AU2005221832A1 - Novel amido-substituted hydroxy-6-phenylphenanthridines and their use as PDE4 inhibitors - Google Patents
Novel amido-substituted hydroxy-6-phenylphenanthridines and their use as PDE4 inhibitors Download PDFInfo
- Publication number
- AU2005221832A1 AU2005221832A1 AU2005221832A AU2005221832A AU2005221832A1 AU 2005221832 A1 AU2005221832 A1 AU 2005221832A1 AU 2005221832 A AU2005221832 A AU 2005221832A AU 2005221832 A AU2005221832 A AU 2005221832A AU 2005221832 A1 AU2005221832 A1 AU 2005221832A1
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- hydrogen
- methoxy
- hydroxy
- hexahydro
- 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.)
- Abandoned
Links
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title description 6
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 6
- ZCOWHHNEZZCOJZ-UHFFFAOYSA-N 6-phenylphenanthridin-1-ol Chemical class C=12C=CC=CC2=C2C(O)=CC=CC2=NC=1C1=CC=CC=C1 ZCOWHHNEZZCOJZ-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 366
- 229910052739 hydrogen Inorganic materials 0.000 claims description 275
- -1 2,2-difluoroethoxy Chemical group 0.000 claims description 272
- 239000001257 hydrogen Substances 0.000 claims description 270
- 229910052757 nitrogen Inorganic materials 0.000 claims description 179
- 150000002431 hydrogen Chemical class 0.000 claims description 166
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 127
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 122
- 150000003839 salts Chemical class 0.000 claims description 87
- 125000000623 heterocyclic group Chemical group 0.000 claims description 78
- 150000001204 N-oxides Chemical class 0.000 claims description 64
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 61
- 229910052760 oxygen Inorganic materials 0.000 claims description 61
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 60
- 239000001301 oxygen Substances 0.000 claims description 60
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 58
- 125000005842 heteroatom Chemical group 0.000 claims description 58
- 229910052717 sulfur Inorganic materials 0.000 claims description 58
- 239000011593 sulfur Substances 0.000 claims description 58
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 48
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- 125000004076 pyridyl group Chemical group 0.000 claims description 46
- 125000002757 morpholinyl group Chemical group 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 38
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 31
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 25
- VXVVBHZWCMDJPJ-KAYWLYCHSA-N n-[(3r,4r)-4-[[4-(2-hydroxy-5-piperidin-1-ylbenzoyl)benzoyl]amino]azepan-3-yl]pyridine-4-carboxamide Chemical compound N([C@@H]1CNCCC[C@H]1NC(=O)C1=CC=C(C=C1)C(=O)C1=CC(=CC=C1O)N1CCCCC1)C(=O)C1=CC=NC=C1 VXVVBHZWCMDJPJ-KAYWLYCHSA-N 0.000 claims description 24
- 101100070530 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) het-6 gene Proteins 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- YSNIPFQCRHRGSO-UHFFFAOYSA-N 5-[[6-chloro-5-[4-(2-hydroxyphenyl)phenyl]-1H-benzimidazol-2-yl]oxy]-N-hydroxy-2-methylbenzamide Chemical compound ClC=1C(=CC2=C(NC(=N2)OC=2C=CC(=C(C(=O)NO)C=2)C)C=1)C1=CC=C(C=C1)C1=C(C=CC=C1)O YSNIPFQCRHRGSO-UHFFFAOYSA-N 0.000 claims description 17
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- KCNKJCHARANTIP-SNAWJCMRSA-N allyl-{4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl}-methyl-amine Chemical compound C=1OC2=CC(OC/C=C/CN(CC=C)C)=CC=C2C=1C1=CC=C(Br)C=C1 KCNKJCHARANTIP-SNAWJCMRSA-N 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
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- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 9
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- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- GWRSATNRNFYMDI-UHFFFAOYSA-N 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound FC=1C=C(NC=2N=C3N(C4CCCC4)CC(F)(F)C(=O)N(C)C3=CN=2)C(OC)=CC=1C(=O)NC1CCN(C)CC1 GWRSATNRNFYMDI-UHFFFAOYSA-N 0.000 claims description 5
- MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- HHAZUISNXJLXHR-UHFFFAOYSA-N 2-morpholin-4-ylbenzamide Chemical compound NC(=O)C1=CC=CC=C1N1CCOCC1 HHAZUISNXJLXHR-UHFFFAOYSA-N 0.000 claims description 2
- GKYXLBMYLBGZBX-UHFFFAOYSA-N 4-(2-morpholin-4-ylethyl)piperazine-1-carbaldehyde Chemical compound C1CN(C=O)CCN1CCN1CCOCC1 GKYXLBMYLBGZBX-UHFFFAOYSA-N 0.000 claims description 2
- ZRTYTTTXTWFPBW-UHFFFAOYSA-N 4-pyridin-2-ylpiperazine-1-carbaldehyde Chemical compound C1CN(C=O)CCN1C1=CC=CC=N1 ZRTYTTTXTWFPBW-UHFFFAOYSA-N 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- LFHYTFLZVJJDAQ-UHFFFAOYSA-N 2-[4-[4-[9-(difluoromethoxy)-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl]benzoyl]piperazin-1-yl]-n,n-dimethylacetamide Chemical compound N=1C2CCC(O)CC2C=2C=C(OC(F)F)C(OC)=CC=2C=1C(C=C1)=CC=C1C(=O)N1CCN(CC(=O)N(C)C)CC1 LFHYTFLZVJJDAQ-UHFFFAOYSA-N 0.000 claims 1
- IMNDHOCGZLYMRO-UHFFFAOYSA-N n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1 IMNDHOCGZLYMRO-UHFFFAOYSA-N 0.000 claims 1
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- 208000023504 respiratory system disease Diseases 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 189
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
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- 150000003254 radicals Chemical class 0.000 description 33
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- 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
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04100990.3 | 2004-03-10 | ||
| EP04100990 | 2004-03-10 | ||
| EP04106677 | 2004-12-17 | ||
| EP04106677.0 | 2004-12-17 | ||
| PCT/EP2005/051054 WO2005087745A1 (en) | 2004-03-10 | 2005-03-09 | Novel amido-substituted hydroxy-6-phenylphenanthridines and their use as pde4 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2005221832A1 true AU2005221832A1 (en) | 2005-09-22 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2005221832A Abandoned AU2005221832A1 (en) | 2004-03-10 | 2005-03-09 | Novel amido-substituted hydroxy-6-phenylphenanthridines and their use as PDE4 inhibitors |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US20070185149A1 (https=) |
| EP (1) | EP1725534A1 (https=) |
| JP (1) | JP2007527901A (https=) |
| KR (1) | KR20060130697A (https=) |
| CN (1) | CN1926113B (https=) |
| AR (1) | AR049324A1 (https=) |
| AU (1) | AU2005221832A1 (https=) |
| BR (1) | BRPI0508481A (https=) |
| CA (1) | CA2558391A1 (https=) |
| IL (1) | IL177496A0 (https=) |
| MX (1) | MXPA06009892A (https=) |
| NO (1) | NO20064415L (https=) |
| NZ (1) | NZ549254A (https=) |
| TW (1) | TW200600499A (https=) |
| WO (1) | WO2005087745A1 (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| GB0316915D0 (en) | 2003-07-18 | 2003-08-20 | Glaxo Group Ltd | Compounds |
| CA2556086C (en) | 2004-02-18 | 2014-04-01 | Altana Pharma Ag | 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 |
| PL2589599T4 (pl) | 2004-03-03 | 2015-06-30 | Takeda Gmbh | Nowe hydroksy-6-heteroarylofenantrydyny i ich zastosowanie jako inhibitorów PDE4 |
| EP1791847A2 (en) | 2004-09-08 | 2007-06-06 | Altana Pharma AG | Novel 3-thia-10-aza-phenanthrene derivatives |
| ATE508130T1 (de) | 2004-09-08 | 2011-05-15 | Nycomed Gmbh | 3-oxa-10-aza-phenanthrene als pde4- oder pde3/4- inhibitoren |
| 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 |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| JP2010508315A (ja) | 2006-10-30 | 2010-03-18 | ノバルティス アーゲー | 抗炎症剤としてのヘテロ環式化合物 |
| ES2460897T3 (es) | 2007-10-04 | 2014-05-14 | F. Hoffmann-La Roche Ag | Derivados de ciclopropil aril amida y usos de los mismos |
| AU2009203693B2 (en) | 2008-01-11 | 2012-06-07 | Novartis Ag | Pyrimidines as kinase inhibitors |
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| MA34969B1 (fr) | 2011-02-25 | 2014-03-01 | Irm Llc | Composes et compositions en tant qu inibiteurs de trk |
