PT2114933E - Agonistas do gpcr de piperidina - Google Patents
Agonistas do gpcr de piperidina Download PDFInfo
- Publication number
- PT2114933E PT2114933E PT08702095T PT08702095T PT2114933E PT 2114933 E PT2114933 E PT 2114933E PT 08702095 T PT08702095 T PT 08702095T PT 08702095 T PT08702095 T PT 08702095T PT 2114933 E PT2114933 E PT 2114933E
- Authority
- PT
- Portugal
- Prior art keywords
- piperidine
- propyl
- oxadiazol
- pharmaceutically acceptable
- acceptable salt
- Prior art date
Links
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title claims description 49
- 229940125633 GPCR agonist Drugs 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 177
- 150000003839 salts Chemical class 0.000 claims abstract description 57
- 238000011282 treatment Methods 0.000 claims abstract description 39
- 208000008589 Obesity Diseases 0.000 claims abstract description 20
- 235000020824 obesity Nutrition 0.000 claims abstract description 20
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
- -1 oxadiazol-5-yl Chemical group 0.000 claims description 74
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 7
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
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- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
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- 208000002705 Glucose Intolerance Diseases 0.000 claims description 5
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000036186 satiety Effects 0.000 claims description 5
- 235000019627 satiety Nutrition 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
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- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
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- DYWOLPXRUNVGOO-UHFFFAOYSA-N 3-tert-butyl-5-[4-[3-(3-fluoro-4-methylsulfonylphenoxy)propyl]piperidin-1-yl]-1,2,4-oxadiazole Chemical compound CC(C)(C)C1=NOC(N2CCC(CCCOC=3C=C(F)C(=CC=3)S(C)(=O)=O)CC2)=N1 DYWOLPXRUNVGOO-UHFFFAOYSA-N 0.000 claims description 2
- DPSQJTZWTDOKFO-UHFFFAOYSA-N 5-[4-[3-(3-fluoro-4-methylsulfonylphenoxy)propyl]piperidin-1-yl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(N2CCC(CCCOC=3C=C(F)C(=CC=3)S(C)(=O)=O)CC2)=N1 DPSQJTZWTDOKFO-UHFFFAOYSA-N 0.000 claims description 2
- IATPCIBOIGPQOH-UHFFFAOYSA-N 5-[4-[3-(3-fluoro-4-methylsulfonylphenoxy)propyl]piperidin-1-yl]-3-propyl-1,2,4-oxadiazole Chemical compound CCCC1=NOC(N2CCC(CCCOC=3C=C(F)C(=CC=3)S(C)(=O)=O)CC2)=N1 IATPCIBOIGPQOH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
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- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
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- 101000996752 Homo sapiens Glucose-dependent insulinotropic receptor Proteins 0.000 description 15
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- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 13
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
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- 235000020374 simple syrup Nutrition 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- DHHKPEUQJIEKOA-UHFFFAOYSA-N tert-butyl 2-[6-(nitromethyl)-6-bicyclo[3.2.0]hept-3-enyl]acetate Chemical compound C1C=CC2C(CC(=O)OC(C)(C)C)(C[N+]([O-])=O)CC21 DHHKPEUQJIEKOA-UHFFFAOYSA-N 0.000 description 1
- VEHRZLJDGVLUBF-OAHLLOKOSA-N tert-butyl 4-[(2r)-4-(3-fluoro-4-methylsulfonylphenoxy)butan-2-yl]piperidine-1-carboxylate Chemical compound C([C@@H](C)C1CCN(CC1)C(=O)OC(C)(C)C)COC1=CC=C(S(C)(=O)=O)C(F)=C1 VEHRZLJDGVLUBF-OAHLLOKOSA-N 0.000 description 1
- ZNMOGDZMYWYMJL-UHFFFAOYSA-N tert-butyl 4-[3-(3-chloro-4-methylsulfonylphenoxy)propyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCCOC1=CC=C(S(C)(=O)=O)C(Cl)=C1 ZNMOGDZMYWYMJL-UHFFFAOYSA-N 0.000 description 1
