JP2007527900A - チオ含有の新規のヒドロキシ−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 - Google Patents
チオ含有の新規のヒドロキシ−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 Download PDFInfo
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- JP2007527900A JP2007527900A JP2007502342A JP2007502342A JP2007527900A JP 2007527900 A JP2007527900 A JP 2007527900A JP 2007502342 A JP2007502342 A JP 2007502342A JP 2007502342 A JP2007502342 A JP 2007502342A JP 2007527900 A JP2007527900 A JP 2007527900A
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- Prior art keywords
- hydrogen
- alkyl
- methoxy
- phenyl
- 4ars
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- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title abstract description 5
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title abstract description 5
- 125000000446 sulfanediyl group Chemical group *S* 0.000 title description 3
- ZCOWHHNEZZCOJZ-UHFFFAOYSA-N 6-phenylphenanthridin-1-ol Chemical compound C=12C=CC=CC2=C2C(O)=CC=CC2=NC=1C1=CC=CC=C1 ZCOWHHNEZZCOJZ-UHFFFAOYSA-N 0.000 title description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 205
- 239000001257 hydrogen Substances 0.000 claims abstract description 205
- -1 2,2-difluoro-ethoxy Chemical group 0.000 claims abstract description 134
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 86
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 81
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 44
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 43
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 21
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 150000002367 halogens Chemical group 0.000 claims abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 367
- 150000003839 salts Chemical class 0.000 claims description 67
- 150000001204 N-oxides Chemical class 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 48
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 239000011737 fluorine Substances 0.000 claims description 14
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 10
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical group C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 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 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 229910052717 sulfur Chemical group 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
- LGHMEPPEZLGICK-XFQXTVEOSA-N (2r,4ar,10br)-9-ethoxy-8-methoxy-6-(4-methylsulfanylphenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-ol Chemical compound N([C@@H]1CC[C@@H](O)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C1=CC=C(SC)C=C1 LGHMEPPEZLGICK-XFQXTVEOSA-N 0.000 claims description 2
- TVBOYUWMRQNCKY-UHFFFAOYSA-N 4-(2-hydroxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl)-n,n-dipropylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(CCC)CCC)=CC=C1C(C1=CC(OC)=C(OC)C=C11)=NC2C1CC(O)CC2 TVBOYUWMRQNCKY-UHFFFAOYSA-N 0.000 claims description 2
- ZLNKCILVUPCDMK-UHFFFAOYSA-N 4-(9-ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl)-n-(2-methoxyethyl)-n-methylbenzenesulfonamide Chemical compound C1=2C=C(OC)C(OCC)=CC=2C2CC(O)CCC2N=C1C1=CC=C(S(=O)(=O)N(C)CCOC)C=C1 ZLNKCILVUPCDMK-UHFFFAOYSA-N 0.000 claims description 2
- FPZPVAPRNYQXEV-UHFFFAOYSA-N 4-fluoro-n-[4-(2-hydroxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl)phenyl]benzenesulfonamide Chemical compound C1=2C=C(OC)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(F)C=C1 FPZPVAPRNYQXEV-UHFFFAOYSA-N 0.000 claims description 2
- AIXUMCSAWMORJJ-UHFFFAOYSA-N 8,9-dimethoxy-6-(3-methylsulfonylphenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-ol Chemical compound C1=2C=C(OC)C(OC)=CC=2C2CC(O)CCC2N=C1C1=CC=CC(S(C)(=O)=O)=C1 AIXUMCSAWMORJJ-UHFFFAOYSA-N 0.000 claims description 2
