NO332535B1 - Indazoler, benzotiazoler og benzoisotiazoler, anvendelse derav for fremstilling av et medikament, og farmasoytisk preparat omfattende forbindelsen - Google Patents
Indazoler, benzotiazoler og benzoisotiazoler, anvendelse derav for fremstilling av et medikament, og farmasoytisk preparat omfattende forbindelsen Download PDFInfo
- Publication number
- NO332535B1 NO332535B1 NO20051985A NO20051985A NO332535B1 NO 332535 B1 NO332535 B1 NO 332535B1 NO 20051985 A NO20051985 A NO 20051985A NO 20051985 A NO20051985 A NO 20051985A NO 332535 B1 NO332535 B1 NO 332535B1
- Authority
- NO
- Norway
- Prior art keywords
- oct
- azabicyclo
- carboxamide
- carbon atoms
- indazole
- Prior art date
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- 239000003814 drug Substances 0.000 title claims description 29
- 238000004519 manufacturing process Methods 0.000 title claims description 15
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 title abstract description 6
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- 239000008194 pharmaceutical composition Substances 0.000 title 1
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- 150000003839 salts Chemical class 0.000 claims description 30
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- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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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Landscapes
- Health & Medical Sciences (AREA)
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US41315102P | 2002-09-25 | 2002-09-25 | |
US44846903P | 2003-02-21 | 2003-02-21 | |
PCT/US2003/029976 WO2004029050A1 (en) | 2002-09-25 | 2003-09-25 | Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof |
Publications (2)
Publication Number | Publication Date |
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NO20051985L NO20051985L (no) | 2005-06-09 |
NO332535B1 true NO332535B1 (no) | 2012-10-15 |
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Family Applications (1)
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NO20051985A NO332535B1 (no) | 2002-09-25 | 2005-04-22 | Indazoler, benzotiazoler og benzoisotiazoler, anvendelse derav for fremstilling av et medikament, og farmasoytisk preparat omfattende forbindelsen |
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EP (2) | EP2305675A1 (et) |
JP (2) | JP4890762B2 (et) |
KR (1) | KR101129933B1 (et) |
CN (1) | CN100484937C (et) |
AU (1) | AU2003276919B2 (et) |
BG (1) | BG109117A (et) |
BR (1) | BR0314485A (et) |
CA (1) | CA2499128C (et) |
CZ (1) | CZ2005252A3 (et) |
EC (1) | ECSP055699A (et) |
EE (1) | EE05516B1 (et) |
ES (1) | ES2405594T3 (et) |
HK (1) | HK1083831A1 (et) |
HR (1) | HRP20050266A2 (et) |
HU (1) | HUP0500610A3 (et) |
MA (1) | MA27453A1 (et) |
MX (1) | MXPA05003317A (et) |
NO (1) | NO332535B1 (et) |
NZ (1) | NZ539049A (et) |
PL (1) | PL210065B1 (et) |
RS (1) | RS53147B (et) |
RU (1) | RU2391341C2 (et) |
SK (1) | SK288115B6 (et) |
WO (1) | WO2004029050A1 (et) |
ZA (1) | ZA200502465B (et) |
Families Citing this family (62)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
GB0220581D0 (en) | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
ES2405594T3 (es) * | 2002-09-25 | 2013-05-31 | Memory Pharmaceuticals Corporation | Idazoles, benzotiazoles y benzisotiazoles, y preparación y usos de los mismos |