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| DE69231395T3 (de) * | 1991-09-20 | 2005-07-21 | Glaxo Group Ltd., Greenford | Neue medizinische Indikation für Tachykinin-Antagonisten |
| BR9707233A (pt) * | 1996-01-31 | 1999-07-20 | Byk Gulden Lomberg Chem Fab | Fenantridinas |
| 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 |
| WO1999005112A1 (en) * | 1997-07-25 | 1999-02-04 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Substituted 6-alkylphenanthridines |
| 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 |
| PT998460E (pt) * | 1997-07-25 | 2004-07-30 | Altana Pharma Ag | Novos derivados de tetrazole |
| DK1075477T3 (da) * | 1998-05-05 | 2003-06-30 | Altana Pharma Ag | Nye benzonaphthyridin-N-oxider |
| ES2241571T3 (es) * | 1999-01-15 | 2005-11-01 | Altana Pharma Ag | N-oxidos de fenantrinida con actividad inhividora de pde-iv. |
| DE60020079T2 (de) * | 1999-01-15 | 2006-01-19 | Altana Pharma Ag | Phenanthridin-N-oxide mit PDE-IV-hemmender Wirkung |
| TR200501553T2 (tr) * | 1999-01-15 | 2005-06-21 | Altana Pharma Ag | PDE-IV inhibe edici aktivitesi olan fenilfenantridinler |
| ES2236288T3 (es) * | 2000-07-14 | 2005-07-16 | Altana Pharma Ag | 6-heteroarilfenantridinas. |
| US6936622B2 (en) * | 2001-02-21 | 2005-08-30 | Altana Pharma Ag | 6-phenylbenzonaphthyridines |
| 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 |
| US20060110819A1 (en) * | 2002-09-30 | 2006-05-25 | Lomas Lee O | Apparatus and method for expression and capture of biomolecules and complexes on adsorbent surfaces |
| 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 |
| WO2005085203A1 (en) * | 2004-03-10 | 2005-09-15 | Altana Pharma Ag | Novel difluoroethoxy-substituted hydroxy-6-phenylphenanthridines and their use as pde4 inhibitors |
| US20080119505A1 (en) * | 2005-02-01 | 2008-05-22 | Altana Pharma Ag | Novel 6-Pyridylphenanthridines |
| 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 |
| US20080167316A1 (en) * | 2005-03-02 | 2008-07-10 | Altana Pharma Ag | 6-Heteroaryl-1,2,3,4,4A, 10B-Hexahydrophenanthridines as Pde4-Inhibitors for the Treatment of Inflammatory Disorders |
| CA2599368A1 (en) * | 2005-03-09 | 2006-09-14 | Nycomed Gmbh | Amido-substituted 6-phenylphenanthridines |
-
2005
- 2005-03-09 EP EP05740073A patent/EP1725534A1/en not_active Withdrawn
- 2005-03-09 AU AU2005221832A patent/AU2005221832A1/en not_active Abandoned
- 2005-03-09 BR BRPI0508481-4A patent/BRPI0508481A/pt not_active IP Right Cessation
- 2005-03-09 CN CN2005800068554A patent/CN1926113B/zh not_active Expired - Fee Related
- 2005-03-09 US US10/591,480 patent/US20070185149A1/en not_active Abandoned
- 2005-03-09 MX MXPA06009892A patent/MXPA06009892A/es not_active Application Discontinuation
- 2005-03-09 JP JP2007502343A patent/JP2007527901A/ja not_active Withdrawn
- 2005-03-09 CA CA002558391A patent/CA2558391A1/en not_active Abandoned
- 2005-03-09 NZ NZ549254A patent/NZ549254A/en unknown
- 2005-03-09 KR KR1020067020318A patent/KR20060130697A/ko not_active Ceased
- 2005-03-09 WO PCT/EP2005/051054 patent/WO2005087745A1/en not_active Ceased
- 2005-03-10 TW TW094107344A patent/TW200600499A/zh unknown
- 2005-03-11 AR ARP050100931A patent/AR049324A1/es unknown
-
2006
- 2006-08-15 IL IL177496A patent/IL177496A0/en unknown
- 2006-09-29 NO NO20064415A patent/NO20064415L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005087745A1 (en) | 2005-09-22 |
| TW200600499A (en) | 2006-01-01 |
| CN1926113A (zh) | 2007-03-07 |
| WO2005087745A8 (en) | 2006-10-26 |
| MXPA06009892A (es) | 2007-03-01 |
| JP2007527901A (ja) | 2007-10-04 |
| BRPI0508481A (pt) | 2007-07-31 |
| NZ549254A (en) | 2010-06-25 |
| CA2558391A1 (en) | 2005-09-22 |
| NO20064415L (no) | 2006-10-10 |
| CN1926113B (zh) | 2010-06-23 |
| AR049324A1 (es) | 2006-07-19 |
| IL177496A0 (en) | 2006-12-10 |
| KR20060130697A (ko) | 2006-12-19 |
| US20070185149A1 (en) | 2007-08-09 |
| EP1725534A1 (en) | 2006-11-29 |
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| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |