DE60318860T2 - Chinucledin - derivate und deren verwendung - Google Patents
Chinucledin - derivate und deren verwendung Download PDFInfo
- Publication number
- DE60318860T2 DE60318860T2 DE60318860T DE60318860T DE60318860T2 DE 60318860 T2 DE60318860 T2 DE 60318860T2 DE 60318860 T DE60318860 T DE 60318860T DE 60318860 T DE60318860 T DE 60318860T DE 60318860 T2 DE60318860 T2 DE 60318860T2
- Authority
- DE
- Germany
- Prior art keywords
- aza
- yloxy
- bicyclo
- octane
- disorder
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK200201208 | 2002-08-14 | ||
| DKPA200201208 | 2002-08-14 | ||
| DKPA200201472 | 2002-10-02 | ||
| DK200201472 | 2002-10-02 | ||
| PCT/DK2003/000538 WO2004016608A1 (en) | 2002-08-14 | 2003-08-13 | Novel quinuclidine derivatives and their use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60318860D1 DE60318860D1 (de) | 2008-03-13 |
| DE60318860T2 true DE60318860T2 (de) | 2008-05-21 |
Family
ID=31889349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60318860T Expired - Lifetime DE60318860T2 (de) | 2002-08-14 | 2003-08-13 | Chinucledin - derivate und deren verwendung |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US20050245567A1 (https=) |
| EP (2) | EP1532144B1 (https=) |
| JP (1) | JP2005538187A (https=) |
| KR (1) | KR20050055711A (https=) |
| CN (1) | CN100513406C (https=) |
| AT (1) | ATE384720T1 (https=) |
| AU (1) | AU2003250322B2 (https=) |
| BR (1) | BR0313153A (https=) |
| CA (1) | CA2493245A1 (https=) |
| DE (1) | DE60318860T2 (https=) |
| IL (1) | IL166254A0 (https=) |
| IS (1) | IS7742A (https=) |
| MX (1) | MXPA05001702A (https=) |
| NO (1) | NO20051264L (https=) |
| NZ (1) | NZ538058A (https=) |
| PL (1) | PL375533A1 (https=) |
| RU (1) | RU2323217C2 (https=) |
| WO (1) | WO2004016608A1 (https=) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6262265A (ja) * | 1985-09-13 | 1987-03-18 | Hitachi Ltd | 復水器自動検査補修システム |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| GB0220581D0 (en) | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
| WO2004083388A2 (en) | 2003-03-14 | 2004-09-30 | Bristol-Myers Squibb Company | Polynucleotide encoding a novel human g-protein coupled receptor variant of hm74, hgprbmy74 |
| DE602004031124D1 (de) | 2003-08-13 | 2011-03-03 | Neurosearch As | Neue chinuklidinderivative und deren pharmazeutische verwendung |
| US20050137203A1 (en) * | 2003-12-22 | 2005-06-23 | Jianguo Ji | 3-quinuclidinyl amino-substituted biaryl derivatives |
| US7655657B2 (en) | 2003-12-22 | 2010-02-02 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US20050245531A1 (en) * | 2003-12-22 | 2005-11-03 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US7160876B2 (en) | 2003-12-22 | 2007-01-09 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US7241773B2 (en) | 2003-12-22 | 2007-07-10 | Abbott Laboratories | 3-quinuclidinyl heteroatom bridged biaryl derivatives |
| US20050137398A1 (en) * | 2003-12-22 | 2005-06-23 | Jianguo Ji | 3-Quinuclidinyl heteroatom bridged biaryl derivatives |
| US7309699B2 (en) | 2003-12-22 | 2007-12-18 | Abbott Laboratories | 3-Quinuclidinyl amino-substituted biaryl derivatives |
