FI98460C - Menetelmä terapeuttisesti käyttökelpoisen 4H-1-bentsopyran-4-onijohdoksen tai sen suolan valmistamiseksi ja menetelmässä käyttökelpoinen välituote - Google Patents
Menetelmä terapeuttisesti käyttökelpoisen 4H-1-bentsopyran-4-onijohdoksen tai sen suolan valmistamiseksi ja menetelmässä käyttökelpoinen välituote Download PDFInfo
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- FI98460C FI98460C FI884626A FI884626A FI98460C FI 98460 C FI98460 C FI 98460C FI 884626 A FI884626 A FI 884626A FI 884626 A FI884626 A FI 884626A FI 98460 C FI98460 C FI 98460C
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- 150000003839 salts Chemical class 0.000 title claims abstract description 49
- 238000000034 method Methods 0.000 title claims abstract description 35
- 230000008569 process Effects 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title claims description 17
- 150000004777 chromones Chemical class 0.000 claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims description 389
- 239000000203 mixture Substances 0.000 claims description 177
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 94
- -1 cyano, carboxyl Chemical group 0.000 claims description 77
- 125000000217 alkyl group Chemical group 0.000 claims description 66
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 36
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 125000002252 acyl group Chemical group 0.000 claims description 26
- 239000003795 chemical substances by application Substances 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 125000005843 halogen group Chemical group 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
- 125000003277 amino group Chemical group 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 125000004442 acylamino group Chemical group 0.000 claims description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- IYYUWAULZBEIST-UHFFFAOYSA-N 4-pyridin-1-ium-1-ylpyridine Chemical group C1=CC=CC=[N+]1C1=CC=NC=C1 IYYUWAULZBEIST-UHFFFAOYSA-N 0.000 claims description 2
- OZLBDYMWFAHSOQ-UHFFFAOYSA-N diphenyliodanium Chemical compound C=1C=CC=CC=1[I+]C1=CC=CC=C1 OZLBDYMWFAHSOQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 1
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical compound O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 300
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 229
- 239000002904 solvent Substances 0.000 description 189
- 238000006243 chemical reaction Methods 0.000 description 182
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 150
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 132
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 120
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 110
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- 238000002844 melting Methods 0.000 description 105
- 230000008018 melting Effects 0.000 description 105
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 104
- 239000000243 solution Substances 0.000 description 99
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 96
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 93
- 230000002829 reductive effect Effects 0.000 description 85
- 238000004821 distillation Methods 0.000 description 70
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- 239000012044 organic layer Substances 0.000 description 60