AU2012202336B2 (en) * | 2004-03-25 | 2015-01-22 | Memory Pharmaceuticals Corporation | Indazoles, Benzothiazoles, Benzoisothiazoles, Benzisoxazoles, and Preparation and Uses Thereof |
MXPA06010852A (es) * | 2004-03-25 | 2007-01-16 | Memory Pharm Corp | Indazoles, benzotiazoles, benzoisotiazoles, bencisoxazoles y preparacion y usos de los mismos. |
ATE487716T1 (de) * | 2004-04-22 | 2010-11-15 | Memory Pharm Corp | Indole, 1h-indazole, 1,2-benzisoxazole, 1,2- benzoisothiazole, deren herstellung und verwendungen |
AR049401A1 (es) | 2004-06-18 | 2006-07-26 | Novartis Ag | Aza-biciclononanos |
GB0415746D0 (en) | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
DE602005019094D1 (de) | 2004-12-22 | 2010-03-11 | Memory Pharmaceutical Corp | Nikotinische alpha-7-rezeptorliganden gegen erkrankungen des zns |
US7307094B2 (en) * | 2005-02-17 | 2007-12-11 | Amr Technology, Inc. | Benzoxazole carboxamides for treating CINV and IBS-D |
CA2622677A1 (en) * | 2005-09-23 | 2007-04-05 | Richard Schumacher | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
US8106066B2 (en) * | 2005-09-23 | 2012-01-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
GB0521508D0 (en) | 2005-10-21 | 2005-11-30 | Novartis Ag | Organic compounds |
EP1963332A1 (en) * | 2005-11-09 | 2008-09-03 | Memory Pharmaceuticals Corporation | 1 h-indazoles, benzothiazoles, 1,2-benzoisoxazoles, 1,2-benzoisothiazoles, and chromones and preparation and uses thereof |
GB0525672D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
GB0525673D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
CN101528225B (zh) * | 2006-08-07 | 2013-07-17 | 阿尔巴尼分子研究公司 | 作为5ht3调节剂的2-氨基苯并噁唑羧酰胺 |
US20080153810A1 (en) * | 2006-11-15 | 2008-06-26 | Forest Laboratories Holdings Limited | Indazole derivatives useful as melanin concentrating receptor ligands |
CN102838532A (zh) * | 2006-11-24 | 2012-12-26 | Ac免疫有限公司 | 用于治疗与淀粉样物质或淀粉样蛋白有关的疾病的吡唑胺和噻唑胺衍生物 |
ES2371514T3 (es) | 2007-07-03 | 2012-01-04 | Actelion Pharmaceuticals Ltd. | Compuestos de 3-aza-biciclo[3.3.0]octano. |
KR20100046047A (ko) | 2007-07-27 | 2010-05-04 | 액테리온 파마슈티칼 리미티드 | 2-아자-비시클로[3.3.0]옥탄 유도체 |
SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
EP2178869B1 (en) * | 2007-08-17 | 2013-06-12 | LG Life Sciences Ltd. | Indole compounds as an inhibitor of cellular necrosis |
ES2362326T3 (es) * | 2007-10-01 | 2011-07-01 | Comentis, Inc. | Derivados de 1h-indol-3-carboxilato de quinuclidin-4-ilmetilo como ligandos del receptor nicotínico alfa 7 de la acetilcolina para el tratamiento de enfermedad de alzheimer. |
EP2205573B1 (en) | 2007-10-04 | 2013-10-23 | F. Hoffmann-La Roche AG | Tetrazole-substituted aryl amide derivatives and uses thereof |
WO2009146031A1 (en) * | 2008-03-31 | 2009-12-03 | University Of South Florida | Methods of treating disease-induced ataxia and non-ataxic imbalance |
EP2300012A4 (en) * | 2008-05-23 | 2011-07-06 | Univ South Florida | METHOD FOR TREATING SENSORY LOSS OF PERIPHERAL NERVE WITH COMPOUNDS HAVING ACETYLCHOLINE NICOTINIC RECEPTOR ACTIVITY |
AU2009266552B2 (en) * | 2008-07-01 | 2014-01-23 | De Staat Der Nederlanden, Vert. Door De Minister Van Vws | Vaccine against amyloid folding intermediate |
MY173229A (en) | 2008-11-19 | 2020-01-07 | Forum Pharmaceuticals Inc | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
