NO320182B1 - Fenylfenantridiner med PDE-IV inhiberende aktivitet, legemidler omfattende dem samt anvendelse av forbindelsene. - Google Patents
Fenylfenantridiner med PDE-IV inhiberende aktivitet, legemidler omfattende dem samt anvendelse av forbindelsene. Download PDFInfo
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- NO320182B1 NO320182B1 NO20013341A NO20013341A NO320182B1 NO 320182 B1 NO320182 B1 NO 320182B1 NO 20013341 A NO20013341 A NO 20013341A NO 20013341 A NO20013341 A NO 20013341A NO 320182 B1 NO320182 B1 NO 320182B1
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- hydrogen
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- methoxy
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- 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
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- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
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- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
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- Neurology (AREA)
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- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
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- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Toxicology (AREA)
- Ophthalmology & Optometry (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Communicable Diseases (AREA)
- Transplantation (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99100694 | 1999-01-15 | ||
PCT/EP2000/000172 WO2000042020A1 (en) | 1999-01-15 | 2000-01-12 | Phenylphenanthridines with pde-iv inhibiting activity |
Publications (3)
Publication Number | Publication Date |
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NO20013341D0 NO20013341D0 (no) | 2001-07-05 |
NO20013341L NO20013341L (no) | 2001-09-17 |
NO320182B1 true NO320182B1 (no) | 2005-11-07 |
Family
ID=8237351
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20013341A NO320182B1 (no) | 1999-01-15 | 2001-07-05 | Fenylfenantridiner med PDE-IV inhiberende aktivitet, legemidler omfattende dem samt anvendelse av forbindelsene. |
Country Status (32)
Country | Link |
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US (1) | US6476025B1 (ru) |
EP (2) | EP1650193A3 (ru) |
JP (1) | JP4653314B2 (ru) |
KR (1) | KR100720906B1 (ru) |
CN (1) | CN1152864C (ru) |
AT (1) | ATE312081T1 (ru) |
AU (1) | AU774868B2 (ru) |
BG (1) | BG65126B1 (ru) |
BR (1) | BR0007527B1 (ru) |
CA (1) | CA2359440C (ru) |
CY (1) | CY1106436T1 (ru) |
CZ (1) | CZ300366B6 (ru) |
DE (1) | DE60024581T2 (ru) |
DK (1) | DK1147089T3 (ru) |
EA (1) | EA003780B1 (ru) |
EE (1) | EE05105B1 (ru) |
ES (1) | ES2254132T3 (ru) |
HK (1) | HK1040997B (ru) |
HR (1) | HRP20010578A2 (ru) |
HU (1) | HU227624B1 (ru) |
ID (1) | ID29070A (ru) |
IL (2) | IL144026A0 (ru) |
NO (1) | NO320182B1 (ru) |
NZ (1) | NZ512872A (ru) |
PL (1) | PL205670B1 (ru) |
RS (1) | RS50297B (ru) |
SI (1) | SI1147089T1 (ru) |
SK (1) | SK286946B6 (ru) |
TR (2) | TR200101938T2 (ru) |
UA (1) | UA69436C2 (ru) |
WO (1) | WO2000042020A1 (ru) |
ZA (1) | ZA200104864B (ru) |
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 |
AU2003253408A1 (en) * | 2002-08-17 | 2004-03-11 | Nycomed Gmbh | Novel phenanthridines |
DE60310576T2 (de) | 2002-08-29 | 2007-10-31 | Altana Pharma Ag | 2-hydroxy-6-phenylphenanthridine als pde-4-hemmer |
WO2004019945A1 (en) * | 2002-08-29 | 2004-03-11 | Altana Pharma Ag | 3-hydroxy-6-phenylphenanthridines as pde-4 inhibitors |
US6894061B2 (en) | 2002-12-04 | 2005-05-17 | Wyeth | Substituted dihydrophenanthridinesulfonamides |
JP2007500686A (ja) * | 2003-07-31 | 2007-01-18 | アルタナ ファルマ アクチエンゲゼルシャフト | 新規の6−フェニルフェナントリジン |
WO2005012252A1 (en) * | 2003-07-31 | 2005-02-10 | Altana Pharma Ag | Novel 6-phenylphenantridines |
US7776893B2 (en) | 2003-09-05 | 2010-08-17 | Nycomed Gmbh | Use of PDE4 inhibitors for the treatment of diabetes mellitus |