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 58
- 229920006395 saturated elastomer Polymers 0.000 description 58
- 239000013078 crystal Substances 0.000 description 57
- 239000011780 sodium chloride Substances 0.000 description 55
- 239000011541 reaction mixture Substances 0.000 description 54
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 51
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 49
- 239000002585 base Substances 0.000 description 48
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 45
- 238000004519 manufacturing process Methods 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 40
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 39
- 238000001914 filtration Methods 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 230000002411 adverse Effects 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 27
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 25
- 239000002253 acid Substances 0.000 description 25
- 229910052783 alkali metal Inorganic materials 0.000 description 25
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 22
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 22
- 239000003480 eluent Substances 0.000 description 21
- 239000012312 sodium hydride Substances 0.000 description 21
- 229910000104 sodium hydride Inorganic materials 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 20
- 150000001298 alcohols Chemical class 0.000 description 20
- 239000000460 chlorine Substances 0.000 description 20
- 239000000284 extract Substances 0.000 description 20
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 20
- 150000001408 amides Chemical class 0.000 description 19
- 239000005457 ice water Substances 0.000 description 19
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 229960001701 chloroform Drugs 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 13
- 150000002170 ethers Chemical class 0.000 description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 235000011181 potassium carbonates Nutrition 0.000 description 13
- 238000007363 ring formation reaction Methods 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical group C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 12
- 230000000704 physical effect Effects 0.000 description 12
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 12
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 11
- 0 Cc1cc(C(C(*)C(*)OC2)=C)cc2c1** Chemical compound Cc1cc(C(C(*)C(*)OC2)=C)cc2c1** 0.000 description 11
- 235000019253 formic acid Nutrition 0.000 description 11
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 11
- 150000008282 halocarbons Chemical class 0.000 description 11
- 230000002401 inhibitory effect Effects 0.000 description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 150000003462 sulfoxides Chemical class 0.000 description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 230000002140 halogenating effect Effects 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- KJJUXOQDQJGDTI-UHFFFAOYSA-N n-(4-oxo-6-phenoxychromen-7-yl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=2OC=CC(=O)C=2C=C1OC1=CC=CC=C1 KJJUXOQDQJGDTI-UHFFFAOYSA-N 0.000 description 10
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- XJFYTOULOUYZFL-UHFFFAOYSA-N n-(3-amino-4-oxo-6-phenoxychromen-7-yl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=2OC=C(N)C(=O)C=2C=C1OC1=CC=CC=C1 XJFYTOULOUYZFL-UHFFFAOYSA-N 0.000 description 9