JP2012521429A (ja) * | 2009-03-23 | 2012-09-13 | メルク・シャープ・エンド・ドーム・コーポレイション | 疼痛治療用のp2x3受容体アンタゴニスト |
TWI558398B (zh) | 2009-09-22 | 2016-11-21 | 諾華公司 | 菸鹼乙醯膽鹼受體α7活化劑之用途 |
EP2311823A1 (en) | 2009-10-15 | 2011-04-20 | AC Immune S.A. | 2,6-Diaminopyridine compounds for treating diseases associated with amyloid proteins or for treating ocular diseases |
US20110172428A1 (en) | 2010-01-12 | 2011-07-14 | Shan-Ming Kuang | Methods for the preparation of indazole-3-carboxylic acid and n-(s)-1-azabicyclo[2.2.2]oct-3-yl-1h-indazole-3-carboxamide hydrochloride salt |
JP2013526542A (ja) | 2010-05-12 | 2013-06-24 | アッヴィ・インコーポレイテッド | キナーゼのインダゾール阻害薬 |
SI3029039T1 (en) | 2010-05-17 | 2018-04-30 | Forum Pharmaceuticals Inc. | Pharmaceutical formulations containing crystalline forms of (R) -7-chloro-N- (quinuclidin-3-yl) benzo (b) thiophene-2-carboxamide hydrochloride monohydrate |
US8242276B2 (en) | 2010-06-30 | 2012-08-14 | Hoffmann-La Roche Inc. | Methods for the preparation of N-(S)-1-azabicyclo[2.2.2]oct-3-yl-1H-indazole-3-carboxamide hydrochloride salt |
JP2014507370A (ja) | 2010-07-26 | 2014-03-27 | エンヴィヴォ ファーマシューティカルズ,インコーポレイテッド | 特定のα−7ニコチン酸受容体アゴニストを、アセチルコリンエステラーゼ阻害剤と組み合わせて、用いた認知障害の処置 |
US8999966B2 (en) * | 2010-10-29 | 2015-04-07 | Merck Sharp & Dohme Corp. | Compounds that are ERK inhibitors |
WO2012101060A1 (en) | 2011-01-27 | 2012-08-02 | Novartis Ag | Use of nicotinic acetylcholine receptor alpha 7 activators |
KR101928505B1 (ko) * | 2011-01-28 | 2018-12-12 | 에스케이바이오팜 주식회사 | 피리돈 유도체 및 이를 포함하는 약학적 조성물 |
MX2013010698A (es) | 2011-03-18 | 2014-02-17 | Novartis Ag | Combinaciones de activadores del receptor de acetil-colina nicotinico alfa-7 y antagonistas del receptor de glutamato metabotropico 5 (mglur5) para usarse en la discinesia inducida por dopamina en la enfermedad de parkinson. |
EP2768507B1 (en) | 2011-10-20 | 2019-12-11 | Novartis AG | Biomarkers predictive of responsiveness to alpha 7 nicotinic acetylcholine receptor activator treatment |
AU2013259871A1 (en) | 2012-05-08 | 2014-11-20 | Forum Pharmaceuticals Inc. | Methods of maintaining, treating or improving cognitive function |
JOP20130213B1 (ar) | 2012-07-17 | 2021-08-17 | Takeda Pharmaceuticals Co | معارضات لمستقبلht3-5 |
RU2528641C2 (ru) * | 2012-08-22 | 2014-09-20 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Воронежская государственная медицинская академия им. Н.Н. Бурденко" Министерства здравоохранения и социального развития Российской Федерации | Способ лечения больных с синдромом диспепсии в сочетании с избыточной массой тела |
JP2014101316A (ja) * | 2012-11-20 | 2014-06-05 | Toyobo Co Ltd | ベンゾ[1,2−d;4,5−d’]ビスチアゾール化合物の製造方法 |
AU2013356914B2 (en) | 2012-12-11 | 2017-01-05 | Novartis Ag | Biomarker predictive of responsiveness to alpha 7 nicotinic acetylcholine receptor activator treatment |
BR112015016995B8 (pt) | 2013-01-15 | 2022-07-26 | Novartis Ag | Uso de agonistas do receptor alfa 7 nicotínico de acetilcolina |
US20150313884A1 (en) * | 2013-01-15 | 2015-11-05 | Novartis Ag | Use of alpha 7 nicotinic acetylcholine receptor agonists |
BR112015016994A8 (pt) * | 2013-01-15 | 2018-01-23 | Novartis Ag | uso de agonistas do receptor alfa 7 nicotínico de acetilcolina |
BR112015016992A8 (pt) | 2013-01-15 | 2018-01-23 | Novartis Ag | uso de agonistas do receptor alfa 7 nicotínico de acetilcolina |