| EP1824848A1 (en) * | 2004-12-10 | 2007-08-29 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US7365193B2 (en) | 2004-02-04 | 2008-04-29 | Abbott Laboratories | Amino-substituted tricyclic derivatives and methods of use |
| US20050171079A1 (en) * | 2004-02-04 | 2005-08-04 | Schrimpf Michael R. | Amino-substituted tricyclic derivatives and methods of use |
| SE0400970D0 (sv) * | 2004-04-14 | 2004-04-14 | Astrazeneca Ab | Nicotinic acetylcholine receptor ligands |
| PE20060437A1 (es) | 2004-06-18 | 2006-06-08 | Novartis Ag | COMPUESTOS AZA-BICICLONONANOS COMO LIGANDOS COLINERGICOS DE nAChR |
| GB0415746D0 (en) * | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
| GB0424564D0 (en) | 2004-11-05 | 2004-12-08 | Novartis Ag | Organic compounds |
| RU2418797C2 (ru) * | 2004-12-22 | 2011-05-20 | Мемори Фармасьютиклз Корпорейшн | Лиганды никотинового рецептора альфа-7, их получение и применение |
| AU2006295397A1 (en) * | 2005-09-23 | 2007-04-05 | 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 |
| GB0525673D0 (en) * | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| GB0525672D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| FR2904002A1 (fr) * | 2006-07-19 | 2008-01-25 | Galderma Res & Dev S N C Snc | Modulateurs de la lanosterol synthetase dans le traitement de l'acne ou de l'hyperseborrhee |
| US8314119B2 (en) | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| 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 |
| US8383657B2 (en) | 2007-12-21 | 2013-02-26 | Abbott Laboratories | Thiazolylidine urea and amide derivatives and methods of use 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 |
| CN102573842A (zh) * | 2009-07-23 | 2012-07-11 | 诺瓦提斯公司 | 氮杂双环烷基衍生物或吡咯烷-2-酮衍生物的用途 |
| JO3250B1 (ar) | 2009-09-22 | 2018-09-16 | Novartis Ag | إستعمال منشطات مستقبل نيكوتينيك أسيتيل كولين ألفا 7 |
| AR081402A1 (es) | 2010-05-17 | 2012-08-29 | Envivo Pharmaceuticals Inc | Una forma cristalina de clorhidrato de (r)-7-cloro-n-(quinuclidin-3-il) benzo(b)tiofeno-2-carboxamida monohidrato |
| CN103180321A (zh) | 2010-09-23 | 2013-06-26 | Abbvie公司 | 氮杂金刚烷衍生物的一水合物 |
| US20120220729A1 (en) * | 2011-02-28 | 2012-08-30 | Boehringer Ingelheim International Gmbh | Liquid phase separation of plasmid dna isoforms and topoisomers |
| CA2872005A1 (en) | 2012-05-08 | 2013-11-14 | Forum Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
| BR112015016992A8 (pt) * | 2013-01-15 | 2018-01-23 | Novartis Ag | uso de agonistas do receptor alfa 7 nicotínico de acetilcolina |
| CN105263492B (zh) * | 2013-01-15 | 2018-04-10 | 诺华有限公司 | α7烟碱型乙酰胆碱受体激动剂在治疗发作性睡病中的应用 |
| US20150313884A1 (en) | 2013-01-15 | 2015-11-05 | Novartis Ag | Use of alpha 7 nicotinic acetylcholine receptor agonists |
| WO2016100184A1 (en) | 2014-12-16 | 2016-06-23 | Forum Pharmaceuticals, Inc. | Geminal substituted quinuclidine amide compounds as agonists of alpha-7 nicotinic acetylcholine receptors |
| MX2017016231A (es) | 2015-06-10 | 2018-11-29 | Axovant Sciences Gmbh | Compuestos de aminobencisoxazol como agonistas de receptores a7-nicotínicos de acetilcolina. |
| WO2017027600A1 (en) | 2015-08-12 | 2017-02-16 | Forum Pharmaceuticals, Inc. | GEMINAL SUBSTITUTED AMINOBENZISOXAZOLE COMPOUNDS AS AGONISTS OF α7-NICOTINIC ACETYLCHOLINE RECEPTORS |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3534053A (en) * | 1967-05-24 | 1970-10-13 | American Home Prod | Quinuclidine derivatives |