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 9
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 8
- 150000008041 alkali metal carbonates Chemical class 0.000 description 8
- 150000001340 alkali metals Chemical class 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 150000001735 carboxylic acids Chemical class 0.000 description 8
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 8
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- CMYTTYZJZGQZMC-UHFFFAOYSA-N n-(4-acetyl-5-hydroxy-2-phenoxyphenyl)methanesulfonamide Chemical compound C1=C(O)C(C(=O)C)=CC(OC=2C=CC=CC=2)=C1NS(C)(=O)=O CMYTTYZJZGQZMC-UHFFFAOYSA-N 0.000 description 8
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 8
- 229910000105 potassium hydride Inorganic materials 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 7
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 7
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 239000008186 active pharmaceutical agent Substances 0.000 description 7
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 7
- 150000008046 alkali metal hydrides Chemical class 0.000 description 7
- 239000001768 carboxy methyl cellulose Substances 0.000 description 7
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 7
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 150000002576 ketones Chemical class 0.000 description 7
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 7
- 150000007530 organic bases Chemical class 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000008096 xylene Substances 0.000 description 7
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical class CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- MZIABRHUWQDTKM-UHFFFAOYSA-N n-(3-formyl-4-oxo-6-phenoxychromen-7-yl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=2OC=C(C=O)C(=O)C=2C=C1OC1=CC=CC=C1 MZIABRHUWQDTKM-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 239000001632 sodium acetate Substances 0.000 description 6
- 235000017281 sodium acetate Nutrition 0.000 description 6
- 230000001562 ulcerogenic effect Effects 0.000 description 6
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 5
- 229910015900 BF3 Inorganic materials 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 239000002841 Lewis acid Substances 0.000 description 5
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 150000007517 lewis acids Chemical class 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 229960003975 potassium Drugs 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
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- DTYQJFABBDEYMI-UHFFFAOYSA-N n-[2-[7-(methanesulfonamido)-4-oxochromen-6-yl]oxyphenyl]formamide Chemical compound CS(=O)(=O)NC1=CC=2OC=CC(=O)C=2C=C1OC1=CC=CC=C1NC=O DTYQJFABBDEYMI-UHFFFAOYSA-N 0.000 description 1
- PCSPZDPPVCTHRI-UHFFFAOYSA-N n-[2-amino-3-(2-hydroxypropanoyl)-4-oxo-6-phenoxychromen-7-yl]methanesulfonamide Chemical compound C1=C2C(=O)C(C(=O)C(O)C)=C(N)OC2=CC(NS(C)(=O)=O)=C1OC1=CC=CC=C1 PCSPZDPPVCTHRI-UHFFFAOYSA-N 0.000 description 1
- KGFSRZKSIRZDAA-UHFFFAOYSA-N n-[2-cyano-7-(methanesulfonamido)-4-oxo-6-phenoxychromen-3-yl]formamide Chemical compound CS(=O)(=O)NC1=CC=2OC(C#N)=C(NC=O)C(=O)C=2C=C1OC1=CC=CC=C1 KGFSRZKSIRZDAA-UHFFFAOYSA-N 0.000 description 1
