kinases |
| DK1355644T3 (da) | 2001-01-26 | 2006-10-23 | Schering Corp | Anvendelse af substituerede azetidinonforbindelser til behandling af sitosterolæmi |
| JP2004529100A (ja) | 2001-01-30 | 2004-09-24 | ユニバーシティ オブ バージニア パテント ファウンデーション | スフィンゴシン−１−ホスフェートレセプターのアゴニストおよびアンタゴニスト |
| EP1357908A4 (en) | 2001-01-30 | 2009-07-15 | Merck & Co Inc | "ACYLSULFAMIDES FOR THE TREATMENT OF FATIBILITY, DIABETES AND LIPID DISORDERS" |
| CN100439370C (zh) | 2001-02-08 | 2008-12-03 | 记忆药物公司 | 作为磷酸二酯酶4抑制剂的三氟甲基嘌呤 |
| CA2437118A1 (en) | 2001-02-09 | 2002-08-22 | Merck & Co., Inc. | 2-aryloxy-2-arylalkanoic acids for diabetes and lipid disorders |
| DE10110754A1 (de) | 2001-03-07 | 2002-09-19 | Bayer Ag | Substituierte 2-Thio-3,5-dicyano-4-aryl-6-aminopyridine und ihre Verwendung |
| WO2002072101A1 (en) | 2001-03-13 | 2002-09-19 | Bristol-Myers Squibb Pharma Company | A corticotropin releasing factor receptor ligand, its enantiomer and pharmaceutically acceptable salts |
| WO2002079131A1 (en) | 2001-03-29 | 2002-10-10 | Kansai Research Institute, Inc. | Optically active compound and photosensitive resin composition |
| WO2002081454A1 (en) | 2001-04-09 | 2002-10-17 | Dr. Reddy's Laboratories Ltd. | Derivatives of aryl acids, their use in medicine, process for their preparation and pharmaceutical compositions containing them |
| CN1293072C (zh) | 2001-04-20 | 2007-01-03 | 惠氏公司 | 作为5－羟色胺－6配体的杂环基氧基－、－硫代－和－氨基吲哚衍生物 |
| ES2316613T3 (es) | 2001-05-10 | 2009-04-16 | Ono Pharmaceutical Co., Ltd. | Derivados de acido crboxilico y composiciones farmaceuticas que contienen los mismos como ingrediente activo. |
| DK1397351T3 (da) | 2001-06-01 | 2010-01-18 | Hoffmann La Roche | Pyrimidin-, triazin- og pyrazinderivater som glutamatreceptorer |
| CA2450934A1 (en) | 2001-06-19 | 2002-12-27 | Marco Dodier | Pyrimidine inhibitors of phosphodiesterase (pde) 7 |
| US6825198B2 (en) | 2001-06-21 | 2004-11-30 | Pfizer Inc | 5-HT receptor ligands and uses thereof |
| AU2002316421B2 (en) | 2001-06-26 | 2008-05-15 | Bristol-Myers Squibb Company | N-heterocyclic inhibitors of TNF-ALPHA expression |
| UA74912C2 (en) | 2001-07-06 | 2006-02-15 | Merck & Co Inc | Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes |
| GB0117899D0 (en) | 2001-07-23 | 2001-09-12 | Astrazeneca Ab | Chemical compounds |
| WO2003026661A1 (fr) | 2001-09-14 | 2003-04-03 | Yamanouchi Pharmaceutical Co., Ltd. | Accelerateur de secretion de l'insuline et nouveau derive de pyrimidine |
| CA2461212C (en) | 2001-09-27 | 2010-08-17 | Kyorin Pharmaceutical Co., Ltd. | Diaryl sulfide derivatives, salts thereof and immunosuppressive agents using the same |
| EP1438048A1 (en) | 2001-10-18 | 2004-07-21 | Boehringer Ingelheim Pharmaceuticals Inc. | 1,4-disubstituted benzo-fused urea compounds as cytokine inhibitors |
| SE0104334D0 (sv) | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| GB0229931D0 (en) | 2002-12-21 | 2003-01-29 | Astrazeneca Ab | Therapeutic agents |
| WO2003059378A2 (en) | 2001-12-29 | 2003-07-24 | Novo Nordisk A/S | Combined use of a glp-1 compound and another drug for treating dyslipidemia |
| WO2003057689A1 (en) | 2002-01-02 | 2003-07-17 | Fujisawa Pharmaceutical Co., Ltd. | Aminopyrimidine compounds, processes for their preparation and pharmaceutical compositions containing them |
| US20070225351A1 (en) | 2002-01-11 | 2007-09-27 | Lippa Arnold S | Methods and compositions for controlling body weight and appetite |
| WO2003061567A2 (en) | 2002-01-18 | 2003-07-31 | Merck & Co., Inc. | Selective s1p1/edg1 receptor agonists |
| JP2005516967A (ja) | 2002-01-18 | 2005-06-09 | ザ ジェネティクス カンパニー インコーポレーティッド | β−セクレターゼインヒビター |
| JP4430941B2 (ja) | 2002-01-18 | 2010-03-10 | 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 |
| GB0201850D0 (en) | 2002-01-26 | 2002-03-13 | Astrazeneca Ab | Therapeutic treatment |
| 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 |
| WO2003074008A2 (en) | 2002-03-01 | 2003-09-12 | Merck & Co., Inc. | Aminoalkylphosphonates and related compounds as edg receptor agonists |
| ATE507210T1 (de) | 2002-03-07 | 2011-05-15 | X Ceptor Therapeutics Inc | Chinazolinon modulatoren von nukleinrezeptoren |
| US7731985B2 (en) | 2002-03-15 | 2010-06-08 | Ciba Specialty Chemicals Corporation | 4-aminopyrimidines and their use for the antimicrobial treatment of surfaces |
| TW200810743A (en) | 2002-03-22 | 2008-03-01 | Novartis Ag | Combination of organic compounds |
| AU2003225027A1 (en) | 2002-04-16 | 2003-11-03 | Merck And Co., Inc. | Combination therapy using a ppar alpha/gamma agonist |
| AU2003222786A1 (en) | 2002-04-18 | 2003-10-27 | Ucb, S.A. | Chemical compounds with dual activity, processes for their preparation and pharmaceutical compositions |
| DE10219435A1 (de) | 2002-05-02 | 2003-11-13 | Bayer Cropscience Ag | Substituierte Pyrazolo-pyrimidin-4-one |
| WO2003094845A2 (en) | 2002-05-08 | 2003-11-20 | Bristol-Myers Squibb Company | Pyridine-based thyroid receptor ligands |
| US7057046B2 (en) | 2002-05-20 | 2006-06-06 | Bristol-Myers Squibb Company | Lactam glycogen phosphorylase inhibitors and method of use |
