EA015130B1 - Пиперидиновые агонисты gpcr - Google Patents
Пиперидиновые агонисты gpcr Download PDFInfo
- Publication number
- EA015130B1 EA015130B1 EA200900880A EA200900880A EA015130B1 EA 015130 B1 EA015130 B1 EA 015130B1 EA 200900880 A EA200900880 A EA 200900880A EA 200900880 A EA200900880 A EA 200900880A EA 015130 B1 EA015130 B1 EA 015130B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- pharmaceutically acceptable
- piperidin
- isopropyl
- oxadiazol
- acceptable salt
- Prior art date
Links
- 229940125633 GPCR agonist Drugs 0.000 title abstract 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title description 4
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- -1 2-hydroxy-1-methylethyl Chemical group 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 41
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
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- MVWISLIFGSKBLY-UHFFFAOYSA-N 2-methyl-6-[3-[1-(5-propan-2-yl-1,2,4-oxadiazol-3-yl)piperidin-4-yl]propoxy]pyridine-3-carboxamide Chemical compound O1C(C(C)C)=NC(N2CCC(CCCOC=3N=C(C)C(C(N)=O)=CC=3)CC2)=N1 MVWISLIFGSKBLY-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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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
- A61P3/04—Anorexiants; Antiobesity agents
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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
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0700125A GB0700125D0 (en) | 2007-01-04 | 2007-01-04 | GPCR agonists |
| GB0708746A GB0708746D0 (en) | 2007-05-08 | 2007-05-08 | GPCR agonists |
| GB0719763A GB0719763D0 (en) | 2007-10-10 | 2007-10-10 | GPCR agonists |
| PCT/GB2008/050013 WO2008081207A1 (en) | 2007-01-04 | 2008-01-04 | Piperidine gpcr agonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200900880A1 EA200900880A1 (ru) | 2010-02-26 |
| EA015130B1 true EA015130B1 (ru) | 2011-06-30 |
Family
ID=39199058
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200900880A EA015130B1 (ru) | 2007-01-04 | 2008-01-04 | Пиперидиновые агонисты gpcr |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US20100105732A1 (enExample) |
| EP (2) | EP2377864A1 (enExample) |
| JP (1) | JP2010514831A (enExample) |
| AR (1) | AR064735A1 (enExample) |
| AT (1) | ATE517103T1 (enExample) |
| BR (1) | BRPI0806500A2 (enExample) |
| CA (1) | CA2674455A1 (enExample) |
| CL (1) | CL2008000018A1 (enExample) |
| CY (1) | CY1112474T1 (enExample) |
| DK (1) | DK2114935T3 (enExample) |
| EA (1) | EA015130B1 (enExample) |
| HR (1) | HRP20110750T1 (enExample) |
| PE (1) | PE20081659A1 (enExample) |
| PL (1) | PL2114935T3 (enExample) |
| PT (1) | PT2114935E (enExample) |
| RS (1) | RS51943B (enExample) |
| SA (1) | SA08280757B1 (enExample) |
| SI (1) | SI2114935T1 (enExample) |
| TW (1) | TW200835482A (enExample) |
| WO (1) | WO2008081207A1 (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2591922A1 (en) * | 2004-12-24 | 2006-06-29 | Prosidion Limited | G-protein coupled receptor (gpr116) agonists and use thereof for treating obesity and diabetes |
| AU2006264649A1 (en) * | 2005-06-30 | 2007-01-11 | Prosidion Limited | GPCR agonists |
| CL2008000017A1 (es) * | 2007-01-04 | 2008-08-01 | Prosidion Ltd | Compuestos derivados de heterociclos de nitrogeno y oxigeno, agonistas de gpcr; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento de la obesidad, diabetes, sindrome metabolico, hiperlipidemia, toleranci |
| WO2009034388A1 (en) | 2007-09-10 | 2009-03-19 | Prosidion Limited | Compounds for the treatment of metabolic disorders |