- WGRBXCWSQWOFAJ-UHFFFAOYSA-N n-[3-(1-hydroxyethyl)-4-oxo-6-phenoxychromen-7-yl]methanesulfonamide Chemical compound C1=C2C(=O)C(C(O)C)=COC2=CC(NS(C)(=O)=O)=C1OC1=CC=CC=C1 WGRBXCWSQWOFAJ-UHFFFAOYSA-N 0.000 description 1
- AJXHGSWNCIOYLL-UHFFFAOYSA-N n-[3-(aminomethyl)-4-oxo-6-phenoxychromen-7-yl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=2OC=C(CN)C(=O)C=2C=C1OC1=CC=CC=C1 AJXHGSWNCIOYLL-UHFFFAOYSA-N 0.000 description 1
- CJOFPCLZJXOOJW-UHFFFAOYSA-N n-[3-(ethylamino)-4-oxo-6-phenoxychromen-7-yl]methanesulfonamide Chemical compound C1=C2C(=O)C(NCC)=COC2=CC(NS(C)(=O)=O)=C1OC1=CC=CC=C1 CJOFPCLZJXOOJW-UHFFFAOYSA-N 0.000 description 1
- WPKMKPYKRIHDJJ-UHFFFAOYSA-N n-[3-(hydroxymethyl)-4-oxo-6-phenoxychromen-7-yl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=2OC=C(CO)C(=O)C=2C=C1OC1=CC=CC=C1 WPKMKPYKRIHDJJ-UHFFFAOYSA-N 0.000 description 1
- GVJJMGWEDYPDDA-UHFFFAOYSA-N n-[3-(methanesulfonamido)-4-oxo-6-phenoxychromen-7-yl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=2OC=C(NS(C)(=O)=O)C(=O)C=2C=C1OC1=CC=CC=C1 GVJJMGWEDYPDDA-UHFFFAOYSA-N 0.000 description 1
- OCMBABJJMLUIGI-UHFFFAOYSA-N n-[3-[(2,4-dimethoxyphenyl)methylamino]-2-methyl-4-oxo-6-phenoxychromen-7-yl]methanesulfonamide Chemical compound COC1=CC(OC)=CC=C1CNC(C(C1=C2)=O)=C(C)OC1=CC(NS(C)(=O)=O)=C2OC1=CC=CC=C1 OCMBABJJMLUIGI-UHFFFAOYSA-N 0.000 description 1
- UQHIWVYDLIHLCS-UHFFFAOYSA-N n-[4-[3-(3,4-dimethoxyphenyl)prop-2-enoyl]-5-hydroxy-2-phenoxyphenyl]methanesulfonamide Chemical compound C1=C(OC)C(OC)=CC=C1C=CC(=O)C1=CC(OC=2C=CC=CC=2)=C(NS(C)(=O)=O)C=C1O UQHIWVYDLIHLCS-UHFFFAOYSA-N 0.000 description 1
- DUQQHNZJVFSERJ-UHFFFAOYSA-N n-[4-acetyl-2-(2,4-difluorophenoxy)-5-hydroxyphenyl]methanesulfonamide Chemical compound C1=C(O)C(C(=O)C)=CC(OC=2C(=CC(F)=CC=2)F)=C1NS(C)(=O)=O DUQQHNZJVFSERJ-UHFFFAOYSA-N 0.000 description 1
- DJBNZXIZYODHKV-UHFFFAOYSA-N n-[4-oxo-3-(2-oxopyrrolidin-1-yl)-6-phenoxychromen-7-yl]methanesulfonamide Chemical compound O=C1C=2C=C(OC=3C=CC=CC=3)C(NS(=O)(=O)C)=CC=2OC=C1N1CCCC1=O DJBNZXIZYODHKV-UHFFFAOYSA-N 0.000 description 1
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- XCLSILOGAVPZEG-UHFFFAOYSA-N n-[5-hydroxy-2-(4-methoxyphenoxy)phenyl]methanesulfonamide Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(O)C=C1NS(C)(=O)=O XCLSILOGAVPZEG-UHFFFAOYSA-N 0.000 description 1
- WJJASBGZGFKEDO-UHFFFAOYSA-N n-[5-hydroxy-4-(3-oxopropanoyl)-2-phenoxyphenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(O)=C(C(=O)CC=O)C=C1OC1=CC=CC=C1 WJJASBGZGFKEDO-UHFFFAOYSA-N 0.000 description 1
- HAOPKNXYKDELFS-UHFFFAOYSA-N n-[5-methoxy-2-(3-methylphenoxy)phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(OC)=CC=C1OC1=CC=CC(C)=C1 HAOPKNXYKDELFS-UHFFFAOYSA-N 0.000 description 1
- SYUDVYBKMPRJOU-UHFFFAOYSA-N n-[6-(2-fluorophenoxy)-7-(methanesulfonamido)-4-oxochromen-3-yl]formamide Chemical compound CS(=O)(=O)NC1=CC=2OC=C(NC=O)C(=O)C=2C=C1OC1=CC=CC=C1F SYUDVYBKMPRJOU-UHFFFAOYSA-N 0.000 description 1
- WZMBUNYKYDPPBG-UHFFFAOYSA-N n-[7-(methanesulfonamido)-2-methoxy-4-oxo-6-phenoxychromen-3-yl]formamide Chemical compound C1=C2C(=O)C(NC=O)=C(OC)OC2=CC(NS(C)(=O)=O)=C1OC1=CC=CC=C1 WZMBUNYKYDPPBG-UHFFFAOYSA-N 0.000 description 1
- UDDXYCUCSMDUSQ-UHFFFAOYSA-N n-[7-(methanesulfonamido)-4-oxo-6-phenoxychromen-2-yl]acetamide Chemical compound CS(=O)(=O)NC=1C=C2OC(NC(=O)C)=CC(=O)C2=CC=1OC1=CC=CC=C1 UDDXYCUCSMDUSQ-UHFFFAOYSA-N 0.000 description 1
