TW201120034A - Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts - Google Patents
Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts Download PDFInfo
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- TW201120034A TW201120034A TW099133406A TW99133406A TW201120034A TW 201120034 A TW201120034 A TW 201120034A TW 099133406 A TW099133406 A TW 099133406A TW 99133406 A TW99133406 A TW 99133406A TW 201120034 A TW201120034 A TW 201120034A
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- NWRUDSBAGUHOPD-UHFFFAOYSA-N 2-[5-(phenoxymethyl)-2-piperidin-1-yl-6-(tetrazol-1-yl)pyrimidin-4-yl]-1,3-thiazole Chemical class N=1C=CSC=1C=1N=C(N2CCCCC2)N=C(N2N=NN=C2)C=1COC1=CC=CC=C1 NWRUDSBAGUHOPD-UHFFFAOYSA-N 0.000 title 1
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- -1 pyridinium-pyridylpyrimidine Chemical compound 0.000 claims description 13
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Classifications
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- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
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| TW (1) | TW201120034A (https=) |
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| US7638541B2 (en) | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| AU2008279447A1 (en) * | 2007-07-19 | 2009-01-29 | Metabolex, Inc. | N-azacyclic substituted pyrrole, pyrazole, imidazole, triazole and tetrazole derivatives as agonists of the RUP3 or GPR119 receptor for the treatment of diabetes and metabolic disorders |
| AU2009231906A1 (en) * | 2008-03-31 | 2009-10-08 | Metabolex, Inc. | Oxymethylene aryl compounds and uses thereof |
| US20110160222A1 (en) * | 2008-11-26 | 2011-06-30 | Metabolex, Inc. | Modulators of glucose homeostasis for the treatment of diabetes and metabolic disorders |
| JP5909185B2 (ja) | 2009-10-01 | 2016-04-26 | シマベイ セラピューティクス， インコーポレーテッド | 置換テトラゾール−１−イルフェノキシメチルチアゾール−２−イルピペリジニルピリミジン塩 |
| US20110313160A1 (en) * | 2010-06-04 | 2011-12-22 | Metabolex, Inc. | Preparation of 5-ethyl-2--pyrimidine |
| JP5847813B2 (ja) * | 2010-06-23 | 2016-01-27 | シマベイ セラピューティクス， インコーポレーテッド | ５−エチル−２−｛４−［４−（４−テトラゾル−１−イル−フェノキシメチル）−チアゾール−２−イル］−ピペリジン−１−イル｝−ピリミジンの組成物 |
| CA2836487A1 (en) | 2011-06-09 | 2012-12-13 | Rhizen Pharmaceuticals Sa | Novel compounds as modulators of gpr-119 |
| CN103910710B (zh) * | 2012-12-29 | 2017-06-16 | 乳源东阳光药业有限公司 | 阿格列汀新晶型及其制备方法 |
| US20190008864A1 (en) * | 2014-01-23 | 2019-01-10 | Pharmedix.Co., Ltd. | Pharmaceutical composition containing gpr119 ligand as effective ingredient for preventing or treating non-alcoholic steatohepatitis |
| AU2017305392A1 (en) | 2016-08-03 | 2019-02-21 | Cymabay Therapeutics, Inc. | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
| WO2019018406A1 (en) * | 2017-07-18 | 2019-01-24 | Agrimetis, Llc | METHODS OF PURIFYING L-GLUFOSINATE |
| TW202140440A (zh) | 2020-02-28 | 2021-11-01 | 美商克力歐普股份有限公司 | Gpr40激動劑 |
| WO2021236617A1 (en) | 2020-05-19 | 2021-11-25 | Kallyope, Inc. | Ampk activators |
| CN116390925A (zh) | 2020-06-26 | 2023-07-04 | 卡尔优普公司 | Ampk活化剂 |
Family Cites Families (132)
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| US3108117A (en) | 1959-02-12 | 1963-10-22 | Mead Johnson & Co | 3-benzyl-1, 2-diloweralkyl-3-pyrrolidinols |
| US3778443A (en) * | 1969-02-13 | 1973-12-11 | Ciba Geigy Ag | 4-tetrahydro pyridyl,hydroxy alkyl pyrazoles |