| SU495310A1 (ru) * | 1974-03-05 | 1975-12-15 | Всесоюзный Научно-Исследовательский Химико-Фармацевтический Институт Им.С.Орджоникидзе | Хинуклидил-3-диарал(гетерил) карбинолы, про вл ющие антигистаминную, антисеротониновую и антиаллергическую активность и способ их получени |
| DE3718317A1 (de) * | 1986-12-10 | 1988-06-16 | Bayer Ag | Substituierte basische 2-aminotetraline |
| CA1307790C (en) * | 1987-08-04 | 1992-09-22 | Ian Anthony Cliffe | Ethers |
| US5405853A (en) * | 1987-09-10 | 1995-04-11 | Merck Sharpe & Dohme Ltd. | Thiadiazoles useful in the treatment of senile dementia |
| JP2752143B2 (ja) * | 1988-04-01 | 1998-05-18 | 三共株式会社 | カルバペネム誘導体 |
| EP0363085A3 (en) * | 1988-10-03 | 1991-03-27 | Beecham Group Plc | Novel compounds |
| IT1227729B (it) * | 1988-12-23 | 1991-05-06 | Savio Spa | Procedimento e dispositivo per la rimozione delle fibre deteriorate durante il riattacco del filo in un filatoio open-end |
| YU84791A (sh) * | 1990-05-19 | 1994-06-10 | Boehringer Ingelheim Kg. | Biciklicni 1-aza-cikloalkalni |
| US5589477A (en) * | 1990-08-31 | 1996-12-31 | Nippon Shinyaku Company, Limited | Pyrimidine derivatives and drugs |
| ZA92278B (en) * | 1991-02-01 | 1992-10-28 | Akzo Nv | 3-quinuclidine derivatives |
| GB9201749D0 (en) * | 1992-01-28 | 1992-03-11 | Smithkline Beecham Plc | Medicaments |
| US5948793A (en) * | 1992-10-09 | 1999-09-07 | Abbott Laboratories | 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling neurotransmitter release |
| EP0758330A1 (en) * | 1994-05-06 | 1997-02-19 | Smithkline Beecham Plc | Biphenylcarboxamides useful as 5-ht1d antagonists |
| JPH0840999A (ja) * | 1994-08-04 | 1996-02-13 | Yamanouchi Pharmaceut Co Ltd | フルオロインダン誘導体 |
| US5998404A (en) * | 1994-10-24 | 1999-12-07 | Eli Lilly And Company | Heterocyclic compounds and their use |
| US5646289A (en) * | 1994-10-24 | 1997-07-08 | Eli Lilly And Company | Heterocyclic compounds and their preparation and use |
| JPH08134067A (ja) * | 1994-11-11 | 1996-05-28 | Yamanouchi Pharmaceut Co Ltd | キヌクリジン誘導体 |
| US5512574A (en) * | 1994-12-21 | 1996-04-30 | American Home Products Corporation | Quinuclidine and azabicyclo 2.2.1! heptane pyrazinyl ethers as muscarinic agonists |
| US5852037A (en) * | 1995-11-13 | 1998-12-22 | Eli Lilly And Company | Method for treating anxiety |
| JP2000500452A (ja) * | 1995-11-13 | 2000-01-18 | イーライ・リリー・アンド・カンパニー | 不安の処置法 |
| US5763457A (en) * | 1995-11-13 | 1998-06-09 | Eli Lilly And Company | Method for treating anxiety |
| FR2754261B1 (fr) * | 1996-10-08 | 1998-10-30 | Synthelabo | Derives de quinuclidine, leur preparation et leur application en therapeutique |
| WO1998027983A1 (en) * | 1996-12-20 | 1998-07-02 | Novo Nordisk A/S | A method of treating hypercholesterolemia and related disorders |
| HN1998000118A (es) * | 1997-08-27 | 1999-02-09 | Pfizer Prod Inc | 2 - aminopiridinas que contienen sustituyentes de anillos condensados. |
| FR2772378B1 (fr) * | 1997-12-12 | 2000-02-04 | Synthelabo | Derives d'imidazole, leur preparation et leur application en therapeutique |