- VEYGYIUBIIUIOO-UHFFFAOYSA-N 8-(difluoromethoxy)-9-methoxy-6-(3-morpholin-4-ylsulfonylphenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-ol Chemical compound C1=2C=C(OC(F)F)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=1)=CC=CC=1S(=O)(=O)N1CCOCC1 VEYGYIUBIIUIOO-UHFFFAOYSA-N 0.000 claims description 2
- FUNLWRBTQMXPDS-UHFFFAOYSA-N 8-(difluoromethoxy)-9-methoxy-6-(3-piperidin-1-ylsulfonylphenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-ol Chemical compound C1=2C=C(OC(F)F)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=1)=CC=CC=1S(=O)(=O)N1CCCCC1 FUNLWRBTQMXPDS-UHFFFAOYSA-N 0.000 claims description 2
- PUWZSYQMTRFIOS-UHFFFAOYSA-N 8-(difluoromethoxy)-9-methoxy-6-(3-pyrrolidin-1-ylsulfonylphenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-ol Chemical compound C1=2C=C(OC(F)F)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=1)=CC=CC=1S(=O)(=O)N1CCCC1 PUWZSYQMTRFIOS-UHFFFAOYSA-N 0.000 claims description 2
- KQFPMOUKQAALNS-UHFFFAOYSA-N 8-(difluoromethoxy)-9-methoxy-6-(4-pyrrolidin-1-ylsulfonylphenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-ol Chemical compound C1=2C=C(OC(F)F)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=C1)=CC=C1S(=O)(=O)N1CCCC1 KQFPMOUKQAALNS-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- NGYRGWAKJULXKZ-UHFFFAOYSA-N n-[4-(2-hydroxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl)-2-methylphenyl]-4-methylbenzenesulfonamide Chemical compound C1=2C=C(OC)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=C1C)=CC=C1NS(=O)(=O)C1=CC=C(C)C=C1 NGYRGWAKJULXKZ-UHFFFAOYSA-N 0.000 claims description 2
- WJALITREPKNFHM-UHFFFAOYSA-N n-[4-(2-hydroxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl)phenyl]-4-methylbenzenesulfonamide Chemical compound C1=2C=C(OC)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(C)C=C1 WJALITREPKNFHM-UHFFFAOYSA-N 0.000 claims description 2
- TZWQEFCHDOOVRJ-UHFFFAOYSA-N n-[4-(2-hydroxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl)phenyl]-n,4-dimethylbenzenesulfonamide Chemical compound C1=2C=C(OC)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=C1)=CC=C1N(C)S(=O)(=O)C1=CC=C(C)C=C1 TZWQEFCHDOOVRJ-UHFFFAOYSA-N 0.000 claims description 2
- OUBMTAUZCZAKCX-UHFFFAOYSA-N n-[4-[8-(difluoromethoxy)-2-hydroxy-9-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl]phenyl]-4-methylbenzenesulfonamide Chemical compound C1=2C=C(OC(F)F)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(C)C=C1 OUBMTAUZCZAKCX-UHFFFAOYSA-N 0.000 claims description 2
- JFEPOSTVNXVXMR-UHFFFAOYSA-N n-[4-[8-(difluoromethoxy)-2-hydroxy-9-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl]phenyl]methanesulfonamide Chemical compound C1=2C=C(OC(F)F)C(OC)=CC=2C2CC(O)CCC2N=C1C1=CC=C(NS(C)(=O)=O)C=C1 JFEPOSTVNXVXMR-UHFFFAOYSA-N 0.000 claims description 2
- ZMXXNGCADPTWAQ-UHFFFAOYSA-N n-[4-[9-(difluoromethoxy)-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl]phenyl]-4-methylbenzenesulfonamide Chemical compound N=1C2CCC(O)CC2C=2C=C(OC(F)F)C(OC)=CC=2C=1C(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(C)C=C1 ZMXXNGCADPTWAQ-UHFFFAOYSA-N 0.000 claims description 2
- WIQVBNVCSXRDET-UHFFFAOYSA-N n-[[4-(2-hydroxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl)phenyl]methyl]-4-methylbenzenesulfonamide Chemical compound C1=2C=C(OC)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=C1)=CC=C1CNS(=O)(=O)C1=CC=C(C)C=C1 WIQVBNVCSXRDET-UHFFFAOYSA-N 0.000 claims description 2
- QZZRXLYUGXDACT-UHFFFAOYSA-N n-[[4-[8-(difluoromethoxy)-2-hydroxy-9-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl]phenyl]methyl]-4-methylbenzenesulfonamide Chemical compound C1=2C=C(OC(F)F)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=C1)=CC=C1CNS(=O)(=O)C1=CC=C(C)C=C1 QZZRXLYUGXDACT-UHFFFAOYSA-N 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- 208000023504 respiratory system disease Diseases 0.000 claims 2
