AU2003273805B8 - 3-hydroxy-6-phenylphenanthridines as PDE-4 inhibitors - Google Patents
3-hydroxy-6-phenylphenanthridines as PDE-4 inhibitors Download PDFInfo
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- AU2003273805B8 AU2003273805B8 AU2003273805A AU2003273805A AU2003273805B8 AU 2003273805 B8 AU2003273805 B8 AU 2003273805B8 AU 2003273805 A AU2003273805 A AU 2003273805A AU 2003273805 A AU2003273805 A AU 2003273805A AU 2003273805 B8 AU2003273805 B8 AU 2003273805B8
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
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| PCT/EP2003/009601 WO2004019945A1 (en) | 2002-08-29 | 2003-08-29 | 3-hydroxy-6-phenylphenanthridines as pde-4 inhibitors |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999005112A1 (en) * | 1997-07-25 | 1999-02-04 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Substituted 6-alkylphenanthridines |
| WO1999057118A1 (de) * | 1998-05-05 | 1999-11-11 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue n-oxide |
| WO2002005616A1 (en) * | 2000-07-14 | 2002-01-24 | Altana Pharma Ag | Novel 6-phenylphenanthridines |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9027055D0 (en) | 1990-12-13 | 1991-02-06 | Sandoz Ltd | Organic compounds |
| UA48216C2 (uk) * | 1996-01-31 | 2002-08-15 | Бік Гулден Ломберг Кеміше Фабрік Гмбх | Фенантридини та лікарський засіб для лікування захворювань дихальних шляхів |
| WO1997035854A1 (de) | 1996-03-26 | 1997-10-02 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue in 6-position substituierte phenanthridine |
| US6127378A (en) * | 1996-03-26 | 2000-10-03 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phenanthridines substituted in the 6 position |
| DE69822162T2 (de) | 1997-07-25 | 2005-01-27 | Altana Pharma Ag | Neue tetrazolderivate |
| JP2001510827A (ja) | 1997-07-25 | 2001-08-07 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | 置換６−フェニルフェナントリジン |
| SI1147087T1 (en) | 1999-01-15 | 2005-10-31 | Altana Pharma Ag | Phenanthridine-n-oxides with pde-iv inhibiting activity |
| CA2360386A1 (en) | 1999-01-15 | 2000-07-20 | Beate Gutterer | Polysubstituted 6-phenylphenanthridines with pde-iv inhibiting activity |
| EP1650193A3 (en) * | 1999-01-15 | 2006-10-04 | ALTANA Pharma AG | 6-Phenylphenanthridines with PDE-IV inhibiting activity |
| ATE294793T1 (de) | 1999-01-15 | 2005-05-15 | Altana Pharma Ag | Phenantrhridin-n-oxides mit pde-iv hemmender wirkung |
| WO2000042019A1 (en) | 1999-01-15 | 2000-07-20 | Byk Gulden Lomberg Chemische Fabrik Gmbh | 6-arylphenanthridines with pde-iv inhibiting activity |
| CA2396026A1 (en) * | 2000-01-11 | 2001-07-19 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phenanthridine-n-oxides |
| PT1303506E (pt) | 2000-07-14 | 2005-06-30 | Altana Pharma Ag | 6-heteroarilfenantridinas |
| WO2002006238A1 (en) * | 2000-07-14 | 2002-01-24 | Altana Pharma Ag | Cycloalkyl - or cycloalkylmethyl-substituted 6-phenylphenanthridines |
| US6936622B2 (en) | 2001-02-21 | 2005-08-30 | Altana Pharma Ag | 6-phenylbenzonaphthyridines |
| AU2003253408A1 (en) | 2002-08-17 | 2004-03-11 | Nycomed Gmbh | Novel phenanthridines |
