JP2005524713A - 新規ジアザビシクロビアリール誘導体 - Google Patents
新規ジアザビシクロビアリール誘導体 Download PDFInfo
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- JP2005524713A JP2005524713A JP2004502920A JP2004502920A JP2005524713A JP 2005524713 A JP2005524713 A JP 2005524713A JP 2004502920 A JP2004502920 A JP 2004502920A JP 2004502920 A JP2004502920 A JP 2004502920A JP 2005524713 A JP2005524713 A JP 2005524713A
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- alkyl
- diazabicyclobiaryl
- monocyclic heterocyclic
- aromatic monocyclic
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| DKPA200200692 | 2002-05-07 | ||
| DKPA200201739 | 2002-11-11 | ||
| PCT/DK2003/000295 WO2003094831A2 (en) | 2002-05-07 | 2003-05-06 | Novel diazabicyclic biaryl derivatives |
Publications (2)
| Publication Number | Publication Date |
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| JP2005524713A true JP2005524713A (ja) | 2005-08-18 |
| JP2005524713A5 JP2005524713A5 (enExample) | 2006-06-15 |
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| JP2004502920A Pending JP2005524713A (ja) | 2002-05-07 | 2003-05-06 | 新規ジアザビシクロビアリール誘導体 |
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| EP (1) | EP1506200B1 (enExample) |
| JP (1) | JP2005524713A (enExample) |
| CN (1) | CN1653068A (enExample) |
| AT (1) | ATE348831T1 (enExample) |
| AU (1) | AU2003223927B2 (enExample) |
| CA (1) | CA2480488A1 (enExample) |
| DE (1) | DE60310548T2 (enExample) |
| DK (1) | DK1506200T3 (enExample) |
| MX (1) | MXPA04010966A (enExample) |
| NZ (1) | NZ535642A (enExample) |
| WO (1) | WO2003094831A2 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007521323A (ja) * | 2003-09-19 | 2007-08-02 | アボット・ラボラトリーズ | α７ニコチン性アセチルコリン受容体でのリガンドとしての置換ジアザビシクロアルカン誘導体 |
| US20160028110A1 (en) * | 2013-10-29 | 2016-01-28 | Lg Chem, Ltd. | Gel polymer electrolyte and lithium secondary battery comprising the same |
| JP2016505051A (ja) * | 2013-01-23 | 2016-02-18 | ノバルティス アーゲー | そのチアジアゾール類似体およびｓｍｎ欠損に関連する状態を処置するための方法 |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| US7399765B2 (en) | 2003-09-19 | 2008-07-15 | Abbott Laboratories | Substituted diazabicycloalkane derivatives |
| TW200534855A (en) * | 2004-01-13 | 2005-11-01 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| US7582631B2 (en) | 2004-01-14 | 2009-09-01 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| JP2007528420A (ja) * | 2004-03-11 | 2007-10-11 | グラクソ グループ リミテッド | 新規ｍ３ムスカリン性アセチルコリン受容体アンタゴニスト |
| JP2007529511A (ja) * | 2004-03-17 | 2007-10-25 | グラクソ グループ リミテッド | Ｍ３ムスカリン性アセチルコリン受容体アンタゴニスト |
| AU2005295441B2 (en) | 2004-10-18 | 2009-04-23 | Amgen, Inc. | Thiadiazole compounds and methods of use |
| JP2008530172A (ja) * | 2005-02-16 | 2008-08-07 | ノイロサーチ アクティーゼルスカブ | ジアザ二環系アリール誘導体及びそれらのニコチン様アセチルコリン受容体におけるコリン作動性リガンドとしての使用 |
| ATE495178T1 (de) | 2005-02-16 | 2011-01-15 | Neurosearch As | Diazabicyclische arylderivate und ihre verwendung als chinolinergische liganden an nikotin- acetylcholin-rezeptoren |
| EP1866314B1 (en) | 2005-02-16 | 2010-09-15 | NeuroSearch A/S | Novel diazabicyclic aryl derivatives and their medical use |
| US7897766B2 (en) * | 2005-09-23 | 2011-03-01 | Abbott Laboratories | Amino-aza-adamantane derivatives and methods of use |
| EP1963323B1 (en) * | 2005-12-06 | 2010-07-14 | Neurosearch A/S | Novel diazabicyclic aryl derivatives and their medical use |
| JO3019B1 (ar) | 2006-04-19 | 2016-09-05 | Janssen Pharmaceutica Nv | ثلاثي مستبدل 4،2،1-ثلاثي زولات |
| US8314119B2 (en) | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| US7897619B2 (en) | 2007-07-17 | 2011-03-01 | Amgen Inc. | Heterocyclic modulators of PKB |
| AU2008276512A1 (en) | 2007-07-17 | 2009-01-22 | Amgen Inc. | Thiadiazole modulators of PKB |
| JO2784B1 (en) * | 2007-10-18 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | 5,3,1 - Triazole substitute derivative |
| JP2011500625A (ja) * | 2007-10-18 | 2011-01-06 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | トリ置換された１，２，４−トリアゾール |