JP4728259B2 (ja) * | 2004-02-18 | 2011-07-20 | 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 | 効果的なホスホジエステラーゼ(pde)4インヒビターとしての新規のグアニジニル置換されたヒドロキシ−6−フェニルフェナントリジン |
AU2005219576B2 (en) | 2004-03-03 | 2011-06-30 | Takeda Gmbh | Novel hydroxy-6-heteroarylphenanthridines and their use as PDE4 inhibitors |
AR049419A1 (es) * | 2004-03-03 | 2006-08-02 | Altana Pharma Ag | Hidroxi-6-fenilfenantridinas sustituidas con heterociclilo |
WO2005084104A2 (en) * | 2004-03-09 | 2005-09-15 | Altana Pharma Ag | Novel isoamido-substituted hydroxy-6-phenylphenanthridines and their use as pde4 inhibitors |
BRPI0508471A8 (pt) * | 2004-03-10 | 2019-01-15 | Altana Pharma Ag | compostos de hidróxi-6-fenilfenantidinas substituídas por difluoroetóxi, composição farmacêutica e uso para a produção dos mesmos |
US20080161339A1 (en) * | 2004-03-10 | 2008-07-03 | Altana Pharma Ag | Novel Thio-Containing Hydroxy-6-Phenylphenanthridines and their Use as Pde4 Inhibitors |
US20070185149A1 (en) * | 2004-03-10 | 2007-08-09 | Altana Pharma Ag | Novel amido-substituted hydroxy-6-phenylphenanthridines and their use as pde4 inhibtors |
AU2005281703B2 (en) | 2004-09-08 | 2011-11-17 | Takeda Gmbh | Novel 3-thia-10-aza-phenanthrene derivatives |
US7411093B2 (en) * | 2004-12-20 | 2008-08-12 | Hoffman-La Roche Inc. | Aminocycloalkanes as DPP-IV inhibitors |
KR101352687B1 (ko) | 2005-03-02 | 2014-02-17 | 다케다 게엠베하 | 6-헤테로시클릴 치환된 헥사히드로페난트리딘 유도체의신규한 염 |
AU2006222060B2 (en) | 2005-03-08 | 2011-09-01 | Takeda Gmbh | Roflumilast for the treatment of diabetes mellitus |
EA200701813A1 (ru) * | 2005-03-09 | 2008-06-30 | Никомед Гмбх | Новые амидозамещенные 6-фенилфенантридины |
MX2010003155A (es) | 2007-10-04 | 2010-04-01 | Hoffmann La Roche | Derivados de ciclopropil aril amida y uso de los mismos. |
DK2794565T3 (da) | 2011-12-21 | 2017-11-13 | Novira Therapeutics Inc | Antivirale midler mod hepatitis b |
JOP20130256B1 (ar) | 2012-08-28 | 2021-08-17 | Janssenٍ Sciences Ireland Uc | مركبات سلفامويل اريل اميدات واستعمالها كمواد علاجية لمعالجة التهاب الكبد نوع بي |
AU2014222641B2 (en) | 2013-02-28 | 2018-03-15 | Janssen Sciences Ireland Uc | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of Hepatitis B |
DK2981536T3 (en) | 2013-04-03 | 2017-09-25 | Janssen Sciences Ireland Uc | N-PHENYLC CARBOXAMIDE DERIVATIVES AND THE USE THEREOF AS MEDICINES FOR THE TREATMENT OF HEPATITIS B |
JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
SI2997019T1 (sl) | 2013-05-17 | 2018-12-31 | Janssen Sciences Ireland Uc, | Derivati sulfamoiliofenamida in njihova uporaba kot zdravila za zdravljenje hepatitisa B |
ES2670571T3 (es) | 2013-07-25 | 2018-05-31 | Janssen Sciences Ireland Uc | Derivados de pirrolamida sustituidos con glioxamida y su uso como medicamentos para el tratamiento de la hepatitis B |
EP3060547B1 (en) | 2013-10-23 | 2017-10-11 | Janssen Sciences Ireland UC | Carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
JP6553059B2 (ja) | 2014-02-05 | 2019-07-31 | ノヴィラ・セラピューティクス・インコーポレイテッド | Hbv感染の治療のための併用療法 |
US11078193B2 (en) | 2014-02-06 | 2021-08-03 | Janssen Sciences Ireland Uc | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
WO2016149581A1 (en) | 2015-03-19 | 2016-09-22 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis b infections |
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 |
CA3000197A1 (en) | 2015-09-29 | 2017-04-06 | Novira Therapeutics, Inc. | Crystalline forms of a hepatitis b antiviral agent |
BR112018071048A2 (pt) | 2016-04-15 | 2019-05-07 | Janssen Sciences Ireland Uc | combinações e métodos que compreendem um inibidor da montagem de capsídeos |
CA3090125A1 (en) | 2018-03-14 | 2019-09-19 | Janssen Sciences Ireland Unlimited Company | Capsid assembly modulator dosing regimen |
KR20210130753A (ko) | 2019-02-22 | 2021-11-01 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | Hbv 감염 또는 hbv-유발성 질환의 치료에 유용한 아미드 유도체 |
CN113795486A (zh) | 2019-05-06 | 2021-12-14 | 爱尔兰詹森科学公司 | 用于治疗hbv感染或hbv诱发的疾病的酰胺衍生物 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3899494A (en) * | 1970-05-13 | 1975-08-12 | Sandoz Ltd | Substituted 6-phenyl benzo-naphthyridines |