| WO1999042461A1 (en) * | 1998-02-23 | 1999-08-26 | Warner-Lambert Company | Substituted quinoxaline derivatives as interleukin-8 receptor antagonists |
| 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 |
| US6884807B2 (en) * | 2000-12-01 | 2005-04-26 | Neurosearch, A/S | 3-substituted quinuclidines and their use as nicotinic agonists |
-
2003
- 2003-08-13 AU AU2003250322A patent/AU2003250322B2/en not_active Ceased
- 2003-08-13 WO PCT/DK2003/000538 patent/WO2004016608A1/en not_active Ceased
- 2003-08-13 RU RU2005101748/04A patent/RU2323217C2/ru not_active IP Right Cessation
- 2003-08-13 CA CA002493245A patent/CA2493245A1/en not_active Abandoned
- 2003-08-13 CN CNB038190788A patent/CN100513406C/zh not_active Expired - Fee Related
- 2003-08-13 US US10/522,150 patent/US20050245567A1/en not_active Abandoned
- 2003-08-13 JP JP2005502013A patent/JP2005538187A/ja active Pending
- 2003-08-13 DE DE60318860T patent/DE60318860T2/de not_active Expired - Lifetime
- 2003-08-13 AT AT03787742T patent/ATE384720T1/de not_active IP Right Cessation
- 2003-08-13 PL PL03375533A patent/PL375533A1/xx not_active Application Discontinuation
- 2003-08-13 MX MXPA05001702A patent/MXPA05001702A/es active IP Right Grant
- 2003-08-13 EP EP03787742A patent/EP1532144B1/en not_active Expired - Lifetime
- 2003-08-13 BR BR0313153-0A patent/BR0313153A/pt not_active IP Right Cessation
- 2003-08-13 NZ NZ538058A patent/NZ538058A/en not_active IP Right Cessation
- 2003-08-13 KR KR1020057002514A patent/KR20050055711A/ko not_active Ceased
- 2003-08-13 EP EP08100204A patent/EP1905771A3/en not_active Withdrawn
-
2005
- 2005-01-12 IL IL16625405A patent/IL166254A0/xx unknown
- 2005-03-11 NO NO20051264A patent/NO20051264L/no not_active Application Discontinuation
- 2005-03-14 IS IS7742A patent/IS7742A/is unknown
-
2008
- 2008-09-08 US US12/206,302 patent/US20090005390A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DE60318860D1 (de) | 2008-03-13 |
| AU2003250322A1 (en) | 2004-03-03 |
| JP2005538187A (ja) | 2005-12-15 |
| NZ538058A (en) | 2006-11-30 |
| CN1675205A (zh) | 2005-09-28 |
| WO2004016608A1 (en) | 2004-02-26 |
| EP1532144A1 (en) | 2005-05-25 |
| ATE384720T1 (de) | 2008-02-15 |
| EP1532144B1 (en) | 2008-01-23 |
| PL375533A1 (en) | 2005-11-28 |
| RU2005101748A (ru) | 2006-01-20 |
| US20090005390A1 (en) | 2009-01-01 |
| EP1905771A3 (en) | 2008-11-26 |
| BR0313153A (pt) | 2005-06-28 |
| KR20050055711A (ko) | 2005-06-13 |
| EP1905771A2 (en) | 2008-04-02 |
| IS7742A (is) | 2005-03-14 |
| NO20051264L (no) | 2005-05-18 |
| IL166254A0 (en) | 2006-01-15 |
| AU2003250322B2 (en) | 2010-01-21 |
| CN100513406C (zh) | 2009-07-15 |
| CA2493245A1 (en) | 2004-02-26 |
| MXPA05001702A (es) | 2005-04-19 |
| US20050245567A1 (en) | 2005-11-03 |
| RU2323217C2 (ru) | 2008-04-27 |
| HK1080860A1 (zh) | 2006-05-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8381 | Inventor (new situation) |
Inventor name: PETERS, DAN, 2750 BALLERUP, DK Inventor name: OLSEN, GUNNAR M., 2750 BALLERUP, DK Inventor name: NIELSEN, ELSEBET OSTERGAARD, 2750 BALLERUP, DK Inventor name: AHRING, PHILIP K., 2750 BALLERUP, DK Inventor name: JORGENSEN, TINO DYHRING, 2750 BALLERUP, DK |
|
| 8364 | No opposition during term of opposition |