- HQDHGXPLARSDSG-UHFFFAOYSA-N tert-butyl 4-[3-(3-fluoro-4-methylsulfonylphenoxy)propyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCCOC1=CC=C(S(C)(=O)=O)C(F)=C1 HQDHGXPLARSDSG-UHFFFAOYSA-N 0.000 description 1
- UIYOVVYZPVVUMJ-UHFFFAOYSA-N tert-butyl carbamoyl carbonate Chemical compound CC(C)(C)OC(=O)OC(N)=O UIYOVVYZPVVUMJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
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| GB0700123A GB0700123D0 (en) | 2007-01-04 | 2007-01-04 | GPCR agonists |
| GB0719760A GB0719760D0 (en) | 2007-10-10 | 2007-10-10 | GPCR agonists |
Publications (1)
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| PT2114933E true PT2114933E (pt) | 2011-12-20 |
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| PT08702095T PT2114933E (pt) | 2007-01-04 | 2008-01-04 | Agonistas do gpcr de piperidina |
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| DK (1) | DK2114933T3 (enExample) |
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| ES (1) | ES2373181T3 (enExample) |
| HR (1) | HRP20110852T1 (enExample) |
| PL (1) | PL2114933T3 (enExample) |
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| RS (1) | RS52065B (enExample) |
| SI (1) | SI2114933T1 (enExample) |
| WO (1) | WO2008081204A1 (enExample) |
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| PE20081849A1 (es) * | 2007-01-04 | 2009-01-26 | Prosidion Ltd | Derivados de piperidin-4-il-propoxi-benzamida como agonistas de gpcr |
| EP2200609A1 (en) | 2007-09-10 | 2010-06-30 | Prosidion Limited | Compounds for the treatment of metabolic disorders |
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| 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 |
| NZ596445A (en) | 2009-06-24 | 2013-04-26 | Boehringer Ingelheim Int | New compounds, pharmaceutical composition and methods relating thereto |
| TW201113269A (en) | 2009-06-24 | 2011-04-16 | Boehringer Ingelheim Int | New compounds, pharmaceutical composition and methods relating thereto |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2011113947A1 (en) | 2010-03-18 | 2011-09-22 | 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 |
| GB201006167D0 (en) | 2010-04-14 | 2010-05-26 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| GB201006166D0 (en) | 2010-04-14 | 2010-05-26 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| ITMI20100770A1 (it) | 2010-05-03 | 2011-11-04 | Dipharma Francis Srl | Procedimento per la preparazione di 3-(4-piridinil)-propanolo e suoi intermedi |
| TW201209054A (en) | 2010-05-28 | 2012-03-01 | Prosidion Ltd | Novel compounds |
| ITMI20100984A1 (it) | 2010-05-31 | 2011-12-01 | Dipharma Francis Srl | Procedimento per la preparazione di ossadiazoli |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | 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 |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, 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 |
| MX2013002422A (es) | 2010-09-01 | 2013-05-17 | Arena Pharm Inc | Sales de lorcaserina con acidos opticamente activos. |
| SG188363A1 (en) | 2010-09-01 | 2013-04-30 | Arena Pharm Inc | Fast-dissolve dosage forms of 5-ht2c agonists |
| WO2012030957A2 (en) | 2010-09-01 | 2012-03-08 | Arena Pharmaceuticals, Inc. | Non-hygroscopic salts of 5-ht2c agonists |
| KR20180118801A (ko) | 2010-09-01 | 2018-10-31 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 체중 관리에 유용한 5-ｈｔ2ｃ 작동제의 변형-방출 투여 형태 |
| 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 |
| WO2012170867A1 (en) | 2011-06-09 | 2012-12-13 | Rhizen Pharmaceuticals Sa | Novel compounds as modulators of gpr-119 |
| 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 |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013187646A1 (en) | 2012-06-12 | 2013-12-19 | Chong Kun Dang Pharmaceutical Corp. | Piperidine derivatives for gpr119 agonist |