| US3536809A (en) | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
| US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| GB1422263A (en) | 1973-01-30 | 1976-01-21 | Ferrosan As | 4-phenyl-piperidine compounds |
| US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
| DE2701705A1 (de) | 1976-01-28 | 1977-08-04 | Sandoz Ag | Neue organische verbindungen, ihre verwendung und herstellung |
| US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
| CA1146866A (en) * | 1979-07-05 | 1983-05-24 | Yamanouchi Pharmaceutical Co. Ltd. | Process for the production of sustained release pharmaceutical composition of solid medical material |
| DE3438830A1 (de) * | 1984-10-23 | 1986-04-30 | Rentschler Arzneimittel | Nifedipin enthaltende darreichungsform und verfahren zu ihrer herstellung |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| WO1992018106A1 (fr) * | 1991-04-16 | 1992-10-29 | Nippon Shinyaku Co., Ltd. | Procede de production d'une dispersion solide |
| US5817667A (en) * | 1991-04-17 | 1998-10-06 | University Of Georgia Research Foudation | Compounds and methods for the treatment of cancer |
| US5187677A (en) | 1991-08-23 | 1993-02-16 | Hewlett-Packard Company | Waveform synthesizer through simulating multiplication |
| US5340591A (en) * | 1992-01-24 | 1994-08-23 | Fujisawa Pharmaceutical Co., Ltd. | Method of producing a solid dispersion of the sparingly water-soluble drug, nilvadipine |
| JP3265680B2 (ja) * | 1992-03-12 | 2002-03-11 | 大正製薬株式会社 | 経口製剤用組成物 |
| AU4444393A (en) * | 1992-09-01 | 1994-03-10 | Zeneca Limited | Pyrrolidine derivatives |
| GB9310713D0 (en) | 1993-05-24 | 1993-07-07 | Zeneca Ltd | Aryl substituted heterocycles |
| EP0802912B1 (en) * | 1995-01-12 | 2004-10-13 | Glaxo Group Limited | Piperidine derivatives having tachykinin antagonist activity |
| ATE294778T1 (de) | 1995-01-23 | 2005-05-15 | Daiichi Suntory Pharma Co Ltd | Verbesserung oder heilung von durch ischämischen krankheiten hervorgerufenen symtomen und dafür verwendbare phenylpiperidinverbingungen |
| DE19504832A1 (de) * | 1995-02-14 | 1996-08-22 | Basf Ag | Feste Wirkstoff-Zubereitungen |
| DE19519496A1 (de) | 1995-05-27 | 1996-11-28 | Lau Matthias Dipl Ing | Sauerstoffsensitives Einschichtsystem und Verfahren zur Anordnung des Systems |
| TR199800409T1 (xx) * | 1995-09-07 | 1998-05-21 | F.Hoffmann-La Roche Ag | Kalp ve b�brek yetersizli�inin tedavii�in yeni 4-(oksialkoksifenil)-3-oksi-piperidinler |
| US5792769A (en) | 1995-09-29 | 1998-08-11 | 3-Dimensional Pharmaceuticals, Inc. | Guanidino protease inhibitors |
| JPH11513382A (ja) | 1995-10-20 | 1999-11-16 | ドクトル カルル トーマエ ゲゼルシャフト ミット ベシュレンクテル ハフツング | ５員複素環化合物、これらの化合物を含む医薬品、それらの使用及びそれらの調製方法 |
| AU710594B2 (en) | 1996-07-22 | 1999-09-23 | Asubio Pharma Co., Ltd. | Arylpiperidinol and arylpiperidine derivatives and pharmaceuticals containing the same |
| KR20000029548A (ko) | 1996-07-25 | 2000-05-25 | 더블유. 지. 콜 | 가바수용체에대한리간드로서의치환된트리아졸로-피리다진유도체 |
| US5880138A (en) | 1996-10-01 | 1999-03-09 | Eli Lilly And Company | NMDA receptor selective antagonists |
| ES2287971T3 (es) | 1997-08-11 | 2007-12-16 | Pfizer Products Inc. | Dispersiones farmaceuticas solidas con biodisponibilidad incrementada. |
| ATE451346T1 (de) | 1998-03-10 | 2009-12-15 | Ono Pharmaceutical Co | Carbonsäurederivate und medikamente die diese als aktiven wirkstoff enthalten |