| BRPI0817881A2 (pt) | 2007-10-10 | 2015-03-31 | Novartis Ag | Compostos orgânicos e seus usos |
| GB0812649D0 (en) * | 2008-07-10 | 2008-08-20 | Prosidion Ltd | Compounds |
| GB0812641D0 (en) * | 2008-07-10 | 2008-08-20 | Prosidion Ltd | Compounds |
| GB0812648D0 (en) * | 2008-07-10 | 2008-08-20 | Prosidion Ltd | Compounds |
| US8742117B2 (en) | 2008-12-24 | 2014-06-03 | Cadila Healthcare Limited | Oxime derivatives |
| GB0904285D0 (en) | 2009-03-12 | 2009-04-22 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| GB0904287D0 (en) | 2009-03-12 | 2009-04-22 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| GB0904284D0 (en) | 2009-03-12 | 2009-04-22 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| US8293729B2 (en) | 2009-06-24 | 2012-10-23 | Boehringer Ingelheim International Gmbh | Compounds, pharmaceutical composition and methods relating thereto |
| JP2012530758A (ja) | 2009-06-24 | 2012-12-06 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規化合物、医薬組成物及びそれに関する方法 |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2547339A1 (en) | 2010-03-18 | 2013-01-23 | Boehringer Ingelheim International GmbH | Combination of a gpr119 agonist and the dpp-iv inhibitor linagliptin for use in the treatment of diabetes and related conditions |
| GB201006166D0 (en) | 2010-04-14 | 2010-05-26 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| GB201006167D0 (en) | 2010-04-14 | 2010-05-26 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| TW201209054A (en) | 2010-05-28 | 2012-03-01 | Prosidion Ltd | Novel compounds |
| WO2011157827A1 (de) | 2010-06-18 | 2011-12-22 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| GB201114389D0 (en) | 2011-08-22 | 2011-10-05 | Prosidion Ltd | Novel compounds |
| AR083904A1 (es) | 2010-11-18 | 2013-04-10 | Prosidion Ltd | Derivados de 1,4-pirrolidinas disustituidos y 3-il-aminas y sus usos en el tratamiento de desordenes metabolicos |
| CN103958495B (zh) | 2011-06-09 | 2018-06-22 | 理森制药股份公司 | 作为gpr-119的调节剂的化合物 |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| CN104610390A (zh) * | 2015-02-13 | 2015-05-13 | 佛山市赛维斯医药科技有限公司 | 一种含氨基葡萄糖和腈基吡啶结构的gpr119激动剂及其用途 |
| CN104610393A (zh) * | 2015-02-13 | 2015-05-13 | 佛山市赛维斯医药科技有限公司 | 一类含氨基葡萄糖和卤代吡啶结构化合物及其用途 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006067531A1 (en) * | 2004-12-24 | 2006-06-29 | Prosidion Ltd | G-protein coupled receptor (gpr116) agonists and use thereof for treating obesity and diabetes |
| WO2007003962A2 (en) * | 2005-06-30 | 2007-01-11 | Prosidion Limited | Gpcr agonists |
| WO2007116229A1 (en) * | 2006-04-06 | 2007-10-18 | Prosidion Limited | Heterocyclic gpcr agonists |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3576810A (en) * | 1968-06-20 | 1971-04-27 | Robins Co Inc A H | 1-substituted-3-(-4)-aroylpiperidines |
| US5252586A (en) * | 1990-09-28 | 1993-10-12 | The Du Pont Merck Pharmaceutical Company | Ether derivatives of alkyl piperidines and pyrrolidines as antipsychotic agents |
| FR2692575B1 (fr) | 1992-06-23 | 1995-06-30 | Sanofi Elf | Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| FR2713225B1 (fr) | 1993-12-02 | 1996-03-01 | Sanofi Sa | N-pipéridino-3-pyrazolecarboxamide substitué. |
| DE4222565A1 (de) * | 1992-07-09 | 1994-01-13 | Hoechst Ag | Meta-substituierte Sechsringaromaten zur Verwendung in Flüssigkristallmischungen |
| US6100042A (en) * | 1993-03-31 | 2000-08-08 | Cadus Pharmaceutical Corporation | Yeast cells engineered to produce pheromone system protein surrogates, and uses therefor |
| DE4311967A1 (de) * | 1993-04-10 | 1994-10-13 | Hoechst Ag | Smektische Flüssigkristallmischung |
| DE4311968A1 (de) * | 1993-04-10 | 1994-10-20 | Hoechst Ag | Smektische Flüssigkristallmischung |