MX2016012208A (es) | 2014-03-20 | 2017-01-26 | Samumed Llc | Indazol-3-carboxamidas 5-substituidas y preparacion y uso de las mismas. |
PL3201203T3 (pl) | 2014-09-29 | 2021-11-22 | Takeda Pharmaceutical Company Limited | Krystaliczna postać 1-(1-metylo-1h-pirazol-4-ilo)-n-((1r,5s,7s)-9-metylo-3-oksa-9-azabicyklo[3.3.1]nonan-7-ylo)-1h-indolo-3-karboksyamidu |
GB2535427A (en) | 2014-11-07 | 2016-08-24 | Nicoventures Holdings Ltd | Solution |
CN107033087B (zh) * | 2016-02-04 | 2020-09-04 | 西华大学 | 1h-吲唑-4-胺类化合物及其作为ido抑制剂的用途 |
MX2019007684A (es) * | 2016-12-26 | 2019-09-09 | Meiji Seika Pharma Co Ltd | Compuesto novedoso y sal de este aceptable desde el punto de vista farmacologico. |
CN108689938B (zh) * | 2017-04-10 | 2021-07-30 | 西华大学 | 多取代的吲唑类化合物及其作为ido抑制剂的用途 |
EA202090306A1 (ru) * | 2017-07-21 | 2020-06-25 | Кадмон Корпорейшн, Ллк | ИНГИБИТОРЫ Rho-АССОЦИИРОВАННОЙ, СОДЕРЖАЩЕЙ СУПЕРСПИРАЛЬ ПРОТЕИНКИНАЗЫ |
JP2020528415A (ja) * | 2017-07-21 | 2020-09-24 | カドモン コーポレイション,リミティド ライアビリティ カンパニー | Rho関連コイルドコイル含有プロテインキナーゼの阻害剤 |
WO2019057946A1 (en) | 2017-09-25 | 2019-03-28 | F. Hoffmann-La Roche Ag | MULTI-CYCLIC AROMATIC COMPOUNDS AS D-FACTOR INHIBITORS |
CN112020501A (zh) | 2018-02-23 | 2020-12-01 | 萨穆梅德有限公司 | 5-杂芳基取代的吲唑-3-基甲酰胺类及其制备和用途 |
Family Cites Families (96)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL59004A0 (en) | 1978-12-30 | 1980-03-31 | Beecham Group Ltd | Substituted benzamides their preparation and pharmaceutical compositions containing them |
FR2531083B1 (fr) | 1982-06-29 | 1986-11-28 | Sandoz Sa | Nouveaux derives de la piperidine, leur preparation et leur utilisation comme medicaments |
JPS5936675A (ja) | 1982-07-13 | 1984-02-28 | サンド・アクチエンゲゼルシヤフト | 二環性複素環式カルボン酸アザビシクロアルキルエステルまたはアミド |
FR2548666A1 (fr) | 1983-07-08 | 1985-01-11 | Delalande Sa | Nouveaux derives du nor-tropane et du granatane, leur procede de preparation et leur application en therapeutique |
WO1985001048A1 (en) | 1983-08-26 | 1985-03-14 | Sandoz Ag | Aromatic esters or amides of carboxylic acid and sulfonic acid |
US4605652A (en) * | 1985-02-04 | 1986-08-12 | A. H. Robins Company, Inc. | Method of enhancing memory or correcting memory deficiency with arylamido (and arylthioamido)-azabicycloalkanes |
US4937247A (en) | 1985-04-27 | 1990-06-26 | Beecham Group P.L.C. | 1-acyl indazoles |
EP0498466B1 (en) | 1985-04-27 | 2002-07-24 | F. Hoffmann-La Roche Ag | Indazole-3-carboxamide and -3-carboxylic acid derivatives |
GB8623142D0 (en) | 1986-09-26 | 1986-10-29 | Beecham Group Plc | Compounds |
US5204356A (en) | 1985-07-24 | 1993-04-20 | Glaxo Group Limited | Treatment of anxiety |
GB8518658D0 (en) | 1985-07-24 | 1985-08-29 | Glaxo Group Ltd | Medicaments |
GB8520616D0 (en) | 1985-08-16 | 1985-09-25 | Beecham Group Plc | Compounds |
IN166416B (et) | 1985-09-18 | 1990-05-05 | Pfizer | |
US4910193A (en) | 1985-12-16 | 1990-03-20 | Sandoz Ltd. | Treatment of gastrointestinal disorders |
HU895334D0 (en) | 1986-07-30 | 1990-01-28 | Sandoz Ag | Process for the preparation of nasal pharmaceutical compositions |
GB8701022D0 (en) | 1987-01-19 | 1987-02-18 | Beecham Group Plc | Treatment |
DE3872872T2 (de) | 1987-11-14 | 1993-02-04 | Beecham Group Plc | 5-ht3-rezeptor-antagonisten zur behandlung von husten und bronchokonstriktion. |
EP0350130A3 (en) | 1988-07-07 | 1991-07-10 | Duphar International Research B.V | New substituted 1,7-annelated 1h-indazoles |
