AU774868B2 - Phenylphenanthridines with PDE-IV inhibiting activity - Google Patents
Phenylphenanthridines with PDE-IV inhibiting activity Download PDFInfo
- Publication number
- AU774868B2 AU774868B2 AU22896/00A AU2289600A AU774868B2 AU 774868 B2 AU774868 B2 AU 774868B2 AU 22896/00 A AU22896/00 A AU 22896/00A AU 2289600 A AU2289600 A AU 2289600A AU 774868 B2 AU774868 B2 AU 774868B2
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- Australia
- Prior art keywords
- hydrogen
- compounds
- formula
- phenyl
- salts
- 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.)
- Ceased
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- 230000002401 inhibitory effect Effects 0.000 title description 4
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- 150000001875 compounds Chemical class 0.000 claims abstract description 139
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- 150000003839 salts Chemical class 0.000 claims description 65
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
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- 229910052736 halogen Inorganic materials 0.000 claims description 27
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 22
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- 238000011282 treatment Methods 0.000 claims description 18
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 11
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- 239000007858 starting material Substances 0.000 claims description 7
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- 239000003112 inhibitor Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—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
- 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
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- General Health & Medical Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99100694 | 1999-01-15 | ||
| EP99100694 | 1999-01-15 | ||
| PCT/EP2000/000172 WO2000042020A1 (en) | 1999-01-15 | 2000-01-12 | Phenylphenanthridines with pde-iv inhibiting activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2289600A AU2289600A (en) | 2000-08-01 |
| AU774868B2 true AU774868B2 (en) | 2004-07-08 |
Family
ID=8237351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU22896/00A Ceased AU774868B2 (en) | 1999-01-15 | 2000-01-12 | Phenylphenanthridines with PDE-IV inhibiting activity |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US6476025B1 (https=) |
| EP (2) | EP1147089B1 (https=) |
| JP (1) | JP4653314B2 (https=) |
| KR (1) | KR100720906B1 (https=) |
| CN (1) | CN1152864C (https=) |
| AT (1) | ATE312081T1 (https=) |
| AU (1) | AU774868B2 (https=) |
| BG (1) | BG65126B1 (https=) |
| BR (1) | BR0007527B1 (https=) |
| CA (1) | CA2359440C (https=) |
| CY (1) | CY1106436T1 (https=) |
| CZ (1) | CZ300366B6 (https=) |
| DE (1) | DE60024581T2 (https=) |
| DK (1) | DK1147089T3 (https=) |
| EA (1) | EA003780B1 (https=) |
| EE (1) | EE05105B1 (https=) |
| ES (1) | ES2254132T3 (https=) |
| HK (1) | HK1040997B (https=) |
| HR (1) | HRP20010578A2 (https=) |
| HU (1) | HU227624B1 (https=) |
| ID (1) | ID29070A (https=) |
| IL (2) | IL144026A0 (https=) |
| NO (1) | NO320182B1 (https=) |
| NZ (1) | NZ512872A (https=) |
| PL (1) | PL205670B1 (https=) |
| RS (1) | RS50297B (https=) |
| SI (1) | SI1147089T1 (https=) |
| SK (1) | SK286946B6 (https=) |
| TR (2) | TR200501553T2 (https=) |
| UA (1) | UA69436C2 (https=) |
| WO (1) | WO2000042020A1 (https=) |