| US5338738A (en) * | 1993-04-19 | 1994-08-16 | Bristol-Myers Squibb Company | Cerebral function enhancers: acyclic amide derivatives of pyrimidinylpiperidines |
| FR2705346B1 (fr) * | 1993-05-18 | 1995-08-11 | Union Pharma Scient Appl | Nouveaux dérivés de pipéridinyl thio indole, leurs procédés de préparation, compositions pharmaceutiques les contenant, utiles notamment comme antalgiques . |
| EP0858457A1 (de) * | 1995-10-20 | 1998-08-19 | Dr. Karl Thomae GmbH | 5-gliedrige heterocyclen, diese verbindungen enthaltende arzneimittel und deren verwendung sowie verfahren zu ihrer herstellung |
| CA2262569A1 (en) * | 1996-08-09 | 1998-02-19 | Norihito Ohi | Benzopiperidine derivatives |
| GB9719496D0 (en) | 1997-09-13 | 1997-11-19 | Glaxo Group Ltd | G protien chimeras |
| EP1123391A2 (en) | 1998-09-01 | 2001-08-16 | BASF Aktiengesellschaft | Methods for improving the function of heterologous g protein-coupled receptors |
| US6221660B1 (en) | 1999-02-22 | 2001-04-24 | Synaptic Pharmaceutical Corporation | DNA encoding SNORF25 receptor |
| KR100635892B1 (ko) * | 2000-11-21 | 2006-10-18 | 미쓰비시 가가꾸 가부시키가이샤 | 2-(4-피리딜)에탄티올의 제조 방법 |
| FR2829028B1 (fr) | 2001-08-29 | 2004-12-17 | Aventis Pharma Sa | Association d'un antagoniste du recepteur cb1 et d'un produit qui active la neurotransmission dopaminergique dans le cerveau, les compositions pharmaceutiques les contenant et leur utilisation pour le traitement de la maladie de |
| FR2829027A1 (fr) | 2001-08-29 | 2003-03-07 | Aventis Pharma Sa | Association avec un antagoniste du recepteur cb1, les compositions pharmaceutiques les contenant et leur utilisation pour le traitement de la maladie de parkinson |
| CA2457922A1 (en) | 2001-08-31 | 2003-03-13 | University Of Connecticut | Novel pyrazole analogs acting on cannabinoid receptors |
| JP4313672B2 (ja) | 2001-09-21 | 2009-08-12 | ソルベイ・フアーマシユーチカルズ・ベー・ブイ | 強力なｃｂ１−拮抗活性を有する４，５−ジヒドロ−１ｈ−ピラゾール誘導体 |
| TWI231757B (en) | 2001-09-21 | 2005-05-01 | Solvay Pharm Bv | 1H-Imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity |
| AU2002333852B2 (en) | 2001-09-21 | 2006-07-13 | Solvay Pharmaceuticals B.V. | Novel 4,5-dihydro-1H-pyrazole derivativeshaving CB1-antagonistic activity |
| FR2831883B1 (fr) | 2001-11-08 | 2004-07-23 | Sanofi Synthelabo | Forme polymorphe du rimonabant, son procede de preparation et les compositions pharmaceutiques en contenant |
| SE0104332D0 (sv) | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| SE0104330D0 (sv) | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| FR2833842B1 (fr) | 2001-12-21 | 2004-02-13 | Aventis Pharma Sa | Compositions pharmaceutiques a base de derives d'azetidine |
| WO2003063781A2 (en) | 2002-01-29 | 2003-08-07 | Merck & Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
| WO2003075660A1 (en) | 2002-03-06 | 2003-09-18 | Merck & Co., Inc. | Method of treatment or prevention of obesity |
| DE60334787D1 (de) | 2002-03-12 | 2010-12-16 | Merck Sharp & Dohme | Substituierte amide |
| AR038966A1 (es) | 2002-03-18 | 2005-02-02 | Solvay Pharm Bv | Derivados de tiazol que tienen actividad antagonista, agonista o agonista parcial de cb1 |
| WO2003082190A2 (en) | 2002-03-26 | 2003-10-09 | Merck & Co., Inc. | Spirocyclic amides as cannabinoid receptor modulators |
| ES2192494B1 (es) | 2002-03-27 | 2005-02-16 | Consejo Superior De Investigaciones Cientificas | Derivados de 1,2,4-triazol con propiedades cannabinoides. |
| JP2005531520A (ja) | 2002-03-28 | 2005-10-20 | メルク エンド カムパニー インコーポレーテッド | 置換２，３−ジフェニルピリジン類 |
| CA2480856A1 (en) | 2002-04-05 | 2003-10-23 | Merck & Co., Inc. | Substituted aryl amides |