- UOLCQXYQYHNNRC-UHFFFAOYSA-N n-[7-(methanesulfonamido)-4-oxo-6-phenoxychromen-2-yl]formamide Chemical compound CS(=O)(=O)NC1=CC=2OC(NC=O)=CC(=O)C=2C=C1OC1=CC=CC=C1 UOLCQXYQYHNNRC-UHFFFAOYSA-N 0.000 description 1
- MEQMVWMVQXKRQA-UHFFFAOYSA-N n-[7-(methanesulfonamido)-6-(2-methoxyphenoxy)-4-oxochromen-3-yl]formamide Chemical compound COC1=CC=CC=C1OC1=CC(C(C(NC=O)=CO2)=O)=C2C=C1NS(C)(=O)=O MEQMVWMVQXKRQA-UHFFFAOYSA-N 0.000 description 1
- ZMLCMHAPPBNIHD-UHFFFAOYSA-N n-[[7-(methanesulfonamido)-4-oxo-6-phenoxychromen-3-yl]methyl]acetamide Chemical compound C1=C2C(=O)C(CNC(=O)C)=COC2=CC(NS(C)(=O)=O)=C1OC1=CC=CC=C1 ZMLCMHAPPBNIHD-UHFFFAOYSA-N 0.000 description 1
- IXEONQBSYYFREJ-UHFFFAOYSA-N n-methylsulfonyl-n-(4-oxo-6-phenoxychromen-7-yl)acetamide Chemical compound CC(=O)N(S(C)(=O)=O)C1=CC=2OC=CC(=O)C=2C=C1OC1=CC=CC=C1 IXEONQBSYYFREJ-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 238000005121 nitriding Methods 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- JWUKZUIGOJBEPC-UHFFFAOYSA-N phenyl thiohypochlorite Chemical compound ClSC1=CC=CC=C1 JWUKZUIGOJBEPC-UHFFFAOYSA-N 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 229960000380 propiolactone Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- FUCBQMFTYFQCOB-UHFFFAOYSA-N trityl perchlorate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCl(=O)(=O)=O)C1=CC=CC=C1 FUCBQMFTYFQCOB-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/24—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 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 in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
- C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/42—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4
- C07D311/44—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3
- C07D311/54—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3 substituted in the carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/42—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4
- C07D311/56—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 without hydrogen atoms in position 3
-
- 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
- C07D405/12—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 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
- C07D409/12—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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP25425187 | 1987-10-08 | ||
JP25425187 | 1987-10-08 | ||
JP11999088 | 1988-05-17 | ||
JP11999088 | 1988-05-17 | ||
JP63250811A JPH0753725B2 (ja) | 1987-10-08 | 1988-10-06 | 4h―1―ベンゾピラン―4―オン誘導体およびその塩、それらの製造法並びにそれらを含有する抗炎症剤 |
JP25081188 | 1988-10-06 |
Publications (4)
Publication Number | Publication Date |
---|---|
FI884626A0 FI884626A0 (fi) | 1988-10-07 |
FI884626A7 FI884626A7 (fi) | 1989-04-09 |
FI98460B FI98460B (fi) | 1997-03-14 |
FI98460C true FI98460C (fi) | 1997-06-25 |
Family
ID=27313952
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI884626A FI98460C (fi) | 1987-10-08 | 1988-10-07 | Menetelmä terapeuttisesti käyttökelpoisen 4H-1-bentsopyran-4-onijohdoksen tai sen suolan valmistamiseksi ja menetelmässä käyttökelpoinen välituote |
Country Status (16)
Country | Link |
---|---|
US (1) | US4954518A (en, 2012) |
JP (1) | JPH0753725B2 (en, 2012) |
