RU2478099C2 - Производные 2-аза-бицикло[3.3.0]октана - Google Patents
Производные 2-аза-бицикло[3.3.0]октана Download PDFInfo
- Publication number
- RU2478099C2 RU2478099C2 RU2010106854/04A RU2010106854A RU2478099C2 RU 2478099 C2 RU2478099 C2 RU 2478099C2 RU 2010106854/04 A RU2010106854/04 A RU 2010106854/04A RU 2010106854 A RU2010106854 A RU 2010106854A RU 2478099 C2 RU2478099 C2 RU 2478099C2
- Authority
- RU
- Russia
- Prior art keywords
- carboxylic acid
- azabicyclo
- amide
- carbonyl
- octan
- Prior art date
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- ADKDJHASTPQGEO-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[b]pyrrole Chemical class C1CNC2CCCC21 ADKDJHASTPQGEO-UHFFFAOYSA-N 0.000 title abstract description 10
- -1 benzoisoxazolyl group Chemical group 0.000 claims abstract description 54
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 27
- 150000002367 halogens Chemical class 0.000 claims abstract description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 21
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 7
- 230000000694 effects Effects 0.000 claims abstract description 5
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims abstract description 3
- 229940123730 Orexin receptor antagonist Drugs 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 54
- 125000001424 substituent group Chemical group 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 208000019116 sleep disease Diseases 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 5
- CHDSHBWEGSCEDX-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1CCO2 CHDSHBWEGSCEDX-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
- LJZNNVINQVABLC-JBACZVJFSA-N C1(CC1)C=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1=CC=CC2=C1C(=NO2)C(=O)N)C2=CC=CC=C2 Chemical compound C1(CC1)C=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1=CC=CC2=C1C(=NO2)C(=O)N)C2=CC=CC=C2 LJZNNVINQVABLC-JBACZVJFSA-N 0.000 claims description 2
- NMECYMRCJJLFGF-VSZGBHKWSA-N C1(CC1)C=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1OC=2C(C1)=C(C=CC2)C(=O)N)C2=CC=CC=C2 Chemical compound C1(CC1)C=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1OC=2C(C1)=C(C=CC2)C(=O)N)C2=CC=CC=C2 NMECYMRCJJLFGF-VSZGBHKWSA-N 0.000 claims description 2
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- DOTCHYMEKCDVKK-LRQRDZAKSA-N n-[[(2s,3as,6as)-1-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-1,2-benzoxazole-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C3=CC=CC=C3ON=2)=C1C1=CC=CC(Cl)=C1 DOTCHYMEKCDVKK-LRQRDZAKSA-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
- C07D413/02—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
- C07D413/12—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 linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A—HUMAN NECESSITIES
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—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
- 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
-
- 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
- C07D513/02—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 two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychology (AREA)
- Anesthesiology (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| IB2007052991 | 2007-07-27 | ||