| FR2838438A1 (fr) | 2002-04-11 | 2003-10-17 | Sanofi Synthelabo | Derives de diphenylpyridine,leur preparation, les compositions pharmaceutiques en contenant |
| FR2838439B1 (fr) | 2002-04-11 | 2005-05-20 | Sanofi Synthelabo | Derives de terphenyle, leur preparation, les compositions pharmaceutqiues en contenant |
| AU2003223510B2 (en) | 2002-04-12 | 2008-05-08 | Merck Sharp & Dohme Corp. | Bicyclic amides |
| US6825209B2 (en) | 2002-04-15 | 2004-11-30 | Research Triangle Institute | Compounds having unique CB1 receptor binding selectivity and methods for their production and use |
| AU2003250117B2 (en) | 2002-07-29 | 2007-05-10 | F. Hoffmann-La Roche Ag | Novel benzodioxoles |
| EP1558252B1 (en) | 2002-08-02 | 2007-10-10 | Merck & Co., Inc. | Substituted furo [2,3-b]pyridine derivatives |
| WO2004034968A2 (en) | 2002-08-20 | 2004-04-29 | The Regents Of The University Of California | Combination therapy for controlling appetites |
| HRP20050053A2 (en) | 2002-09-19 | 2005-04-30 | Solvay Pharmaceuticals B.V. | 1 h-1,2,4-triazole-3-carboxamide derivatives as cannabinoid-cb1 receptor ligands |
| CA2499497A1 (en) | 2002-09-27 | 2004-04-08 | Merck & Co., Inc. | Substituted pyrimidines |
| CA2502511A1 (en) | 2002-10-18 | 2004-05-29 | Pfizer Products Inc. | Cannabinoid receptor ligands and uses thereof |
| US7129239B2 (en) | 2002-10-28 | 2006-10-31 | Pfizer Inc. | Purine compounds and uses thereof |
| US7247628B2 (en) | 2002-12-12 | 2007-07-24 | Pfizer, Inc. | Cannabinoid receptor ligands and uses thereof |
| EP1575901B1 (en) | 2002-12-19 | 2012-10-10 | Merck Sharp & Dohme Corp. | Substituted amides |
| GB0230087D0 (en) | 2002-12-24 | 2003-01-29 | Astrazeneca Ab | Therapeutic agents |
| MXPA05007114A (es) | 2003-01-02 | 2005-08-26 | Hoffmann La Roche | Nuevos agonistas inversos del receptor cb1. |
| TW200412344A (en) | 2003-01-02 | 2004-07-16 | Hoffmann La Roche | Novel CB 1 receptor inverse agonists |
| US7329658B2 (en) | 2003-02-06 | 2008-02-12 | Pfizer Inc | Cannabinoid receptor ligands and uses thereof |
| PL377660A1 (pl) | 2003-02-13 | 2006-02-06 | Sanofi-Aventis Deutschland Gmbh | Podstawione przy azocie pochodne heksahydropirazyno [1,2-a] pirymidyno-4,7-dionu, sposób ich wytwarzania i ich zastosowanie jako środków leczniczych |
| EP1599480B1 (de) | 2003-02-13 | 2010-06-30 | Sanofi-Aventis Deutschland GmbH | Substituierte hexahydro-pyrazino(1,2-a)pyrimidin-4,7-dionderivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| US20040167188A1 (en) * | 2003-02-14 | 2004-08-26 | Zhili Xin | Protein-tyrosine phosphatase inhibitors and uses thereof |
| US7169797B2 (en) * | 2003-02-14 | 2007-01-30 | Abbott Laboratories | Protein-tyrosine phosphatase inhibitors and uses thereof |
| US20060172019A1 (en) | 2003-03-07 | 2006-08-03 | Ralston Stuart H | Cannabinoid receptor inverse agonists and neutral antagonists as therapeutic agents for the treatment of bone disorders |
| US7232823B2 (en) | 2003-06-09 | 2007-06-19 | Pfizer, Inc. | Cannabinoid receptor ligands and uses thereof |
| AR045496A1 (es) * | 2003-08-29 | 2005-11-02 | Schering Corp | Analolgos de benzimidazolpiperidinas 2- substiyuidas como antagonistas de los receptores de la hormona que concentra melanina selectivos para el tratamiento de la obesidad y trastornos relacionados |
| US8207147B2 (en) | 2003-12-24 | 2012-06-26 | Prosidion Limited | Heterocyclic derivatives as GPCR receptor agonists |
| WO2006067532A1 (en) | 2004-12-24 | 2006-06-29 | Prosidion Ltd | 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 |
| JP5114395B2 (ja) | 2005-06-30 | 2013-01-09 | プロシディオン・リミテッド | Ｇｐｃｒアゴニスト |