KR (1) | KR910007970B1 (en, 2012) |
AT (1) | AT397088B (en, 2012) |
AU (1) | AU605363B2 (en, 2012) |
BE (1) | BE1002226A5 (en, 2012) |
CA (1) | CA1320959C (en, 2012) |
CH (1) | CH679397A5 (en, 2012) |
DE (1) | DE3834204A1 (en, 2012) |
ES (8) | ES2013801A6 (en, 2012) |
FI (1) | FI98460C (en, 2012) |
FR (1) | FR2621585B1 (en, 2012) |
GB (1) | GB2210879B (en, 2012) |
IT (1) | IT1235048B (en, 2012) |
NL (1) | NL194914C (en, 2012) |
SE (1) | SE468595B (en, 2012) |
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DE3924417A1 (de) * | 1989-07-24 | 1991-01-31 | Merck Patent Gmbh | Chromanderivate |
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JPH07110853B2 (ja) * | 1990-09-07 | 1995-11-29 | シェリング・コーポレーション | 抗ウイルス化合物および抗高血圧化合物 |
FR2695387B1 (fr) * | 1992-09-09 | 1994-10-21 | Adir | Nouveaux composés benzopyraniques, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
ES2160626T3 (es) * | 1993-04-09 | 2001-11-16 | Toyama Chemical Co Ltd | Inmunomodulador, inhibidor de la adherencia celular, y agente que permite tratar y prevenir enfermedades autoinmunes. |
WO1995033462A1 (en) * | 1994-06-02 | 1995-12-14 | Smithkline Beecham Corporation | Anti-inflammatory compounds |
IT1288123B1 (it) | 1996-09-04 | 1998-09-10 | Nicox Sa | Uso di nitroderivati per l'incontinenza urinaria |
DK1043317T3 (da) | 1997-11-19 | 2009-07-06 | Kowa Co | Pyridazinderivater og medikamenter indeholdende dem som aktiv bestanddel |
TWI241295B (en) | 1998-03-02 | 2005-10-11 | Kowa Co | Pyridazine derivative and medicine containing the same as effect component |
US6649645B1 (en) * | 1998-12-23 | 2003-11-18 | Pharmacia Corporation | Combination therapy of radiation and a COX-2 inhibitor for treatment of neoplasia |
JP2000247959A (ja) | 1999-02-26 | 2000-09-12 | Kowa Co | ピリダジン−3−オン誘導体及びこれを含有する医薬 |
JP2001055331A (ja) * | 1999-06-11 | 2001-02-27 | Toyama Chem Co Ltd | アトピー性皮膚炎治療剤 |
US6664256B1 (en) | 2000-07-10 | 2003-12-16 | Kowa Co., Ltd. | Phenylpyridazine compounds and medicines containing the same |
GB0119865D0 (en) * | 2001-08-14 | 2001-10-10 | Cancer Res Campaign Tech | DNA-PK inhibitors |
GB0119863D0 (en) * | 2001-08-14 | 2001-10-10 | Cancer Res Campaign Tech | DNA-PK inhibitors |
AR038957A1 (es) | 2001-08-15 | 2005-02-02 | Pharmacia Corp | Terapia de combinacion para el tratamiento del cancer |
JP3972663B2 (ja) * | 2002-01-22 | 2007-09-05 | 松下電器産業株式会社 | 高周波信号受信装置 |
US7049313B2 (en) * | 2002-02-25 | 2006-05-23 | Kudos Pharmaceuticals Ltd. | ATM inhibitors |
NZ536190A (en) * | 2002-04-17 | 2007-08-31 | Cytokinetics Inc | Compounds for treating cellular proliferative diseases by modulating the activity of the mitotic kinesin KSP |
EP1507756B1 (en) | 2002-05-24 | 2015-07-22 | Millennium Pharmaceuticals, Inc. | Ccr9 inhibitors and methods of use thereof |
AU2003252025A1 (en) * | 2002-07-17 | 2004-02-02 | Cytokinetics, Inc. | Compounds, compositions, and methods |
JP2005539062A (ja) * | 2002-09-13 | 2005-12-22 | サイトキネティクス・インコーポレーテッド | 化合物、組成物および方法 |
AU2003298661B2 (en) | 2002-11-18 | 2007-05-10 | Chemocentryx, Inc. | Aryl sulfonamides |
US7741519B2 (en) * | 2007-04-23 | 2010-06-22 | Chemocentryx, Inc. | Bis-aryl sulfonamides |
US20070021466A1 (en) * | 2002-11-18 | 2007-01-25 | Solomon Ungashe | CCR2 inhibitors and methods of use thereof |
US7420055B2 (en) * | 2002-11-18 | 2008-09-02 | Chemocentryx, Inc. | Aryl sulfonamides |