| US6274735B1 (en) * | 1998-08-10 | 2001-08-14 | Hoffmann-La Roche Inc. | Process and intermediates for preparation of substituted piperidines |
| IT1303737B1 (it) * | 1998-11-11 | 2001-02-23 | Smithkline Beecham Spa | Derivati fenilpiperidinici procedimento per la loro preparazione eloro uso come ligandi del recettore orl-1. |
| US20030017528A1 (en) * | 1998-11-20 | 2003-01-23 | Ruoping Chen | Human orphan G protein-coupled receptors |
| DK1584683T3 (da) | 1998-11-20 | 2007-10-29 | Arena Pharm Inc | Human G-protein-koblet orphan receptor RUP3 |
| US6221660B1 (en) | 1999-02-22 | 2001-04-24 | Synaptic Pharmaceutical Corporation | DNA encoding SNORF25 receptor |
| DE60021254T2 (de) | 1999-03-15 | 2006-04-20 | AXYS Pharmaceuticals, Inc., South San Francisco | N-cyanomethylamide als protease inhibitoren |
| GB9912416D0 (en) * | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| US6015712A (en) | 1999-07-19 | 2000-01-18 | Isis Pharmaceuticals Inc. | Antisense modulation of FADD expression |
| AR035016A1 (es) | 1999-08-25 | 2004-04-14 | Takeda Chemical Industries Ltd | Composicion de azol promotor de produccion/secrecion de neurotrofina, compuesto prodroga del mismo, composicion farmaceutica que lo comprende y uso del mismo para preparar esta ultima. |
| GB9923177D0 (en) | 1999-09-30 | 1999-12-01 | Pfizer Ltd | Novel polypeptide |
| IL139073A0 (en) | 1999-10-21 | 2001-11-25 | Pfizer | Treatment of neuropathy |
| YU51701A (sh) | 2000-07-28 | 2003-12-31 | Pfizer Inc. | Postupak za dobijanje jedinjenja pirazola/4,3-d/ pirimidin-7-ona i njihovih derivata |
| US6770645B2 (en) * | 2001-03-16 | 2004-08-03 | Pfizer Inc. | Pharmaceutically active compounds |
| US6784185B2 (en) * | 2001-03-16 | 2004-08-31 | Pfizer Inc. | Pharmaceutically active compounds |
| EP1389194A2 (en) | 2001-04-27 | 2004-02-18 | Vertex Pharmaceuticals Incorporated | Inhibitors of bace |
| US20030003157A1 (en) | 2001-06-06 | 2003-01-02 | University Of Medicine & Dentistry Of New Jersey | Collagen compositions and methods for making and using the same |
| EP1422228A1 (en) | 2001-08-08 | 2004-05-26 | Takeda Chemical Industries, Ltd. | BENZAZEPINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE |
| EP1480957A1 (en) | 2002-03-01 | 2004-12-01 | Smithkline Beecham Corporation | Hppars activators |
| JPWO2003091216A1 (ja) | 2002-04-25 | 2005-09-02 | 住友製薬株式会社 | 新規ピペリジン誘導体 |
| US7091232B2 (en) | 2002-05-21 | 2006-08-15 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
| US7576074B2 (en) | 2002-07-15 | 2009-08-18 | Rice Kenneth D | Receptor-type kinase modulators and methods of use |
| GB0224919D0 (en) | 2002-10-25 | 2002-12-04 | Pfizer Ltd | Triazole compounds useful in therapy |
| US7084145B2 (en) | 2002-10-25 | 2006-08-01 | Pfizer Inc. | Triazole compounds useful in therapy |
| GB0230162D0 (en) * | 2002-12-24 | 2003-02-05 | Metris Therapeutics Ltd | Compounds useful in inhibiting angiogenesis |
| WO2004076413A2 (en) | 2003-02-24 | 2004-09-10 | Arena Pharmaceuticals, Inc. | Phenyl- and pyridylpiperidine-derivatives as modulators of glucose metabolism |
| DE60306690T2 (de) | 2003-03-05 | 2007-06-28 | Maus S.P.A. | Verfahren zum bearbeiten von bremsscheiben |
| GB0308333D0 (en) | 2003-04-10 | 2003-05-14 | Glaxo Group Ltd | Novel compounds |
| JP2006525355A (ja) | 2003-05-01 | 2006-11-09 | アボット・ラボラトリーズ | ナトリウムチャンネルモジュレーターとしてのピラゾール−アミドおよびスルホンアミド |