| IBPCT/IB2007/052991 | 2007-07-27 | ||
| PCT/IB2008/052989 WO2009016564A2 (en) | 2007-07-27 | 2008-07-25 | 2-aza-bicyclo[3.3.0]octane derivatives |
Publications (2)
| Publication Number | Publication Date |
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| RU2010106854A RU2010106854A (ru) | 2011-09-10 |
| RU2478099C2 true RU2478099C2 (ru) | 2013-03-27 |
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| RU2010106854/04A RU2478099C2 (ru) | 2007-07-27 | 2008-07-25 | Производные 2-аза-бицикло[3.3.0]октана |
Country Status (13)
| Country | Link |
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| US (1) | US8288429B2 (en:Method) |
| EP (1) | EP2183246A2 (en:Method) |
| JP (1) | JP2010534647A (en:Method) |
| KR (1) | KR20100046047A (en:Method) |
| CN (1) | CN101874028B (en:Method) |
| AU (1) | AU2008281399A1 (en:Method) |
| BR (1) | BRPI0814593A2 (en:Method) |
| CA (1) | CA2693820A1 (en:Method) |
| MA (1) | MA31593B1 (en:Method) |
| NZ (1) | NZ583487A (en:Method) |
| RU (1) | RU2478099C2 (en:Method) |
| WO (1) | WO2009016564A2 (en:Method) |
| ZA (1) | ZA201001434B (en:Method) |
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| WO2008038251A2 (en) * | 2006-09-29 | 2008-04-03 | Actelion Pharmaceuticals Ltd | 3-aza-bicyclo[3.1.0]hexane derivatives |
| US8133901B2 (en) | 2006-12-01 | 2012-03-13 | Actelion Pharmaceuticals Ltd. | 3-heteroaryl (amino or amido)-1-(biphenyl or phenylthiazolyl) carbonylpiperidine derivatives as orexin receptor inhibitors |
| AR064561A1 (es) * | 2006-12-28 | 2009-04-08 | Actelion Pharmaceuticals Ltd | Derivados de 2-aza-biciclo[3.1.0]hexano y su uso en la preparacion de un medicamento para el tratamiento de enfermedades relacionadas con disfunciones generales del sistema de la orexina. |
| CL2008000836A1 (es) * | 2007-03-26 | 2008-11-07 | Actelion Pharmaceuticals Ltd | Compuestos derivados de tiazolidina, antagonistas del receptor de orexina; composicion farmaceutica que los comprende; y su uso en el tratamiento de neurosis emocional, depresion grave, trastornos psicoticos, alzheimer, parkinson, dolor, entre otras. |
| WO2008150364A1 (en) | 2007-05-23 | 2008-12-11 | Merck & Co., Inc. | Cyclopropyl pyrrolidine orexin receptor antagonists |
| AU2008272449A1 (en) * | 2007-07-03 | 2009-01-08 | Actelion Pharmaceuticals Ltd | 3-aza-bicyclo[3.3.0]octane compounds |
| JP2010540429A (ja) * | 2007-09-24 | 2010-12-24 | アクテリオン ファーマシューティカルズ リミテッド | オレキシン受容体拮抗薬としてのピロリジン類及びピペリジン類 |
| WO2009104155A1 (en) * | 2008-02-21 | 2009-08-27 | Actelion Pharmaceuticals Ltd | 2-aza-bicyclo[2.2.1]heptane derivatives |
| WO2009133522A1 (en) * | 2008-04-30 | 2009-11-05 | Actelion Pharmaceuticals Ltd | Piperidine and pyrrolidine compounds |
| WO2010044054A1 (en) * | 2008-10-14 | 2010-04-22 | Actelion Pharmaceuticals Ltd | Phenethylamide derivatives and their heterocyclic analogues |
| ME02437B (me) | 2009-10-23 | 2016-09-20 | Janssen Pharmaceutica Nv | Disupstituirani oktahidropirolo[3,4-c]piroli kao modulatori oreksin receptora |
| DK2519514T3 (en) * | 2009-12-29 | 2015-11-16 | Suven Life Sciences Ltd | Neuronal nicotinic alpha4beta2-acetylcholine receptor ligands |
| WO2011082268A2 (en) | 2009-12-30 | 2011-07-07 | Arqule Inc. | Substituted naphthalenyl-pyrimidine compounds |