| WO2003103640A1 (en) | 2002-06-10 | 2003-12-18 | Elan Pharma International, Ltd | Nanoparticulate formulations comprising hmg coa reductase inhibitor derivatives (“statins”), novel combinations thereof as well as manufacturing of these pharmaceutical compositions |
| JP4533134B2 (ja) | 2002-06-10 | 2010-09-01 | エラン ファーマ インターナショナル，リミティド | ナノ粒子ポリコサノール製剤および新規なポリコサノールの組合せ |
| AR040241A1 (es) | 2002-06-10 | 2005-03-23 | Merck & Co Inc | Inhibidores de la 11-beta-hidroxiesteroide deshidrogrenasa 1 para el tratamiento de la diabetes obesidad y dislipidemia |
| CA2488617A1 (en) | 2002-06-10 | 2003-12-18 | Eugene R. Cooper | Nanoparticulate sterol formulations and sterol combinations |
| WO2003105763A2 (en) | 2002-06-14 | 2003-12-24 | Amylin Pharmaceuticals, Inc. | Prevention and/or treatment of inflammatory bowel disease using pyy or agonists thereof |
| DE10226943A1 (de) | 2002-06-17 | 2004-01-08 | Bayer Ag | Phenylaminopyrimidine und ihre Verwendung |
| 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 |
| GB0214254D0 (en) | 2002-06-20 | 2002-07-31 | Glaxo Group Ltd | Chemical compounds |
| SE0201980D0 (sv) | 2002-06-24 | 2002-06-24 | Astrazeneca Ab | Novel compounds |
| SE0201976D0 (sv) | 2002-06-24 | 2002-06-24 | Astrazeneca Ab | Novel compounds |
| US20060014717A1 (en) | 2002-06-28 | 2006-01-19 | Glykos Finland Oy | Therapeutic compositions for use in prophylaxis or treatment of diarrheas |
| US7071210B2 (en) | 2002-07-02 | 2006-07-04 | Pfizer Inc. | CETP inhibitors in combination with antihypertensive agents and uses thereof |
| US20040053842A1 (en) | 2002-07-02 | 2004-03-18 | Pfizer Inc. | Methods of treatment with CETP inhibitors and antihypertensive agents |
| AU2003252478A1 (en) | 2002-07-10 | 2004-02-02 | Ono Pharmaceutical Co., Ltd. | Ccr4 antagonist and medicinal use thereof |
| AU2003261204A1 (en) | 2002-07-23 | 2004-02-09 | Smithkline Beecham Corporation | Pyrazolopyrimidines as kinase inhibitors |
| AU2003254053A1 (en) | 2002-07-23 | 2004-02-09 | Smithkline Beecham Corporation | Pyrazolopyrimidines as protein kinase inhibitors |
| JP2006514918A (ja) | 2002-07-23 | 2006-05-18 | スミスクライン ビーチャム コーポレーション | キナーゼインヒビターとしてのピラゾロピリミジン |
| US20060105445A1 (en) | 2002-07-29 | 2006-05-18 | Klaus Godl | Medium and method for enriching, purifying or depleting atp binding proteins from a pool of proteins |
| EP1539137B1 (en) | 2002-07-30 | 2010-05-26 | Merck Sharp & Dohme Corp. | Ppar alpha selective compounds for the treatment of dyslipidemia and other lipid disorders |
| JP4475406B2 (ja) | 2002-07-30 | 2010-06-09 | メルク・シャープ・エンド・ドーム・コーポレイション | 異常脂血症および他の脂質障害の治療用のＰＰＡＲα選択的化合物 |
| US7241790B2 (en) | 2002-07-30 | 2007-07-10 | University Of Virginia Patent Foundation | Compounds active in spinigosine 1-phosphate signaling |
| JP2004067575A (ja) | 2002-08-06 | 2004-03-04 | Yaizu Suisankagaku Industry Co Ltd | 糖尿病治療薬効果促進剤 |
| AR041191A1 (es) | 2002-08-08 | 2005-05-04 | Amgen Inc | Ligandos del receptor vanilloide y su uso en tratamientos |
| DE10237722A1 (de) | 2002-08-17 | 2004-08-19 | Aventis Pharma Deutschland Gmbh | Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase |
| US20060167045A1 (en) | 2002-08-21 | 2006-07-27 | Joanne Waldstreicher | Combination therapy using a dual ppar alpha/gamma agonist and an angiotensin II type I receptor antagonist |
| EP1546142A4 (en) | 2002-08-29 | 2007-10-17 | Merck & Co Inc | INDOLES HAVING ANTIDIABETIC EFFECT |
| CN100457730C (zh) | 2002-08-29 | 2009-02-04 | 默克公司 | 具有抗糖尿病活性的吲哚化合物 |
| EP1538217A4 (en) | 2002-09-11 | 2006-09-27 | Astellas Pharma Inc | SCREENING METHOD FOR INSULATION STOP ENHANCER |
| JP2006510597A (ja) | 2002-09-27 | 2006-03-30 | メルク エンド カムパニー インコーポレーテッド | 置換ピリミジン類 |
| US7067658B2 (en) | 2002-09-30 | 2006-06-27 | Bristol-Myers Squibb Company | Pyridino and pyrimidino pyrazinones |
| AU2003282679A1 (en) | 2002-10-04 | 2004-05-04 | Arena Pharmaceuticals, Inc. | Hydroxypyrazoles for use against metabolic-related disorders |
| AU2003284111A1 (en) | 2002-10-09 | 2004-05-04 | Genaissance Pharmaceuticals, Inc. | Itgb3 gene haplotypes and atorvastatin dose effects on hdl cholesterol |
| EP1551842A1 (en) | 2002-10-15 | 2005-07-13 | Smithkline Beecham Corporation | Pyradazine compounds as gsk-3 inhibitors |
| US7129239B2 (en) | 2002-10-28 | 2006-10-31 | Pfizer Inc. | Purine compounds and uses thereof |
| CA2503715A1 (en) | 2002-10-30 | 2004-05-21 | Merck & Co., Inc. | Kinase inhibitors |
| CA2505322A1 (en) | 2002-11-08 | 2004-05-21 | Takeda Pharmaceutical Company Limited | Receptor function regulator |
| US7098235B2 (en) | 2002-11-14 | 2006-08-29 | Bristol-Myers Squibb Co. | Triglyceride and triglyceride-like prodrugs of glycogen phosphorylase inhibiting compounds |
| US20040110241A1 (en) | 2002-12-06 | 2004-06-10 | Segal Mark S. | Materials and methods for monitoring vascular endothelial function |
| DE60335827D1 (de) | 2002-12-20 | 2011-03-03 | Merck Sharp & Dohme | 1-(amino)indane als edg-rezeptoragonisten |
| EP1578715B1 (en) | 2002-12-20 | 2011-03-02 | Bayer Pharmaceuticals Corporation | Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation |
| WO2004058727A1 (en) | 2002-12-20 | 2004-07-15 | Bayer Pharmaceuticals Corporation | Substituted 3,5-dihydro-4h-imidazol-4-ones for the treatment of obesity |
