JP2005537312A - 新規のフェナントリジン - Google Patents
新規のフェナントリジン Download PDFInfo
- Publication number
- JP2005537312A JP2005537312A JP2004530135A JP2004530135A JP2005537312A JP 2005537312 A JP2005537312 A JP 2005537312A JP 2004530135 A JP2004530135 A JP 2004530135A JP 2004530135 A JP2004530135 A JP 2004530135A JP 2005537312 A JP2005537312 A JP 2005537312A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- hydrogen
- alkoxy
- group
- dimethyl
- 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.)
- Withdrawn
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- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 153
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims abstract description 6
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims abstract description 6
- -1 cyano, hydroxy Chemical group 0.000 claims description 418
- 229910052739 hydrogen Inorganic materials 0.000 claims description 150
- 239000001257 hydrogen Substances 0.000 claims description 150
- 150000002431 hydrogen Chemical group 0.000 claims description 82
- 229910052736 halogen Inorganic materials 0.000 claims description 57
- 150000002367 halogens Chemical group 0.000 claims description 57
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 52
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 30
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 30
- 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 30
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 18
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 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 14
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 14
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical group FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 12
- 150000001204 N-oxides Chemical class 0.000 claims description 11
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 11
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- JYNZIOFUHBJABQ-UHFFFAOYSA-N allyl-{6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl-}-methyl-amin Chemical compound C=1OC2=CC(OCCCCCCN(C)CC=C)=CC=C2C=1C1=CC=C(Br)C=C1 JYNZIOFUHBJABQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000004544 purin-8-yl group Chemical group N1=CN=C2N=C(NC2=C1)* 0.000 claims description 6
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 208000017520 skin disease Diseases 0.000 claims description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
- SDGKUVSVPIIUCF-UHFFFAOYSA-N 2,6-dimethylpiperidine Chemical compound CC1CCCC(C)N1 SDGKUVSVPIIUCF-UHFFFAOYSA-N 0.000 claims description 2
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- 208000023504 respiratory system disease Diseases 0.000 claims 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 17
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 238000005259 measurement Methods 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000000443 aerosol Substances 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- 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 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 6
- 208000010668 atopic eczema Diseases 0.000 description 6
- 229940095074 cyclic amp Drugs 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000005022 packaging material Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 0 CN(*)C(N(*)*)=N* Chemical compound CN(*)C(N(*)*)=N* 0.000 description 4
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical class OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-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
- 239000000706 filtrate Substances 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical class OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 238000006480 benzoylation reaction Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
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- 239000000843 powder Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
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- 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 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
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- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 101100135868 Dictyostelium discoideum pde3 gene Proteins 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 description 2
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- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
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- 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
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Landscapes
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- Chemical & Material Sciences (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02018530 | 2002-08-17 | ||
| PCT/EP2003/008967 WO2004018431A2 (en) | 2002-08-17 | 2003-08-13 | Novel phenanthridines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005537312A true JP2005537312A (ja) | 2005-12-08 |
| JP2005537312A5 JP2005537312A5 (https=) | 2006-10-12 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004530135A Withdrawn JP2005537312A (ja) | 2002-08-17 | 2003-08-13 | 新規のフェナントリジン |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20060116518A1 (https=) |
| EP (1) | EP1537086A2 (https=) |
| JP (1) | JP2005537312A (https=) |
| AU (1) | AU2003253408A1 (https=) |
| CA (1) | CA2495597A1 (https=) |
| HR (1) | HRP20050228A2 (https=) |
| IS (1) | IS7730A (https=) |
| PL (1) | PL374014A1 (https=) |
| RS (1) | RS20050116A (https=) |
| WO (1) | WO2004018431A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007523130A (ja) * | 2004-02-18 | 2007-08-16 | アルタナ ファルマ アクチエンゲゼルシャフト | 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 |
Families Citing this family (59)
| 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 |
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| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
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| GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