| BR112014019426A8 (pt) | 2012-02-07 | 2017-07-11 | Eolas Therapeutics Inc | Prolinas/ piperidinas substituídas como antagonistas do receptor de orexina |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| ITMI20120424A1 (it) | 2012-03-19 | 2013-09-20 | Rottapharm Spa | Composti chimici |
| TWI510481B (zh) | 2012-06-04 | 2015-12-01 | Actelion Pharmaceuticals Ltd | 苯并咪唑脯胺酸衍生物 |
| MX2015004638A (es) | 2012-10-10 | 2015-07-14 | Actelion Pharmaceuticals Ltd | Antagonistas de receptores de orexina los cuales son derivados de [orto bi-(hetero-) aril]-[2-meta bi-(hetero-) aril)-pirrolidin-1-il]-metanona. |
| JP2016510810A (ja) | 2013-03-12 | 2016-04-11 | アクテリオン ファーマシューティカルズ リミテッドＡｃｔｅｌｉｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｌｔｄ | オレキシン受容体アンタゴニストとしてのアゼチジンアミド誘導体 |
| HUE035731T2 (hu) | 2013-12-03 | 2018-05-28 | Idorsia Pharmaceuticals Ltd | (S)-(2-(6-klór-7-metil-1H-benzo[d]imidazol-2-il)-2-metilpirrolidin-1-il)(5-metoxi-2- (2H-l,2,3-triazol-2-il)fenil)metanon kristályos formája és alkalmazása orexin receptor antagonistaként |
| UA119151C2 (uk) | 2013-12-03 | 2019-05-10 | Ідорсія Фармасьютікалз Лтд | КРИСТАЛІЧНА СОЛЬОВА ФОРМА (S)-(2-(6-ХЛОР-7-МЕТИЛ-1H-БЕНЗО[d]ІМІДАЗОЛ-2-ІЛ)-2-МЕТИЛПІРОЛІДИН-1-ІЛ)(5-МЕТОКСИ-2-(2H-1,2,3-ТРИАЗОЛ-2-ІЛ)ФЕНІЛ)МЕТАНОНУ ЯК АНТАГОНІСТ ОРЕКСИНОВОГО РЕЦЕПТОРА |
| LT3077391T (lt) | 2013-12-04 | 2018-10-25 | Idorsia Pharmaceuticals Ltd | Benzimidazolo prolino darinių panaudojimas |
| AR101558A1 (es) | 2014-08-13 | 2016-12-28 | Eolas Therapeutics Inc | Difluoropirrolidinas como moduladores del receptor de orexina |
| AU2017217931B2 (en) | 2016-02-12 | 2020-10-22 | Astrazeneca Ab | Halo-substituted piperidines as orexin receptor modulators |
| IL288321B2 (en) | 2016-03-10 | 2025-08-01 | Janssen Pharmaceutica Nv | Methods of treating depression using orexin-2 receptor antagonists |
| EP3454857A1 (en) | 2016-05-10 | 2019-03-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of autoimmune inflammatory diseases |
| GB201618181D0 (en) | 2016-10-27 | 2016-12-14 | J Banks & Co Ltd | Slide turn door assembly and support mechanism therefor |
| WO2020007964A1 (en) | 2018-07-05 | 2020-01-09 | Idorsia Pharmaceuticals Ltd | 2-(2-azabicyclo[3.1.0]hexan-1-yl)-1h-benzimidazole derivatives |
| WO2020099511A1 (en) | 2018-11-14 | 2020-05-22 | Idorsia Pharmaceuticals Ltd | Benzimidazole-2-methyl-morpholine derivatives |
| US12497362B2 (en) | 2020-08-18 | 2025-12-16 | Merck Sharp & Dohme Llc | Cyclopentapyrrole orexin receptor agonists |
| WO2023218023A1 (en) | 2022-05-13 | 2023-11-16 | Idorsia Pharmaceuticals Ltd | Thiazoloaryl-methyl substituted cyclic hydrazine-n-carboxamide derivatives |
| WO2025224168A1 (en) | 2024-04-24 | 2025-10-30 | Idorsia Pharmaceuticals Ltd | Aryl sulfone and sulfanone derivatives as orexin receptor modulators |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1676451A3 (ru) * | 1987-09-23 | 1991-09-07 | Иституто Де Анджели С.П.А. (Фирма) | Способ получени производных бензимидазола в виде смеси изомеров или индивидуальных изомеров в свободном виде или в виде их физиологически приемлемых солей |
| RU2135503C1 (ru) * | 1992-06-19 | 1999-08-27 | Басф Акциенгезельшафт | N-замещенные производные 3-азабицикло (3.2.0)гептана или их соли с физиологически совместимыми кислотами |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57139032A (en) | 1981-02-20 | 1982-08-27 | Takasago Corp | 2-(butan-2-on-3-yl)-5-methylphenol and perfumery composition containing the same |
| GB9319732D0 (en) * | 1993-09-24 | 1993-11-10 | Ucb Sa | Use of (s)-alpha-ethyl-2-oxo-l-pyrrolidineacetamide for the treatment of anxiety |
| AU2381995A (en) | 1994-04-29 | 1995-11-29 | Pharmacia & Upjohn Company | Methanol derivatives for treatment of retroviral infections especially hiv infections |
| ATE293101T1 (de) * | 2000-06-16 | 2005-04-15 | Smithkline Beecham Plc | Piperidine zur verwendung als orexin rezeptor antagonisten |
| US7244721B2 (en) | 2000-07-21 | 2007-07-17 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| DE60108420T2 (de) * | 2000-11-28 | 2005-12-22 | Smithkline Beecham P.L.C., Brentford | Morpholinderivate als antagonisten an orexinrezeptoren |
| ATE383359T1 (de) | 2001-05-05 | 2008-01-15 | Smithkline Beecham Plc | N-aroyl zyklische amine |
| JP2004534026A (ja) | 2001-05-05 | 2004-11-11 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとしてのｎ−アロイルサイクリックアミン誘導体 |
| GB0115862D0 (en) | 2001-06-28 | 2001-08-22 | Smithkline Beecham Plc | Compounds |
| ES2266549T3 (es) | 2001-06-28 | 2007-03-01 | Smithkline Beecham Plc | Derivados de n-aroil-amina ciclicos como antagonistas del receptor de orexina. |
| GB0124463D0 (en) | 2001-10-11 | 2001-12-05 | Smithkline Beecham Plc | Compounds |
| GB0127145D0 (en) * | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Compounds |
| GB0130335D0 (en) | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| GB0130393D0 (en) | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| JP2006504695A (ja) * | 2002-09-18 | 2006-02-09 | グラクソ グループ リミテッド | オレキシン受容体アンタゴニストとしてのｎ−アロイル環状アミン |
| EE05516B1 (et) | 2002-09-25 | 2012-02-15 | Memory@Pharmaceuticals@Corporation | Indasoolid bensotiasoolid ja bensoisotiasoolid nende valmistamine ning kasutamine |
| GB0225884D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| GB0225944D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| GB0225938D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| CA2560741C (en) | 2004-03-25 | 2013-08-06 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| US20060014733A1 (en) | 2004-07-19 | 2006-01-19 | Pfizer Inc | Histamine-3 agonists and antagonists |
| WO2008038251A2 (en) * | 2006-09-29 | 2008-04-03 | Actelion Pharmaceuticals Ltd | 3-aza-bicyclo[3.1.0]hexane derivatives |
| US8133901B2 (en) * | 2006-12-01 | 2012-03-13 | Actelion Pharmaceuticals Ltd. | 3-heteroaryl (amino or amido)-1-(biphenyl or phenylthiazolyl) carbonylpiperidine derivatives as orexin receptor inhibitors |
| CL2008000836A1 (es) * | 2007-03-26 | 2008-11-07 | Actelion Pharmaceuticals Ltd | Compuestos derivados de tiazolidina, antagonistas del receptor de orexina; composicion farmaceutica que los comprende; y su uso en el tratamiento de neurosis emocional, depresion grave, trastornos psicoticos, alzheimer, parkinson, dolor, entre otras. |
| US20100222328A1 (en) * | 2007-05-14 | 2010-09-02 | Hamed Aissaoui | 2-cyclopropyl-thiazole derivatives |
| WO2008150364A1 (en) | 2007-05-23 | 2008-12-11 | Merck & Co., Inc. | Cyclopropyl pyrrolidine orexin receptor antagonists |
| CN101679366B (zh) * | 2007-05-23 | 2013-08-07 | 默沙东公司 | 吡啶基哌啶食欲素受体拮抗剂 |
| GB0712888D0 (en) * | 2007-07-03 | 2007-08-15 | Glaxo Group Ltd | Novel compounds |
| EP2176258A1 (en) * | 2007-07-03 | 2010-04-21 | Glaxo Group Limited | Piperidine derivatives useful as orexin receptor antagonists |
| AR067665A1 (es) * | 2007-07-27 | 2009-10-21 | Actelion Pharmaceuticals Ltd | Derivados de trans-3- aza-biciclo ( 3.1.0) hexano |
| JP2010540429A (ja) * | 2007-09-24 | 2010-12-24 | アクテリオン ファーマシューティカルズ リミテッド | オレキシン受容体拮抗薬としてのピロリジン類及びピペリジン類 |
| WO2009080533A1 (en) * | 2007-12-21 | 2009-07-02 | F. Hoffmann-La Roche Ag | Heteroaryl derivatives as orexin receptor antagonists |
| WO2009104155A1 (en) * | 2008-02-21 | 2009-08-27 | Actelion Pharmaceuticals Ltd | 2-aza-bicyclo[2.2.1]heptane derivatives |
| WO2009133522A1 (en) * | 2008-04-30 | 2009-11-05 | Actelion Pharmaceuticals Ltd | Piperidine and pyrrolidine compounds |
| CN102123999B (zh) | 2008-05-22 | 2014-06-18 | 默沙东公司 | 制备食欲素受体拮抗剂的方法 |
-
2008
- 2008-07-25 NZ NZ583487A patent/NZ583487A/en not_active IP Right Cessation
- 2008-07-25 JP JP2010517536A patent/JP2010534647A/ja active Pending
- 2008-07-25 AU AU2008281399A patent/AU2008281399A1/en not_active Abandoned
- 2008-07-25 KR KR1020107004524A patent/KR20100046047A/ko not_active Withdrawn
- 2008-07-25 CA CA2693820A patent/CA2693820A1/en not_active Abandoned
- 2008-07-25 US US12/670,823 patent/US8288429B2/en not_active Expired - Fee Related
- 2008-07-25 EP EP08789443A patent/EP2183246A2/en not_active Withdrawn
- 2008-07-25 CN CN200880100389XA patent/CN101874028B/zh not_active Expired - Fee Related
- 2008-07-25 BR BRPI0814593-8A2A patent/BRPI0814593A2/pt not_active IP Right Cessation
- 2008-07-25 RU RU2010106854/04A patent/RU2478099C2/ru not_active IP Right Cessation
- 2008-07-25 WO PCT/IB2008/052989 patent/WO2009016564A2/en not_active Ceased
-
2010
- 2010-02-05 MA MA32589A patent/MA31593B1/fr unknown
- 2010-02-26 ZA ZA2010/01434A patent/ZA201001434B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1676451A3 (ru) * | 1987-09-23 | 1991-09-07 | Иституто Де Анджели С.П.А. (Фирма) | Способ получени производных бензимидазола в виде смеси изомеров или индивидуальных изомеров в свободном виде или в виде их физиологически приемлемых солей |
| RU2135503C1 (ru) * | 1992-06-19 | 1999-08-27 | Басф Акциенгезельшафт | N-замещенные производные 3-азабицикло (3.2.0)гептана или их соли с физиологически совместимыми кислотами |
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| Publication number | Publication date |
|---|---|
| ZA201001434B (en) | 2013-08-28 |
| CN101874028A (zh) | 2010-10-27 |
| US20110009461A1 (en) | 2011-01-13 |
| CN101874028B (zh) | 2012-11-14 |
| KR20100046047A (ko) | 2010-05-04 |
| AU2008281399A1 (en) | 2009-02-05 |
| NZ583487A (en) | 2011-09-30 |
| WO2009016564A3 (en) | 2009-03-26 |
| BRPI0814593A2 (pt) | 2015-01-20 |
| WO2009016564A2 (en) | 2009-02-05 |
| RU2010106854A (ru) | 2011-09-10 |
| US8288429B2 (en) | 2012-10-16 |
| JP2010534647A (ja) | 2010-11-11 |
| MA31593B1 (fr) | 2010-08-02 |
| CA2693820A1 (en) | 2009-02-05 |
| EP2183246A2 (en) | 2010-05-12 |
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