US6191138B1 (en) * | 1996-01-31 | 2001-02-20 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phenanthridines |
DK0889886T5 (da) * | 1996-03-26 | 2003-02-24 | Altana Pharma Ag | Hidtil ukendte, i 6-stilling substituerede phenanthridiner |
US6127378A (en) | 1996-03-26 | 2000-10-03 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phenanthridines substituted in the 6 position |
ES2195189T3 (es) * | 1996-11-11 | 2003-12-01 | Altana Pharma Ag | Benzonaftiridinas como agentes terapeuticos bronquiales. |
JP2001514640A (ja) | 1997-03-07 | 2001-09-11 | 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 | 新規のテトラゾール |
US6384047B1 (en) | 1997-06-03 | 2002-05-07 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Benzonaphthyridine |
AU753615B2 (en) * | 1997-07-25 | 2002-10-24 | Altana Pharma Ag | Novel tetrazole derivatives |
WO1999005113A1 (en) * | 1997-07-25 | 1999-02-04 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Substituted 6-phenylphenanthridines |
DE60019894T2 (de) * | 1999-01-15 | 2006-01-12 | Altana Pharma Ag | Phenantrhridin-n-oxides mit pde-iv hemmender wirkung |
AU2107700A (en) * | 1999-01-15 | 2000-08-01 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phenanthridine-n-oxides with pde-iv inhibiting activity |
CA2359416A1 (en) * | 1999-01-15 | 2000-07-20 | Beate Gutterer | 6-arylphenanthridines with pde-iv inhibiting activity |
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2000
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- 2000-01-12 WO PCT/EP2000/000172 patent/WO2000042020A1/en not_active Application Discontinuation
- 2000-01-12 KR KR1020017008670A patent/KR100720906B1/ko not_active IP Right Cessation
- 2000-01-12 TR TR2001/01938T patent/TR200101938T2/xx unknown
- 2000-01-12 EE EEP200100350A patent/EE05105B1/xx not_active IP Right Cessation
- 2000-01-12 US US09/889,144 patent/US6476025B1/en not_active Expired - Lifetime
- 2000-01-12 DE DE60024581T patent/DE60024581T2/de not_active Expired - Lifetime
- 2000-01-12 IL IL14402600A patent/IL144026A0/xx active IP Right Grant
- 2000-01-12 EA EA200100731A patent/EA003780B1/ru not_active IP Right Cessation
- 2000-01-12 BR BRPI0007527-2A patent/BR0007527B1/pt not_active IP Right Cessation
- 2000-01-12 TR TR2005/01553T patent/TR200501553T2/xx unknown
- 2000-01-12 ID IDW00200101411A patent/ID29070A/id unknown
- 2000-01-12 AT AT00901534T patent/ATE312081T1/de active
- 2000-01-12 EP EP05108689A patent/EP1650193A3/en not_active Withdrawn
- 2000-01-12 ES ES00901534T patent/ES2254132T3/es not_active Expired - Lifetime
- 2000-01-12 CA CA002359440A patent/CA2359440C/en not_active Expired - Fee Related
- 2000-01-12 SI SI200030806T patent/SI1147089T1/sl unknown
- 2000-01-12 CZ CZ20012248A patent/CZ300366B6/cs not_active IP Right Cessation
- 2000-01-12 EP EP00901534A patent/EP1147089B1/en not_active Expired - Lifetime
- 2000-01-12 SK SK980-2001A patent/SK286946B6/sk not_active IP Right Cessation
- 2000-01-12 JP JP2000593588A patent/JP4653314B2/ja not_active Expired - Fee Related
- 2000-01-12 HU HU0105001A patent/HU227624B1/hu not_active IP Right Cessation
- 2000-01-12 RS YUP-487/01A patent/RS50297B/sr unknown
- 2000-01-12 AU AU22896/00A patent/AU774868B2/en not_active Ceased
- 2000-01-12 NZ NZ512872A patent/NZ512872A/en not_active IP Right Cessation
- 2000-01-12 DK DK00901534T patent/DK1147089T3/da active
- 2000-01-12 CN CNB008027951A patent/CN1152864C/zh not_active Expired - Fee Related
- 2000-12-01 UA UA2001085778A patent/UA69436C2/ru unknown
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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
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2002
- 2002-04-10 HK HK02102714.9A patent/HK1040997B/zh not_active IP Right Cessation
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2006
- 2006-02-14 CY CY20061100209T patent/CY1106436T1/el unknown
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