| JO2397B1 (en) | 2002-12-20 | 2007-06-17 | ميرك شارب اند دوم كوربوريشن | Terazol derivatives as beta-hydroxy steroid dihydrogenase-1 inhibitors |
| GB0230020D0 (en) | 2002-12-23 | 2003-01-29 | Syngenta Ltd | Fungicides |
| GB0230021D0 (en) | 2002-12-23 | 2003-01-29 | Syngenta Ltd | Fungicides |
| MXPA05007485A (es) | 2003-01-14 | 2006-01-30 | Arena Pharm Inc | Derivados de arilo y heteroarilo 1,2,3-trisubstituidos como moduladores del metabolismo y la profilaxis y tratamiento de trastornos relacionados con ello tales como diabetes e hiperglicemia. |
| WO2004062665A1 (en) | 2003-01-16 | 2004-07-29 | Sb Pharmco Puerto Rico Inc | Heteroaryl- substituted pyrrolo` 2, 3- b! pyridine derivatives as crf receptor antagonists |
| AU2004207444B2 (en) | 2003-01-17 | 2008-07-31 | Merck & Co., Inc. | N-cyclohexylaminocarbonyl benzenesulfonamide derivatives |
| GB0301259D0 (en) | 2003-01-20 | 2003-02-19 | Novartis Ag | Organic compounds |
| PL378134A1 (pl) | 2003-02-11 | 2006-03-06 | Irm Llc | Nowe pochodne bicykliczne i kompozycje farmaceutyczne zawierające pochodne bicykliczne |
| TW200418829A (en) | 2003-02-14 | 2004-10-01 | Avanir Pharmaceutics | Inhibitors of macrophage migration inhibitory factor and methods for identifying the same |
| BRPI0407658A (pt) | 2003-02-18 | 2006-02-21 | Kyorin Seiyaku Kk | derivados de ácido aminofosfÈnico, seus sais e hidratos que atuam como moduladores de receptor de s1p e agente farmacêutico |
| WO2004076413A2 (en) | 2003-02-24 | 2004-09-10 | Arena Pharmaceuticals, Inc. | Phenyl- and pyridylpiperidine-derivatives as modulators of glucose metabolism |
| JP2004269468A (ja) | 2003-03-12 | 2004-09-30 | Yamanouchi Pharmaceut Co Ltd | ピリミジン誘導体又はその塩 |
| JP2004269469A (ja) | 2003-03-12 | 2004-09-30 | Yamanouchi Pharmaceut Co Ltd | ピリミジン誘導体又はその塩 |
| JP2006521344A (ja) | 2003-03-28 | 2006-09-21 | ファイザー・プロダクツ・インク | アテローム性動脈硬化症および肥満の治療のためのｃｅｔｐ阻害剤としての１，２，４−置換１，２，３，４−テトラヒドロ−および１，２−ジヒドロ−キノリンおよび１，２，３，４−テトラヒドロ−キノキサリン誘導体 |
| CN1777575B (zh) | 2003-04-30 | 2010-05-12 | 诺瓦提斯公司 | 作为1-磷酸-鞘氨醇受体调节剂的氨基-丙醇衍生物 |
| MXPA05011597A (es) | 2003-04-30 | 2005-12-15 | Novartis Ag | Derivados de aminopropanol como moduladores del receptor 1-fosfato de esfingosina. |
| US7329680B2 (en) | 2003-04-30 | 2008-02-12 | The Institute For Pharmaceutical Discovery, Llc | Heterocycle substituted carboxylic acids |
| TWI494102B (zh) | 2003-05-02 | 2015-08-01 | Japan Tobacco Inc | 包含ｓ-〔２（〔〔１-（２-乙基丁基）環己基〕羰基〕胺基）苯基〕２-甲基丙烷硫酯及ｈｍｇ輔酶ａ還原酶抑制劑之組合 |
| ES2351624T3 (es) | 2003-05-06 | 2011-02-08 | Ústav Experimentálni Botaniky Av Cr, V.V.I. (Institute Of Experimental Botany Academy Of Sciences Of The Czech Republic, Pro) | Pirazolo[4,3-d]pirimidinas, procedimiento para su preparación y uso. |
| SE0301368D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Chemical compounds |
| US7083933B1 (en) | 2003-05-09 | 2006-08-01 | Prosidion Limited | Methods for identification of modulators of OSGPR116 activity |
| 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 |
| WO2004104205A2 (en) | 2003-05-16 | 2004-12-02 | Merck & Co., Inc. | Enzymatic preparation of chiral indole esters |
| MY150088A (en) | 2003-05-19 | 2013-11-29 | Irm Llc | Immunosuppressant compounds and compositions |
| MXPA05012459A (es) | 2003-05-19 | 2006-02-22 | Irm Llc | Compuestos y composiciones inmunosupresoras. |
| EP1644367B1 (en) | 2003-05-19 | 2015-10-14 | Novartis AG | Immunosuppressant compounds and compositions |
| 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. |
| US6987118B2 (en) | 2003-05-21 | 2006-01-17 | Pfizer Inc. | Tetrahydroisoquinoline derivatives as PPAR-alpha activators |
| EP1635773A2 (en) | 2003-06-06 | 2006-03-22 | Merck & Co., Inc. (a New Jersey corp.) | Combination therapy for the treatment of hypertension |
| AU2003902882A0 (en) | 2003-06-10 | 2003-06-26 | Fujisawa Pharmaceutical Co., Ltd. | Piperidyl derivatives |
| GB0313612D0 (en) | 2003-06-12 | 2003-07-16 | Novartis Ag | Organic compounds |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| RS20060018A (sr) | 2003-07-14 | 2007-12-31 | Arena Pharmaceuticals Inc., | Derivati spojenih arila i heteroarila kao modulatori metabolizma u profilaksi i lečenju sa njima povezanih stanja |
| JPWO2005012221A1 (ja) | 2003-08-04 | 2006-09-14 | 小野薬品工業株式会社 | ジフェニルエーテル化合物、その製造方法および用途 |
| PT1660458E (pt) | 2003-08-15 | 2012-04-27 | Novartis Ag | 2,4-pirimidinodiaminas úteis no tratamento de doenças neoplásicas, desordens inflamatórias e do sistema imunitário |
| ATE449069T1 (de) | 2003-08-28 | 2009-12-15 | Novartis Pharma Gmbh | Aminopropanolderivate |
| US7825109B2 (en) | 2003-08-29 | 2010-11-02 | Ono Pharmaceutical Co., Ltd. | Compound capable of binding S1P receptor and pharmaceutical use thereof |
| JP2007504230A (ja) | 2003-09-02 | 2007-03-01 | メルク エンド カムパニー インコーポレーテッド | ジペプチジルペプチダーゼ−ｉｖ阻害剤のリン酸塩の新規結晶性形態 |
| WO2005023762A1 (en) | 2003-09-04 | 2005-03-17 | Abbott Laboratories | Pyrrolidine-2-carbonitrile derivatives and their use as inhibitors of dipeptidyl peptidase-iv (dpp-iv) |
| WO2005023771A1 (ja) | 2003-09-05 | 2005-03-17 | Ono Pharmaceutical Co., Ltd. | ケモカインレセプターアンタゴニストおよびその医薬用途 |