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| WO2007045477A2 (en) | 2005-10-21 | 2007-04-26 | Novartis Ag | Human antibodies against il-13 and therapeutic uses |
| GB0526244D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| PT2322525E (pt) | 2006-04-21 | 2013-12-26 | Novartis Ag | Derivados de purina para utilização como agonistas do recetor de adenosina a2a |
| WO2008037477A1 (en) | 2006-09-29 | 2008-04-03 | Novartis Ag | Pyrazolopyrimidines as p13k lipid kinase inhibitors |
| 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 |
| RS51644B (sr) | 2007-01-10 | 2011-10-31 | Irm Llc. | Jedinjenja i preparati kao inhibitori kanal aktivirajuće proteaze |
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| CL2008003651A1 (es) | 2007-12-10 | 2009-06-19 | Novartis Ag | Compuestos derivados de 3,5-diamino-6-cloropirazinamida sustituida; composicion farmaceutica; combinacion farmaceutica; y uso en el tratamiento de una condición inflamatoria o alergica, en particular una enfermedad inflamatoria u obstructiva de las vias respiratorias. |
| AU2009203693B2 (en) | 2008-01-11 | 2012-06-07 | Novartis Ag | Pyrimidines as kinase inhibitors |
| CA2727196A1 (en) | 2008-06-10 | 2009-12-17 | Novartis Ag | Organic compounds |
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| EA201200260A1 (ru) | 2009-08-12 | 2012-09-28 | Новартис Аг | Гетероциклические гидразоны и их применение для лечения рака и воспаления |
| NZ598220A (en) | 2009-08-17 | 2014-02-28 | Intellikine Llc | Heterocyclic compounds and uses thereof |
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| WO2012116237A2 (en) | 2011-02-23 | 2012-08-30 | Intellikine, Llc | Heterocyclic compounds and uses thereof |
| MA34969B1 (fr) | 2011-02-25 | 2014-03-01 | Irm Llc | Composes et compositions en tant qu inibiteurs de trk |
| US8883819B2 (en) | 2011-09-01 | 2014-11-11 | Irm Llc | Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension |
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| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
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| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
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| EP2968340A4 (en) | 2013-03-15 | 2016-08-10 | Intellikine Llc | COMBINING KINASE INHIBITORS AND USES THEREOF |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| US9862711B2 (en) | 2014-04-24 | 2018-01-09 | Novartis Ag | Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| CA2945212A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Amino pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| BR112016024484A2 (pt) | 2014-04-24 | 2017-08-15 | Novartis Ag | derivados de aminopiridina como inibidores de fosfatidilinositol 3-quinase |
| WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
| CA2954862A1 (en) | 2014-07-31 | 2016-02-04 | Novartis Ag | Combination therapy |
| WO2018069210A1 (en) | 2016-10-10 | 2018-04-19 | Takeda Gmbh | Tetrahydrofuro[3,4-c]isoquinolines as inhibitors of pde4 |
| 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 |
| AU2020290094B2 (en) | 2019-06-10 | 2024-01-18 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF, COPD, and bronchiectasis |
| AU2020338971B2 (en) | 2019-08-28 | 2023-11-23 | Novartis Ag | Substituted 1,3-phenyl heteroaryl derivatives and their use in the treatment of disease |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9027055D0 (en) * | 1990-12-13 | 1991-02-06 | Sandoz Ltd | Organic compounds |
| 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 |
| 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 |
| CA2360386A1 (en) * | 1999-01-15 | 2000-07-20 | Beate Gutterer | Polysubstituted 6-phenylphenanthridines with pde-iv inhibiting activity |
| TR200501553T2 (tr) * | 1999-01-15 | 2005-06-21 | Altana Pharma Ag | PDE-IV inhibe edici aktivitesi olan fenilfenantridinler |
| WO2000042019A1 (en) * | 1999-01-15 | 2000-07-20 | Byk Gulden Lomberg Chemische Fabrik Gmbh | 6-arylphenanthridines with pde-iv inhibiting activity |
| DE60125026T2 (de) * | 2000-03-23 | 2007-06-28 | Takeda Pharmaceutical Co. Ltd. | Fluorisochinolinderivate, verfahren zu ihrer herstellung und ihre anwendung |
| ES2236288T3 (es) * | 2000-07-14 | 2005-07-16 | Altana Pharma Ag | 6-heteroarilfenantridinas. |
| WO2002006238A1 (en) * | 2000-07-14 | 2002-01-24 | Altana Pharma Ag | Cycloalkyl - or cycloalkylmethyl-substituted 6-phenylphenanthridines |
| US6936622B2 (en) * | 2001-02-21 | 2005-08-30 | Altana Pharma Ag | 6-phenylbenzonaphthyridines |
| 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 |
| CA2556086C (en) * | 2004-02-18 | 2014-04-01 | Altana Pharma Ag | Novel guanidinyl-substituted hydroxy-6-phenylphenenthridines as effective phosphodiesterase (pde) 4 inhibitors |
-
2003
- 2003-08-13 CA CA002495597A patent/CA2495597A1/en not_active Abandoned
- 2003-08-13 US US10/524,634 patent/US20060116518A1/en not_active Abandoned
- 2003-08-13 PL PL03374014A patent/PL374014A1/xx not_active Application Discontinuation
- 2003-08-13 AU AU2003253408A patent/AU2003253408A1/en not_active Abandoned
- 2003-08-13 WO PCT/EP2003/008967 patent/WO2004018431A2/en not_active Ceased
- 2003-08-13 EP EP03792307A patent/EP1537086A2/en not_active Withdrawn
- 2003-08-13 RS YUP-2005/0116A patent/RS20050116A/sr unknown
- 2003-08-13 JP JP2004530135A patent/JP2005537312A/ja not_active Withdrawn
- 2003-08-13 HR HR20050228A patent/HRP20050228A2/xx not_active Application Discontinuation
-
2005
- 2005-03-08 IS IS7730A patent/IS7730A/is unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007523130A (ja) * | 2004-02-18 | 2007-08-16 | アルタナ ファルマ アクチエンゲゼルシャフト | 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| PL374014A1 (en) | 2005-09-19 |
| US20060116518A1 (en) | 2006-06-01 |
| WO2004018431A3 (en) | 2004-04-22 |
| IS7730A (is) | 2005-03-08 |
| AU2003253408A1 (en) | 2004-03-11 |
| WO2004018431A2 (en) | 2004-03-04 |
| CA2495597A1 (en) | 2004-03-04 |
| HRP20050228A2 (en) | 2006-07-31 |
| EP1537086A2 (en) | 2005-06-08 |
| RS20050116A (sr) | 2007-11-15 |
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