JP2008528556A - 新規の６−ピリジルフェナントリジン - Google Patents
新規の６−ピリジルフェナントリジン Download PDFInfo
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- JP2008528556A JP2008528556A JP2007552659A JP2007552659A JP2008528556A JP 2008528556 A JP2008528556 A JP 2008528556A JP 2007552659 A JP2007552659 A JP 2007552659A JP 2007552659 A JP2007552659 A JP 2007552659A JP 2008528556 A JP2008528556 A JP 2008528556A
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- Prior art keywords
- alkoxy
- alkyl
- compounds
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- formula
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- JTKIQRJYVVHKRH-UHFFFAOYSA-N 6-pyridin-2-ylphenanthridine Chemical compound N1=CC=CC=C1C1=NC2=CC=CC=C2C2=CC=CC=C12 JTKIQRJYVVHKRH-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 167
- -1 compounds N-oxide Chemical class 0.000 claims description 92
- 150000003839 salts Chemical class 0.000 claims description 45
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 125000004076 pyridyl group Chemical group 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 31
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 30
- 150000001204 N-oxides Chemical class 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 229910052731 fluorine Inorganic materials 0.000 claims description 21
- 239000011737 fluorine Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 20
- 125000001153 fluoro group Chemical group F* 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical group 0.000 claims description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 208000023504 respiratory system disease Diseases 0.000 claims 2
- 230000006806 disease prevention Effects 0.000 claims 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 abstract description 5
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 abstract description 5
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 25
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 25
- 239000000203 mixture Substances 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 229910052740 iodine Inorganic materials 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 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 description 9
- 210000004027 cell Anatomy 0.000 description 9
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- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 7
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000000443 aerosol Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229940095074 cyclic amp Drugs 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 208000010668 atopic eczema Diseases 0.000 description 6
- 125000000468 ketone group Chemical group 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 150000002085 enols Chemical group 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000005022 packaging material Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000002821 scintillation proximity assay Methods 0.000 description 5
- SYJMYDMKPSZMSB-AATRIKPKSA-N 1,2-dimethoxy-4-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C=C1OC SYJMYDMKPSZMSB-AATRIKPKSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 230000000172 allergic effect Effects 0.000 description 4
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- 239000003814 drug Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
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- 238000002360 preparation method Methods 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 208000017520 skin disease Diseases 0.000 description 4
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- 239000006228 supernatant Substances 0.000 description 4
- CKUUWZSXSMTFIO-RYUDHWBXSA-N 1,2-dimethoxy-4-[(1s,2s)-2-nitrocyclohexyl]benzene Chemical compound C1=C(OC)C(OC)=CC=C1[C@H]1[C@@H]([N+]([O-])=O)CCCC1 CKUUWZSXSMTFIO-RYUDHWBXSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003431 cross linking reagent Substances 0.000 description 3
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- MKHGFJHFHNBMBC-NVXWUHKLSA-N n-[(1r,2r)-2-(3,4-dimethoxyphenyl)cyclohexyl]-2,6-dimethoxypyridine-3-carboxamide Chemical compound COC1=NC(OC)=CC=C1C(=O)N[C@H]1[C@@H](C=2C=C(OC)C(OC)=CC=2)CCCC1 MKHGFJHFHNBMBC-NVXWUHKLSA-N 0.000 description 3
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- PPQRENIHHPALGQ-VQIMIIECSA-N (4ar,10br)-9-ethoxy-6-(5-ethoxy-6-methoxypyridin-3-yl)-8-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridine Chemical compound N([C@@H]1CCCC[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C1=CN=C(OC)C(OCC)=C1 PPQRENIHHPALGQ-VQIMIIECSA-N 0.000 description 2
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- CKUUWZSXSMTFIO-VXGBXAGGSA-N 1,2-dimethoxy-4-[(1r,2r)-2-nitrocyclohexyl]benzene Chemical compound C1=C(OC)C(OC)=CC=C1[C@@H]1[C@H]([N+]([O-])=O)CCCC1 CKUUWZSXSMTFIO-VXGBXAGGSA-N 0.000 description 2
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
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- Chemical & Material Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
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- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05100690 | 2005-02-01 | ||
| PCT/EP2006/050557 WO2006082185A1 (en) | 2005-02-01 | 2006-01-31 | Novel 6-pyridylphenanthridines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008528556A true JP2008528556A (ja) | 2008-07-31 |
| JP2008528556A5 JP2008528556A5 (enExample) | 2009-03-19 |
Family
ID=34938616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007552659A Withdrawn JP2008528556A (ja) | 2005-02-01 | 2006-01-31 | 新規の６−ピリジルフェナントリジン |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20080119505A1 (enExample) |
| EP (1) | EP1846390B1 (enExample) |
| JP (1) | JP2008528556A (enExample) |
| AT (1) | ATE461189T1 (enExample) |
| AU (1) | AU2006210231A1 (enExample) |
| CA (1) | CA2595252A1 (enExample) |
| DE (1) | DE602006012938D1 (enExample) |
| EA (1) | EA200701626A1 (enExample) |
| ES (1) | ES2342728T3 (enExample) |
| WO (1) | WO2006082185A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR049419A1 (es) * | 2004-03-03 | 2006-08-02 | Altana Pharma Ag | Hidroxi-6-fenilfenantridinas sustituidas con heterociclilo |
| MXPA06009892A (es) * | 2004-03-10 | 2007-03-01 | Altana Pharma Ag | Nuevas hidroxi-6-fenilfenantridinas sustituidas con amido y su uso como inhibidores de la fosfodiesterasa tipo 4 (pde4). |
| WO2009109525A1 (en) * | 2008-03-03 | 2009-09-11 | Nycomed Gmbh | Use of a specific pde4 inhibitor for the treatment and/or prophylaxis of non-alcoholic fatty liver disease |
| US8987461B2 (en) | 2012-12-06 | 2015-03-24 | Quanticel Pharmaceuticals, Inc. | Histone demethylase inhibitors |
| CN108658778A (zh) * | 2018-06-19 | 2018-10-16 | 上海华堇生物技术有限责任公司 | 一种3,4-二甲氧基-β-硝基苯乙烯的新制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2250569C (en) | 1996-03-26 | 2005-05-10 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Novel phenanthridines substituted in the 6 position |
| PL2589599T4 (pl) | 2004-03-03 | 2015-06-30 | Takeda Gmbh | Nowe hydroksy-6-heteroarylofenantrydyny i ich zastosowanie jako inhibitorów PDE4 |
-
2006
- 2006-01-31 WO PCT/EP2006/050557 patent/WO2006082185A1/en not_active Ceased
- 2006-01-31 JP JP2007552659A patent/JP2008528556A/ja not_active Withdrawn
- 2006-01-31 EP EP06707926A patent/EP1846390B1/en not_active Expired - Lifetime
- 2006-01-31 AT AT06707926T patent/ATE461189T1/de not_active IP Right Cessation
- 2006-01-31 CA CA002595252A patent/CA2595252A1/en not_active Abandoned
- 2006-01-31 ES ES06707926T patent/ES2342728T3/es not_active Expired - Lifetime
- 2006-01-31 DE DE602006012938T patent/DE602006012938D1/de not_active Expired - Lifetime
- 2006-01-31 EA EA200701626A patent/EA200701626A1/ru unknown
- 2006-01-31 US US11/795,981 patent/US20080119505A1/en not_active Abandoned
- 2006-01-31 AU AU2006210231A patent/AU2006210231A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2006210231A1 (en) | 2006-08-10 |
| ATE461189T1 (de) | 2010-04-15 |
| CA2595252A1 (en) | 2006-08-10 |
| DE602006012938D1 (de) | 2010-04-29 |
| US20080119505A1 (en) | 2008-05-22 |
| EP1846390B1 (en) | 2010-03-17 |
| ES2342728T3 (es) | 2010-07-13 |
| WO2006082185A1 (en) | 2006-08-10 |
| EA200701626A1 (ru) | 2008-06-30 |
| EP1846390A1 (en) | 2007-10-24 |
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