- YKYBWJPJPYUMMX-UHFFFAOYSA-N 4-[8-(difluoromethoxy)-2-hydroxy-9-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl]-n,n-dipropylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(CCC)CCC)=CC=C1C(C1=CC(OC(F)F)=C(OC)C=C11)=NC2C1CC(O)CC2 YKYBWJPJPYUMMX-UHFFFAOYSA-N 0.000 claims 1
- AAHXSKMTZNLLDS-UHFFFAOYSA-N 9-(2,2-difluoroethoxy)-8-methoxy-6-(3-methylsulfinylphenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-ol Chemical compound N=1C2CCC(O)CC2C=2C=C(OCC(F)F)C(OC)=CC=2C=1C1=CC=CC(S(C)=O)=C1 AAHXSKMTZNLLDS-UHFFFAOYSA-N 0.000 claims 1
- CTMIWKUQCCVGMQ-UHFFFAOYSA-N 9-(2,2-difluoroethoxy)-8-methoxy-6-(4-methylsulfanylphenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-ol Chemical compound N=1C2CCC(O)CC2C=2C=C(OCC(F)F)C(OC)=CC=2C=1C1=CC=C(SC)C=C1 CTMIWKUQCCVGMQ-UHFFFAOYSA-N 0.000 claims 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- LVRGSLAOKXFTHB-UHFFFAOYSA-N n-cyclopropyl-3-[8-(difluoromethoxy)-2-hydroxy-9-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl]benzenesulfonamide Chemical compound C1=2C=C(OC(F)F)C(OC)=CC=2C2CC(O)CCC2N=C1C(C=1)=CC=CC=1S(=O)(=O)NC1CC1 LVRGSLAOKXFTHB-UHFFFAOYSA-N 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 abstract description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- 239000002904 solvent Substances 0.000 description 29
- 239000000203 mixture Substances 0.000 description 27
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 25
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 229910052740 iodine Inorganic materials 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 229960000583 acetic acid Drugs 0.000 description 18
- 239000007858 starting material Substances 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 235000011054 acetic acid Nutrition 0.000 description 15
- 238000006722 reduction reaction Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- FHCWNNUEPYCSRE-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-4-nitrocyclohexan-1-ol Chemical compound C1=C(OC)C(OC)=CC=C1C1C([N+]([O-])=O)CCC(O)C1 FHCWNNUEPYCSRE-UHFFFAOYSA-N 0.000 description 8
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
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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
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
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- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- UZEIGZZNZFNRTK-UHFFFAOYSA-N [4-amino-3-(3,4-dimethoxyphenyl)cyclohexyl] acetate Chemical compound C1=C(OC)C(OC)=CC=C1C1C(N)CCC(OC(C)=O)C1 UZEIGZZNZFNRTK-UHFFFAOYSA-N 0.000 description 6
- 208000010668 atopic eczema Diseases 0.000 description 6
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- 125000006239 protecting group Chemical group 0.000 description 6
- 238000007363 ring formation reaction Methods 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
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- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
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- 239000003431 cross linking reagent Substances 0.000 description 5
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- 238000001035 drying Methods 0.000 description 5
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- 239000003112 inhibitor Substances 0.000 description 5
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 5
- 229940011051 isopropyl acetate Drugs 0.000 description 5
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- C07D221/12—Phenanthridines
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Landscapes
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Psychiatry (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04100988 | 2004-03-10 | ||
| EP05100692 | 2005-02-01 | ||
| PCT/EP2005/051052 WO2005087744A1 (en) | 2004-03-10 | 2005-03-09 | Novel thio-containing hydroxy-6-phenylphenanthridines and their use as pde4 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007527900A true JP2007527900A (ja) | 2007-10-04 |
| JP2007527900A5 JP2007527900A5 (https=) | 2008-04-24 |
Family
ID=34961402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007502342A Withdrawn JP2007527900A (ja) | 2004-03-10 | 2005-03-09 | チオ含有の新規のヒドロキシ−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 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20080161339A1 (https=) |
| EP (1) | EP1725533A1 (https=) |
| JP (1) | JP2007527900A (https=) |
| KR (1) | KR20060124783A (https=) |
| AR (1) | AR048001A1 (https=) |
| AU (1) | AU2005221831A1 (https=) |
| BR (1) | BRPI0508473A (https=) |
| CA (1) | CA2558390A1 (https=) |
| IL (1) | IL177499A0 (https=) |
| NO (1) | NO20064416L (https=) |
| TW (1) | TW200540159A (https=) |
| WO (1) | WO2005087744A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE353217T1 (de) | 2002-08-29 | 2007-02-15 | Altana Pharma Ag | 3-hydroxy-6-phenylphenanthridine als pde-4 inhibitoren |
| 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 |
| EP1725534A1 (en) * | 2004-03-10 | 2006-11-29 | Altana Pharma AG | Novel amido-substituted hydroxy-6-phenylphenanthridines and their use as pde4 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 |
| 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 |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| MA34969B1 (fr) | 2011-02-25 | 2014-03-01 | Irm Llc | Composes et compositions en tant qu inibiteurs de trk |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| SI0889886T1 (en) * | 1996-03-26 | 2003-02-28 | Altana Pharma Ag | Novel phenanthridines substituted in the 6 position |
| 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 |
| DK1075477T3 (da) * | 1998-05-05 | 2003-06-30 | Altana Pharma Ag | Nye benzonaphthyridin-N-oxider |
| TR200501553T2 (tr) * | 1999-01-15 | 2005-06-21 | Altana Pharma Ag | PDE-IV inhibe edici aktivitesi olan fenilfenantridinler |
| 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 |
-
2005
- 2005-03-09 CA CA002558390A patent/CA2558390A1/en not_active Abandoned
- 2005-03-09 KR KR1020067020591A patent/KR20060124783A/ko not_active Withdrawn
- 2005-03-09 AU AU2005221831A patent/AU2005221831A1/en not_active Abandoned
- 2005-03-09 JP JP2007502342A patent/JP2007527900A/ja not_active Withdrawn
- 2005-03-09 EP EP05716969A patent/EP1725533A1/en not_active Withdrawn
- 2005-03-09 US US10/591,768 patent/US20080161339A1/en not_active Abandoned
- 2005-03-09 WO PCT/EP2005/051052 patent/WO2005087744A1/en not_active Ceased
- 2005-03-09 BR BRPI0508473-3A patent/BRPI0508473A/pt not_active IP Right Cessation
- 2005-03-10 AR ARP050100916A patent/AR048001A1/es unknown
- 2005-03-10 TW TW094107371A patent/TW200540159A/zh unknown
-
2006
- 2006-08-15 IL IL177499A patent/IL177499A0/en unknown
- 2006-09-29 NO NO20064416A patent/NO20064416L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AR048001A1 (es) | 2006-03-15 |
| WO2005087744A8 (en) | 2006-10-26 |
| CA2558390A1 (en) | 2005-09-22 |
| EP1725533A1 (en) | 2006-11-29 |
| IL177499A0 (en) | 2006-12-10 |
| AU2005221831A1 (en) | 2005-09-22 |
| WO2005087744A1 (en) | 2005-09-22 |
| TW200540159A (en) | 2005-12-16 |
| BRPI0508473A (pt) | 2007-07-31 |
| NO20064416L (no) | 2006-12-07 |
| US20080161339A1 (en) | 2008-07-03 |
| KR20060124783A (ko) | 2006-12-05 |
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