NO327924B1 - Benzofuranderivater, deres fremstilling og anvendelse samt preparater inneholdende nevnte derivater - Google Patents
Benzofuranderivater, deres fremstilling og anvendelse samt preparater inneholdende nevnte derivater Download PDFInfo
- Publication number
- NO327924B1 NO327924B1 NO20012726A NO20012726A NO327924B1 NO 327924 B1 NO327924 B1 NO 327924B1 NO 20012726 A NO20012726 A NO 20012726A NO 20012726 A NO20012726 A NO 20012726A NO 327924 B1 NO327924 B1 NO 327924B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- dihydro
- benzofuran
- pentamethyl
- salt
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 32
- 150000001907 coumarones Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 535
- 150000003839 salts Chemical class 0.000 claims abstract description 128
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 26
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 25
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 14
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 116
- -1 thienyl-Ci-6-alkyl Chemical group 0.000 claims description 105
- 125000001424 substituent group Chemical group 0.000 claims description 98
- 238000000034 method Methods 0.000 claims description 67
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 55
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
- 150000002367 halogens Chemical class 0.000 claims description 43
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 239000003795 chemical substances by application Substances 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 239000011737 fluorine Substances 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 20
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 20
- 208000024827 Alzheimer disease Diseases 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 17
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 16
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims description 16
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 16
- 208000018737 Parkinson disease Diseases 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 12
- 230000000508 neurotrophic effect Effects 0.000 claims description 11
- YEGLBVMYDDOCKS-UHFFFAOYSA-N 5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-3h-1-benzofuran-5-yl]-1,3-dihydroisoindole Chemical compound C1C=2C=C(OC)C(OC)=CC=2CN1C(C(=C(C)C=1OC2(C)C)C)=C(C)C=1C2C1=CC=C(C)C=C1 YEGLBVMYDDOCKS-UHFFFAOYSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 10
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 9
- JDRGXWQSWBEKGG-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-2,2,4,6,7-pentamethyl-3-(4-propan-2-ylphenyl)-3h-1-benzofuran-5-amine Chemical compound C1=CC(C(C)C)=CC=C1C1C(C)(C)OC2=C1C(C)=C(NCC=1C=CC(F)=CC=1)C(C)=C2C JDRGXWQSWBEKGG-UHFFFAOYSA-N 0.000 claims description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- HCXOMWUQGVRYFM-UHFFFAOYSA-N 5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-3h-1-benzofuran-5-yl]-1,3-dihydroisoindole;hydrochloride Chemical compound Cl.C1C=2C=C(OC)C(OC)=CC=2CN1C(C(=C(C)C=1OC2(C)C)C)=C(C)C=1C2C1=CC=C(C)C=C1 HCXOMWUQGVRYFM-UHFFFAOYSA-N 0.000 claims description 8
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 7
- 231100000135 cytotoxicity Toxicity 0.000 claims description 7
- 230000003013 cytotoxicity Effects 0.000 claims description 7
- MQTZSARRNGCQED-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-n,2,2,4,6,7-hexamethyl-3-(4-propan-2-ylphenyl)-3h-1-benzofuran-5-amine Chemical compound C1=CC(OC)=CC=C1CN(C)C(C(=C1C)C)=C(C)C2=C1OC(C)(C)C2C1=CC=C(C(C)C)C=C1 MQTZSARRNGCQED-UHFFFAOYSA-N 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- WZTGNRSYKVAYHL-UHFFFAOYSA-N 3-(4-fluorophenyl)-n-[(4-fluorophenyl)methyl]-2,4,6,7-tetramethyl-1-benzofuran-5-amine Chemical compound CC1=C2C(C=3C=CC(F)=CC=3)=C(C)OC2=C(C)C(C)=C1NCC1=CC=C(F)C=C1 WZTGNRSYKVAYHL-UHFFFAOYSA-N 0.000 claims description 5