| ZA (1) | ZA200104864B (https=) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002006238A1 (en) * | 2000-07-14 | 2002-01-24 | Altana Pharma Ag | Cycloalkyl - or cycloalkylmethyl-substituted 6-phenylphenanthridines |
| CA2495597A1 (en) * | 2002-08-17 | 2004-03-04 | Altana Pharma Ag | Novel phenanthridines |
| JP4587294B2 (ja) | 2002-08-29 | 2010-11-24 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｐｄｅ４インヒビターとしての２−ヒドロキシ−６−フェニルフェナントリジン |
| ATE353217T1 (de) | 2002-08-29 | 2007-02-15 | Altana Pharma Ag | 3-hydroxy-6-phenylphenanthridine als pde-4 inhibitoren |
| US6894061B2 (en) | 2002-12-04 | 2005-05-17 | Wyeth | Substituted dihydrophenanthridinesulfonamides |
| CA2533636A1 (en) * | 2003-07-31 | 2005-02-10 | Altana Pharma Ag | Novel 6-phenylphenanthridines |
| EP1658270A1 (en) * | 2003-07-31 | 2006-05-24 | ALTANA Pharma AG | Novel 6-phenylphenantridines |
| JP2007504201A (ja) * | 2003-09-05 | 2007-03-01 | アルタナ ファルマ アクチエンゲゼルシャフト | 真性糖尿病の治療のためのｐｄｅ４阻害剤の使用 |
| CA2556086C (en) | 2004-02-18 | 2014-04-01 | Altana Pharma Ag | Novel guanidinyl-substituted hydroxy-6-phenylphenenthridines as effective phosphodiesterase (pde) 4 inhibitors |
| PL2589599T4 (pl) | 2004-03-03 | 2015-06-30 | Takeda Gmbh | Nowe hydroksy-6-heteroarylofenantrydyny i ich zastosowanie jako inhibitorów PDE4 |
| AR049419A1 (es) * | 2004-03-03 | 2006-08-02 | Altana Pharma Ag | Hidroxi-6-fenilfenantridinas sustituidas con heterociclilo |
| AU2005220034A1 (en) * | 2004-03-09 | 2005-09-15 | Nycomed Gmbh | Novel isoamido-substituted hydroxy-6-phenylphenanthridines and their use as PDE4 inhibitors |
| CA2558390A1 (en) * | 2004-03-10 | 2005-09-22 | Altana Pharma Ag | Novel thio-containing hydroxy-6-phenylphenanthridines and their use as pde4 inhibitors |
| EP1725534A1 (en) * | 2004-03-10 | 2006-11-29 | Altana Pharma AG | Novel amido-substituted hydroxy-6-phenylphenanthridines and their use as pde4 inhibitors |
| WO2005085203A1 (en) * | 2004-03-10 | 2005-09-15 | Altana Pharma Ag | Novel difluoroethoxy-substituted hydroxy-6-phenylphenanthridines and their use as pde4 inhibitors |
| EP1791847A2 (en) | 2004-09-08 | 2007-06-06 | Altana Pharma AG | Novel 3-thia-10-aza-phenanthrene derivatives |
| US7411093B2 (en) * | 2004-12-20 | 2008-08-12 | Hoffman-La Roche Inc. | Aminocycloalkanes as DPP-IV inhibitors |
| PL1856093T3 (pl) | 2005-03-02 | 2010-05-31 | Takeda Gmbh | Chlorowodorek (2R,4aR,10bR)-6-(2,6-dimetoksy-pirydyn-3-ylo)-9-etoksy-8-metoksy-1,2,3,4,4a,10b-heksahydrofenantrydyn-2-olu |
| EP1874308A1 (en) | 2005-03-08 | 2008-01-09 | Nycomed GmbH | Roflumilast for the treatment of diabetes mellitus |
| CA2599368A1 (en) * | 2005-03-09 | 2006-09-14 | Nycomed Gmbh | Amido-substituted 6-phenylphenanthridines |
| ES2460897T3 (es) | 2007-10-04 | 2014-05-14 | F. Hoffmann-La Roche Ag | Derivados de ciclopropil aril amida y usos de los mismos |
| BR112014015197A8 (pt) | 2011-12-21 | 2017-06-13 | Novira Therapeutics Inc | agentes antivirais de hepatite b |
| KR102271574B1 (ko) | 2012-08-28 | 2021-07-01 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 설파모일-아릴아미드 및 b형 간염 치료제로서의 그 용도 |
| WO2014131847A1 (en) | 2013-02-28 | 2014-09-04 | Janssen R&D Ireland | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b |
| MX353412B (es) | 2013-04-03 | 2018-01-10 | Janssen Sciences Ireland Uc | Derivados de n-fenil-carboxamida y su uso como medicamentos para el tratamiento de la hepatitis b. |
