NO971674L - Pyrrolyl-tetrahydrobenzokinoksalin-dioner, deres fremstilling og anvendelse som glutamatreseptor-antagonister - Google Patents
Pyrrolyl-tetrahydrobenzokinoksalin-dioner, deres fremstilling og anvendelse som glutamatreseptor-antagonisterInfo
- Publication number
- NO971674L NO971674L NO971674A NO971674A NO971674L NO 971674 L NO971674 L NO 971674L NO 971674 A NO971674 A NO 971674A NO 971674 A NO971674 A NO 971674A NO 971674 L NO971674 L NO 971674L
- Authority
- NO
- Norway
- Prior art keywords
- mmol
- product
- alkyl
- phenyl
- hydrogen
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title abstract description 19
- -1 Pyrrolyl-tetrahydrobenzoquinoxaline ions Chemical class 0.000 title description 51
- 239000003825 glutamate receptor antagonist Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- WGVUBNHZRIFOSW-UHFFFAOYSA-N 1-(1h-pyrrol-2-yl)-4a,5-dihydro-4h-benzo[f]quinoxaline-2,3-dione Chemical class O=C1C(=O)NC2CC=C3C=CC=CC3=C2N1C1=CC=CN1 WGVUBNHZRIFOSW-UHFFFAOYSA-N 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 210000003169 central nervous system Anatomy 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 230000004770 neurodegeneration Effects 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 3
- 230000003556 anti-epileptic effect Effects 0.000 claims description 3
- 239000001961 anticonvulsive agent Substances 0.000 claims description 3
- 239000000935 antidepressant agent Substances 0.000 claims description 3
- 229940005513 antidepressants Drugs 0.000 claims description 3
- 229960003965 antiepileptics Drugs 0.000 claims description 3
- 239000002249 anxiolytic agent Substances 0.000 claims description 3
- 230000000949 anxiolytic effect Effects 0.000 claims description 3
- 229940005530 anxiolytics Drugs 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 208000007125 Neurotoxicity Syndromes Diseases 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 231100000189 neurotoxic Toxicity 0.000 claims description 2
- 230000002887 neurotoxic effect Effects 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- LJGCJQYWDPDYRL-UHFFFAOYSA-N 4-(1h-pyrrol-2-yl)-8,8a-dihydro-1h-quinoxaline-2,3-dione Chemical class O=C1C(=O)NC2CC=CC=C2N1C1=CC=CN1 LJGCJQYWDPDYRL-UHFFFAOYSA-N 0.000 claims 1
- 239000005557 antagonist Substances 0.000 abstract description 9
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- 108010027915 Glutamate Receptors Proteins 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 121
- 238000005160 1H NMR spectroscopy Methods 0.000 description 77
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 56
- 239000000126 substance Substances 0.000 description 48
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 239000002244 precipitate Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 229960000583 acetic acid Drugs 0.000 description 21
- 239000012528 membrane Substances 0.000 description 21
- 238000000354 decomposition reaction Methods 0.000 description 20
- 235000019441 ethanol Nutrition 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 15
- 239000002904 solvent Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000004471 Glycine Substances 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 238000005119 centrifugation Methods 0.000 description 8
- ABJFBJGGLJVMAQ-UHFFFAOYSA-N 1,4-dihydroquinoxaline-2,3-dione Chemical class C1=CC=C2NC(=O)C(=O)NC2=C1 ABJFBJGGLJVMAQ-UHFFFAOYSA-N 0.000 description 7
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 7
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- 239000012148 binding buffer Substances 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- SEPKUNXLGWMPHL-UHFFFAOYSA-N quinoxaline-2,3-dione Chemical class C1=CC=CC2=NC(=O)C(=O)N=C21 SEPKUNXLGWMPHL-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000001408 amides Chemical group 0.000 description 6
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- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- SHVQTVUFXYPLGB-UHFFFAOYSA-N (2,5-dimethoxyoxolan-3-yl)methanamine Chemical compound COC1CC(CN)C(OC)O1 SHVQTVUFXYPLGB-UHFFFAOYSA-N 0.000 description 5
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
- JSFLFNPZGIDUBV-UHFFFAOYSA-N 3-(2-amino-3-hydroxy-5-methyl-3h-1,2-oxazol-4-yl)propanoic acid Chemical compound CC1=C(CCC(O)=O)C(O)N(N)O1 JSFLFNPZGIDUBV-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-GUEYOVJQSA-N acetic acid-d4 Chemical compound [2H]OC(=O)C([2H])([2H])[2H] QTBSBXVTEAMEQO-GUEYOVJQSA-N 0.000 description 5
- 150000007513 acids Chemical group 0.000 description 5
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- GFNKTLQTQSALEJ-UHFFFAOYSA-N 1-isocyanato-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(N=C=O)C=C1 GFNKTLQTQSALEJ-UHFFFAOYSA-N 0.000 description 4
- OJVAMHKKJGICOG-UHFFFAOYSA-N 2,5-hexanedione Chemical compound CC(=O)CCC(C)=O OJVAMHKKJGICOG-UHFFFAOYSA-N 0.000 description 4
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- 241000700159 Rattus Species 0.000 description 4
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- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 239000000052 vinegar Substances 0.000 description 4
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- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 3
- UVEUAIKRGLBCAP-UHFFFAOYSA-N 1-hydroxy-4a,5,6,10b-tetrahydro-4h-benzo[f]quinoxaline-2,3-dione Chemical compound C1=CC=C2C3N(O)C(=O)C(=O)NC3CCC2=C1 UVEUAIKRGLBCAP-UHFFFAOYSA-N 0.000 description 3
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
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- QZTWVDCKDWZCLV-UHFFFAOYSA-N 1-isocyanato-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(N=C=O)C=C1 QZTWVDCKDWZCLV-UHFFFAOYSA-N 0.000 description 2
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- KFOPKOFKGJJEBW-ZSSYTAEJSA-N methyl 2-[(1s,7r,8s,9s,10r,13r,14s,17r)-1,7-dihydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]acetate Chemical compound C([C@H]1O)C2=CC(=O)C[C@H](O)[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC(=O)OC)[C@@]1(C)CC2 KFOPKOFKGJJEBW-ZSSYTAEJSA-N 0.000 description 1
- XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- FTWUXYZHDFCGSV-UHFFFAOYSA-N n,n'-diphenyloxamide Chemical compound C=1C=CC=CC=1NC(=O)C(=O)NC1=CC=CC=C1 FTWUXYZHDFCGSV-UHFFFAOYSA-N 0.000 description 1
- MZFQLQDRVFNQCV-UHFFFAOYSA-N n-(2,4-dinitro-5,6,7,8-tetrahydronaphthalen-1-yl)acetamide Chemical compound C1CCCC2=C([N+]([O-])=O)C=C([N+]([O-])=O)C(NC(=O)C)=C21 MZFQLQDRVFNQCV-UHFFFAOYSA-N 0.000 description 1
- NAJYMWNQSHRCGP-UHFFFAOYSA-N n-(5,6,7,8-tetrahydronaphthalen-1-yl)acetamide Chemical compound C1CCCC2=C1C=CC=C2NC(=O)C NAJYMWNQSHRCGP-UHFFFAOYSA-N 0.000 description 1
- VSBDBCYIIRSOFM-UHFFFAOYSA-N n-[(2,5-dimethoxyoxolan-2-yl)methyl]-2,2,2-trifluoroacetamide Chemical compound COC1CCC(CNC(=O)C(F)(F)F)(OC)O1 VSBDBCYIIRSOFM-UHFFFAOYSA-N 0.000 description 1
- VPKUNEKIPAJXQF-UHFFFAOYSA-N n-[(2,5-dimethoxyoxolan-2-yl)methyl]acetamide Chemical compound COC1CCC(CNC(C)=O)(OC)O1 VPKUNEKIPAJXQF-UHFFFAOYSA-N 0.000 description 1
- ICDRHCMYKXVZEK-UHFFFAOYSA-N n-[(2,5-dimethoxyoxolan-3-yl)methyl]-2,2,2-trifluoroacetamide Chemical compound COC1CC(CNC(=O)C(F)(F)F)C(OC)O1 ICDRHCMYKXVZEK-UHFFFAOYSA-N 0.000 description 1