| CA2495827C (en) * | 2002-08-29 | 2012-05-08 | Altana Pharma Ag | 2-hydroxy-6-phenylphenanthridines as pde-4 inhibitors |
| AU2005212857B2 (en) | 2004-02-18 | 2011-04-28 | Takeda Gmbh | Novel guanidinyl-substituted hydroxy-6-phenylphenenthridines as effective phosphodiesterase (PDE) 4 inhibitors |
| AR049419A1 (es) | 2004-03-03 | 2006-08-02 | Altana Pharma Ag | Hidroxi-6-fenilfenantridinas sustituidas con heterociclilo |
| CN104803974A (zh) | 2004-03-03 | 2015-07-29 | 塔科达有限责任公司 | 新的羟基-6-杂芳基菲啶及其作为pde4抑制剂的用途 |
| JP2007527899A (ja) | 2004-03-09 | 2007-10-04 | アルタナ ファルマ アクチエンゲゼルシャフト | 新規のイソアミド置換されたヒドロキシ−６−フェニルフェナントリジン |
| CA2558390A1 (en) | 2004-03-10 | 2005-09-22 | Altana Pharma Ag | Novel thio-containing hydroxy-6-phenylphenanthridines and their use as pde4 inhibitors |
| JP2007527901A (ja) | 2004-03-10 | 2007-10-04 | アルタナ ファルマ アクチエンゲゼルシャフト | アミド置換された新規のヒドロキシ−６−フェニルフェナントリジン及びｐｄｅ４インヒビターとしてのそれらの使用 |
| EP1725532A1 (en) | 2004-03-10 | 2006-11-29 | Altana Pharma AG | Novel difluoroethoxy-substituted hydroxy-6-phenylphenanthridines and their use as pde4 inhibitors |
| ES2337083T3 (es) | 2005-03-02 | 2010-04-20 | Nycomed Gmbh | (2r,4ar,10br)-6-(2,6-dimetoxipiridin-3-il)-9-exoti-8-metoxi-1,2,3,4,4a,10b-hexahidrofenantridin-2-ol, sal de hc1. |
-
2003
- 2003-08-29 ES ES03757767T patent/ES2281658T3/es not_active Expired - Lifetime
- 2003-08-29 AU AU2003273805A patent/AU2003273805B8/en not_active Ceased
- 2003-08-29 US US10/524,820 patent/US7423046B2/en not_active Expired - Fee Related
- 2003-08-29 EP EP03757767A patent/EP1536798B1/en not_active Expired - Lifetime
- 2003-08-29 DE DE60311662T patent/DE60311662T2/de not_active Expired - Lifetime
- 2003-08-29 AT AT03757767T patent/ATE353217T1/de active
- 2003-08-29 WO PCT/EP2003/009601 patent/WO2004019945A1/en not_active Ceased
- 2003-08-29 JP JP2004532147A patent/JP4587295B2/ja not_active Expired - Fee Related
- 2003-08-29 CA CA2496459A patent/CA2496459C/en not_active Expired - Fee Related
-
2008
- 2008-08-27 US US12/230,301 patent/US8202880B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999005112A1 (en) * | 1997-07-25 | 1999-02-04 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Substituted 6-alkylphenanthridines |
| WO1999057118A1 (de) * | 1998-05-05 | 1999-11-11 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue n-oxide |
| WO2002005616A1 (en) * | 2000-07-14 | 2002-01-24 | Altana Pharma Ag | Novel 6-phenylphenanthridines |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2496459A1 (en) | 2004-03-11 |
| US7423046B2 (en) | 2008-09-09 |
| US8202880B2 (en) | 2012-06-19 |
| ATE353217T1 (de) | 2007-02-15 |
| JP2006508913A (ja) | 2006-03-16 |
| JP4587295B2 (ja) | 2010-11-24 |
| EP1536798A1 (en) | 2005-06-08 |
| ES2281658T3 (es) | 2007-10-01 |
| US20090170892A1 (en) | 2009-07-02 |
| US20050239818A1 (en) | 2005-10-27 |
| AU2003273805A1 (en) | 2004-03-19 |
| WO2004019945A1 (en) | 2004-03-11 |
| EP1536798B1 (en) | 2007-02-07 |
| CA2496459C (en) | 2013-06-25 |
| DE60311662T2 (de) | 2007-10-25 |
| AU2003273805B2 (en) | 2009-10-01 |
| DE60311662D1 (en) | 2007-03-22 |
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