- QRPMTUCSLLZBEO-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-2,2,4,6,7-pentamethyl-3-phenyl-3h-1-benzofuran-5-amine Chemical compound CC=1C(C)=C2OC(C)(C)C(C=3C=CC=CC=3)C2=C(C)C=1NCC1=CC=C(F)C=C1 QRPMTUCSLLZBEO-UHFFFAOYSA-N 0.000 claims description 5
- CWDUYYQIUJZGHI-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-2,4,6,7-tetramethyl-3-(4-propan-2-ylphenyl)-1-benzofuran-5-amine Chemical compound C1=CC(C(C)C)=CC=C1C(C1=C2C)=C(C)OC1=C(C)C(C)=C2NCC1=CC=C(F)C=C1 CWDUYYQIUJZGHI-UHFFFAOYSA-N 0.000 claims description 5
- NRCAXGIYEBRCRO-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-3h-1-benzofuran-5-amine Chemical compound C1=CC(OC)=CC=C1CNC(C(=C1C)C)=C(C)C2=C1OC(C)(C)C2C1=CC=C(C)C=C1 NRCAXGIYEBRCRO-UHFFFAOYSA-N 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 230000001747 exhibiting effect Effects 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 4
- GHNGBJQPDDWCJJ-UHFFFAOYSA-N 2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-3h-1-benzofuran-5-yl]-1,3-dihydroisoindole Chemical compound C1=CC(C)=CC=C1C1C(C)(C)OC2=C1C(C)=C(N1CC3=CC=CC=C3C1)C(C)=C2C GHNGBJQPDDWCJJ-UHFFFAOYSA-N 0.000 claims description 3
- KYKSMISRQZMWEV-UHFFFAOYSA-N 5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-propan-2-ylphenyl)-3h-1-benzofuran-5-yl]-1,3-dihydroisoindole Chemical compound C1C=2C=C(OC)C(OC)=CC=2CN1C(C(=C(C)C=1OC2(C)C)C)=C(C)C=1C2C1=CC=C(C(C)C)C=C1 KYKSMISRQZMWEV-UHFFFAOYSA-N 0.000 claims description 3
- DXTOPGJKORGLNN-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-2,2,4,6,7-pentamethyl-3-(4-propan-2-ylphenyl)-3h-1-benzofuran-5-amine;hydrochloride Chemical compound Cl.C1=CC(C(C)C)=CC=C1C1C(C)(C)OC2=C1C(C)=C(NCC=1C=CC(F)=CC=1)C(C)=C2C DXTOPGJKORGLNN-UHFFFAOYSA-N 0.000 claims description 3
- GKKXTCWMEZBSLS-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-2,4,6,7-tetramethyl-3-(4-propan-2-ylphenyl)-1-benzofuran-5-amine Chemical compound C1=CC(OC)=CC=C1CNC1=C(C)C(C)=C(OC(C)=C2C=3C=CC(=CC=3)C(C)C)C2=C1C GKKXTCWMEZBSLS-UHFFFAOYSA-N 0.000 claims description 3
- XNFLWANOSNSAKJ-UHFFFAOYSA-N n-[2-(4-methoxyphenyl)ethyl]-2,2,4,6,7-pentamethyl-3-(4-propan-2-ylphenyl)-3h-1-benzofuran-5-amine Chemical compound C1=CC(OC)=CC=C1CCNC(C(=C1C)C)=C(C)C2=C1OC(C)(C)C2C1=CC=C(C(C)C)C=C1 XNFLWANOSNSAKJ-UHFFFAOYSA-N 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- AUPAKLFOUBETAS-UHFFFAOYSA-N 6-(2,2,4,6,7-pentamethyl-3-phenyl-3h-1-benzofuran-5-yl)-5,7-dihydro-[1,3]dioxolo[4,5-f]isoindole Chemical compound C12=C(C)C(N3CC4=CC=5OCOC=5C=C4C3)=C(C)C(C)=C2OC(C)(C)C1C1=CC=CC=C1 AUPAKLFOUBETAS-UHFFFAOYSA-N 0.000 claims description 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
- FDOGEKGFFDGVRV-UHFFFAOYSA-N 6-[2,2,4,6,7-pentamethyl-3-(4-propan-2-ylphenyl)-3h-1-benzofuran-5-yl]-5,7-dihydro-[1,3]dioxolo[4,5-f]isoindole Chemical compound C1=CC(C(C)C)=CC=C1C1C(C)(C)OC2=C1C(C)=C(N1CC3=CC=4OCOC=4C=C3C1)C(C)=C2C FDOGEKGFFDGVRV-UHFFFAOYSA-N 0.000 claims 3
- 229940014569 pentam Drugs 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 15
- 125000002252 acyl group Chemical group 0.000 abstract description 13
- 230000001988 toxicity Effects 0.000 abstract description 8
- 231100000419 toxicity Toxicity 0.000 abstract description 8
- 125000001931 aliphatic group Chemical group 0.000 abstract description 7
- 229940126585 therapeutic drug Drugs 0.000 abstract description 7
- 230000009471 action Effects 0.000 abstract description 6
- 210000004556 brain Anatomy 0.000 abstract description 6
- 229940002612 prodrug Drugs 0.000 abstract description 6
- 239000000651 prodrug Substances 0.000 abstract description 6
- 210000005036 nerve Anatomy 0.000 abstract description 5