| TWI359147B (en) | 2003-09-05 | 2012-03-01 | Vertex Pharma | Inhibitors of serine proteases, particularly hcv n |
| EP1699777B1 (en) | 2003-09-08 | 2012-12-12 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| EP1697342A2 (en) | 2003-09-08 | 2006-09-06 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| PE20050948A1 (es) | 2003-09-09 | 2005-12-16 | Japan Tobacco Inc | Compuestos de carbamoil-amina como inhibidores de la dipeptidil peptidasa iv |
| EP1667524A4 (en) | 2003-09-23 | 2009-01-14 | Merck & Co Inc | NEW CRYSTALLINE FORM OF A PHOSPHORIC ACID SALT OF A DIPEPTIDYLPEPTIDASE IV INHIBITOR |
| CN1856307A (zh) | 2003-09-23 | 2006-11-01 | 默克公司 | 喹啉钾通道抑制剂 |
| US20070043014A1 (en) | 2003-10-01 | 2007-02-22 | Merck & Co., Inc. | 3,5-Aryl, heteroaryl or cycloalkyl substituted-1,2,4-oxadiazoles as s1p receptor agonists |
| WO2005033099A2 (en) | 2003-10-03 | 2005-04-14 | Glenmark Pharmaceuticals Ltd. | Novel dipeptidyl peptidase iv inhibitors; processes for their preparation and compositions thereof |
| WO2005037215A2 (en) | 2003-10-14 | 2005-04-28 | Massachusetts Institute Of Technology | Compositions and methods for enhancing cognitive function and synaptic plasticity |
| GB0324236D0 (en) | 2003-10-16 | 2003-11-19 | Astrazeneca Ab | Chemical compounds |
| TW200523252A (en) | 2003-10-31 | 2005-07-16 | Takeda Pharmaceutical | Pyridine compounds |
| US7638637B2 (en) | 2003-11-03 | 2009-12-29 | University Of Virginia Patent Foundation | Orally available sphingosine 1-phosphate receptor agonists and antagonists |
| WO2005044780A1 (ja) | 2003-11-10 | 2005-05-19 | Kyorin Pharmaceutical Co., Ltd. | アミノカルボン酸誘導体とその付加塩及びｓ１ｐ受容体調節剤 |
| AU2004289304A1 (en) | 2003-11-10 | 2005-05-26 | Synta Pharmaceuticals, Corp. | Pyridine compounds |
| SG134333A1 (en) | 2003-11-12 | 2007-08-29 | Phenomix Corp | Heterocyclic boronic acid compounds |
| MY141220A (en) | 2003-11-17 | 2010-03-31 | Astrazeneca Ab | Pyrazole derivatives as inhibitors of receptor tyrosine kinases |
| WO2005058315A1 (en) | 2003-12-12 | 2005-06-30 | Ribapharm, Inc. | Novel heterocyclic compounds as ikk2 inhibitors with anti-hbv activity |
| WO2005058849A1 (en) | 2003-12-15 | 2005-06-30 | Glenmark Pharmaceuticals Ltd. | New dipeptidyl peptidase in inhibitors; process for their preparation and compositions containing them |
| EP1697333A4 (en) | 2003-12-17 | 2009-07-08 | Merck & Co Inc | (3,4-DISUBSTITUTED) PROPANE ACID BOXYLATES AS AGONISTS OF THE S1P (EDG) RECEPTOR |
| ATE528276T1 (de) | 2003-12-19 | 2011-10-15 | Ono Pharmaceutical Co | Lysophosphatidylsäurerezeptor-antagonistische verbindungen und ihre anwendungen |
| GB0329498D0 (en) | 2003-12-19 | 2004-01-28 | Novartis Ag | Organic compounds |
| DE10360835A1 (de) | 2003-12-23 | 2005-07-21 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclische Imidazolverbindungen, deren Herstellung und deren Verwendung als Arzneimittel |
| JP4958560B2 (ja) | 2003-12-24 | 2012-06-20 | プロシディオン・リミテッド | Ｇｐｃｒ受容体作動薬としてのヘテロ環誘導体 |
| US20080227786A1 (en) | 2004-01-16 | 2008-09-18 | Ferlita Russell R | Novel Crystalline Salts of a Dipeptidyl Peptidase-IV Inhibitor |
| GB0401332D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| WO2005075426A1 (en) | 2004-02-03 | 2005-08-18 | Glenmark Pharmaceuticals Ltd. | Novel dipeptidyl peptidase iv inhibitors; processes for their preparation and compositions thereof |
| AU2005212438A1 (en) | 2004-02-11 | 2005-08-25 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| TW200530236A (en) | 2004-02-23 | 2005-09-16 | Chugai Pharmaceutical Co Ltd | Heteroaryl phenylurea |
| US7718704B2 (en) | 2004-02-24 | 2010-05-18 | Irm Llc | Immunosuppressant compounds and compositions |
| NZ549162A (en) | 2004-02-24 | 2009-12-24 | Sankyo Co | Amino-pyrrol alcohol compounds |
| TW200538433A (en) | 2004-02-24 | 2005-12-01 | Irm Llc | Immunosuppressant compounds and compositiions |
| CN1934094A (zh) | 2004-03-05 | 2007-03-21 | 万有制药株式会社 | 二芳基取代杂环5元环衍生物 |
| GB0405289D0 (en) | 2004-03-09 | 2004-04-21 | Novartis Ag | Organic compounds |
| GB0405933D0 (en) | 2004-03-16 | 2004-04-21 | Glaxo Group Ltd | Compounds |
| JP5239071B2 (ja) | 2004-04-02 | 2013-07-17 | メルク・シャープ・アンド・ドーム・コーポレーション | シクロアルカノインドール誘導体の調製のために有用な非対称水素化方法 |
| EP1764367A1 (en) | 2004-04-12 | 2007-03-21 | Sankyo Company, Limited | Thienopyridine derivatives |
| WO2005117909A2 (en) | 2004-04-23 | 2005-12-15 | Exelixis, Inc. | Kinase modulators and methods of use |
| PL1756084T3 (pl) | 2004-06-04 | 2009-06-30 | Arena Pharm Inc | Podstawione pochodne arylowe i heteroarylowe jako modulatory metabolizmu oraz profilaktyka i leczenie zaburzeń z metabolizmem związanych |
| WO2005123677A1 (en) | 2004-06-16 | 2005-12-29 | Actelion Pharmaceuticals Ltd | 4-carbonyl substituted 1,1,2-trimethyl-1a,4,5,5a-tetrahydro-1h-4-aza-cyclopropa'a!pentalene derivatives as agonists for the g-protein-coupled receptor s1p1/edg1 and immunosuppressive agents |
| JP5315611B2 (ja) | 2004-06-23 | 2013-10-16 | 小野薬品工業株式会社 | Ｓ１ｐ受容体結合能を有する化合物およびその用途 |
| US7781617B2 (en) | 2004-07-16 | 2010-08-24 | Kyorin Pharmaceutical Co., Ltd | Effective use method of medicaments and method of preventing expression of side effect |