| US20040220170A1 (en) | 2003-05-01 | 2004-11-04 | Atkinson Robert N. | Pyrazole-amides and sulfonamides as sodium channel modulators |
| EP2385041B1 (en) | 2003-05-01 | 2013-09-18 | Bristol-Myers Squibb Company | Pyrazole-amine compounds useful as kinase inhibitors |
| RU2006100190A (ru) | 2003-06-13 | 2006-08-10 | Шеринг Акциенгезельшафт (De) | Производные хинолиламида в качестве антагонистов ccr-5 |
| 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 |
| SG144942A1 (en) * | 2003-07-14 | 2008-08-28 | Arena Pharm Inc | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| MXPA06001202A (es) | 2003-07-29 | 2006-08-31 | Xenon Pharmaceuticals Inc | Derivados piridilo y su uso como agentes terapeuticos. |
| FR2862647B1 (fr) * | 2003-11-25 | 2008-07-04 | Aventis Pharma Sa | Derives de pyrazolyle, procede de preparation et intermediaires de ce procede a titre de medicaments et de compositions pharmaceutiques les renfermant |
| US7235641B2 (en) | 2003-12-22 | 2007-06-26 | Micromet Ag | Bispecific antibodies |
| 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 |
| TW200538433A (en) | 2004-02-24 | 2005-12-01 | Irm Llc | Immunosuppressant compounds and compositiions |
| JP4787529B2 (ja) | 2004-04-09 | 2011-10-05 | 大塚製薬株式会社 | 医薬組成物 |
| AU2005248722A1 (en) | 2004-04-13 | 2005-12-08 | Arena Pharmaceuticals, Inc. | Human G protein-coupled receptor and modulators thereof for the treatment of hyperglycemia and related disorders |
| DE102004020186A1 (de) | 2004-04-22 | 2005-11-17 | Aventis Pharma Deutschland Gmbh | Heterocyclylessigsäuren als Inhibitoren von TAFla |
| US8710232B2 (en) | 2004-04-22 | 2014-04-29 | Sanofi-Aventis Deutschland Gmbh | Imidazole derivatives used as TAFIa inhibitors |
| ES2346452T3 (es) | 2004-06-08 | 2010-10-15 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Nuevas fenilpiperidinas/piperazinas disustituidas utilizadas como moduladores de la neurotransmision de la dopamina. |
| JP3997491B2 (ja) | 2004-10-29 | 2007-10-24 | ゼリア新薬工業株式会社 | カルバゾール誘導体、その溶媒和物、又は薬学的に許容されるその塩 |
| TW200633990A (en) | 2004-11-18 | 2006-10-01 | Takeda Pharmaceuticals Co | Amide compound |
| 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 |
| GB0428526D0 (en) | 2004-12-30 | 2005-02-09 | Novartis Ag | Organic compounds |
| ATE519759T1 (de) | 2004-12-30 | 2011-08-15 | Exelixis Inc | Pyrimidinderivate als kinasemodulatoren und anwendungsverfahren |
| WO2006073167A1 (ja) | 2005-01-07 | 2006-07-13 | Ono Pharmaceutical Co., Ltd. | ピロリジン誘導体 |
| 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 |
| 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 |
| US8277495B2 (en) | 2005-01-13 | 2012-10-02 | Candela Corporation | Method and apparatus for treating a diseased nail |
| MX2007009949A (es) | 2005-02-16 | 2007-09-26 | Schering Corp | Pirazinil-piperazin-piperidinas sustituidas con heteroarilo con actividad antagonista de cxcr3. |
| GB0504850D0 (en) | 2005-03-09 | 2005-04-13 | Novartis Ag | Organic compounds |
| US20060206074A1 (en) | 2005-03-11 | 2006-09-14 | The Procter & Gamble Company | Absorbent core structures having undulations |
| EP1707202A1 (de) | 2005-03-31 | 2006-10-04 | Speedel Experimenta AG | Organische Verbindungen |
| KR100712289B1 (ko) | 2005-04-07 | 2007-04-27 | 삼성에스디아이 주식회사 | 평판표시장치 및 그의 제조방법 |