US7227035B2 (en) * | 2002-11-18 | 2007-06-05 | Chemocentryx | Bis-aryl sulfonamides |
DE10256182A1 (de) * | 2002-12-02 | 2004-06-24 | Merck Patent Gmbh | 2-Oxadiazolchromonderivate |
US20070287844A1 (en) * | 2003-03-14 | 2007-12-13 | Toyama Chemical Co., Ltd. | Novel Crystal of N-[3-(Formylamino)-4-Oxo-6-Phenoxy-4h-Chromene-7-Yl] Methanesulfonamide |
EP1604984A1 (en) * | 2003-03-18 | 2005-12-14 | Kowa Co., Ltd. | Water-soluble phenylpyridazine derivative and medicine containing the same |
CN100387231C (zh) * | 2003-03-24 | 2008-05-14 | 天津药物研究院 | 一种制备古拉替莫固体制剂的工艺及其固体制剂 |
ES2341342T3 (es) * | 2003-08-13 | 2010-06-18 | Kudos Pharmaceuticals Limited | Aminopironas y su uso como inhibidores de atm. |
US20050165089A1 (en) * | 2003-10-06 | 2005-07-28 | Gustave Bergnes | Compounds, compositions and methods |
EP1794151A1 (en) * | 2004-09-20 | 2007-06-13 | Kudos Pharmaceuticals Limited | Dna-pk inhibitors |
WO2006085067A1 (en) * | 2005-02-09 | 2006-08-17 | Kudos Pharmaceuticals Limited | Atm inhibitors |
AR054438A1 (es) * | 2005-04-15 | 2007-06-27 | Kudos Pharm Ltd | Inhibidores de adn -pk |
KR100704009B1 (ko) * | 2005-08-30 | 2007-04-04 | 한국화학연구원 | 염증억제 활성을 가지는6-알킬아미노-2-메틸-2'-(n-메틸치환술폰아미도)메틸-2h-1-벤조피란 유도체 |
TW200745094A (en) * | 2005-08-31 | 2007-12-16 | Kudos Pharm Ltd | ATM inhibitor |
CN101891726B (zh) * | 2005-10-09 | 2012-05-23 | 天津药物研究院 | 艾拉莫德结晶形态及其组合物 |
CN101885717B (zh) * | 2005-10-09 | 2012-05-23 | 天津药物研究院 | 艾拉莫德结晶形态及其组合物 |
CN101885718B (zh) * | 2005-10-09 | 2012-05-23 | 天津药物研究院 | 艾拉莫德结晶形态及其组合物 |
JP4788955B2 (ja) * | 2006-01-13 | 2011-10-05 | 住友金属工業株式会社 | 鉄道車両における操舵用アクチュエータの制御方法 |
AU2006233256B2 (en) * | 2006-10-30 | 2012-01-19 | Armaron Bio Pty Ltd | Improved flavonols |
US7960567B2 (en) * | 2007-05-02 | 2011-06-14 | Amgen Inc. | Compounds and methods useful for treating asthma and allergic inflammation |
UY31232A1 (es) * | 2007-07-19 | 2009-03-02 | Compuestos derivados de dibenzotifenilamino-cromen-4-onas activas sustituidas y sus isomeros y aplicaciones | |
JP5828235B2 (ja) | 2011-07-21 | 2015-12-02 | 新日鐵住金株式会社 | 鉄道車両用操舵台車 |
PL2929880T3 (pl) * | 2013-07-18 | 2017-03-31 | Toyama Chemical Co., Ltd. | Środek terapeutyczny do leczenia choroby, wykazujący hamujący wpływ na czynnik hamujący migrację makrofagów |
CN107021891A (zh) * | 2017-04-24 | 2017-08-08 | 常州佳德医药科技有限公司 | 一种艾拉莫德中间体的制备方法 |
CN106986797B (zh) * | 2017-04-24 | 2018-09-28 | 常州佳德医药科技有限公司 | N-(2-(4-乙酰苯氧基)-5-甲氧基苯基)甲磺酰胺及其制备方法 |
CN111170914B (zh) * | 2018-11-09 | 2021-12-21 | 成都大学 | 硒/硫化磺酰芳胺类化合物及其硒/硫化方法 |
CN109705000A (zh) * | 2019-02-26 | 2019-05-03 | 南京红杉生物科技有限公司 | 艾拉莫德中间体及其合成方法 |
JP7453365B2 (ja) * | 2020-05-29 | 2024-03-19 | 富士フイルム富山化学株式会社 | 高純度のn-(5-メトキシ―2-フェノキシフェニル)メタンスルホンアミド及びその製造方法 |
CN113968836A (zh) * | 2020-07-25 | 2022-01-25 | 华创合成制药股份有限公司 | 一种苯并吡喃衍生物及其在类风湿性关节炎治疗中的应用 |
CN113968838B (zh) * | 2020-07-25 | 2024-04-02 | 华创合成制药股份有限公司 | 一种硫代苯并吡喃类化合物及其在类风湿性关节炎治疗中的应用 |
CN114539104A (zh) * | 2022-03-09 | 2022-05-27 | 常州佳德医药科技有限公司 | 一种艾拉莫德中间体的制备方法 |
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US3661990A (en) * | 1970-04-13 | 1972-05-09 | Riker Laboratories Inc | N-alkylsulfonyl benzoylhaloalkylsulfonanilides |
US3689523A (en) * | 1971-01-04 | 1972-09-05 | Minnesota Mining & Mfg | Substituted haloalkanesulfonanilides |