| NZ587669A (en) | 2008-03-19 | 2011-07-29 | Janssen Pharmaceutica Nv | Trisubstituted 1, 2, 4 -triazoles as nicotinic acetylcholine receptor modulators |
| EP2280945B1 (en) | 2008-05-09 | 2014-09-03 | Janssen Pharmaceutica, N.V. | Trisubstituted pyrazoles as acetylcholine receptor modulators |
| BR112012013765A2 (pt) * | 2009-12-07 | 2016-04-26 | Targacept Inc | 3,6-diazabiciclo[3.1.1] heptanos como ligantes de receptor nicotínico neuronal de acetilcolina |
| CN103221411B (zh) | 2010-05-17 | 2016-05-11 | 富瑞姆制药公司 | (R)-7-氯-N-(奎宁环-3-基)苯并[b]噻吩-2-甲酰胺盐酸盐单水合物的晶型 |
| CN106074548A (zh) | 2010-09-23 | 2016-11-09 | 艾伯维巴哈马有限公司 | 氮杂金刚烷衍生物的一水合物 |
| AU2013259871A1 (en) | 2012-05-08 | 2014-11-20 | Forum Pharmaceuticals Inc. | Methods of maintaining, treating or improving cognitive function |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000034284A1 (fr) * | 1998-12-04 | 2000-06-15 | Sanofi-Synthelabo | Derives de 2,5-diazabicyclo[2.2.1]heptane, leur preparation et leur application en therapeutique |
| WO2001090109A1 (en) * | 2000-05-25 | 2001-11-29 | Targacept, Inc. | Heteroaryldiazabicycloalkanes as nicotinic cholinergic receptor ligands |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5478939A (en) * | 1994-07-20 | 1995-12-26 | American Cyanamid Company | (R,R) and (S,S) 2,5-diazabicyclo [2,2,1]heptane derivatives |
| DE60006213T2 (de) * | 1999-01-29 | 2004-07-29 | Abbott Laboratories, Abbott Park | Diazabicyloderivate als nikotin-acetylcholin-rezeptorliganden |
-
2003
- 2003-05-06 WO PCT/DK2003/000295 patent/WO2003094831A2/en not_active Ceased
- 2003-05-06 CN CNA03810198XA patent/CN1653068A/zh active Pending
- 2003-05-06 AU AU2003223927A patent/AU2003223927B2/en not_active Ceased
- 2003-05-06 NZ NZ535642A patent/NZ535642A/en not_active IP Right Cessation
- 2003-05-06 DE DE60310548T patent/DE60310548T2/de not_active Expired - Lifetime
- 2003-05-06 EP EP03720288A patent/EP1506200B1/en not_active Expired - Lifetime
- 2003-05-06 JP JP2004502920A patent/JP2005524713A/ja active Pending
- 2003-05-06 AT AT03720288T patent/ATE348831T1/de not_active IP Right Cessation
- 2003-05-06 DK DK03720288T patent/DK1506200T3/da active
- 2003-05-06 CA CA002480488A patent/CA2480488A1/en not_active Abandoned
- 2003-05-06 US US10/513,398 patent/US7300933B2/en not_active Expired - Fee Related
- 2003-05-06 MX MXPA04010966A patent/MXPA04010966A/es active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000034284A1 (fr) * | 1998-12-04 | 2000-06-15 | Sanofi-Synthelabo | Derives de 2,5-diazabicyclo[2.2.1]heptane, leur preparation et leur application en therapeutique |
| WO2001090109A1 (en) * | 2000-05-25 | 2001-11-29 | Targacept, Inc. | Heteroaryldiazabicycloalkanes as nicotinic cholinergic receptor ligands |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007521323A (ja) * | 2003-09-19 | 2007-08-02 | アボット・ラボラトリーズ | α７ニコチン性アセチルコリン受容体でのリガンドとしての置換ジアザビシクロアルカン誘導体 |
| JP2016505051A (ja) * | 2013-01-23 | 2016-02-18 | ノバルティス アーゲー | そのチアジアゾール類似体およびｓｍｎ欠損に関連する状態を処置するための方法 |
| US20160028110A1 (en) * | 2013-10-29 | 2016-01-28 | Lg Chem, Ltd. | Gel polymer electrolyte and lithium secondary battery comprising the same |
| US11121404B2 (en) * | 2013-10-29 | 2021-09-14 | Lg Chem, Ltd. | Gel polymer electrolyte and lithium secondary battery comprising the same |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1653068A (zh) | 2005-08-10 |
| EP1506200A2 (en) | 2005-02-16 |
| US7300933B2 (en) | 2007-11-27 |
| AU2003223927B2 (en) | 2009-12-17 |
| WO2003094831A2 (en) | 2003-11-20 |
| AU2003223927A1 (en) | 2003-11-11 |
| DK1506200T3 (da) | 2007-04-10 |
| MXPA04010966A (es) | 2005-01-25 |
| DE60310548T2 (de) | 2007-05-10 |
| DE60310548D1 (de) | 2007-02-01 |
| EP1506200B1 (en) | 2006-12-20 |
| US20050131236A1 (en) | 2005-06-16 |
| WO2003094831A3 (en) | 2004-01-15 |
| CA2480488A1 (en) | 2003-11-20 |
| ATE348831T1 (de) | 2007-01-15 |
| NZ535642A (en) | 2006-10-27 |
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