US4895943A (en) | 1988-10-25 | 1990-01-23 | Pfizer Inc. | Preparation of 1,4-diazabicyclo(3.2.2)nonane |
US5223625A (en) | 1988-12-22 | 1993-06-29 | Duphar International Research B.V. | Annelated indolo [3,2,-C]lactams |
EP0377238A1 (en) | 1988-12-22 | 1990-07-11 | Duphar International Research B.V | New annelated indolo (3,2-c)-lactams |
AU5650890A (en) | 1989-05-24 | 1990-12-18 | Nippon Shinyaku Co. Ltd. | Indole derivatives and medicine |
US5446050A (en) | 1989-11-17 | 1995-08-29 | Pfizer Inc. | Azabicyclo amides and esters as 5-HT3 receptor antagonists |
GB8928837D0 (en) | 1989-12-21 | 1990-02-28 | Beecham Group Plc | Pharmaceuticals |
US5098889A (en) | 1990-09-17 | 1992-03-24 | E. R. Squibb & Sons, Inc. | Method for preventing or inhibiting loss of cognitive function employing a combination of an ace inhibitor and a drug that acts at serotonin receptors |
US5192770A (en) | 1990-12-07 | 1993-03-09 | Syntex (U.S.A.) Inc. | Serotonergic alpha-oxoacetamides |
HU211081B (en) | 1990-12-18 | 1995-10-30 | Sandoz Ag | Process for producing indole derivatives as serotonin antagonists and pharmaceutical compositions containing the same |
EP0566609A1 (en) | 1991-01-09 | 1993-10-27 | Smithkline Beecham Plc | Azabicydic and azatricydic derivatives, process and intermediates for their preparation and pharmaceutical compositions containing them |
KR0175638B1 (ko) | 1991-03-01 | 1999-02-18 | 카렌 에이.홀브루크 | 신경계 퇴행성 질환 치료용 니코틴 아날로그의 개량된 제조방법 |
GB9121835D0 (en) | 1991-10-15 | 1991-11-27 | Smithkline Beecham Plc | Pharmaceuticals |
US5273972A (en) | 1992-03-26 | 1993-12-28 | A. H. Robins Company, Incorporated | [(2-diakylaminomethyl)-3-quinuclidinyl]-benzamides and benzoates |
DE69332641T2 (de) | 1992-08-31 | 2003-11-27 | University Of Florida Research Foundation, Inc. | Anabasein derivate zur behandlung von degenerativen erkrankungen des nervensystems |
US5679673A (en) | 1992-09-24 | 1997-10-21 | The United States Of America, Represented By The Department Of Health And Human Services | Aralkyl bridged diazabicycloalkane derivatives for CNS disorders |
IT1256623B (it) | 1992-12-04 | 1995-12-12 | Federico Arcamone | Antagonisti delle tachichinine, procedimento per la loro preparazione e loro impiego in formulazioni farmaceutiche |
GB9226573D0 (en) | 1992-12-21 | 1993-02-17 | Ici Plc | Heterocyclic compounds |
DE69535592T2 (de) | 1994-03-25 | 2008-06-12 | Isotechnika, Inc., Edmonton | Verbesserung der effektivität von arzneimitteln duren deuterierung |
US6334997B1 (en) | 1994-03-25 | 2002-01-01 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
GB9406857D0 (en) | 1994-04-07 | 1994-06-01 | Sandoz Ltd | Improvements in or relating to organic compounds |
PT780372E (pt) | 1995-12-21 | 2002-04-29 | Syngenta Participations Ag | Derivados do acido 3-amino-2-mercaptobenzoico e processos para a sua preparacao |
SE9600683D0 (sv) | 1996-02-23 | 1996-02-23 | Astra Ab | Azabicyclic esters of carbamic acids useful in therapy |
US5714946A (en) | 1996-04-26 | 1998-02-03 | Caterpillar Inc. | Apparatus for communicating with a machine when the machine ignition is turned off |
US6624173B1 (en) | 1997-06-30 | 2003-09-23 | Targacept, Inc. | Pharmaceutical compositions for treating and/or preventing CNS disorders |
KR100247563B1 (ko) | 1997-07-16 | 2000-04-01 | 박영구 | 키랄3,4-에폭시부티르산및이의염의제조방법 |
US6277870B1 (en) | 1998-05-04 | 2001-08-21 | Astra Ab | Use |
US6441049B2 (en) | 1998-06-01 | 2002-08-27 | Ortho-Mcneil Pharmaceutical, Inc. | Method of treating neurodegenerative disorders via inhibition of amyloid beta peptide binding |
US6953855B2 (en) | 1998-12-11 | 2005-10-11 | Targacept, Inc. | 3-substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof |
SE9900100D0 (sv) | 1999-01-15 | 1999-01-15 | Astra Ab | New compounds |
FR2788982B1 (fr) | 1999-02-02 | 2002-08-02 | Synthelabo | Compositions pharmaceutiques contenant de la nicotine et leur application dans le sevrage tabagique |
FR2791678B1 (fr) | 1999-03-30 | 2001-05-04 | Synthelabo | Derives de 1,4-diazabicyclo [3.2.2] nonane-4-carboxylates et -carboxamides, leur preparation et leur application en therapeutique |
US6313110B1 (en) | 1999-06-02 | 2001-11-06 | Dupont Pharmaceuticals Company | Substituted 2H-1,3-diazapin-2-one useful as an HIV protease inhibitor |
DE19928846A1 (de) | 1999-06-24 | 2001-03-08 | Bosch Gmbh Robert | Common-Rail-Injektor |
BR0014331A (pt) | 1999-09-28 | 2003-06-10 | Eisai Co Ltd | Composto, inibidor de enzima sintetizadora de esqualeno, composição medicinal, processo para produção de um composto quinuclidìnico e processo para prevenção ou cura de uma doença |
SE9903760D0 (sv) | 1999-10-18 | 1999-10-18 | Astra Ab | New compounds |
SE9903997D0 (sv) | 1999-11-03 | 1999-11-03 | Astra Ab | New compounds |
SE9903998D0 (sv) | 1999-11-03 | 1999-11-03 | Astra Ab | New compounds |
SE9904176D0 (sv) | 1999-11-18 | 1999-11-18 | Astra Ab | New use |
US6747638B2 (en) * | 2000-01-31 | 2004-06-08 | Semiconductor Energy Laboratory Co., Ltd. | Adhesion type area sensor and display device having adhesion type area sensor |
AU2001234958A1 (en) * | 2000-02-11 | 2001-08-20 | Bristol-Myers Squibb Company | Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators for treating respiratory and non-respiratory diseases |
GB0010955D0 (en) | 2000-05-05 | 2000-06-28 | Novartis Ag | Organic compounds |
EP1289996B1 (en) | 2000-05-25 | 2005-04-06 | Targacept, Inc. | Heteroaryldiazabicycloalkanes as nicotinic cholinergic receptor ligands |
FR2809732B1 (fr) | 2000-05-31 | 2002-07-19 | Sanofi Synthelabo | DERIVES DE 4(-2-PHENYLTHIAZOL-5-yl)-1,4-DIAZABICYCLO-[3.2.2] NONANE, LEUR PREPARATION ET LEUR APPLICATION ENTHERAPEUTIQUE |
JP4616971B2 (ja) | 2000-07-18 | 2011-01-19 | 田辺三菱製薬株式会社 | 1−アザビシクロアルカン化合物およびその医薬用途 |
US6492385B2 (en) | 2000-08-18 | 2002-12-10 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
WO2002015662A2 (en) | 2000-08-21 | 2002-02-28 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease (nicotinic acetylcholine receptor antagonists |
US6500840B2 (en) | 2000-08-21 | 2002-12-31 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
WO2002036114A1 (en) | 2000-11-01 | 2002-05-10 | Respiratorius Ab | Composition comprising serotonin receptor antagonists, 5 ht-2 and 5 ht-3 |
US20020086871A1 (en) | 2000-12-29 | 2002-07-04 | O'neill Brian Thomas | Pharmaceutical composition for the treatment of CNS and other disorders |
ES2275808T3 (es) | 2001-02-06 | 2007-06-16 | Pfizer Products Inc. | Composiciones farmaceuticas para el tratamiento de trastornos del snc y otros trastornos. |
PE20021019A1 (es) | 2001-04-19 | 2002-11-13 | Upjohn Co | Grupos azabiciclicos sustituidos |