| EP1888529A2 (en) | 2005-05-18 | 2008-02-20 | Wyeth | 3-cyanoquinoline inhibitors of tpl2 kinase and methods of making and using the same |
| EP1888512A2 (en) | 2005-06-06 | 2008-02-20 | Smithkline Beecham Corporation | Chemical compounds |
| CA2611216A1 (en) | 2005-06-15 | 2006-12-21 | Pfizer Limited | 3-phenylazetidine derivatives as dopamine agonists |
| WO2007023507A2 (en) | 2005-06-20 | 2007-03-01 | Wockhardt Limited | Oxazolidinones bearing antimicrobial activity composition and methods of preparation |
| US20090325924A1 (en) | 2005-06-30 | 2009-12-31 | Stuart Edward | GPCR Agonists |
| US20090221644A1 (en) | 2005-06-30 | 2009-09-03 | Stuart Edward Bradley | Gpcr Agonists |
| TW200738701A (en) | 2005-07-26 | 2007-10-16 | Du Pont | Fungicidal carboxamides |
| JP2007045752A (ja) | 2005-08-10 | 2007-02-22 | Takeda Chem Ind Ltd | ５員芳香族複素環誘導体、その製造法および用途 |
| US20100160359A1 (en) | 2005-09-16 | 2010-06-24 | Arena Pharmaceuticals, Inc. | Modulators of Metabolism and the Treatment of Disorders Related Thereto |
| CA2624102A1 (en) | 2005-09-29 | 2007-04-12 | Sanofi-Aventis | Phenyl- and pyridinyl- 1, 2 , 4 - oxadiazolone derivatives, processes for their preparation and their use as pharmaceuticals |
| JP5201817B2 (ja) | 2005-10-28 | 2013-06-05 | 大塚製薬株式会社 | 医薬組成物 |
| 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 |
| FR2902767B1 (fr) | 2006-06-22 | 2008-09-19 | J P B Creations Sa | Dispositif de conditionnement d'un produit a base de colle |
| DE602007010458D1 (de) | 2006-06-23 | 2010-12-23 | Basf Se | Reversible thermochrome zusammensetzungen |
| EP2043744A2 (en) | 2006-07-13 | 2009-04-08 | SmithKline Beecham Corporation | Chemical compounds |
| WO2008025799A1 (en) | 2006-08-30 | 2008-03-06 | Biovitrum Ab (Publ) | Pyridazine compounds for treating gpr119 related disorders |
| 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 |
| WO2008073929A1 (en) | 2006-12-11 | 2008-06-19 | Wyeth | Ion channel modulators |
| WO2008073936A1 (en) | 2006-12-11 | 2008-06-19 | Wyeth | Carboxamide derivatives as ion channel modulators |
| MX2009006401A (es) | 2006-12-20 | 2009-06-23 | Nerviano Medical Sciences Srl | Derivados de indazol como inhibidores de cinasa para el tratamiento del cancer. |
| CN101616586B (zh) | 2006-12-28 | 2014-08-13 | 赛马拜制药公司 | 治疗糖尿病和代谢性病症的杂环受体激动剂 |
| US7638541B2 (en) * | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| JP2010520878A (ja) | 2007-03-08 | 2010-06-17 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｇｐｒ１１９活性の調節剤としての化合物および組成物 |
| ES2388315T3 (es) | 2007-05-04 | 2012-10-11 | Bristol-Myers Squibb Company | Agonistas [6,5]-bicíclicos de receptores GPR119 acoplados a la proteína G |
| US20110046137A1 (en) | 2007-05-10 | 2011-02-24 | Glaxo Group Limited | Pyrazole Derivatives as P2X7 Modulators |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| UY31232A1 (es) | 2007-07-19 | 2009-03-02 | Compuestos derivados de dibenzotifenilamino-cromen-4-onas activas sustituidas y sus isomeros y aplicaciones | |
| AU2008279447A1 (en) * | 2007-07-19 | 2009-01-29 | Metabolex, Inc. | N-azacyclic substituted pyrrole, pyrazole, imidazole, triazole and tetrazole derivatives as agonists of the RUP3 or GPR119 receptor for the treatment of diabetes and metabolic disorders |
| MY150032A (en) | 2007-07-19 | 2013-11-29 | Merck Sharp & Dohme | Heterocyclic amide compounds as protein kinase inhibitors |
| FR2918986B1 (fr) | 2007-07-19 | 2009-09-04 | Sanofi Aventis Sa | Derives de 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]- pyridazine, leur preparation et leur application en therapeutique |
| AU2008277796A1 (en) | 2007-07-19 | 2009-01-22 | F. Hoffmann-La Roche Ag | Novel heterocyclyl compounds and their use as chemokine antagonists |
| SI2019104T1 (sl) | 2007-07-19 | 2013-12-31 | Sanofi | Citotoksična sredstva, ki obsegajo nove tomaimicinske derivate, in njihova terapevtska uporaba |
| US20100249163A1 (en) | 2007-12-04 | 2010-09-30 | Daniel Dube | Renin inhibitors |
| AU2009231906A1 (en) * | 2008-03-31 | 2009-10-08 | Metabolex, Inc. | Oxymethylene aryl compounds and uses thereof |
| US8188098B2 (en) * | 2008-05-19 | 2012-05-29 | Hoffmann-La Roche Inc. | GPR119 receptor agonists |
| CA2727174A1 (en) | 2008-06-20 | 2010-01-21 | Jiangao Song | Aryl gpr119 agonists and uses thereof |
| EP2311822A4 (en) * | 2008-08-01 | 2011-08-31 | Nippon Chemiphar Co | GPR119 AGONIST |
| CN102149407A (zh) * | 2008-09-10 | 2011-08-10 | 贝林格尔.英格海姆国际有限公司 | 治疗糖尿病和相关病症的组合疗法 |
| WO2010048149A2 (en) | 2008-10-20 | 2010-04-29 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| US20110160222A1 (en) * | 2008-11-26 | 2011-06-30 | Metabolex, Inc. | Modulators of glucose homeostasis for the treatment of diabetes and metabolic disorders |
| JP5909185B2 (ja) | 2009-10-01 | 2016-04-26 | シマベイ セラピューティクス， インコーポレーテッド | 置換テトラゾール−１−イルフェノキシメチルチアゾール−２−イルピペリジニルピリミジン塩 |
| US20110313160A1 (en) * | 2010-06-04 | 2011-12-22 | Metabolex, Inc. | Preparation of 5-ethyl-2--pyrimidine |
| JP5847813B2 (ja) * | 2010-06-23 | 2016-01-27 | シマベイ セラピューティクス， インコーポレーテッド | ５−エチル−２−｛４−［４−（４−テトラゾル−１−イル−フェノキシメチル）−チアゾール−２−イル］−ピペリジン−１−イル｝−ピリミジンの組成物 |
| US20120184572A1 (en) * | 2011-01-13 | 2012-07-19 | Metabolex, Inc. | Aryl gpr119 agonists and uses thereof |
-
2010
- 2010-09-20 JP JP2012532124A patent/JP5909185B2/ja not_active Expired - Fee Related
- 2010-09-20 CA CA2775840A patent/CA2775840C/en active Active
- 2010-09-20 CN CN201080042922.9A patent/CN102666553B/zh not_active Expired - Fee Related
- 2010-09-20 EP EP10759779.1A patent/EP2483281B1/en active Active
- 2010-09-20 ES ES10759779.1T patent/ES2497566T3/es active Active
- 2010-09-20 WO PCT/US2010/049486 patent/WO2011041154A1/en not_active Ceased
- 2010-09-20 US US12/886,470 patent/US8410127B2/en not_active Expired - Fee Related
- 2010-09-22 AR ARP100103461A patent/AR078434A1/es unknown
- 2010-09-30 TW TW099133406A patent/TW201120034A/zh unknown
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2013
- 2013-03-28 US US13/853,000 patent/US8815886B2/en active Active
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2011041154A1 (en) | 2011-04-07 |
| EP2483281A1 (en) | 2012-08-08 |
| JP5909185B2 (ja) | 2016-04-26 |
| AR078434A1 (es) | 2011-11-09 |
| US8410127B2 (en) | 2013-04-02 |
| US20150197518A1 (en) | 2015-07-16 |
| JP2013506670A (ja) | 2013-02-28 |
| CN102666553A (zh) | 2012-09-12 |
| CN102666553B (zh) | 2015-05-06 |
| CA2775840A1 (en) | 2011-04-07 |
| CA2775840C (en) | 2018-02-06 |
| US20110152270A1 (en) | 2011-06-23 |
| ES2497566T3 (es) | 2014-09-23 |
| EP2483281B1 (en) | 2014-06-04 |
| US9150567B2 (en) | 2015-10-06 |
| US20140038971A1 (en) | 2014-02-06 |
| US8815886B2 (en) | 2014-08-26 |
| HK1174617A1 (en) | 2013-06-14 |
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