| JP2007284350A (ja) | 2004-07-27 | 2007-11-01 | Takeda Chem Ind Ltd | 糖尿病治療剤 |
| TW200611687A (en) | 2004-07-29 | 2006-04-16 | Sankyo Co | Pharmaceutical compositions used for immunosuppressant |
| WO2006010379A1 (en) | 2004-07-29 | 2006-02-02 | Actelion Pharmaceuticals Ltd. | Novel thiophene derivatives as immunosuppressive agents |
| US8022225B2 (en) | 2004-08-04 | 2011-09-20 | Taisho Pharmaceutical Co., Ltd | Triazole derivative |
| US20060223866A1 (en) | 2004-08-13 | 2006-10-05 | Praecis Pharmaceuticals, Inc. | Methods and compositions for modulating sphingosine-1-phosphate (S1P) receptor activity |
| MX2007001661A (es) | 2004-08-13 | 2007-04-23 | Praecis Pharm Inc | Metodos y composiciones para modular la actividad del receptor de esfingosina -1 fosfato (sip). |
| EP1827438B2 (en) | 2004-09-20 | 2014-12-10 | Xenon Pharmaceuticals Inc. | Piperazin derivatives for inhibiting human stearoyl-coa-desaturase |
| WO2006034337A2 (en) | 2004-09-23 | 2006-03-30 | Wyeth | Carbazole and cyclopentaindole derivatives to treat infection with hepatitis c virus |
| JP4797021B2 (ja) | 2004-10-01 | 2011-10-19 | メルク・シャープ・エンド・ドーム・コーポレイション | 糖尿病の治療または予防用のジペプチジルペプチダ−ゼ−ｉｖ阻害剤としてのアミノピペリジン |
| US7557112B2 (en) | 2004-10-08 | 2009-07-07 | Astellas Pharma Inc. | Aromatic-ring-fused pyrimidine derivative |
| CA2583947A1 (en) | 2004-10-12 | 2006-04-20 | Forbes Medi-Tech (Research) Inc. | Compounds and methods of treating insulin resistance and cardiomyopathy |
| TW200621257A (en) | 2004-10-20 | 2006-07-01 | Astellas Pharma Inc | Pyrimidine derivative fused with nonaromatic ring |
| PL1650186T3 (pl) | 2004-10-22 | 2008-11-28 | Bioprojet Soc Civ | Nowe pochodne kwasów dikarboksylowych |
| CA2583681A1 (en) | 2004-10-22 | 2006-05-04 | Merck & Co., Inc. | 2-(aryl)azacyclylmethyl carboxylates, sulfonates, phosphonates, phosphinates and heterocycles as s1p receptor agonists |
| AR051596A1 (es) | 2004-10-26 | 2007-01-24 | Irm Llc | Compuestos heterociclicos condensados nitrogenados como inhibidores de la actividad del receptor canabinoide 1; composiciones farmaceuticas que los contienen y su empleo en la preparacion de medicamentos para el tratamiento de trastornos alimentarios |
| WO2006052566A2 (en) | 2004-11-03 | 2006-05-18 | Arena Pharmaceuticals, Inc. | Gpr41 and modulators thereof for the treatment of insulin-related disorders |
| GB0425035D0 (en) | 2004-11-12 | 2004-12-15 | Novartis Ag | Organic compounds |
| JP2008520692A (ja) | 2004-11-18 | 2008-06-19 | ジ インスチチュート フォー ファーマシューティカル ディスカバリー、エルエルシー | 複素環置換カルボン酸 |
| JPWO2006057448A1 (ja) | 2004-11-26 | 2008-06-05 | 武田薬品工業株式会社 | アリールアルカン酸誘導体 |
| US20060160785A1 (en) | 2004-12-03 | 2006-07-20 | Judith Aronhime | Ezetimibe polymorphs |
| WO2006063033A2 (en) | 2004-12-06 | 2006-06-15 | University Of Virginia Patent Foundation | Aryl amide sphingosine 1-phosphate analogs |
| BRPI0519012A2 (pt) | 2004-12-13 | 2008-12-23 | Ono Pharmaceutical Co | derivado do Ácido aminocarboxÍlico e seu uso medicinal |
| BRPI0519006A2 (pt) | 2004-12-13 | 2008-12-23 | Daiichi Sankyo Co Ltd | uso de um inibidor de fbpase, kit de uma composiÇço farmacÊutica, uso de uma preparaÇço de biguanida e um inibidor de fbpase, agente terapÊutico para diabetes melito, e, combinaÇço de agentes terapÊuticos |
| NZ556017A (en) | 2004-12-24 | 2009-10-30 | Prosidion Ltd | G-protein coupled receptor (gpr116) agonists and use thereof for treating obesity and diabetes |
| EP1838706A1 (en) | 2004-12-24 | 2007-10-03 | Prosidion Limited | G-protein coupled receptor agonists |
| GB0428514D0 (en) | 2004-12-31 | 2005-02-09 | Prosidion Ltd | Compounds |
| DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| DOP2006000010A (es) | 2005-01-10 | 2006-07-31 | Arena Pharm Inc | Procedimiento para preparar eteres aromáticos |
| MY148521A (en) | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
| DOP2006000009A (es) | 2005-01-13 | 2006-08-15 | Arena Pharm Inc | Procedimiento para preparar eteres de pirazolo [3,4-d] pirimidina |
| WO2006078992A2 (en) | 2005-01-19 | 2006-07-27 | Neurogen Corporation | Heteroaryl substituted piperazinyl-pyridine analogues |
| DE112005003337T5 (de) | 2005-01-25 | 2008-02-21 | Merck Patent Gmbh | Mesogene Verbindungen, Flüssigkristallmedium und Flüssigkristallanzeige |
| EP1685841A1 (en) | 2005-01-31 | 2006-08-02 | Bayer Health Care Aktiengesellschaft | Prevention and treatment of thromboembolic disorders |
| US7754703B2 (en) | 2005-02-14 | 2010-07-13 | University Of Virginia Patent Foundation | Cycloalkane-containing sphingosine 1-phosphate agonists |
| KR20080002850A (ko) | 2005-03-23 | 2008-01-04 | 액테리온 파마슈티칼 리미티드 | 신규한 티오펜 유도체 |
| 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 |
| WO2006131336A1 (en) | 2005-06-08 | 2006-12-14 | Novartis Ag | POLYCYCLIC OXADIAZOLES OR I SOXAZOLES AND THEIR USE AS SlP RECEPTOR LIGANDS |
| US20090105136A1 (en) | 2005-06-09 | 2009-04-23 | Jun Suzuki | NPY Y2 Agonist for Use as Therapeutic Agent for Disease Accompanied by Diarrhea |
| US7951794B2 (en) | 2005-06-24 | 2011-05-31 | Actelion Pharmaceuticals Ltd. | Thiophene derivatives |