- CCVQLWIJEFBLPW-UHFFFAOYSA-N n-[(2,5-dimethoxyoxolan-3-yl)methyl]-4-nitrobenzenesulfonamide Chemical compound COC1OC(OC)CC1CNS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 CCVQLWIJEFBLPW-UHFFFAOYSA-N 0.000 description 1
- VMZIJHUYDSTERG-UHFFFAOYSA-N n-[(2,5-dimethoxyoxolan-3-yl)methyl]benzamide Chemical compound COC1OC(OC)CC1CNC(=O)C1=CC=CC=C1 VMZIJHUYDSTERG-UHFFFAOYSA-N 0.000 description 1
- LGQBFIIHACEXEM-UHFFFAOYSA-N n-[[1-(1-hydroxy-2,3-dioxo-5,6,7,8-tetrahydro-4h-benzo[f]quinoxalin-9-yl)pyrrol-3-yl]methyl]benzamide Chemical compound C1CC=2NC(=O)C(=O)N(O)C=2C(C=2)=C1CCC=2N(C=1)C=CC=1CNC(=O)C1=CC=CC=C1 LGQBFIIHACEXEM-UHFFFAOYSA-N 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001021 polysulfide Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 229940116357 potassium thiocyanate Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003252 quinoxalines Chemical class 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000004763 sulfides Chemical class 0.000 description 1
- 150000003464 sulfur compounds Chemical class 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4436852A DE4436852A1 (de) | 1994-10-14 | 1994-10-14 | Pyrrolyl-tetrahydrobenzochinoxalindione, ihre Herstellung und Verwendung |
| PCT/EP1995/003902 WO1996011922A1 (de) | 1994-10-14 | 1995-10-02 | Pyrrolyl-tetrahydrobenzochinoxalindione, ihre herstellung und verwendung als glutamatrezeptor-antagonisten |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO971674D0 NO971674D0 (no) | 1997-04-11 |
| NO971674L true NO971674L (no) | 1997-06-11 |
Family
ID=6530834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO971674A NO971674L (no) | 1994-10-14 | 1997-04-11 | Pyrrolyl-tetrahydrobenzokinoksalin-dioner, deres fremstilling og anvendelse som glutamatreseptor-antagonister |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5849744A (fi) |
| EP (1) | EP0785932B1 (fi) |
| JP (1) | JPH10507186A (fi) |
| KR (1) | KR970707117A (fi) |
| CN (1) | CN1078208C (fi) |
| AT (1) | ATE188214T1 (fi) |
| AU (1) | AU3803495A (fi) |
| BG (1) | BG101407A (fi) |
| BR (1) | BR9509337A (fi) |
| CA (1) | CA2201527A1 (fi) |
| CZ (1) | CZ113197A3 (fi) |
| DE (2) | DE4436852A1 (fi) |
| DK (1) | DK0785932T3 (fi) |
| FI (1) | FI971528A (fi) |
| IL (1) | IL115625A0 (fi) |
| MX (1) | MX9702659A (fi) |
| NO (1) | NO971674L (fi) |
| PL (1) | PL319660A1 (fi) |
| WO (1) | WO1996011922A1 (fi) |
| ZA (1) | ZA958643B (fi) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19521058A1 (de) * | 1995-06-09 | 1996-12-12 | Basf Ag | Verfahren zur Herstellung von Aromaten enthaltenden Polyetherpolyolen |
| DE19532050A1 (de) * | 1995-08-31 | 1997-03-06 | Basf Ag | Pyrrolyl-tetrahydrochinoxalindione, ihre Herstellung und Verwendung zur Bekämpfung von Krankheiten |
| AU3571997A (en) * | 1996-08-01 | 1998-02-25 | Warner-Lambert Company | Novel glutamate receptor antagonists: fused cycloalkyl quinoxalinediones |
| GB2346883B (en) * | 1996-09-02 | 2001-02-14 | Lilly Industries Ltd | GluR5 receptor binding assay |
| ES2266214T3 (es) * | 2000-01-24 | 2007-03-01 | Neurosearch A/S | Derivados de isatina con actividad neurotrofica. |
| EP2338492A1 (en) | 2009-12-24 | 2011-06-29 | Universidad del Pais Vasco | Methods and compositions for the treatment of alzheimer |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US488955A (en) * | 1892-12-27 | Hedge-fence trainer | ||
| IE66149B1 (en) * | 1986-09-16 | 1995-12-13 | Novo Nordisk As | Quinoxaline compounds and their preparation and use |
| DK146787A (da) * | 1987-03-23 | 1988-09-24 | Ferrosan | Heterocykliske forbindelser, deres fremstilling og anvendelse |
| NO179551C (no) * | 1987-11-10 | 1996-10-30 | Novo Nordisk As | Analogifremgangsmåte for fremstilling av terapeutisk virksomme kinoxalinforbindelser |
| DK716188D0 (da) * | 1988-12-22 | 1988-12-22 | Ferrosan As | Quinoxalinforbindelser, deres fremstilling og anvendelse |
| DK715888D0 (da) * | 1988-12-22 | 1988-12-22 | Ferrosan As | Quinoxalinforbindelser, deres fremstilling og anvendelse |
| DK69790D0 (da) * | 1990-03-16 | 1990-03-16 | Novo Nordisk As | Heterocykliske forbindelser, deres fremstilling af anvendelse |
| ES2150417T3 (es) * | 1990-11-06 | 2000-12-01 | Yamanouchi Pharma Co Ltd | Derivados de pirazina fusionados. |
| DE4135871A1 (de) * | 1991-10-26 | 1993-04-29 | Schering Ag | Chinoxalinderivate, deren herstellung und verwendung in arzneimitteln |
| JPH069382A (ja) * | 1992-04-17 | 1994-01-18 | Takeda Chem Ind Ltd | 安定化された固型製剤およびその製造方法 |
| DE4217952A1 (de) * | 1992-05-30 | 1993-12-02 | Basf Ag | Chinoxalin-2,3(1H,4H)-dione |
| US5721234A (en) * | 1994-12-07 | 1998-02-24 | Warner-Lambert Company | Glutamate receptor antagonists: fused cycloalkylouinoxalinediones |
-
1994
- 1994-10-14 DE DE4436852A patent/DE4436852A1/de not_active Withdrawn
-
1995
- 1995-10-02 EP EP95935894A patent/EP0785932B1/de not_active Expired - Lifetime
- 1995-10-02 JP JP8512892A patent/JPH10507186A/ja not_active Abandoned
- 1995-10-02 DK DK95935894T patent/DK0785932T3/da active
- 1995-10-02 WO PCT/EP1995/003902 patent/WO1996011922A1/de not_active Application Discontinuation
- 1995-10-02 CA CA002201527A patent/CA2201527A1/en not_active Abandoned
- 1995-10-02 DE DE59507539T patent/DE59507539D1/de not_active Expired - Fee Related
- 1995-10-02 BR BR9509337A patent/BR9509337A/pt not_active Application Discontinuation
- 1995-10-02 CN CN95195650A patent/CN1078208C/zh not_active Expired - Fee Related
- 1995-10-02 CZ CZ971131A patent/CZ113197A3/cs unknown
- 1995-10-02 KR KR1019970702412A patent/KR970707117A/ko not_active Application Discontinuation
- 1995-10-02 US US08/809,697 patent/US5849744A/en not_active Expired - Fee Related
- 1995-10-02 PL PL95319660A patent/PL319660A1/xx unknown
- 1995-10-02 AU AU38034/95A patent/AU3803495A/en not_active Abandoned
- 1995-10-02 MX MX9702659A patent/MX9702659A/es unknown
- 1995-10-02 AT AT95935894T patent/ATE188214T1/de not_active IP Right Cessation
- 1995-10-13 IL IL11562595A patent/IL115625A0/xx unknown
- 1995-10-13 ZA ZA958643A patent/ZA958643B/xx unknown
-
1997
- 1997-04-11 NO NO971674A patent/NO971674L/no unknown
- 1997-04-11 BG BG101407A patent/BG101407A/xx unknown
- 1997-04-11 FI FI971528A patent/FI971528A/fi unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1160400A (zh) | 1997-09-24 |
| FI971528A0 (fi) | 1997-04-11 |
| IL115625A0 (en) | 1996-01-19 |
| PL319660A1 (en) | 1997-08-18 |
| CZ113197A3 (cs) | 1998-03-18 |
| DE59507539D1 (de) | 2000-02-03 |
| ZA958643B (en) | 1997-04-14 |
| DE4436852A1 (de) | 1996-04-18 |
| CA2201527A1 (en) | 1996-04-25 |
| EP0785932A1 (de) | 1997-07-30 |
| JPH10507186A (ja) | 1998-07-14 |
| NO971674D0 (no) | 1997-04-11 |
| WO1996011922A1 (de) | 1996-04-25 |
| ATE188214T1 (de) | 2000-01-15 |
| EP0785932B1 (de) | 1999-12-29 |
| MX9702659A (es) | 1997-06-28 |
| KR970707117A (ko) | 1997-12-01 |
| BG101407A (en) | 1997-09-30 |
| BR9509337A (pt) | 1998-01-27 |
| US5849744A (en) | 1998-12-15 |
| DK0785932T3 (da) | 2000-05-01 |
| CN1078208C (zh) | 2002-01-23 |
| AU3803495A (en) | 1996-05-06 |
| FI971528A (fi) | 1997-04-11 |
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