| CN110028494A (zh) | 2013-11-26 | 2019-07-19 | 株式会社钟根堂 | 酰胺衍生物、其立体异构体或其药学上可接受的盐及包含其的药物组合物 |
| KR101726819B1 (ko) * | 2014-10-27 | 2017-04-13 | 동아에스티 주식회사 | Gpr119 작용 활성을 갖는 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 약제학적 조성물 |
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 |
| FR2713225B1 (fr) | 1993-12-02 | 1996-03-01 | Sanofi Sa | N-pipéridino-3-pyrazolecarboxamide substitué. |
| FR2692575B1 (fr) | 1992-06-23 | 1995-06-30 | Sanofi Elf | Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| 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 |
| ES2140543T3 (es) | 1993-08-13 | 2000-03-01 | Zeneca Ltd | Derivados de tia- y oxadiazol y su uso como fungicidas o insecticidas. |
| 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 |
| US6518423B1 (en) | 1996-08-09 | 2003-02-11 | Eisai Co., Ltd. | Benzopiperidine derivatives |
| GB9719496D0 (en) | 1997-09-13 | 1997-11-19 | Glaxo Group Ltd | G protien chimeras |
| AU5700999A (en) | 1998-09-01 | 2000-03-21 | Basf Aktiengesellschaft | Enhanced functional expression of g protein-coupled receptors |
| US6221660B1 (en) | 1999-02-22 | 2001-04-24 | Synaptic Pharmaceutical Corporation | DNA encoding SNORF25 receptor |
| GB0109103D0 (en) | 2001-04-11 | 2001-05-30 | Pfizer Ltd | Novel compounds |
| 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 |
| 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 |
| EP1421077A4 (en) | 2001-08-31 | 2004-11-17 | Univ Connecticut | NEW PYRAZOLANALOGS ON CANNABINOID RECEPTORS |
| AU2002333852B2 (en) | 2001-09-21 | 2006-07-13 | Solvay Pharmaceuticals B.V. | Novel 4,5-dihydro-1H-pyrazole derivativeshaving CB1-antagonistic activity |
| CN1529595A (zh) | 2001-09-21 | 2004-09-15 | ������ҩ������˾ | 具有效cb1-拮抗活性的4,5-2氢-1h-吡唑衍生物 |
| TWI231757B (en) | 2001-09-21 | 2005-05-01 | Solvay Pharm Bv | 1H-Imidazole derivatives having CB1 agonistic, CB1 partial agonistic or 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 |
| US20050171161A1 (en) | 2002-03-06 | 2005-08-04 | Fong Tung M. | Method of treatment or prevention of obesity |
| JP3813152B2 (ja) | 2002-03-12 | 2006-08-23 | メルク エンド カムパニー インコーポレーテッド | 置換アミド類 |
| AR038966A1 (es) | 2002-03-18 | 2005-02-02 | Solvay Pharm Bv | Derivados de tiazol que tienen actividad antagonista, agonista o agonista parcial de cb1 |
| US7423067B2 (en) | 2002-03-26 | 2008-09-09 | Merck & Co., Inc. | Diphenyl cyclopentyl amides as cannabinoid-1 receptor inverse agonists |
| ES2192494B1 (es) | 2002-03-27 | 2005-02-16 | Consejo Superior De Investigaciones Cientificas | Derivados de 1,2,4-triazol con propiedades cannabinoides. |
| AU2003225964B2 (en) | 2002-03-28 | 2008-11-20 | Merck Sharp & Dohme Corp. | Substituted 2,3-diphenyl pyridines |
| US20050154202A1 (en) | 2002-04-05 | 2005-07-14 | Hagmann William K. | Substituted aryl amides |
| FR2838439B1 (fr) | 2002-04-11 | 2005-05-20 | Sanofi Synthelabo | Derives de terphenyle, leur preparation, les compositions pharmaceutqiues en contenant |
| FR2838438A1 (fr) | 2002-04-11 | 2003-10-17 | Sanofi Synthelabo | Derives de diphenylpyridine,leur preparation, les compositions pharmaceutiques en contenant |
| WO2003086288A2 (en) | 2002-04-12 | 2003-10-23 | Merck & Co., Inc. | 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 |
| PL375441A1 (en) | 2002-07-29 | 2005-11-28 | F.Hoffmann-La Roche Ag | Novel benzodioxoles |
| AU2003257145B2 (en) | 2002-08-02 | 2008-11-13 | Merck Sharp & Dohme Corp. | 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 |
| WO2004029204A2 (en) | 2002-09-27 | 2004-04-08 | Merck & Co., Inc. | Substituted pyrimidines |
| MXPA05004115A (es) | 2002-10-18 | 2005-06-22 | Pfizer Prod Inc | Ligandos del receptor cannabionoide y usos de los mismos. |
| 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 |
| KR20050088194A (ko) | 2002-12-19 | 2005-09-02 | 머크 앤드 캄파니 인코포레이티드 | 치환된 아미드 |
| GB0230087D0 (en) | 2002-12-24 | 2003-01-29 | Astrazeneca Ab | Therapeutic agents |
| CN101012193A (zh) | 2003-01-02 | 2007-08-08 | 霍夫曼-拉罗奇有限公司 | 新cb 1受体反激动剂 |
| US7135488B2 (en) | 2003-01-02 | 2006-11-14 | Hoffmann-La Roche Inc. | Pyrrolyl-thiazole derivatives |
| US7329658B2 (en) | 2003-02-06 | 2008-02-12 | Pfizer Inc | Cannabinoid receptor ligands and uses thereof |
| CA2514791A1 (en) | 2003-02-13 | 2004-08-26 | Aventis Pharma Deutschland Gmbh | Nitrogen-substituted hexahydropyrazino[1,2-a]pyrimidine-4,7-dione derivatives, method for the production and use thereof as medicaments |
| KR20050111588A (ko) | 2003-02-13 | 2005-11-25 | 사노피-아벤티스 도이칠란트 게엠베하 | 치환된 헥사하이드로피라지노[1,2-ａ]피리미딘-4,7-디온유도체, 이의 제조방법 및 약제로서의 이의 용도 |
| 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 |
| CN1898235A (zh) | 2003-12-24 | 2007-01-17 | 普罗西迪恩有限公司 | 作为gpcr受体激动剂的杂环衍生物 |
| BRPI0517232A (pt) | 2004-11-02 | 2008-10-07 | Banyu Pharma Co Ltd | composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, ativador da glicocinase, e, agentes terapêuticos e/ou profiláticos para diabetes e para obesidade |
| NZ556017A (en) * | 2004-12-24 | 2009-10-30 | Prosidion Ltd | G-protein coupled receptor (gpr116) agonists and use thereof for treating obesity and diabetes |
| 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 |
| EP2308840A1 (en) * | 2005-06-30 | 2011-04-13 | Prosidion Limited | GPCR agonists |
| US20090203676A1 (en) | 2005-06-30 | 2009-08-13 | Oscar Barba | G-protein Coupled Receptor Agonists |
| 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 |
| US20090221644A1 (en) | 2005-06-30 | 2009-09-03 | Stuart Edward Bradley | Gpcr Agonists |
| KR20080109075A (ko) * | 2006-04-06 | 2008-12-16 | 프로시디온 리미티드 | 헤테로사이클릭 ｇｐｃｒ 작용제 |
-
2008
- 2008-01-04 ES ES08702095T patent/ES2373181T3/es active Active
- 2008-01-04 US US12/522,015 patent/US20100048632A1/en not_active Abandoned
- 2008-01-04 EA EA200900877A patent/EA015129B1/ru not_active IP Right Cessation
- 2008-01-04 JP JP2009544447A patent/JP2010514828A/ja active Pending
- 2008-01-04 EP EP11174256A patent/EP2377863A1/en not_active Withdrawn
- 2008-01-04 EP EP08702095A patent/EP2114933B1/en active Active
- 2008-01-04 WO PCT/GB2008/050010 patent/WO2008081204A1/en not_active Ceased
- 2008-01-04 BR BRPI0806498-9A2A patent/BRPI0806498A2/pt not_active IP Right Cessation
- 2008-01-04 HR HR20110852T patent/HRP20110852T1/hr unknown
- 2008-01-04 SI SI200830454T patent/SI2114933T1/sl unknown
- 2008-01-04 RS RS20110523A patent/RS52065B/sr unknown
- 2008-01-04 CA CA002674348A patent/CA2674348A1/en not_active Abandoned
- 2008-01-04 PL PL08702095T patent/PL2114933T3/pl unknown
- 2008-01-04 AT AT08702095T patent/ATE523507T1/de active
- 2008-01-04 DK DK08702095.4T patent/DK2114933T3/da active
- 2008-01-04 PT PT08702095T patent/PT2114933E/pt unknown
-
2011
- 2011-11-25 CY CY20111101161T patent/CY1112483T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HK1135703A1 (en) | 2010-06-11 |
| JP2010514828A (ja) | 2010-05-06 |
| EP2114933B1 (en) | 2011-09-07 |
| CY1112483T1 (el) | 2015-12-09 |
| EA015129B1 (ru) | 2011-06-30 |
| WO2008081204A1 (en) | 2008-07-10 |
| PL2114933T3 (pl) | 2012-02-29 |
| RS52065B (sr) | 2012-06-30 |
| EP2377863A1 (en) | 2011-10-19 |
| CA2674348A1 (en) | 2008-07-10 |
| ES2373181T3 (es) | 2012-02-01 |
| US20100048632A1 (en) | 2010-02-25 |
| EP2114933A1 (en) | 2009-11-11 |
| ATE523507T1 (de) | 2011-09-15 |
| HRP20110852T1 (hr) | 2011-12-31 |
| DK2114933T3 (da) | 2012-01-02 |
| EA200900877A1 (ru) | 2010-02-26 |
| SI2114933T1 (sl) | 2012-01-31 |
| BRPI0806498A2 (pt) | 2014-04-22 |
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