US3840597A (en) * | 1971-02-24 | 1974-10-08 | Riker Laboratories Inc | Substituted 2-phenoxy alkane-sulfonanilides |
GB1499323A (en) * | 1974-03-22 | 1978-02-01 | Fisons Ltd | 6-substituted chromones and chromanones |
DE2537204A1 (de) * | 1974-08-23 | 1976-03-04 | Fisons Ltd | Neue benzopyrane und verfahren zu ihrer herstellung |
EP0009554B1 (de) * | 1978-07-27 | 1983-04-27 | Schering Aktiengesellschaft | Indanyl-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Präparate |
DE3110009A1 (de) * | 1981-03-11 | 1982-09-30 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue benzofuran-derivate, ihre herstellung und verwendung |
DE3208079A1 (de) * | 1982-03-04 | 1983-09-08 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue indanyl-derivate, ihre herstellung und verwendung |
FR2543140B1 (fr) * | 1983-03-24 | 1985-06-21 | Cortial | Nouveaux acides flavone-carboxyliques-4', leur methode de preparation et leur application en therapeutique |
DE3343331A1 (de) * | 1983-11-28 | 1985-06-05 | Schering AG, 1000 Berlin und 4709 Bergkamen | Verfahren zur herstellung von indanyl-derivaten und deren verwendung |
US4713393A (en) * | 1985-04-25 | 1987-12-15 | Merck & Co., Inc. | Phenylpropyl-2,3-dihydrobenzofurans useful as anti-inflammatory agents |
PT86407B (pt) * | 1986-12-31 | 1990-11-20 | Fujisawa Pharmaceutical Co | Processo para a preparacao de novos derivados de alcano-sulfonanilida, e de composicoes farmaceuticas compreendendo os mesmos |
-
1988
- 1988-10-06 JP JP63250811A patent/JPH0753725B2/ja not_active Expired - Lifetime
- 1988-10-07 BE BE8801158A patent/BE1002226A5/fr not_active IP Right Cessation
- 1988-10-07 GB GB8823567A patent/GB2210879B/en not_active Expired - Lifetime
- 1988-10-07 NL NL8802464A patent/NL194914C/nl not_active IP Right Cessation
- 1988-10-07 FR FR8813205A patent/FR2621585B1/fr not_active Expired - Lifetime
- 1988-10-07 AU AU23489/88A patent/AU605363B2/en not_active Expired
- 1988-10-07 CH CH3763/88A patent/CH679397A5/de not_active IP Right Cessation
- 1988-10-07 SE SE8803570A patent/SE468595B/sv not_active IP Right Cessation
- 1988-10-07 CA CA000579624A patent/CA1320959C/en not_active Expired - Lifetime
- 1988-10-07 FI FI884626A patent/FI98460C/fi not_active IP Right Cessation
- 1988-10-07 DE DE3834204A patent/DE3834204A1/de active Granted
- 1988-10-07 US US07/255,121 patent/US4954518A/en not_active Expired - Lifetime
- 1988-10-07 ES ES8803062A patent/ES2013801A6/es not_active Expired - Lifetime
- 1988-10-08 KR KR1019880013144A patent/KR910007970B1/ko not_active Expired
- 1988-10-10 AT AT0249588A patent/AT397088B/de not_active IP Right Cessation
- 1988-10-10 IT IT8848441A patent/IT1235048B/it active
-
1989
- 1989-10-13 ES ES8903467A patent/ES2017838A6/es not_active Expired - Lifetime
- 1989-10-13 ES ES8903465A patent/ES2018112A6/es not_active Expired - Lifetime
- 1989-10-13 ES ES8903469A patent/ES2018113A6/es not_active Expired - Lifetime
- 1989-10-13 ES ES8903463A patent/ES2018111A6/es not_active Expired - Lifetime
- 1989-10-13 ES ES8903468A patent/ES2017839A6/es not_active Expired - Lifetime
- 1989-10-13 ES ES8903464A patent/ES2017836A6/es not_active Expired - Lifetime
- 1989-10-13 ES ES8903466A patent/ES2017837A6/es not_active Expired - Lifetime
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Owner name: TOYAMA CHEMICAL CO., LTD. |
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