| TWI418350B (zh) | 2005-06-24 | 2013-12-11 | Sankyo Co | 含有ｐｐａｒ調節劑之醫藥組成物的用途 |
| JP2008545010A (ja) | 2005-06-30 | 2008-12-11 | プロシディオン・リミテッド | Ｇタンパク質共役受容体アゴニスト |
| JP5054004B2 (ja) | 2005-07-01 | 2012-10-24 | アイアールエム・リミテッド・ライアビリティ・カンパニー | タンパク質キナーゼ阻害剤としてのピリミジン置換ベンゾイミダゾール誘導体 |
| US20070060573A1 (en) | 2005-08-10 | 2007-03-15 | Lars Wortmann | Acyltryptophanols |
| BRPI0615133A2 (pt) | 2005-08-23 | 2011-05-03 | Irm Llc | compostos imunossupressores, composições farmacêuticas contendo os mesmos assim como referido uso |
| US20100160359A1 (en) | 2005-09-16 | 2010-06-24 | Arena Pharmaceuticals, Inc. | Modulators of Metabolism and the Treatment of Disorders Related Thereto |
| TW200745055A (en) | 2005-09-23 | 2007-12-16 | Organon Nv | 4-Phenyl-6-substituted-pyrimidine-2-carbonitrile derivatives |
| JPWO2007037196A1 (ja) | 2005-09-29 | 2009-04-09 | 山本化成株式会社 | インドリン系化合物及びその製造方法 |
| PL1932522T3 (pl) | 2005-10-07 | 2012-09-28 | Kyorin Seiyaku Kk | Środek terapeutyczny do leczenia choroby wątroby zawierający jako składnik czynny pochodną 2-amino-1,3-propanodiolu |
| EP1965807A4 (en) | 2005-11-23 | 2010-10-27 | Epix Delaware Inc | S1P RECEPTOR MODULATING COMPOUNDS AND THEIR USE |
| AR057894A1 (es) | 2005-11-23 | 2007-12-26 | Actelion Pharmaceuticals Ltd | Derivados de tiofeno |
| CA2635531C (en) | 2005-12-29 | 2014-06-17 | Lexicon Pharmaceutical Inc. | Multicyclic amino acid derivatives and methods of their use |
| TWI404706B (zh) | 2006-01-11 | 2013-08-11 | Actelion Pharmaceuticals Ltd | 新穎噻吩衍生物 |
| TW200736234A (en) | 2006-01-17 | 2007-10-01 | Astrazeneca Ab | Chemical compounds |
| PL1973884T3 (pl) | 2006-01-19 | 2017-05-31 | Orchid Pharma Limited | Nowe związki heterocykliczne |
| AU2007209051A1 (en) | 2006-01-24 | 2007-08-02 | Actelion Pharmaceuticals Ltd | Novel pyridine derivatives |
| GB0601744D0 (en) | 2006-01-27 | 2006-03-08 | Novartis Ag | Organic compounds |
| TWI389683B (zh) | 2006-02-06 | 2013-03-21 | Kyorin Seiyaku Kk | A therapeutic agent for an inflammatory bowel disease or an inflammatory bowel disease treatment using a 2-amino-1,3-propanediol derivative as an active ingredient |
| JP2009526073A (ja) | 2006-02-09 | 2009-07-16 | 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 | 二環式スフィンゴシン−１−リン酸受容体アナログ |
| TW200806611A (en) | 2006-02-09 | 2008-02-01 | Daiichi Seiyaku Co | Novel amidopropionic acid derivatives and medicine containing the same |
| US20070191371A1 (en) | 2006-02-14 | 2007-08-16 | Kalypsys, Inc. | Heterocyclic modulators of ppar |
| CN101460458A (zh) | 2006-02-15 | 2009-06-17 | 阿勒根公司 | 具有1－磷酸－鞘氨醇(s1p)受体拮抗剂生物活性的带芳基或者杂芳基基团的吲哚－3－羧酸的酰胺、酯、硫代酰胺和硫羟酸酯化合物 |
| AU2007214434B2 (en) | 2006-02-15 | 2012-06-14 | Allergan, Inc. | Indole-3-carboxylic acid amide, ester, thioamide and thiol ester compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (S1P) receptor antagonist biological activity |
| KR20080096780A (ko) | 2006-02-21 | 2008-11-03 | 유니버시티 오브 버지니아 페이턴트 파운데이션 | Ｓ１ｐ 수용체 효능제로서의 페닐-시클로알킬 및 페닐-헤테로시클릭 유도체 |
| US7649098B2 (en) | 2006-02-24 | 2010-01-19 | Lexicon Pharmaceuticals, Inc. | Imidazole-based compounds, compositions comprising them and methods of their use |
| MX2008011615A (es) | 2006-03-14 | 2008-09-22 | Amgen Inc | Derivados de acidos carboxilicos biciclicos utiles para tratar trastornos metabolicos. |
| AU2007227274A1 (en) | 2006-03-21 | 2007-09-27 | Epix Delaware, Inc. | S1P receptor modulating compounds |
| JP2007262009A (ja) | 2006-03-29 | 2007-10-11 | Dai Ichi Seiyaku Co Ltd | ヘテロアリール低級カルボン酸誘導体 |
| PL2003132T3 (pl) | 2006-04-03 | 2014-10-31 | Astellas Pharma Inc | Pochodne oksadiazolu jako agoniści S1P1 |
| US7833730B2 (en) | 2006-04-11 | 2010-11-16 | Arena Pharmaceuticals, Inc. | Methods of using GPR119 to identify compounds useful for increasing bone mass in an individual |
| PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| GB0607389D0 (en) | 2006-04-12 | 2006-05-24 | Novartis Ag | Organic compounds |
| EP2258700A1 (en) | 2006-05-09 | 2010-12-08 | Pfizer Products Inc. | Cycloalkylamino acid derivatives and pharmaceutical compositions thereof |
| WO2007129473A1 (ja) | 2006-05-09 | 2007-11-15 | Daiichi Sankyo Company, Limited | 二環性アリール誘導体 |
| WO2007129745A1 (ja) | 2006-05-09 | 2007-11-15 | Daiichi Sankyo Company, Limited | ヘテロアリールアミド低級カルボン酸誘導体 |
| TW200811147A (en) | 2006-07-06 | 2008-03-01 | Arena Pharm Inc | Modulators of metabolism and the treatment of disorders related thereto |
| TW200811140A (en) | 2006-07-06 | 2008-03-01 | Arena Pharm Inc | Modulators of metabolism and the treatment of disorders related thereto |
| EP2043744A2 (en) | 2006-07-13 | 2009-04-08 | SmithKline Beecham Corporation | Chemical compounds |
| AR062156A1 (es) | 2006-08-01 | 2008-10-22 | Praecis Pharm Inc | Compuestos agonistas y selectivos del receptor s1p-1 |
| EP2046766A1 (en) | 2006-08-01 | 2009-04-15 | Praecis Pharmaceuticals Incorporated | Agonists of the sphingosine- 1- phosphate receptor (slp) |
| JP2009545630A (ja) | 2006-08-04 | 2009-12-24 | プリーシス・ファーマシューティカルズ・インコーポレイテッド | 化合物 |
| CA2659598A1 (en) | 2006-08-08 | 2008-02-14 | Kyorin Pharmaceutical Co., Ltd. | Amino phosphate derivative and s1p receptor modulator having same as an active ingredient |
| EP2054377A1 (en) | 2006-08-24 | 2009-05-06 | Praecis Pharmaceuticals Incorporated | Chemical compounds |
| JP2009269819A (ja) | 2006-08-25 | 2009-11-19 | Asahi Kasei Pharma Kk | アミン化合物 |
| WO2008025799A1 (en) | 2006-08-30 | 2008-03-06 | Biovitrum Ab (Publ) | Pyridazine compounds for treating gpr119 related disorders |
| 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. |
| PT2069336E (pt) | 2006-09-07 | 2013-03-07 | Actelion Pharmaceuticals Ltd | Derivados de piridin-4-ilo como agentes imunomoduladores |
| 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 |
| JP5330260B2 (ja) | 2006-12-06 | 2013-10-30 | スミスクライン ビーチャム コーポレーション | 二環式化合物ならびに抗糖尿病薬としての使用 |
| AU2007334519A1 (en) | 2006-12-14 | 2008-06-26 | Merck Sharp & Dohme Corp. | Acyl bipiperidinyl compounds, compositions containing such compounds and methods of treatment |
| EP2109364A4 (en) | 2006-12-15 | 2010-04-14 | Abbott Lab | NOVEL OXADIAZONE COMPOUNDS |
| JO2701B1 (en) | 2006-12-21 | 2013-03-03 | جلاكسو جروب ليميتد | Vehicles |
| BRPI0720478A2 (pt) | 2006-12-21 | 2014-01-14 | Abbott Laboratoires | Compostos agonistas e antagonistas do receptor esfingosina-1-fosfato |
| GB0625648D0 (en) | 2006-12-21 | 2007-01-31 | Glaxo Group Ltd | Compounds |
| MX2009007334A (es) | 2007-01-11 | 2009-07-15 | Allergan Inc | Compuestos de amida del acido indol-3-carboxilico 6-substituido que tienen actividad antagonista biologica del receptor esfingosina-1-fosfato (s1p). |
| WO2008091967A1 (en) | 2007-01-26 | 2008-07-31 | Smithkline Beecham Corporation | Chemical compounds |
| WO2008097819A2 (en) | 2007-02-05 | 2008-08-14 | 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 |
| JP5191497B2 (ja) | 2007-03-21 | 2013-05-08 | エピックス ファーマシューティカルズ，インコーポレイテッド | Ｓ１ｐ受容体調節化合物およびその使用 |
| WO2008128832A1 (en) | 2007-04-18 | 2008-10-30 | Nicox S.A. | Nitroderivatives of non-peptidic renin inhibitors for the treatment of cardiovascular, renal and chronic liver disease, inflammations and metabolic syndrome |
| AU2008240773B2 (en) | 2007-04-19 | 2013-10-03 | Glaxo Group Limited | Oxadiazole substituted indazole derivatives for use as sphingosine 1-phosphate (S1P) agonists |
| US7910583B2 (en) | 2007-05-04 | 2011-03-22 | Bristol-Myers Squibb Company | [6,6] and [6,7]-bicyclic GPR119 G protein-coupled receptor agonists |
| EP2014653A1 (en) | 2007-06-15 | 2009-01-14 | Bioprojet | Novel dicarboxylic acid derivatives as S1P1 receptor agonists |
| WO2009011850A2 (en) | 2007-07-16 | 2009-01-22 | Abbott Laboratories | Novel therapeutic compounds |
| WO2009019506A1 (en) | 2007-08-03 | 2009-02-12 | Astrazeneca Ab | Heterocyclyc sulfonamides having edg-1 antagonistic activity |
| CN101790519B (zh) | 2007-08-08 | 2013-10-16 | 默克雪兰诺有限公司 | 用于治疗多发性硬化症的结合于鞘氨醇1-磷酸(s1p)的6-氨基-嘧啶-4-羧酰胺衍生物及相关化合物 |
| BRPI0817211A2 (pt) | 2007-09-20 | 2017-05-16 | Irm Llc | composto composições como moduladores da atividade de gpr119 |
| TW200930368A (en) | 2007-11-15 | 2009-07-16 | Astrazeneca Ab | Bis-(sulfonylamino) derivatives in therapy |
| US8637704B2 (en) | 2007-11-28 | 2014-01-28 | Synta Pharmaceuticals Corp. | Polymorphs of N-malonyl-bis(N′-methyl-N′-thiobenzoylhydrazide) |
| EP2222668B1 (en) | 2007-12-18 | 2011-11-02 | Arena Pharmaceuticals, Inc. | Tetrahydrocyclopenta[b]indol-3-yl carboxylic acid derivatives useful in the treatment of autoimmune and inflammatory disorders |
| EP2252615A1 (en) | 2008-01-25 | 2010-11-24 | Arena Pharmaceuticals, Inc. | Dihydro- 1h- pyrrolo [1,2-a]indol-1-yl carboxylic derivatives which act as s1p1 agonists |
| AR070398A1 (es) | 2008-02-22 | 2010-03-31 | Gruenenthal Chemie | Derivados sustituidos de indol |
| US20110000153A1 (en) | 2008-02-28 | 2011-01-06 | Solar Roofing Systems, Inc. | Photovoltaic Roofing Tile with Fire Suppression |
| PL2278960T5 (pl) | 2008-03-17 | 2020-06-29 | Actelion Pharmaceuticals Ltd. | Schemat dawkowania dla selektywnego agonisty receptora sip1 |
| EP2108960A1 (en) | 2008-04-07 | 2009-10-14 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditons modulated by PYY |
| WO2009125434A2 (en) | 2008-04-07 | 2009-10-15 | Cadila Healthcare Limited | Oxime derivatives |
| EP2271619A1 (en) | 2008-04-07 | 2011-01-12 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
| EP3782991A1 (en) | 2008-05-14 | 2021-02-24 | The Scripps Research Institute | Novel modulators of sphingosine phosphate receptors |
| WO2009151626A1 (en) | 2008-06-13 | 2009-12-17 | Arena Pharmaceuticals, Inc. | Substituted (1, 2, 4-0xadiaz0l-3-yl) indolin-1-yl carboxylic acid derivatives useful as s1p1 agonists |
| WO2009151621A1 (en) | 2008-06-13 | 2009-12-17 | Arena Pharmaceuticals, Inc. | Substituted (1, 2, 4-0xadiaz0l-3-yl) indolin-1-yl carboxylic acid derivatives useful as s1p1 agonists |
| US8580841B2 (en) | 2008-07-23 | 2013-11-12 | Arena Pharmaceuticals, Inc. | Substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid derivatives useful in the treatment of autoimmune and inflammatory disorders |
| HRP20160890T1 (hr) * | 2008-08-27 | 2016-09-23 | Arena Pharmaceuticals, Inc. | Derivati supstituirane tricikličke kiseline kao agonisti s1p1-receptora korisni u liječenju autoimunih i upalnih poremećaja |