| JP2008545008A (ja) | 2005-06-30 | 2008-12-11 | プロシディオン・リミテッド | Ｇｐｃｒアゴニスト |
| WO2007003964A1 (en) | 2005-06-30 | 2007-01-11 | Prosidion Limited | G-protein coupled receptor agonists |
| BRPI0719941A2 (pt) * | 2006-12-06 | 2014-04-22 | Smithkline Beecham Corp | Composto, uso de um composto, método para o tratamento de distúrbios ou condições metabólicos, composição farmacêutica, e, processo para a preparação de uma composição farmacêutica |
| CL2008000017A1 (es) * | 2007-01-04 | 2008-08-01 | Prosidion Ltd | Compuestos derivados de heterociclos de nitrogeno y oxigeno, agonistas de gpcr; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento de la obesidad, diabetes, sindrome metabolico, hiperlipidemia, toleranci |
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2008
- 2008-01-03 AR ARP080100017A patent/AR064735A1/es unknown
- 2008-01-03 CL CL200800018A patent/CL2008000018A1/es unknown
- 2008-01-03 PE PE2008000084A patent/PE20081659A1/es not_active Application Discontinuation
- 2008-01-04 PT PT08702096T patent/PT2114935E/pt unknown
- 2008-01-04 EP EP11169308A patent/EP2377864A1/en not_active Withdrawn
- 2008-01-04 BR BRPI0806500-4A2A patent/BRPI0806500A2/pt not_active IP Right Cessation
- 2008-01-04 CA CA002674455A patent/CA2674455A1/en not_active Abandoned
- 2008-01-04 DK DK08702096.2T patent/DK2114935T3/da active
- 2008-01-04 HR HR20110750T patent/HRP20110750T1/hr unknown
- 2008-01-04 JP JP2009544450A patent/JP2010514831A/ja active Pending
- 2008-01-04 PL PL08702096T patent/PL2114935T3/pl unknown
- 2008-01-04 EA EA200900880A patent/EA015130B1/ru not_active IP Right Cessation
- 2008-01-04 AT AT08702096T patent/ATE517103T1/de active
- 2008-01-04 WO PCT/GB2008/050013 patent/WO2008081207A1/en not_active Ceased
- 2008-01-04 RS RS20110448A patent/RS51943B/sr unknown
- 2008-01-04 US US12/522,023 patent/US20100105732A1/en not_active Abandoned
- 2008-01-04 EP EP08702096A patent/EP2114935B1/en active Active
- 2008-01-04 TW TW097100416A patent/TW200835482A/zh unknown
- 2008-01-04 SI SI200830401T patent/SI2114935T1/sl unknown
- 2008-01-05 SA SA8280757A patent/SA08280757B1/ar unknown
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2011
- 2011-10-17 CY CY20111100985T patent/CY1112474T1/el unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006067531A1 (en) * | 2004-12-24 | 2006-06-29 | Prosidion Ltd | G-protein coupled receptor (gpr116) agonists and use thereof for treating obesity and diabetes |
| WO2007003962A2 (en) * | 2005-06-30 | 2007-01-11 | Prosidion Limited | Gpcr agonists |
| WO2007116229A1 (en) * | 2006-04-06 | 2007-10-18 | Prosidion Limited | Heterocyclic gpcr agonists |
Also Published As
| Publication number | Publication date |
|---|---|
| PE20081659A1 (es) | 2008-10-24 |
| EA200900880A1 (ru) | 2010-02-26 |
| RS51943B (sr) | 2012-02-29 |
| PT2114935E (pt) | 2011-10-17 |
| EP2114935A1 (en) | 2009-11-11 |
| EP2377864A1 (en) | 2011-10-19 |
| HK1135705A1 (en) | 2010-06-11 |
| JP2010514831A (ja) | 2010-05-06 |
| DK2114935T3 (da) | 2011-10-31 |
| AR064735A1 (es) | 2009-04-22 |
| US20100105732A1 (en) | 2010-04-29 |
| EP2114935B1 (en) | 2011-07-20 |
| CL2008000018A1 (es) | 2008-08-01 |
| SA08280757B1 (ar) | 2011-01-15 |
| WO2008081207A1 (en) | 2008-07-10 |
| BRPI0806500A2 (pt) | 2014-04-22 |
| HRP20110750T1 (hr) | 2011-11-30 |
| TW200835482A (en) | 2008-09-01 |
| CA2674455A1 (en) | 2008-07-10 |
| SI2114935T1 (sl) | 2011-11-30 |
| CY1112474T1 (el) | 2015-12-09 |
| PL2114935T3 (pl) | 2012-03-30 |
| ATE517103T1 (de) | 2011-08-15 |
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Legal Events
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |