SK284295B6 - Derivát 4-(arylaminometylén)-2,4-dihydropyrazol-3-ónu, spôsob jeho prípravy a farmaceutický prostriedok, ktorý ho obsahuje - Google Patents
Derivát 4-(arylaminometylén)-2,4-dihydropyrazol-3-ónu, spôsob jeho prípravy a farmaceutický prostriedok, ktorý ho obsahuje Download PDFInfo
- Publication number
- SK284295B6 SK284295B6 SK589-96A SK58996A SK284295B6 SK 284295 B6 SK284295 B6 SK 284295B6 SK 58996 A SK58996 A SK 58996A SK 284295 B6 SK284295 B6 SK 284295B6
- Authority
- SK
- Slovakia
- Prior art keywords
- dihydro
- pyrazol
- oxo
- methyl
- ethylanilinomethylene
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000000034 method Methods 0.000 title claims description 15
- -1 C1-3alkoxybenzyl Chemical group 0.000 claims abstract description 111
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 17
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims abstract description 15
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims abstract description 11
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims abstract description 11
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 8
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
- 125000005499 phosphonyl group Chemical group 0.000 claims abstract description 5
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 78
- 150000001875 compounds Chemical class 0.000 claims description 72
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004494 ethyl ester group Chemical group 0.000 claims description 13
- 239000005711 Benzoic acid Substances 0.000 claims description 12
- 235000010233 benzoic acid Nutrition 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 8
- 206010019280 Heart failures Diseases 0.000 claims description 7
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000001448 anilines Chemical class 0.000 claims description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 6
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- CNWBKVZRUYOUCH-UHFFFAOYSA-N ethyl 2-[4-[(2-ethylanilino)methylidene]-1-[4-(methoxycarbonylamino)phenyl]-5-oxopyrazol-3-yl]acetate Chemical compound CCOC(=O)CC1=NN(C=2C=CC(NC(=O)OC)=CC=2)C(=O)C1=CNC1=CC=CC=C1CC CNWBKVZRUYOUCH-UHFFFAOYSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 4
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 4
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims description 4
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 3
- CWVBHDWXBKCALE-UHFFFAOYSA-N 4-[(2-ethoxyanilino)methylidene]-5-methyl-2-(4-morpholin-4-ylsulfonylphenyl)pyrazol-3-one Chemical compound CCOC1=CC=CC=C1NC=C1C(=O)N(C=2C=CC(=CC=2)S(=O)(=O)N2CCOCC2)N=C1C CWVBHDWXBKCALE-UHFFFAOYSA-N 0.000 claims description 3
- XOGHDUZPQVXXAZ-UHFFFAOYSA-N 4-[(2-ethylanilino)methylidene]-5-propyl-2-pyridin-4-ylpyrazol-3-one Chemical compound CCCC1=NN(C=2C=CN=CC=2)C(=O)C1=CNC1=CC=CC=C1CC XOGHDUZPQVXXAZ-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000000460 chlorine Chemical group 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 238000011065 in-situ storage Methods 0.000 claims description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- QIJCXMVWZZTGAX-UHFFFAOYSA-N 4-[4-[(2-ethoxyanilino)methylidene]-3-methyl-5-oxopyrazol-1-yl]-n-ethylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCC)=CC=C1N(N=C1C)C(=O)C1=CNC1=CC=CC=C1OCC QIJCXMVWZZTGAX-UHFFFAOYSA-N 0.000 claims description 2
- YARVSHFFVZFIIT-UHFFFAOYSA-N 4-[4-[(2-ethylanilino)methylidene]-5-oxo-3-propylpyrazol-1-yl]-n-hexylbenzamide Chemical compound C1=CC(C(=O)NCCCCCC)=CC=C1N(N=C1CCC)C(=O)C1=CNC1=CC=CC=C1CC YARVSHFFVZFIIT-UHFFFAOYSA-N 0.000 claims description 2
- XTKQOGSBBVWVFQ-UHFFFAOYSA-N 4-[4-[(2-ethylanilino)methylidene]-5-oxo-3-propylpyrazol-1-yl]benzoic acid Chemical compound CCCC1=NN(C=2C=CC(=CC=2)C(O)=O)C(=O)C1=CNC1=CC=CC=C1CC XTKQOGSBBVWVFQ-UHFFFAOYSA-N 0.000 claims description 2
- KKEUJVOCPOLZTF-UHFFFAOYSA-N C(C)NS(=O)(=O)C1(CC=CC=C1)N1N=C(C(C1=O)=CNC1=C(C=CC=C1)CC)C Chemical compound C(C)NS(=O)(=O)C1(CC=CC=C1)N1N=C(C(C1=O)=CNC1=C(C=CC=C1)CC)C KKEUJVOCPOLZTF-UHFFFAOYSA-N 0.000 claims description 2
- GMXPYIXAAJRBSC-UHFFFAOYSA-N CCC1=CC=CC=C1NC=C1C(CC(O)=O)=NN(C=2C=CC(NS(C)(=O)=O)=CC=2)C1=O Chemical compound CCC1=CC=CC=C1NC=C1C(CC(O)=O)=NN(C=2C=CC(NS(C)(=O)=O)=CC=2)C1=O GMXPYIXAAJRBSC-UHFFFAOYSA-N 0.000 claims description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 claims description 2
- VADXLEUTQISLCN-UHFFFAOYSA-N N1N=NN=C1C=1C=C(C=CC1)C=1C(N=NC1)=O Chemical compound N1N=NN=C1C=1C=C(C=CC1)C=1C(N=NC1)=O VADXLEUTQISLCN-UHFFFAOYSA-N 0.000 claims description 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- GFAUNYMRSKVDJL-UHFFFAOYSA-N formyl chloride Chemical compound ClC=O GFAUNYMRSKVDJL-UHFFFAOYSA-N 0.000 claims description 2
- 239000012948 isocyanate Substances 0.000 claims description 2
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- AMQXWOZFRGJOOB-UHFFFAOYSA-N 5-methyl-4-[(2-methylanilino)methylidene]-2-phenylpyrazol-3-one Chemical compound CC1=NN(C=2C=CC=CC=2)C(=O)C1=CNC1=CC=CC=C1C AMQXWOZFRGJOOB-UHFFFAOYSA-N 0.000 claims 4
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- DEIBXAPEZDJDRC-UHFFFAOYSA-M (dimethylaminomethylideneamino)methylidene-dimethylazanium;chloride Chemical compound [Cl-].CN(C)C=NC=[N+](C)C DEIBXAPEZDJDRC-UHFFFAOYSA-M 0.000 claims 1
- CAAFMABGGYVWES-UHFFFAOYSA-N 4-[(2-ethylanilino)methylidene]-5-methyl-2-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]pyrazol-3-one Chemical compound CCC1=CC=CC=C1NC=C1C(=O)N(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)N=C1C CAAFMABGGYVWES-UHFFFAOYSA-N 0.000 claims 1
- FCISBLOHCPTKJZ-UHFFFAOYSA-N 4-[3-methyl-5-oxo-4-[(2-prop-2-ynoxyanilino)methylidene]pyrazol-1-yl]benzoic acid Chemical compound CC1=NN(C=2C=CC(=CC=2)C(O)=O)C(=O)C1=CNC1=CC=CC=C1OCC#C FCISBLOHCPTKJZ-UHFFFAOYSA-N 0.000 claims 1
- AMJFQTMSUWYNPF-UHFFFAOYSA-N C(C)OC(CC1=NN(C(C1=CNC1=C(C=CC=C1)CC)=O)C1=CC=C(C=C1)[N+](=O)[O-])=O.C1(=CC=CC=C1)S(=O)(=O)O Chemical compound C(C)OC(CC1=NN(C(C1=CNC1=C(C=CC=C1)CC)=O)C1=CC=C(C=C1)[N+](=O)[O-])=O.C1(=CC=CC=C1)S(=O)(=O)O AMJFQTMSUWYNPF-UHFFFAOYSA-N 0.000 claims 1
- HMXUQKPHNSUJHA-UHFFFAOYSA-N COC1=C(NC=C2C(=NN(C2=O)C2C=CC(=CC2)S(=O)(=O)N)C)C=CC=C1 Chemical compound COC1=C(NC=C2C(=NN(C2=O)C2C=CC(=CC2)S(=O)(=O)N)C)C=CC=C1 HMXUQKPHNSUJHA-UHFFFAOYSA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 229940124639 Selective inhibitor Drugs 0.000 abstract description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
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- 208000015606 cardiovascular system disease Diseases 0.000 abstract 1
- MLPVBIWIRCKMJV-UHFFFAOYSA-N 2-ethylaniline Chemical compound CCC1=CC=CC=C1N MLPVBIWIRCKMJV-UHFFFAOYSA-N 0.000 description 49
- 238000006243 chemical reaction Methods 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
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- 239000000243 solution Substances 0.000 description 18
- 238000002844 melting Methods 0.000 description 17
- 230000008018 melting Effects 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
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- KQWWVLVLVYYYDT-UHFFFAOYSA-N ethyl 3-oxohexanoate Chemical compound CCCC(=O)CC(=O)OCC KQWWVLVLVYYYDT-UHFFFAOYSA-N 0.000 description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- VNXUPEPDMYVBQY-UHFFFAOYSA-N 2-(4-aminophenyl)-5-methyl-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C(N)C=C1 VNXUPEPDMYVBQY-UHFFFAOYSA-N 0.000 description 9
- PCNFLKVWBDNNOW-UHFFFAOYSA-N 4-hydrazinylbenzoic acid Chemical compound NNC1=CC=C(C(O)=O)C=C1 PCNFLKVWBDNNOW-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- ULHFFAFDSSHFDA-UHFFFAOYSA-N 1-amino-2-ethoxybenzene Chemical compound CCOC1=CC=CC=C1N ULHFFAFDSSHFDA-UHFFFAOYSA-N 0.000 description 7
- LCYJOUXSUHOSCW-UHFFFAOYSA-N 2-(3-aminophenyl)-5-methyl-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=CC(N)=C1 LCYJOUXSUHOSCW-UHFFFAOYSA-N 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 125000005605 benzo group Chemical group 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 4
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- HKCYNIJNRPAVGT-UHFFFAOYSA-N 4-[(2-ethylanilino)methylidene]-5-methyl-2-[3-(2h-tetrazol-5-yl)phenyl]pyrazol-3-one Chemical compound CCC1=CC=CC=C1NC=C1C(=O)N(C=2C=C(C=CC=2)C=2NN=NN=2)N=C1C HKCYNIJNRPAVGT-UHFFFAOYSA-N 0.000 description 3
- MYPAMGFTHVEING-UHFFFAOYSA-N 5-methyl-2-(4-nitrophenyl)-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C([N+]([O-])=O)C=C1 MYPAMGFTHVEING-UHFFFAOYSA-N 0.000 description 3
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- 239000005720 sucrose Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- C07D401/04—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Inks, Pencil-Leads, Or Crayons (AREA)
- Cosmetics (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Photoreceptors In Electrophotography (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19518082A DE19518082A1 (de) | 1995-05-17 | 1995-05-17 | 4(-Arylaminomethylen)-2,4-dihydropyrazol-3-one |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK58996A3 SK58996A3 (en) | 1996-12-04 |
| SK284295B6 true SK284295B6 (sk) | 2005-01-03 |
Family
ID=7762136
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK589-96A SK284295B6 (sk) | 1995-05-17 | 1996-05-09 | Derivát 4-(arylaminometylén)-2,4-dihydropyrazol-3-ónu, spôsob jeho prípravy a farmaceutický prostriedok, ktorý ho obsahuje |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US5869516A (cs) |
| EP (1) | EP0743304B1 (cs) |
| JP (1) | JP3996656B2 (cs) |
| KR (1) | KR100413154B1 (cs) |
| CN (1) | CN1066138C (cs) |
| AT (1) | ATE235469T1 (cs) |
| AU (1) | AU713042B2 (cs) |
| CA (1) | CA2176649C (cs) |
| CZ (1) | CZ291572B6 (cs) |
| DE (2) | DE19518082A1 (cs) |
| DK (1) | DK0743304T3 (cs) |
| ES (1) | ES2192588T3 (cs) |
| HU (1) | HUP9601328A3 (cs) |
| NO (1) | NO306777B1 (cs) |
| PL (1) | PL186049B1 (cs) |
| PT (1) | PT743304E (cs) |
| RU (1) | RU2180659C2 (cs) |
| SI (1) | SI0743304T1 (cs) |
| SK (1) | SK284295B6 (cs) |
| TW (1) | TW349093B (cs) |
| UA (1) | UA59330C2 (cs) |
| ZA (1) | ZA963918B (cs) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19518082A1 (de) * | 1995-05-17 | 1996-11-21 | Merck Patent Gmbh | 4(-Arylaminomethylen)-2,4-dihydropyrazol-3-one |
| DE19642284A1 (de) * | 1996-10-14 | 1998-04-16 | Merck Patent Gmbh | Pyrazolinone zur Behandlung von Potenzstörungen |
| US6331543B1 (en) | 1996-11-01 | 2001-12-18 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
| CA2238283C (en) | 1997-05-30 | 2002-08-20 | Cell Pathways, Inc. | Method for identifying compounds for inhibition of neoplastic lesions, pharmaceutical compositions from such compounds and uses of such compounds and compositions for treating neoplastic lesions |
