RU2560729C2 - Модуляторы никотиновых ацетилхолиновых рецепторов - Google Patents
Модуляторы никотиновых ацетилхолиновых рецепторов Download PDFInfo
- Publication number
- RU2560729C2 RU2560729C2 RU2012129257/04A RU2012129257A RU2560729C2 RU 2560729 C2 RU2560729 C2 RU 2560729C2 RU 2012129257/04 A RU2012129257/04 A RU 2012129257/04A RU 2012129257 A RU2012129257 A RU 2012129257A RU 2560729 C2 RU2560729 C2 RU 2560729C2
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- RU
- Russia
- Prior art keywords
- phenyl
- alkyl
- compound
- substituted
- compounds
- Prior art date
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- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 title claims abstract description 38
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 title claims abstract description 38
- 150000001875 compounds Chemical class 0.000 claims abstract description 158
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
- 239000001257 hydrogen Substances 0.000 claims abstract description 27
- 125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 22
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 16
- 229960002715 nicotine Drugs 0.000 claims abstract description 13
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 10
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 12
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims abstract 2
- 239000001301 oxygen Substances 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 33
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 12
- 229910052727 yttrium Inorganic materials 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 102000005962 receptors Human genes 0.000 claims description 9
- 108020003175 receptors Proteins 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 206010057852 Nicotine dependence Diseases 0.000 claims description 3
- 208000025569 Tobacco Use disease Diseases 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 49
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 30
- 230000000694 effects Effects 0.000 abstract description 23
- 239000003814 drug Substances 0.000 abstract description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 21
- 208000035475 disorder Diseases 0.000 abstract description 21
- 239000000126 substance Substances 0.000 abstract description 20
- 208000024891 symptom Diseases 0.000 abstract description 19
- 238000011282 treatment Methods 0.000 abstract description 17
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 abstract description 12
- 208000002193 Pain Diseases 0.000 abstract description 7
- 230000002265 prevention Effects 0.000 abstract description 5
- 201000005040 opiate dependence Diseases 0.000 abstract description 3
- 244000025254 Cannabis sativa Species 0.000 abstract description 2
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 abstract description 2
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 abstract description 2
- 108010009685 Cholinergic Receptors Proteins 0.000 abstract description 2
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- 208000029197 Amphetamine-Related disease Diseases 0.000 abstract 1
- 208000018526 Narcotic-Related disease Diseases 0.000 abstract 1
- 102000034337 acetylcholine receptors Human genes 0.000 abstract 1
- 229960003920 cocaine Drugs 0.000 abstract 1
- 229940127240 opiate Drugs 0.000 abstract 1
- -1 etc.) Chemical compound 0.000 description 105
- 239000000203 mixture Substances 0.000 description 78
- 239000000243 solution Substances 0.000 description 42
- 125000003710 aryl alkyl group Chemical group 0.000 description 39
- 125000003118 aryl group Chemical group 0.000 description 35
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 7
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
- 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
- A61P25/32—Alcohol-abuse
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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
- A61P25/34—Tobacco-abuse
-
- 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
- A61P25/36—Opioid-abuse
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Health & Medical Sciences (AREA)
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- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- Animal Behavior & Ethology (AREA)
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- General Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29404410P | 2010-01-11 | 2010-01-11 | |
| US61/294,044 | 2010-01-11 | ||
| PCT/US2011/020881 WO2011085389A1 (en) | 2010-01-11 | 2011-01-11 | Nicotinic acetylcholine receptor modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2012129257A RU2012129257A (ru) | 2014-02-20 |
| RU2560729C2 true RU2560729C2 (ru) | 2015-08-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2012129257/04A RU2560729C2 (ru) | 2010-01-11 | 2011-01-11 | Модуляторы никотиновых ацетилхолиновых рецепторов |
Country Status (9)
| Country | Link |
|---|---|
| US (4) | US9062042B2 (OSRAM) |
| EP (1) | EP2523562B1 (OSRAM) |
| JP (1) | JP5840143B2 (OSRAM) |
| CN (1) | CN102905527B (OSRAM) |
| CA (1) | CA2787063C (OSRAM) |
| IL (1) | IL220839B (OSRAM) |
| MX (1) | MX2012008082A (OSRAM) |
| RU (1) | RU2560729C2 (OSRAM) |
| WO (1) | WO2011085389A1 (OSRAM) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2560729C2 (ru) | 2010-01-11 | 2015-08-20 | АСТРАЕА ТЕРАПЕУТИКС, ЭлЭлСи | Модуляторы никотиновых ацетилхолиновых рецепторов |
| CN110804051B (zh) * | 2019-10-17 | 2020-10-20 | 杭州励德生物科技有限公司 | 一种格拉司琼中间体的制备方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060079564A1 (en) * | 2001-07-03 | 2006-04-13 | Jansen Johanna M | Indazole benzimidazole compounds |
| WO2007039563A1 (en) * | 2005-09-30 | 2007-04-12 | N.V. Organon | 9-azabicyclo [3 . 3 . 1] nonane derivatives as monoamine reuptake inhibitors |
| WO2007040280A1 (ja) * | 2005-10-06 | 2007-04-12 | Nippon Soda Co., Ltd. | 環状アミン化合物および有害生物防除剤 |
| WO2008019372A2 (en) * | 2006-08-07 | 2008-02-14 | Albany Molecular Research, Inc. | 2-aminobenzoxazole carboxamides as 5ht3 modulators |
| US20090118326A1 (en) * | 2007-11-02 | 2009-05-07 | Faming Jiang | Nicotinic Acetylcholine Receptor Modulators |
| WO2009058120A1 (en) * | 2007-11-02 | 2009-05-07 | Sri International | Nicotinic acetylcholine receptor modulators |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5198447A (en) * | 1986-11-21 | 1993-03-30 | Glaxo Group Limited | Medicaments |
| US5200413A (en) * | 1987-01-05 | 1993-04-06 | Beecham Group P.L.C. | Indolyl carboxamides useful treating migraine, cluster headache, trigeminal neuralgia or emesis |
| US4835162A (en) * | 1987-02-12 | 1989-05-30 | Abood Leo G | Agonists and antagonists to nicotine as smoking deterents |
| DE3852145T2 (de) * | 1987-02-18 | 1995-04-06 | Beecham Group Plc | Indolderivate, Verfahren zu deren Herstellung und pharmazeutische Präparate, die diese enthalten. |
| DE3822792C2 (de) * | 1987-07-11 | 1997-11-27 | Sandoz Ag | Neue Verwendung von 5HT¶3¶-Antagonisten |
| US5223511A (en) * | 1987-09-23 | 1993-06-29 | Boehringer Ingelheim Italia S.P.A. | Benzimidazoline-2-oxo-1-carboxylic acid compounds useful as 5-HT receptor antagonists |
| EP0315390B1 (en) * | 1987-11-04 | 1994-07-20 | Beecham Group Plc | Novel 4-oxobenzotriazines and 4-oxoquinazolines |
| GB2236751B (en) * | 1989-10-14 | 1993-04-28 | Wyeth John & Brother Ltd | Heterocyclic compounds |
| US5446050A (en) * | 1989-11-17 | 1995-08-29 | Pfizer Inc. | Azabicyclo amides and esters as 5-HT3 receptor antagonists |
| JP3122671B2 (ja) * | 1990-05-23 | 2001-01-09 | 協和醗酵工業株式会社 | 複素環式化合物 |
| JP3087763B2 (ja) * | 1990-11-30 | 2000-09-11 | 三井化学株式会社 | 新規な複素環式化合物およびそれを含有する医薬組成物 |
| US5491148A (en) * | 1991-04-26 | 1996-02-13 | Syntex (U.S.A.) Inc. | Isoquinolinone and dihydroisoquinolinone 5-HT3 receptor antagonists |
| PH30413A (en) * | 1992-03-26 | 1997-05-09 | Boehringer Ingelheim Italia | Crystalline forms of endo-2,3-dihydro-n-(8-methyl)-8-azabicyclo-(3,2,1)oct-3-yl)-2-oxo-1h-benzimidazole-1-carboxamides |
| US5280028A (en) * | 1992-06-24 | 1994-01-18 | G. D. Searle & Co. | Benzimidazole compounds |
| AU701227B2 (en) * | 1993-09-10 | 1999-01-21 | Cytomed, Inc | Epibatidine and derivatives thereof as cholinergic receptor agonists and antagonists |
| US5399562A (en) * | 1994-02-04 | 1995-03-21 | G. D. Searle & Co. | Indolones useful as serotonergic agents |
| US6117889A (en) * | 1994-04-01 | 2000-09-12 | University Of Virginia | 7-Azabicyclo-[2.2.1]-heptane and -heptene derivatives as analgesics and anti-inflammatory agents |
| GB9410441D0 (en) * | 1994-05-25 | 1994-07-13 | Erba Carlo Spa | Azabicycloakyl derivatives of imidazo (1,5-a) indol-3-one and process for their preparation |
| JPH11505547A (ja) * | 1996-03-13 | 1999-05-21 | エール ユニバーシティ | ナルトレキソン及び関連化合物を用いる禁煙処置 |
| DK0984966T3 (da) * | 1997-05-30 | 2003-05-05 | Neurosearch As | 9-azabicyclo[3.3.1]non-2-en derivater, som er cholinerge ligander på nikotin-ACh receptorer |
| CA2289574C (en) * | 1997-05-30 | 2007-04-24 | Neurosearch A/S | 8-azabicyclo(3,2,1)oct-2-ene and octane derivatives as cholinergic ligands at nicotinic ach receptors |
| AU744539B2 (en) * | 1997-10-27 | 2002-02-28 | Neurosearch A/S | Heteroaryl diazacycloalkanes as cholinergic ligands at nicotinic acetylcholine receptors |
| AU2349999A (en) * | 1998-01-29 | 1999-08-16 | Sepracor, Inc. | Pharmacological uses of pure (+) -bupropion |
| IT1303123B1 (it) * | 1998-10-13 | 2000-10-30 | Rotta Research Lab | Derivati basici di benz(e)isoindol-1-oni e pirrolo(3,4-c)chinolin-1-oni ad attivita' 5ht3 antagonista, loro preparazione ed |
| NZ510287A (en) | 1998-11-27 | 2003-05-30 | Neurosearch As | 8-azabicyclo[3.2.1]oct-2-ene and -octane derivatives useful as cholinergic ligands at the nicotinic acetyl choline receptor |
| FR2788982B1 (fr) | 1999-02-02 | 2002-08-02 | Synthelabo | Compositions pharmaceutiques contenant de la nicotine et leur application dans le sevrage tabagique |
| DE10045112A1 (de) | 2000-09-11 | 2002-03-21 | Merck Patent Gmbh | Verwendung von Indolderivaten zur Behandlung von Erkrankungen des zentralen Nervensystems |
| BR0209129A (pt) | 2001-04-18 | 2005-12-20 | Euro Celtique Sa | Compostos, composições farmacêuticas, métodos para tratamento de dores, métodos para modulação de uma resposta farmacológica e usos de compostos |
| AR036041A1 (es) * | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos aromaticos heterociclicos sustituidos con quinuclidina y composiciones farmaceuticas que los contienen |
| US7199147B2 (en) * | 2001-06-12 | 2007-04-03 | Dainippon Sumitomo Pharma Co., Ltd. | Rho kinase inhibitors |
| AR036040A1 (es) * | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
| EP1425286B1 (en) * | 2001-09-12 | 2007-02-28 | Pharmacia & Upjohn Company LLC | Substituted 7-aza-[2.2.1]bicycloheptanes for the treatment of diseases |
| EP1432707B1 (en) * | 2001-10-02 | 2012-03-28 | Pharmacia & Upjohn Company LLC | Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease |
| US6951849B2 (en) * | 2001-10-02 | 2005-10-04 | Acadia Pharmaceuticals Inc. | Benzimidazolidinone derivatives as muscarinic agents |
| US6849620B2 (en) * | 2001-10-26 | 2005-02-01 | Pfizer Inc | N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease |
| MXPA04004464A (es) * | 2001-11-08 | 2004-08-11 | Upjohn Co | Compuestos de heteroarilo sustituido con azabiciclo para el tratamiento de enfermedades. |
| US6951868B2 (en) * | 2001-11-09 | 2005-10-04 | Pfizer Inc. | Azabicyclic-phenyl-fused-heterocyclic compounds for treatment of disease |
| JP2005522456A (ja) * | 2002-02-15 | 2005-07-28 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | Ｃｎｓ関連障害治療のためのアザビシクロ置換ベンゾイルアミドおよびチオアミド |
| BR0307782A (pt) * | 2002-02-19 | 2005-01-04 | Upjohn Co | Compostos azabiciclo para o tratamento de doença |
| US6858613B2 (en) * | 2002-02-19 | 2005-02-22 | Pfizer Inc. | Fused bicyclic-N-bridged-heteroaromatic carboxamides for the treatment of disease |
| US7176198B2 (en) | 2002-08-01 | 2007-02-13 | Pfizer Inc. | 1H-pyrazole and 1H-pyrrole-azabicyclic compounds for the treatment of disease |
| CA2503786A1 (en) * | 2002-11-01 | 2004-05-13 | Pharmacia & Upjohn Company Llc | Compounds having both alpha7 nicotinic agonist activity and 5ht, antagonist activity for treatment of cns diseases |
| AU2003283648A1 (en) | 2002-12-06 | 2004-06-30 | Pharmacia & Upjohn Company Llc | Compounds as radioligands for the diagnosis of disease |
| EP1678172B1 (en) * | 2003-10-15 | 2009-12-09 | Targacept, Inc. | Azabicyclic compounds for relieving pain and treating central nervous system disorders |
| US20050228023A1 (en) * | 2003-12-19 | 2005-10-13 | Sri International | Agonist and antagonist ligands of the nociceptin receptor |
| DE602004010299T2 (de) * | 2003-12-22 | 2008-09-18 | Memory Pharmaceuticals Corp. | Indole, 1h-indazole, 1,2-benzisoxazole und 1,2-benzisothiazole und deren herstellung und anwendungen |
| JP2007534692A (ja) * | 2004-04-22 | 2007-11-29 | メモリー・ファーマシューティカルズ・コーポレイション | インドール、１ｈ−インダゾール、１，２−ベンズイソキサゾール、１，２−ベンゾイソチアゾール、ならびにその調製および使用 |
| JP2007538011A (ja) | 2004-05-07 | 2007-12-27 | メモリー・ファーマシューティカルズ・コーポレイション | １ｈ−インダゾール、ベンゾチアゾール、１，２−ベンゾイソキサゾール、１，２−ベンゾイソチアゾール、およびクロモン、ならびにそれらの調製および使用 |
| US20090131430A1 (en) | 2004-11-23 | 2009-05-21 | Palle Venkata P | Pyrido'2,3-dipyrimidines as anti-inflammatory agents |
| US7868017B2 (en) * | 2005-09-30 | 2011-01-11 | N.V. Organon | 9-azabicyclo[3.3.1]nonane derivatives |
| GB0719644D0 (en) * | 2007-10-05 | 2007-11-14 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| US7902222B2 (en) | 2007-11-21 | 2011-03-08 | Abbott Laboratories | Biaryl substituted azabicyclic alkane derivatives |
| HRP20150341T1 (hr) | 2008-11-14 | 2015-05-08 | Bayer Intellectual Property Gmbh | Heterocikliäśki supstituirani spojevi arila kao inhibitori hif |
| RU2011143740A (ru) | 2009-03-30 | 2013-05-10 | Астеллас Фарма Инк. | Соединение пиримидина |
| RU2560729C2 (ru) | 2010-01-11 | 2015-08-20 | АСТРАЕА ТЕРАПЕУТИКС, ЭлЭлСи | Модуляторы никотиновых ацетилхолиновых рецепторов |
-
2011
- 2011-01-11 RU RU2012129257/04A patent/RU2560729C2/ru active
- 2011-01-11 EP EP11732326.1A patent/EP2523562B1/en active Active
- 2011-01-11 CN CN201180013438.8A patent/CN102905527B/zh active Active
- 2011-01-11 CA CA2787063A patent/CA2787063C/en active Active
- 2011-01-11 JP JP2012548234A patent/JP5840143B2/ja active Active
- 2011-01-11 US US13/004,801 patent/US9062042B2/en active Active
- 2011-01-11 MX MX2012008082A patent/MX2012008082A/es active IP Right Grant
- 2011-01-11 WO PCT/US2011/020881 patent/WO2011085389A1/en not_active Ceased
-
2012
- 2012-07-10 IL IL220839A patent/IL220839B/en active IP Right Grant
-
2015
- 2015-01-20 US US14/601,194 patent/US9670198B2/en active Active
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2017
- 2017-04-23 US US15/494,505 patent/US10085975B2/en active Active
-
2018
- 2018-07-17 US US16/037,001 patent/US20180318270A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060079564A1 (en) * | 2001-07-03 | 2006-04-13 | Jansen Johanna M | Indazole benzimidazole compounds |
| WO2007039563A1 (en) * | 2005-09-30 | 2007-04-12 | N.V. Organon | 9-azabicyclo [3 . 3 . 1] nonane derivatives as monoamine reuptake inhibitors |
| WO2007040280A1 (ja) * | 2005-10-06 | 2007-04-12 | Nippon Soda Co., Ltd. | 環状アミン化合物および有害生物防除剤 |
| WO2008019372A2 (en) * | 2006-08-07 | 2008-02-14 | Albany Molecular Research, Inc. | 2-aminobenzoxazole carboxamides as 5ht3 modulators |
| US20090118326A1 (en) * | 2007-11-02 | 2009-05-07 | Faming Jiang | Nicotinic Acetylcholine Receptor Modulators |
| WO2009058120A1 (en) * | 2007-11-02 | 2009-05-07 | Sri International | Nicotinic acetylcholine receptor modulators |
Non-Patent Citations (3)
| Title |
|---|
| & EA014057 B1. * |
| & RU 2448105A2 . * |
| VALERIA COSTA et al.,A structural model of agonist binding to the alpha3beta4 neuronal nicotinic receptor, BRITISH JOURNAL OF PHARMACOLOGY, 2003, Vol:140, Nr:5, Page(s):921 - 931. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2787063C (en) | 2018-11-27 |
| WO2011085389A1 (en) | 2011-07-14 |
| US9062042B2 (en) | 2015-06-23 |
| EP2523562A1 (en) | 2012-11-21 |
| IL220839A0 (en) | 2012-08-30 |
| US20150148541A1 (en) | 2015-05-28 |
| IL220839B (en) | 2018-07-31 |
| CA2787063A1 (en) | 2011-07-14 |
| US20180318270A1 (en) | 2018-11-08 |
| EP2523562B1 (en) | 2019-01-02 |
| US20170224665A1 (en) | 2017-08-10 |
| CN102905527B (zh) | 2016-08-24 |
| RU2012129257A (ru) | 2014-02-20 |
| JP5840143B2 (ja) | 2016-01-06 |
| MX2012008082A (es) | 2013-02-07 |
| EP2523562A4 (en) | 2013-04-17 |
| JP2013516496A (ja) | 2013-05-13 |
| US9670198B2 (en) | 2017-06-06 |
| US10085975B2 (en) | 2018-10-02 |
| CN102905527A (zh) | 2013-01-30 |
| US20110172264A1 (en) | 2011-07-14 |
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