- 229940043274 prophylactic drug Drugs 0.000 abstract description 5
- 230000000069 prophylactic effect Effects 0.000 abstract description 5
- 125000001183 hydrocarbyl group Chemical group 0.000 abstract 2
- 125000005915 C6-C14 aryl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 255
- 238000006243 chemical reaction Methods 0.000 description 204
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 177
- 238000005160 1H NMR spectroscopy Methods 0.000 description 133
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 132
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 126
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 114
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 111
- 235000002639 sodium chloride Nutrition 0.000 description 111
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 110
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
- 238000002844 melting Methods 0.000 description 108
- 230000008018 melting Effects 0.000 description 108
- 239000000203 mixture Substances 0.000 description 108
- 239000000047 product Substances 0.000 description 98
- 239000002904 solvent Substances 0.000 description 96
- 239000000243 solution Substances 0.000 description 95
- 230000002829 reductive effect Effects 0.000 description 94
- 239000011541 reaction mixture Substances 0.000 description 92
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 90
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 72
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 66
- 235000019341 magnesium sulphate Nutrition 0.000 description 66
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 62
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 56
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 52
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 49
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 48
- 239000002585 base Substances 0.000 description 46
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 44
- 239000000284 extract Substances 0.000 description 41
- 239000000126 substance Substances 0.000 description 40
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 36
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 34
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 32
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 32
- 150000001408 amides Chemical class 0.000 description 32
- 238000010992 reflux Methods 0.000 description 32
- 239000012047 saturated solution Substances 0.000 description 31
- 150000002430 hydrocarbons Chemical group 0.000 description 30
- 239000012046 mixed solvent Substances 0.000 description 29
- 238000000926 separation method Methods 0.000 description 29
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 28
- 239000003377 acid catalyst Substances 0.000 description 28
- 230000035484 reaction time Effects 0.000 description 28
- 239000012043 crude product Substances 0.000 description 27
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 26
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 26
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
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- 239000007864 aqueous solution Substances 0.000 description 25
- 238000004587 chromatography analysis Methods 0.000 description 25
- 150000008282 halocarbons Chemical class 0.000 description 25
- 229930195733 hydrocarbon Natural products 0.000 description 25
- 238000001953 recrystallisation Methods 0.000 description 25
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 24
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 24
- 238000004821 distillation Methods 0.000 description 23
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 23
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- 229910052739 hydrogen Inorganic materials 0.000 description 21
- 239000002253 acid Substances 0.000 description 20
- 229910052794 bromium Inorganic materials 0.000 description 20
- 239000003153 chemical reaction reagent Substances 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 150000003462 sulfoxides Chemical class 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 19
- 239000002841 Lewis acid Substances 0.000 description 19
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 19
- 150000007517 lewis acids Chemical class 0.000 description 19
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- 229910052751 metal Inorganic materials 0.000 description 18
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- 238000004440 column chromatography Methods 0.000 description 17
- 239000001257 hydrogen Substances 0.000 description 17
- 210000002569 neuron Anatomy 0.000 description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 17
- 239000012312 sodium hydride Substances 0.000 description 17
- 229910000104 sodium hydride Inorganic materials 0.000 description 17
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 16
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- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 16
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 15
- 125000005843 halogen group Chemical group 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
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- 239000004215 Carbon black (E152) Substances 0.000 description 14
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 150000001447 alkali salts Chemical class 0.000 description 14
- 229910052500 inorganic mineral Inorganic materials 0.000 description 14
- 235000010755 mineral Nutrition 0.000 description 14
- 239000011707 mineral Substances 0.000 description 14
- GOFKUPUHFLPRKX-UHFFFAOYSA-N n-(4-hydroxy-2,3,6-trimethylphenyl)formamide Chemical compound CC1=CC(O)=C(C)C(C)=C1NC=O GOFKUPUHFLPRKX-UHFFFAOYSA-N 0.000 description 14
- 125000006239 protecting group Chemical group 0.000 description 14
- 239000001632 sodium acetate Substances 0.000 description 14
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Seasonings (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP34536598 | 1998-12-04 | ||
JP34535598 | 1998-12-04 | ||
PCT/JP1999/006764 WO2000034262A1 (fr) | 1998-12-04 | 1999-12-02 | Derives de benzofuranne, leur procede de preparation et leurs utilisations |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20012726D0 NO20012726D0 (no) | 2001-06-01 |
NO20012726L NO20012726L (no) | 2001-07-31 |
NO327924B1 true NO327924B1 (no) | 2009-10-19 |
Family
ID=26578009
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20012726A NO327924B1 (no) | 1998-12-04 | 2001-06-01 | Benzofuranderivater, deres fremstilling og anvendelse samt preparater inneholdende nevnte derivater |
Country Status (14)
Country | Link |
---|---|
US (3) | US6479536B1 (fr) |
EP (1) | EP1136477B1 (fr) |
JP (1) | JP4778570B2 (fr) |
KR (1) | KR100660788B1 (fr) |
CN (1) | CN1297550C (fr) |
AT (1) | ATE261435T1 (fr) |
AU (1) | AU1414600A (fr) |
CA (1) | CA2352786C (fr) |
DE (1) | DE69915508T2 (fr) |
ES (1) | ES2213407T3 (fr) |
HU (1) | HU226652B1 (fr) |
NO (1) | NO327924B1 (fr) |
PT (1) | PT1136477E (fr) |
WO (1) | WO2000034262A1 (fr) |
Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1297550C (zh) * | 1998-12-04 | 2007-01-31 | 武田药品工业株式会社 | 苯并呋喃衍生物及其制备和用途 |
ES2317935T3 (es) * | 2000-10-05 | 2009-05-01 | Takeda Pharmaceutical Company Limited | Promotores de la proliferacion y diferenciacion de celulas pluripotenciales y/o celulas precursoras neuronales. |
CA2432410A1 (fr) | 2000-12-28 | 2002-07-11 | Takeda Chemical Industries, Ltd. | Procede de preparation de composes a base de 2,3-dihydrobenzofurane a activite optique |
EP1411052B1 (fr) | 2001-07-05 | 2011-10-05 | Takeda Pharmaceutical Company Limited | Composes heterocycles a 5 chainons condenses avec un benzo, leur procede de preparation et leur utilisation |
ATE406357T1 (de) * | 2001-07-13 | 2008-09-15 | Takeda Pharmaceutical | Verfahren zur herstellung von benzofuranderivaten |
US20050118202A1 (en) * | 2001-12-19 | 2005-06-02 | Akio Yamashita | Solid compositions containing compounds unstable to oxygen and method for stabilization thereof |
US6653346B1 (en) * | 2002-02-07 | 2003-11-25 | Galileo Pharmaceuticals, Inc. | Cytoprotective benzofuran derivatives |
US7078541B2 (en) * | 2002-02-07 | 2006-07-18 | Galileo Pharmaceuticals, Inc. | Benzofuran derivatives |
JP4537011B2 (ja) * | 2002-03-01 | 2010-09-01 | 武田薬品工業株式会社 | 抗うつ剤 |
US20050148650A1 (en) | 2002-03-01 | 2005-07-07 | Shigenori Ohkawa | Antidepressant |
NZ544298A (en) * | 2003-06-26 | 2009-04-30 | Takeda Pharmaceutical | Cannabinoid receptor modulators including benzofuran derivatives |
EP1589016A1 (fr) * | 2004-04-13 | 2005-10-26 | Cephalon France | Dérivés tricycliques et bicycliques aromatiques de méthansulfinyle, substitués par THIO |
US7119214B2 (en) | 2004-04-13 | 2006-10-10 | Cephalon France | Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives |
DE602005019562D1 (de) * | 2004-05-05 | 2010-04-08 | Hoffmann La Roche | Zur modulation des 5-ht6-rezeptors, des 5-ht2a-rezeptors oder beider rezeptoren geeignete arylsulfonylbenzodioxane |
EP1783121A4 (fr) * | 2004-08-27 | 2009-08-05 | Takeda Pharmaceutical | Composés azoïques, procédé de production de ceux-ci |
US20060125084A1 (en) * | 2004-12-15 | 2006-06-15 | Fazzio Ronald S | Integration of micro-electro mechanical systems and active circuitry |
WO2006066756A1 (fr) | 2004-12-21 | 2006-06-29 | F. Hoffmann-La Roche Ag | Derives de chromane utiles dans le traitement des troubles du systeme nerveux central |
SI1831159T1 (sl) * | 2004-12-21 | 2010-04-30 | Hoffmann La Roche | Derivati tetralina in indana ter njune uporabe |
JP2008524275A (ja) * | 2004-12-21 | 2008-07-10 | エフ.ホフマン−ラ ロシュ アーゲー | クロマン誘導体及び5−htレセプターリガンドとしてのそれらの使用 |
EP1831152B1 (fr) * | 2004-12-21 | 2008-09-24 | F. Hoffmann-La Roche AG | Derives de tetraline et d'indane et utilisations de ceux-ci en tant qu'antagonistes de la 5-ht |
CA2591793A1 (fr) * | 2004-12-21 | 2006-06-29 | F. Hoffmann-La Roche Ag | Derives de tetraline et d'indane, et utilisations de ceux-ci |
PE20070077A1 (es) * | 2005-06-10 | 2007-02-07 | Takeda Pharmaceutical | Comprimido con recubierta con azucar |
KR100984897B1 (ko) * | 2005-11-03 | 2010-10-01 | 에프. 호프만-라 로슈 아게 | 5-ht6 억제제로서 아릴설포닐 크로만 |
WO2007069693A1 (fr) | 2005-12-15 | 2007-06-21 | Seikagaku Corporation | Longue chaine de sucre de chondroitine et son procede de production et procede favorisant la synthese de la chondroitine |
JP2009541248A (ja) * | 2006-06-20 | 2009-11-26 | エフ.ホフマン−ラ ロシュ アーゲー | アリールスルホンアミジルテトラリン誘導体及びそれらの使用 |
JP2009541249A (ja) * | 2006-06-20 | 2009-11-26 | エフ.ホフマン−ラ ロシュ アーゲー | アリールスルホニルナフタレン誘導体およびその使用 |
JP2009541252A (ja) * | 2006-06-20 | 2009-11-26 | エフ.ホフマン−ラ ロシュ アーゲー | テトラリン及びインダン誘導体ならびにそれらの使用 |
AR063618A1 (es) * | 2006-11-09 | 2009-02-04 | Takeda Pharmaceutical | Composicion farmaceutica |
ES2487616T3 (es) | 2009-03-10 | 2014-08-22 | Takeda Pharmaceutical Company Limited | Derivados de benzofurano |
WO2011062194A1 (fr) | 2009-11-18 | 2011-05-26 | 武田薬品工業株式会社 | Dérivé d'aminopyridine |
CN102712853B (zh) | 2009-12-24 | 2014-12-24 | Scg化学有限公司 | 用于减小烃的溴指数的方法 |
CN105294662B (zh) * | 2015-09-11 | 2018-04-20 | 中山大学 | 苯并呋喃喹啉衍生物及其在制备治疗阿尔茨海默病症的药品中的应用 |
CN115260136B (zh) * | 2022-08-09 | 2023-08-15 | 嘉兴学院 | 一种苯酞类化合物及其制备方法 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU163046B (fr) | 1970-08-25 | 1973-05-28 | ||