| TW201028143A (en) | 2008-12-22 | 2010-08-01 | Novartis Ag | Dosage regimen for a S1P receptor agonist |
| JP5657565B2 (ja) | 2008-12-22 | 2015-01-21 | ノバルティス アーゲー | Ｓ１ｐ受容体アゴニストの投与レジメン |
| CA2747809A1 (en) | 2008-12-23 | 2010-07-01 | Joel M. Harris | Bicyclic heterocycle derivatives and methods of use thereof |
| WO2010075273A1 (en) | 2008-12-23 | 2010-07-01 | Schering Corporation | Bicyclic heterocycle derivatives and methods of use thereof |
| WO2010074271A1 (ja) | 2008-12-26 | 2010-07-01 | 武田薬品工業株式会社 | 糖尿病治療剤 |
| US20120016119A1 (en) | 2009-01-22 | 2012-01-19 | Yasunori Tsuboi | NOVEL PYRROLO(2,3-d)PYRIMIDINE COMPOUND |
| PE20120578A1 (es) | 2009-02-10 | 2012-06-17 | Abbott Lab | Agonistas y antagonistas del receptor de s1p5, y metodos de uso de los mismos |
| WO2011005290A1 (en) | 2009-06-23 | 2011-01-13 | Arena Pharmaceuticals, Inc. | Disubstituted oxadiazole derivatives useful in the treatment of autoimmune and inflammatory disorders |
| WO2011005295A1 (en) | 2009-06-24 | 2011-01-13 | Arena Pharmaceuticals, Inc. | Modulators of the sphingosine-1-phosphate (s1p) receptor useful for the treatment of disorders related thereto |
| AR077642A1 (es) | 2009-07-09 | 2011-09-14 | Arena Pharm Inc | Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo |
| AR077638A1 (es) | 2009-07-15 | 2011-09-14 | Lilly Co Eli | Compuesto de (metanosulfonil -piperidin )-( alcoxi-aril) -tetrahidro- piridina , composicion farmaceutica que lo comprende y su uso para preparar un medicamento util para el tratamiento de diabetes u obesidad |
| WO2011030139A1 (en) | 2009-09-11 | 2011-03-17 | Astrazeneca Ab | 4- (pyrimidin-2-yl) -piperazine and 4- (pyrimidin-2-yl) -piperidine derivatives as gpr119 modulators |
| US9216972B2 (en) | 2009-10-29 | 2015-12-22 | Bristol-Myers Squibb Company | Tricyclic heterocyclic compounds |
| US8299059B2 (en) | 2009-10-30 | 2012-10-30 | Eli Lilly And Company | Crystalline compound and a process for its preparation |
| US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| CN102753543A (zh) | 2009-12-30 | 2012-10-24 | 麦迪凯姆股份公司 | 药用用途的1-(1h-1,2,4-三唑-1-基)-2-丁醇衍生物，以及使用具有基本上未定义晶形的1-(1h-1,2,4-三唑-1-基)-2-丁醇衍生物制备所述1-(1h-1,2,4-三唑-1-基) -2-丁醇衍生物 |
| JP5856980B2 (ja) | 2010-01-27 | 2016-02-10 | 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 | （Ｒ）−２−（７−（４−シクロペンチル−３−（トリフルオロメチル）ベンジルオキシ）−１，２，３，４−テトラヒドロシクロペンタ［ｂ］インドール−３−イル）酢酸およびその塩の調製のためのプロセス |
| 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 |
| CA2795513A1 (en) | 2010-04-06 | 2011-10-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| JP2013533286A (ja) | 2010-07-30 | 2013-08-22 | セントルイス ユニバーシティ | 疼痛を治療する方法 |
| EP3323818A1 (en) | 2010-09-22 | 2018-05-23 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| EA034451B1 (ru) | 2011-02-07 | 2020-02-10 | Байоджен Ма Инк. | Модуляторы s1p |
| US20140018371A1 (en) | 2011-04-01 | 2014-01-16 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| WO2012145361A1 (en) | 2011-04-19 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US20140051714A1 (en) | 2011-04-22 | 2014-02-20 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| US20140038889A1 (en) | 2011-04-22 | 2014-02-06 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| WO2012170702A1 (en) | 2011-06-08 | 2012-12-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2013055910A1 (en) | 2011-10-12 | 2013-04-18 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| CN104093310A (zh) | 2012-02-03 | 2014-10-08 | 泰华制药工业有限公司 | 拉喹莫德用于治疗一线抗TNFα疗法失败的克罗恩氏病患者的用途 |
| US20160038506A1 (en) | 2012-02-14 | 2016-02-11 | Repros Therapeutics Inc. | Selective Estrogen Receptor Modulators With Short Half-Lives and Uses Thereof |
| US8962888B2 (en) | 2012-12-03 | 2015-02-24 | Physical Sciences, Inc. | Forming spherical crystal habit |
| JP5589110B1 (ja) | 2013-03-08 | 2014-09-10 | 株式会社ポーラファルマ | 晶癖を有する結晶及び該結晶を有効成分として含有する医薬組成物 |
| PL3242666T3 (pl) | 2015-01-06 | 2025-02-17 | Arena Pharmaceuticals, Inc. | Związek do zastosowania w leczeniu dolegliwości związanych z receptorem s1p1 |
| BR112017027656B1 (pt) * | 2015-06-22 | 2023-12-05 | Arena Pharmaceuticals, Inc. | Hábito cristalino de placa livre de sal de l-arginina de ácido (r)-2-(7-(4- ciclopentil-3-(trifluorometil)benzilóxi)- 1,2,3,4-tetra-hidrociclo-penta[b]indol-3- il)acético, composição farmacêutica que o compreende, seus usos e método de preparação do mesmo |
| MX2019009841A (es) * | 2017-02-16 | 2020-01-30 | Arena Pharm Inc | Compuestos y metodos para el tratamiento de la colangitis biliar primaria. |
| MX2019009843A (es) * | 2017-02-16 | 2020-01-30 | Arena Pharm Inc | Compuestos y metodos para el tratamiento de la enfermedad inflamatoria intestinal con manifestaciones extraintestinales. |
| CA3102136A1 (en) | 2018-06-06 | 2019-12-12 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
| JP7265620B2 (ja) | 2018-10-03 | 2023-04-26 | 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 | 強皮症の治療のための方法 |
| CN118649163A (zh) | 2018-11-30 | 2024-09-17 | 艾尼纳制药公司 | 治疗与s1p1受体有关的病况的方法 |
| CN113874009A (zh) | 2019-01-08 | 2021-12-31 | 艾尼纳制药公司 | 治疗与s1p1受体有关的病况的方法 |
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