| DK2997019T3 (en) | 2013-05-17 | 2018-12-03 | Janssen Sciences Ireland Uc | SULFAMOYLTHIOPHENAMIDE DERIVATIVES AND USE THEREOF AS MEDICINES FOR TREATING HEPATITIS B |
| TWI733288B (zh) | 2013-05-17 | 2021-07-11 | 愛爾蘭商健生科學愛爾蘭無限公司 | 胺磺醯基吡咯醯胺衍生物及其作為用於治療ｂ型肝炎藥物的用途 |
| HRP20180791T1 (hr) | 2013-07-25 | 2018-09-07 | Janssen Sciences Ireland Uc | Glioksamid supstituirani derivati pirolamida i njihova uporaba kao lijekova za liječenje hepatitisa b |
| CA2923712C (en) | 2013-10-23 | 2021-11-02 | Janssen Sciences Ireland Uc | Carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
| US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| CA2936947A1 (en) | 2014-02-05 | 2015-08-13 | Novira Therapeutics, Inc. | Combination therapy for treatment of hbv infections |
| TW201620893A (zh) | 2014-02-06 | 2016-06-16 | 健生科學愛爾蘭無限公司 | 磺醯胺基吡咯醯胺衍生物及其用作治療ｂ型肝炎之醫藥品的用途 |
| JP2018510159A (ja) | 2015-03-19 | 2018-04-12 | ノヴィラ・セラピューティクス・インコーポレイテッド | アゾカン及びアゾナン誘導体及びｂ型肝炎感染症の治療法 |
| US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| TW201718496A (zh) | 2015-09-29 | 2017-06-01 | 諾維拉治療公司 | B型肝炎抗病毒劑之晶型 |
| AU2017248828A1 (en) | 2016-04-15 | 2018-11-01 | Janssen Sciences Ireland Uc | Combinations and methods comprising a capsid assembly inhibitor |
| MX2020009531A (es) | 2018-03-14 | 2020-10-05 | Janssen Sciences Ireland Unlimited Co | Regimen posologico del modulador del ensamblaje de la capside. |
| WO2020169784A1 (en) | 2019-02-22 | 2020-08-27 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of hbv infection or hbv-induced diseases |
| AR119732A1 (es) | 2019-05-06 | 2022-01-05 | Janssen Sciences Ireland Unlimited Co | Derivados de amida útiles en el tratamiento de la infección por vhb o de enfermedades inducidas por vhb |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997028131A1 (de) * | 1996-01-31 | 1997-08-07 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue phenanthridine |
| WO1997035854A1 (de) * | 1996-03-26 | 1997-10-02 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue in 6-position substituierte phenanthridine |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3899494A (en) | 1970-05-13 | 1975-08-12 | Sandoz Ltd | Substituted 6-phenyl benzo-naphthyridines |
| US6127378A (en) | 1996-03-26 | 2000-10-03 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phenanthridines substituted in the 6 position |
| PL189641B1 (pl) | 1996-11-11 | 2005-09-30 | Altana Pharma Ag | Benzonaftyrydyny, środki farmaceutyczne je zawierające oraz zastosowanie benzonaftyrydyn |
| SI0968211T1 (en) | 1997-03-07 | 2004-02-29 | Altana Pharma Ag | Tetrazole derivatives |
| ES2193539T3 (es) | 1997-06-03 | 2003-11-01 | Altana Pharma Ag | Benzonaftiridinas. |
| PT998460E (pt) | 1997-07-25 | 2004-07-30 | Altana Pharma Ag | Novos derivados de tetrazole |
| 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 |
| WO2000042019A1 (en) * | 1999-01-15 | 2000-07-20 | Byk Gulden Lomberg Chemische Fabrik Gmbh | 6-arylphenanthridines with pde-iv inhibiting activity |
| DE60020079T2 (de) * | 1999-01-15 | 2006-01-19 | Altana Pharma Ag | Phenanthridin-N-oxide mit PDE-IV-hemmender Wirkung |
| ES2241571T3 (es) * | 1999-01-15 | 2005-11-01 | Altana Pharma Ag | N-oxidos de fenantrinida con actividad inhividora de pde-iv. |
-
2000
- 2000-01-12 TR TR2005/01553T patent/TR200501553T2/xx unknown
- 2000-01-12 PL PL348925A patent/PL205670B1/pl unknown
- 2000-01-12 EP EP00901534A patent/EP1147089B1/en not_active Expired - Lifetime