US4212865A (en) | 1978-12-26 | 1980-07-15 | Riker Laboratories, Inc. | Amine derivatives of 2-nitro-3-phenylbenzofuran |
US4881967A (en) | 1986-12-10 | 1989-11-21 | E. I. Du Pont De Nemours And Company | Heterocyclic 2,3-dihydrobenzofuran herbicides |
TW199152B (fr) | 1990-11-01 | 1993-02-01 | Takeda Pharm Industry Co Ltd | |
EP0632031B1 (fr) | 1990-12-28 | 2000-05-03 | Teijin Limited | Compose cyclique condense de benzoxa, son procede de production, et composition pharmaceutique le contenant |
EP0539709A1 (fr) * | 1991-09-18 | 1993-05-05 | FUJIREBIO Inc. | Dérivés de l'acide 3,5-dihydroxyheptanoique et leurs lactones comme inhibiteurs d'HMG-CoA réductase |
JP3168728B2 (ja) * | 1991-09-18 | 2001-05-21 | 富士レビオ株式会社 | 3,5−ジヒドロキシヘプタン酸誘導体 |
GB9408577D0 (en) | 1994-04-29 | 1994-06-22 | Fujisawa Pharmaceutical Co | New compound |
DE69507197T2 (de) * | 1994-05-31 | 1999-05-27 | Bayer Ag, 51373 Leverkusen | Aminobenzofuryl- und -thienylderivate |
GB9522007D0 (en) * | 1995-10-27 | 1996-01-03 | Fujisawa Pharmaceutical Co | New compound |
WO1998008842A1 (fr) | 1996-08-29 | 1998-03-05 | Takeda Chemical Industries, Ltd. | Composes ether cyclique utilises en tant que modulateurs des canaux sodiques |
WO1998055454A2 (fr) | 1997-06-05 | 1998-12-10 | Takeda Chemical Industries, Ltd. | Composes heterocycliques, leur preparation et leur utilisation |
CN1297550C (zh) * | 1998-12-04 | 2007-01-31 | 武田药品工业株式会社 | 苯并呋喃衍生物及其制备和用途 |
-
1999
- 1999-12-02 CN CNB998156825A patent/CN1297550C/zh not_active Expired - Fee Related
- 1999-12-02 KR KR1020017006999A patent/KR100660788B1/ko not_active IP Right Cessation
- 1999-12-02 EP EP99973289A patent/EP1136477B1/fr not_active Expired - Lifetime
- 1999-12-02 HU HU0105480A patent/HU226652B1/hu not_active IP Right Cessation
- 1999-12-02 US US09/857,293 patent/US6479536B1/en not_active Expired - Lifetime
- 1999-12-02 AU AU14146/00A patent/AU1414600A/en not_active Abandoned
- 1999-12-02 PT PT99973289T patent/PT1136477E/pt unknown
- 1999-12-02 DE DE69915508T patent/DE69915508T2/de not_active Expired - Lifetime
- 1999-12-02 CA CA002352786A patent/CA2352786C/fr not_active Expired - Fee Related
- 1999-12-02 AT AT99973289T patent/ATE261435T1/de active
- 1999-12-02 WO PCT/JP1999/006764 patent/WO2000034262A1/fr not_active Application Discontinuation
- 1999-12-02 ES ES99973289T patent/ES2213407T3/es not_active Expired - Lifetime
-
2001
- 2001-06-01 NO NO20012726A patent/NO327924B1/no not_active IP Right Cessation
-
2002
- 2002-04-11 US US10/120,102 patent/US7101867B2/en not_active Expired - Fee Related
-
2005
- 2005-03-17 US US11/081,615 patent/US7456162B2/en not_active Expired - Fee Related
-
2009
- 2009-04-08 JP JP2009094172A patent/JP4778570B2/ja not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
US20050187238A1 (en) | 2005-08-25 |
NO20012726D0 (no) | 2001-06-01 |
WO2000034262A1 (fr) | 2000-06-15 |
KR100660788B1 (ko) | 2007-02-28 |
HUP0105480A3 (en) | 2003-07-28 |
JP4778570B2 (ja) | 2011-09-21 |
EP1136477B1 (fr) | 2004-03-10 |
CN1297550C (zh) | 2007-01-31 |
KR20010081113A (ko) | 2001-08-27 |
US20020160996A1 (en) | 2002-10-31 |
CN1333764A (zh) | 2002-01-30 |
CA2352786C (fr) | 2009-02-03 |
US7456162B2 (en) | 2008-11-25 |
AU1414600A (en) | 2000-06-26 |
US6479536B1 (en) | 2002-11-12 |
ES2213407T3 (es) | 2004-08-16 |
EP1136477A4 (fr) | 2002-04-10 |
HUP0105480A2 (hu) | 2002-11-28 |
DE69915508D1 (de) | 2004-04-15 |
PT1136477E (pt) | 2004-08-31 |
NO20012726L (no) | 2001-07-31 |
HU226652B1 (en) | 2009-05-28 |
EP1136477A1 (fr) | 2001-09-26 |
JP2009185049A (ja) | 2009-08-20 |
ATE261435T1 (de) | 2004-03-15 |
US7101867B2 (en) | 2006-09-05 |
DE69915508T2 (de) | 2005-01-27 |
CA2352786A1 (fr) | 2000-06-15 |
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