WO2002096911A1 (en) | 2001-06-01 | 2002-12-05 | Neurosearch A/S | Novel heteroaryl-diazabicyclo-alkanes as cns-modulators |
AR036040A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
US7199147B2 (en) | 2001-06-12 | 2007-04-03 | Dainippon Sumitomo Pharma Co., Ltd. | Rho kinase inhibitors |
AR036041A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos aromaticos heterociclicos sustituidos con quinuclidina y composiciones farmaceuticas que los contienen |
ATE355293T1 (de) | 2001-09-12 | 2006-03-15 | Pharmacia & Upjohn Co Llc | Substituierte 7-aza-(2.2.1)bicycloheptane für die behandlung von krankheiten |
WO2003029252A1 (en) | 2001-10-02 | 2003-04-10 | Pharmacia & Upjohn Company | Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease |
JP2005511574A (ja) | 2001-10-26 | 2005-04-28 | ファルマシア アンド アップジョン カンパニー リミティド ライアビリティー カンパニー | Nachrアゴニストとしてのn−アザビシクロ−置換ヘテロ二環式カルボキサミド |
US6849620B2 (en) | 2001-10-26 | 2005-02-01 | Pfizer Inc | N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease |
MXPA04004373A (es) | 2001-11-09 | 2004-08-11 | Upjohn Co | Compuestos heterociclicos condensados con fenilo azabiciclo para el tratamiento de enfermedades. |
DE10156719A1 (de) | 2001-11-19 | 2003-05-28 | Bayer Ag | Heteroarylcarbonsäureamide |
DE10162375A1 (de) | 2001-12-19 | 2003-07-10 | Bayer Ag | Bicyclische N-Aryl-amide |
WO2003104227A1 (de) | 2002-01-20 | 2003-12-18 | Bayer Healthcare Ag | 2-heteroarylcarbonsäureamide |
DE10305922A1 (de) | 2002-06-10 | 2004-03-04 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
WO2003070731A2 (en) | 2002-02-19 | 2003-08-28 | Pharmacia & Upjohn Company | Azabicyclic compounds for the treatment of disease |
EP1478646A1 (en) | 2002-02-20 | 2004-11-24 | PHARMACIA & UPJOHN COMPANY | Azabicyclic compounds with alfa7 nicotinic acetylcholine receptor activity |
DE10211415A1 (de) | 2002-03-15 | 2003-09-25 | Bayer Ag | Bicyclische N-Biarylamide |
ES2197001B1 (es) | 2002-03-26 | 2004-11-16 | Laboratorios Vita, S.A. | Procedimiento de obtencion de un compuesto farmaceuticamente activo. |
WO2003094830A2 (en) | 2002-05-07 | 2003-11-20 | Neurosearch A/S | Novel azacyclic ethynyl derivatives |
MXPA04011858A (es) | 2002-05-30 | 2005-03-31 | Neurosearch As | Quinuclidinas sustituidas en la posicion 3 y su uso. |
GB0218625D0 (en) | 2002-08-10 | 2002-09-18 | Astex Technology Ltd | Pharmaceutical compounds |
EP1546156A1 (en) | 2002-08-10 | 2005-06-29 | Astex Technology Limited | 3-(carbonyl) 1h-indazole compounds as cyclin dependent kinases (cdk) inhibitors |
SE0202465D0 (sv) | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | New compounds |
SE0202430D0 (sv) | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | New Compounds |
ES2405594T3 (es) | 2002-09-25 | 2013-05-31 | Memory Pharmaceuticals Corporation | Idazoles, benzotiazoles y benzisotiazoles, y preparación y usos de los mismos |
US7456171B2 (en) | 2002-10-08 | 2008-11-25 | Sanofi-Aventis | 1,4-Diazabicyclo[3.2.2]nonanecarboxamide derivatives, preparation and therapeutic use thereof |
EP1587511A2 (en) | 2003-01-22 | 2005-10-26 | Pharmacia & Upjohn Company LLC | Treatment of diseases with alpha-7 nach receptor full agonists |
US8106066B2 (en) | 2005-09-23 | 2012-01-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
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