- 2000-01-12 CA CA002359440A patent/CA2359440C/en not_active Expired - Fee Related
- 2000-01-12 IL IL14402600A patent/IL144026A0/xx active IP Right Grant
- 2000-01-12 US US09/889,144 patent/US6476025B1/en not_active Expired - Lifetime
- 2000-01-12 EA EA200100731A patent/EA003780B1/ru not_active IP Right Cessation
- 2000-01-12 HK HK02102714.9A patent/HK1040997B/en not_active IP Right Cessation
- 2000-01-12 HU HU0105001A patent/HU227624B1/hu not_active IP Right Cessation
- 2000-01-12 EE EEP200100350A patent/EE05105B1/xx not_active IP Right Cessation
- 2000-01-12 BR BRPI0007527-2A patent/BR0007527B1/pt not_active IP Right Cessation
- 2000-01-12 TR TR2001/01938T patent/TR200101938T2/xx unknown
- 2000-01-12 RS YUP-487/01A patent/RS50297B/sr unknown
- 2000-01-12 WO PCT/EP2000/000172 patent/WO2000042020A1/en not_active Ceased
- 2000-01-12 EP EP05108689A patent/EP1650193A3/en not_active Withdrawn
- 2000-01-12 DK DK00901534T patent/DK1147089T3/da active
- 2000-01-12 ES ES00901534T patent/ES2254132T3/es not_active Expired - Lifetime
- 2000-01-12 SK SK980-2001A patent/SK286946B6/sk not_active IP Right Cessation
- 2000-01-12 AU AU22896/00A patent/AU774868B2/en not_active Ceased
- 2000-01-12 JP JP2000593588A patent/JP4653314B2/ja not_active Expired - Fee Related
- 2000-01-12 HR HR20010578A patent/HRP20010578A2/hr not_active Application Discontinuation
- 2000-01-12 NZ NZ512872A patent/NZ512872A/en not_active IP Right Cessation
- 2000-01-12 DE DE60024581T patent/DE60024581T2/de not_active Expired - Lifetime
- 2000-01-12 SI SI200030806T patent/SI1147089T1/sl unknown
- 2000-01-12 CN CNB008027951A patent/CN1152864C/zh not_active Expired - Fee Related
- 2000-01-12 CZ CZ20012248A patent/CZ300366B6/cs not_active IP Right Cessation
- 2000-01-12 AT AT00901534T patent/ATE312081T1/de active
- 2000-01-12 ID IDW00200101411A patent/ID29070A/id unknown
- 2000-01-12 KR KR1020017008670A patent/KR100720906B1/ko not_active Expired - Fee Related
- 2000-12-01 UA UA2001085778A patent/UA69436C2/uk unknown
-
2001
- 2001-06-04 BG BG105561A patent/BG65126B1/bg unknown
- 2001-06-14 ZA ZA200104864A patent/ZA200104864B/en unknown
- 2001-06-27 IL IL144026A patent/IL144026A/en not_active IP Right Cessation
- 2001-07-05 NO NO20013341A patent/NO320182B1/no not_active IP Right Cessation
-
2006
- 2006-02-14 CY CY20061100209T patent/CY1106436T1/el unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997028131A1 (de) * | 1996-01-31 | 1997-08-07 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue phenanthridine |
| WO1997035854A1 (de) * | 1996-03-26 | 1997-10-02 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue in 6-position substituierte phenanthridine |
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Legal Events
| Date | Code | Title | Description |
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| MK6 | Application lapsed section 142(2)(f)/reg. 8.3(3) - pct applic. not entering national phase | ||
| TH | Corrigenda |
Free format text: IN VOL 14, NO 43, PAGE(S) 7730-7733 UNDER THE HEADING APPLICATIONS LAPSED, REFUSED OR WITHDRAWN PLEASE DELETE ALL REFERENCE TO APPLICATION NO. 22896/00 |
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| TC | Change of applicant's name (sec. 104) |
Owner name: ALTANA PHARMA AG Free format text: FORMER NAME: BYK GULDEN LOMBERG CHEMISCHE FABRIK GMBH |
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| FGA | Letters patent sealed or granted (standard patent) |