| US5858694A (en) * | 1997-05-30 | 1999-01-12 | Cell Pathways, Inc. | Method for identifying compounds for inhibition of cancerous lesions |
| US6410584B1 (en) | 1998-01-14 | 2002-06-25 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells with indole derivatives |
| DE19807423A1 (de) * | 1998-02-21 | 1999-08-26 | Hoechst Marion Roussel De Gmbh | Subustituierte Isoindolone, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| US6294558B1 (en) | 1999-05-31 | 2001-09-25 | Pfizer Inc. | Sulfonylbenzene compounds as anti-inflammatory/analgesic agents |
| TNSN99111A1 (fr) * | 1998-06-11 | 2005-11-10 | Pfizer | Derives de sulfonylbenzene nouveaux, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| US6727238B2 (en) * | 1998-06-11 | 2004-04-27 | Pfizer Inc. | Sulfonylbenzene compounds as anti-inflammatory/analgesic agents |
| US6130053A (en) * | 1999-08-03 | 2000-10-10 | Cell Pathways, Inc. | Method for selecting compounds for inhibition of neoplastic lesions |
| US6200771B1 (en) | 1998-10-15 | 2001-03-13 | Cell Pathways, Inc. | Method of using a novel phosphodiesterase in pharmaceutical screeing to identify compounds for treatment of neoplasia |
| US6133271A (en) * | 1998-11-19 | 2000-10-17 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure thienopyrimidine derivatives |
| US6187779B1 (en) | 1998-11-20 | 2001-02-13 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to 2,8-disubstituted quinazoline derivatives |
| US6369092B1 (en) | 1998-11-23 | 2002-04-09 | Cell Pathways, Inc. | Method for treating neoplasia by exposure to substituted benzimidazole derivatives |
| US6486155B1 (en) | 1998-11-24 | 2002-11-26 | Cell Pathways Inc | Method of inhibiting neoplastic cells with isoquinoline derivatives |
| US6034099A (en) * | 1998-11-24 | 2000-03-07 | Cell Pathways, Inc. | Method for inhibiting neoplastic lesions by administering 4-(arylmethylene)- 2, 3- dihydro-pyrazol-3-ones |
| US6077842A (en) * | 1998-11-24 | 2000-06-20 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with pyrazolopyridylpyridazinone derivatives |
| US6025394A (en) | 1999-01-29 | 2000-02-15 | Cell Pathways, Inc. | Method for treating patients with acne by administering substituted sulfonyl indenyl acetic acids, amides and alcohols |
| US6020379A (en) * | 1999-02-19 | 2000-02-01 | Cell Pathways, Inc. | Position 7 substituted indenyl-3-acetic acid derivatives and amides thereof for the treatment of neoplasia |
| US6555547B1 (en) | 2000-02-28 | 2003-04-29 | Cell Pathways, Inc. | Method for treating a patient with neoplasia by treatment with a vinca alkaloid derivative |
| US6569638B1 (en) | 2000-03-03 | 2003-05-27 | Cell Pathways, Inc | Method for screening compounds for the treatment of neoplasia |
| CN1809559B (zh) * | 2003-04-18 | 2010-06-02 | 记忆药物公司 | 作为磷酸二酯酶4抑制剂的吡唑衍生物 |
| CN101166733A (zh) * | 2004-10-15 | 2008-04-23 | 记忆药物公司 | 作为磷酸二酯酶4抑制剂的吡唑衍生物 |
| EP1819692A1 (en) * | 2004-12-08 | 2007-08-22 | Nissan Chemical Industries, Ltd. | 3-ethylidenehydrazino substituted heterocyclic compounds as thrombopoietin receptor activators |
| CA2590204C (en) * | 2004-12-14 | 2012-12-04 | Nissan Chemical Industries, Ltd. | Amide compounds and thrombopoietin receptor activators |
| US8506934B2 (en) | 2005-04-29 | 2013-08-13 | Robert I. Henkin | Methods for detection of biological substances |
| US7678363B2 (en) | 2005-08-26 | 2010-03-16 | Braincells Inc | Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs |
| EP2258357A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| EP1819688A2 (en) * | 2005-10-12 | 2007-08-22 | Sicor, Inc. | Crystalline forms of docetaxel and processes for their preparation |
| US7985756B2 (en) | 2005-10-21 | 2011-07-26 | Braincells Inc. | Modulation of neurogenesis by PDE inhibition |
| EP2314289A1 (en) | 2005-10-31 | 2011-04-27 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| AU2006311577B2 (en) | 2005-11-09 | 2013-02-07 | Zalicus Inc. | Methods, compositions, and kits for the treatment of medical conditions |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| EP1991212A1 (en) * | 2006-03-08 | 2008-11-19 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| JP2009536669A (ja) | 2006-05-09 | 2009-10-15 | ブレインセルス，インコーポレイティド | アンジオテンシン調節による神経新生 |
| US20100009983A1 (en) * | 2006-05-09 | 2010-01-14 | Braincells, Inc. | 5 ht receptor mediated neurogenesis |
| CA2651862A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | 5 ht receptor mediated neurogenesis |
| BRPI0716604A2 (pt) * | 2006-09-08 | 2013-04-09 | Braincells Inc | combinaÇÕes contendo um derivado de 4-acilaminopiridina |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| US20080103165A1 (en) * | 2006-09-19 | 2008-05-01 | Braincells, Inc. | Ppar mediated modulation of neurogenesis |
| US8293489B2 (en) | 2007-01-31 | 2012-10-23 | Henkin Robert I | Methods for detection of biological substances |
| EP2002835A1 (en) * | 2007-06-04 | 2008-12-17 | GenKyo Tex | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2000176A1 (en) * | 2007-06-04 | 2008-12-10 | GenKyo Tex | Tetrahydroindole derivatives as NADPH Oxidase inhibitors |
| US8580801B2 (en) | 2008-07-23 | 2013-11-12 | Robert I. Henkin | Phosphodiesterase inhibitor treatment |
| EP2165707A1 (en) | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2166010A1 (en) | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2166008A1 (en) | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2166009A1 (en) * | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as nadph oxidase inhibitors |
| WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| EP2305679A1 (en) | 2009-09-28 | 2011-04-06 | GenKyoTex SA | Pyrazoline dione derivatives as nadph oxidase inhibitors |
| US20150119399A1 (en) | 2012-01-10 | 2015-04-30 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| EP2903619B1 (en) | 2012-10-05 | 2019-06-05 | Robert I. Henkin | Phosphodiesterase inhibitors for treating taste and smell disorders |
| BR112016017781A2 (pt) | 2014-02-14 | 2017-08-08 | Inception 2 Inc | Compostos de pirazolona e usos dos mesmos |
| WO2015126944A1 (en) | 2014-02-18 | 2015-08-27 | Henkin Robert I | Methods and compositions for diagnosing and treating loss and/or distortion of taste or smell |
| EP3479843A1 (en) | 2017-11-01 | 2019-05-08 | GenKyoTex Suisse SA | Use of nox inhibitors for treatment of cancer |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3905997A (en) * | 1974-06-21 | 1975-09-16 | Warner Lambert Co | 3-Aryl-5-oxo-2-pyrazoline-4-carboxanilides and process therefor |
| US4355159A (en) * | 1979-05-23 | 1982-10-19 | Ciba-Geigy Corporation | Nickel complex pigments of azines |
| US4666908A (en) * | 1985-04-05 | 1987-05-19 | Warner-Lambert Company | 5-Substituted pyrazolo[4,3-d]pyrimidine-7-ones and methods of use |
| DK169672B1 (da) * | 1985-05-20 | 1995-01-09 | Mitsubishi Chem Ind | Farmaceutiske præparater indeholdende pyrazolonderivater som aktiv bestanddel og anvendelsen af pyrazolonderivater til fremstilling af farmaceutiske præparater |
| US5162528A (en) * | 1986-12-17 | 1992-11-10 | Bayer Aktiengesellschaft | Herbicidal and fungicidal agents based on substituted pyrazolin-5-one derivatives |
| DE3728278A1 (de) * | 1986-12-17 | 1988-06-23 | Bayer Ag | Herbizide und fungizide mittel auf basis von substituierten pyrazolin-5-on derivaten |
| US4880804A (en) * | 1988-01-07 | 1989-11-14 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking benzimidazoles |
| GB9119704D0 (en) * | 1991-09-14 | 1991-10-30 | Pfizer Ltd | Therapeutic agents |
| DE4130833A1 (de) * | 1991-09-17 | 1993-03-18 | Bayer Ag | Diarylpyrazolinone |
| DE19518082A1 (de) * | 1995-05-17 | 1996-11-21 | Merck Patent Gmbh | 4(-Arylaminomethylen)-2,4-dihydropyrazol-3-one |
-
1995
- 1995-05-17 DE DE19518082A patent/DE19518082A1/de not_active Withdrawn
-
1996
- 1996-03-18 TW TW085103221A patent/TW349093B/zh active
- 1996-05-09 SK SK589-96A patent/SK284295B6/sk unknown
- 1996-05-10 SI SI9630609T patent/SI0743304T1/xx unknown
- 1996-05-10 DK DK96107518T patent/DK0743304T3/da active
- 1996-05-10 DE DE59610254T patent/DE59610254D1/de not_active Expired - Lifetime
- 1996-05-10 AT AT96107518T patent/ATE235469T1/de not_active IP Right Cessation
- 1996-05-10 PT PT96107518T patent/PT743304E/pt unknown
- 1996-05-10 ES ES96107518T patent/ES2192588T3/es not_active Expired - Lifetime
- 1996-05-10 EP EP96107518A patent/EP0743304B1/de not_active Expired - Lifetime
- 1996-05-13 AU AU52253/96A patent/AU713042B2/en not_active Ceased
- 1996-05-13 UA UA96051861A patent/UA59330C2/uk unknown
- 1996-05-15 CN CN96107453A patent/CN1066138C/zh not_active Expired - Fee Related
- 1996-05-15 NO NO961996A patent/NO306777B1/no not_active IP Right Cessation
- 1996-05-15 CA CA002176649A patent/CA2176649C/en not_active Expired - Fee Related
- 1996-05-16 US US08/648,951 patent/US5869516A/en not_active Expired - Lifetime
- 1996-05-16 CZ CZ19961421A patent/CZ291572B6/cs not_active IP Right Cessation
- 1996-05-16 ZA ZA963918A patent/ZA963918B/xx unknown
- 1996-05-16 KR KR1019960016421A patent/KR100413154B1/ko not_active Expired - Fee Related
- 1996-05-16 HU HU9601328A patent/HUP9601328A3/hu unknown
- 1996-05-16 RU RU96109192/04A patent/RU2180659C2/ru not_active IP Right Cessation
- 1996-05-16 PL PL96314286A patent/PL186049B1/pl not_active IP Right Cessation
- 1996-05-17 JP JP14644696A patent/JP3996656B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU713042B2 (en) | 1999-11-25 |
| SK58996A3 (en) | 1996-12-04 |
| ATE235469T1 (de) | 2003-04-15 |
| PL186049B1 (pl) | 2003-09-30 |
| KR960041166A (ko) | 1996-12-19 |
| US5869516A (en) | 1999-02-09 |
| CZ291572B6 (cs) | 2003-04-16 |
| CN1066138C (zh) | 2001-05-23 |
| HUP9601328A2 (en) | 1997-02-28 |
| HU9601328D0 (en) | 1996-07-29 |
| UA59330C2 (uk) | 2003-09-15 |
| ZA963918B (en) | 1996-11-25 |
| SI0743304T1 (en) | 2003-10-31 |
| DE59610254D1 (de) | 2003-04-30 |
| CA2176649C (en) | 2008-08-05 |
| EP0743304B1 (de) | 2003-03-26 |
| CN1141291A (zh) | 1997-01-29 |
| AU5225396A (en) | 1996-11-28 |
| CA2176649A1 (en) | 1996-11-18 |
| NO961996L (no) | 1996-11-18 |
| CZ142196A3 (en) | 1997-01-15 |
| KR100413154B1 (ko) | 2004-05-12 |
| NO961996D0 (no) | 1996-05-15 |
| PT743304E (pt) | 2003-08-29 |
| RU2180659C2 (ru) | 2002-03-20 |
| EP0743304A1 (de) | 1996-11-20 |
| PL314286A1 (en) | 1996-11-25 |
| HUP9601328A3 (en) | 1999-04-28 |
| JP3996656B2 (ja) | 2007-10-24 |
| ES2192588T3 (es) | 2003-10-16 |
| DE19518082A1 (de) | 1996-11-21 |
| DK0743304T3 (da) | 2003-07-14 |
| JPH08311035A (ja) | 1996-11-26 |
| TW349093B (en) | 1999-01-01 |
| NO306777B1 (no) | 1999-12-20 |
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