FI77246C - Foerfarande foer framstaellning av antiallergiska 4h-furo/3,2-b/indoler. - Google Patents
Foerfarande foer framstaellning av antiallergiska 4h-furo/3,2-b/indoler. Download PDFInfo
- Publication number
- FI77246C FI77246C FI831272A FI831272A FI77246C FI 77246 C FI77246 C FI 77246C FI 831272 A FI831272 A FI 831272A FI 831272 A FI831272 A FI 831272A FI 77246 C FI77246 C FI 77246C
- Authority
- FI
- Finland
- Prior art keywords
- furo
- phenyl
- indole
- methoxy
- carboxylic acid
- Prior art date
Links
- 230000003266 anti-allergic effect Effects 0.000 title claims description 9
- 238000005057 refrigeration Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 46
- -1 1H-tetrazol-5-yl compound Chemical class 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 150000002148 esters Chemical group 0.000 claims description 10
- YCXRJOZNRPGVCN-UHFFFAOYSA-N 3,7-dimethoxy-4-phenyl-n-(2h-tetrazol-5-yl)furo[3,2-b]indole-2-carboxamide Chemical compound C1=2C(OC)=C(C(=O)NC3=NNN=N3)OC=2C2=CC(OC)=CC=C2N1C1=CC=CC=C1 YCXRJOZNRPGVCN-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- DCEMUONUJXUSHM-UHFFFAOYSA-N 3,7-dimethoxy-4-phenyl-2-(2h-tetrazol-5-yl)furo[3,2-b]indole Chemical compound C1=2C(OC)=C(C=3NN=NN=3)OC=2C2=CC(OC)=CC=C2N1C1=CC=CC=C1 DCEMUONUJXUSHM-UHFFFAOYSA-N 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- QDMPKKFNRFFSNK-UHFFFAOYSA-N n-(2h-tetrazol-5-yl)formamide Chemical compound O=CNC1=NN=NN1 QDMPKKFNRFFSNK-UHFFFAOYSA-N 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims 1
- 150000002475 indoles Chemical class 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- 239000000047 product Substances 0.000 description 33
- 238000001953 recrystallisation Methods 0.000 description 33
- 239000000203 mixture Substances 0.000 description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 20
- 239000012043 crude product Substances 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 150000002825 nitriles Chemical class 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 150000003536 tetrazoles Chemical class 0.000 description 6
- VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- HOOUZIRMRBQJEQ-UHFFFAOYSA-N 4h-furo[3,2-b]indole Chemical class N1C2=CC=CC=C2C2=C1C=CO2 HOOUZIRMRBQJEQ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 229960001340 histamine Drugs 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- LBJWKXZFFSDGRE-UHFFFAOYSA-N methyl 3-methoxy-4-phenylfuro[3,2-b]indole-2-carboxylate Chemical compound C1=2C(OC)=C(C(=O)OC)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 LBJWKXZFFSDGRE-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- LTNCFABAGCHHCV-UHFFFAOYSA-N 3,7-dimethoxy-4-phenylfuro[3,2-b]indole-2-carboxylic acid Chemical compound C1=2C(OC)=C(C(O)=O)OC=2C2=CC(OC)=CC=C2N1C1=CC=CC=C1 LTNCFABAGCHHCV-UHFFFAOYSA-N 0.000 description 3
- VFWAJXMRCXLCOW-UHFFFAOYSA-N 3-ethoxy-7-methoxy-4-phenylfuro[3,2-b]indole-2-carboxylic acid Chemical compound C1=2C(OCC)=C(C(O)=O)OC=2C2=CC(OC)=CC=C2N1C1=CC=CC=C1 VFWAJXMRCXLCOW-UHFFFAOYSA-N 0.000 description 3
- KAPSRMBETRZKSK-UHFFFAOYSA-N 3-methoxy-4-methylfuro[3,2-b]indole-2-carboxamide Chemical compound C12=CC=CC=C2N(C)C2=C1OC(C(N)=O)=C2OC KAPSRMBETRZKSK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000003973 alkyl amines Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000005690 diesters Chemical class 0.000 description 3
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- PPYPKYLOIVTCHE-UHFFFAOYSA-N methyl 3,7-dimethoxy-4-phenylfuro[3,2-b]indole-2-carboxylate Chemical compound C1=2C(OC)=C(C(=O)OC)OC=2C2=CC(OC)=CC=C2N1C1=CC=CC=C1 PPYPKYLOIVTCHE-UHFFFAOYSA-N 0.000 description 3
- SQGMODLFBXUZFC-UHFFFAOYSA-N methyl 3-ethoxy-4-phenylfuro[3,2-b]indole-2-carboxylate Chemical compound C1=2C(OCC)=C(C(=O)OC)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 SQGMODLFBXUZFC-UHFFFAOYSA-N 0.000 description 3
- ZUITVCHBXUDBHR-UHFFFAOYSA-N methyl 3-hydroxy-4-phenylfuro[3,2-b]indole-2-carboxylate Chemical compound C1=2C(O)=C(C(=O)OC)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 ZUITVCHBXUDBHR-UHFFFAOYSA-N 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000003437 trachea Anatomy 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- CBTITARLOCZPDU-UHFFFAOYSA-N 1h-indole-2-carbonitrile Chemical compound C1=CC=C2NC(C#N)=CC2=C1 CBTITARLOCZPDU-UHFFFAOYSA-N 0.000 description 2
- YDQILENBFVCDPN-UHFFFAOYSA-N 2-[n-(cyanomethyl)anilino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1N(CC#N)C1=CC=CC=C1 YDQILENBFVCDPN-UHFFFAOYSA-N 0.000 description 2
- JVSMPWHQUPKRNV-UHFFFAOYSA-N 2h-tetrazol-5-amine;hydrate Chemical compound O.NC=1N=NNN=1 JVSMPWHQUPKRNV-UHFFFAOYSA-N 0.000 description 2
- UZEJYGWOAONGCH-UHFFFAOYSA-N 3,7-dimethoxy-4-phenylfuro[3,2-b]indole-2-carboxamide Chemical compound C1=2C(OC)=C(C(N)=O)OC=2C2=CC(OC)=CC=C2N1C1=CC=CC=C1 UZEJYGWOAONGCH-UHFFFAOYSA-N 0.000 description 2
- JOINTFUOXCQRLQ-UHFFFAOYSA-N 3-ethoxy-4-phenyl-2-(2h-tetrazol-5-yl)furo[3,2-b]indole Chemical compound C1=2C(OCC)=C(C=3NN=NN=3)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 JOINTFUOXCQRLQ-UHFFFAOYSA-N 0.000 description 2
- JWJAOYGHEABQSH-UHFFFAOYSA-N 3-ethoxy-4-phenylfuro[3,2-b]indole-2-carbonitrile Chemical compound C1=2C(OCC)=C(C#N)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 JWJAOYGHEABQSH-UHFFFAOYSA-N 0.000 description 2
- YUEDRIPQRRVFJV-UHFFFAOYSA-N 3-ethoxy-4-phenylfuro[3,2-b]indole-2-carboxylic acid Chemical compound C1=2C(OCC)=C(C(O)=O)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 YUEDRIPQRRVFJV-UHFFFAOYSA-N 0.000 description 2
- ZPWMFKICQTVLOU-UHFFFAOYSA-N 3-methoxy-4-methylfuro[3,2-b]indole-2-carboxylic acid Chemical compound C12=CC=CC=C2N(C)C2=C1OC(C(O)=O)=C2OC ZPWMFKICQTVLOU-UHFFFAOYSA-N 0.000 description 2
- BKFIBMISQJZFFP-UHFFFAOYSA-N 3-methoxy-4-phenylfuro[3,2-b]indole-2-carboxamide Chemical compound C1=2C(OC)=C(C(N)=O)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 BKFIBMISQJZFFP-UHFFFAOYSA-N 0.000 description 2
- UIUZYXSRFZINPJ-UHFFFAOYSA-N 3-methoxy-4-phenylfuro[3,2-b]indole-2-carboxylic acid Chemical compound C1=2C(OC)=C(C(O)=O)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 UIUZYXSRFZINPJ-UHFFFAOYSA-N 0.000 description 2
- FRAOAVMBDZUBCZ-UHFFFAOYSA-N 6-methoxy-1-phenyl-2h-3,1-benzoxazin-4-one Chemical compound C1OC(=O)C2=CC(OC)=CC=C2N1C1=CC=CC=C1 FRAOAVMBDZUBCZ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102100038916 Caspase-5 Human genes 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 101100112336 Homo sapiens CASP5 gene Proteins 0.000 description 2
- 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 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 101100273286 Mus musculus Casp4 gene Proteins 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000001483 arginine derivatives Chemical class 0.000 description 2
- 210000003651 basophil Anatomy 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 2
- 229940008406 diethyl sulfate Drugs 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
- QBYZWKQETPWEPB-UHFFFAOYSA-N ethyl 3-(2-ethoxy-2-oxoethoxy)-1-methylindole-2-carboxylate Chemical compound C1=CC=C2C(OCC(=O)OCC)=C(C(=O)OCC)N(C)C2=C1 QBYZWKQETPWEPB-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
- SNBBSWPBQYKAKK-UHFFFAOYSA-N methyl 3-(2-methoxy-2-oxoethoxy)-1-phenylindole-2-carboxylate Chemical compound C12=CC=CC=C2C(OCC(=O)OC)=C(C(=O)OC)N1C1=CC=CC=C1 SNBBSWPBQYKAKK-UHFFFAOYSA-N 0.000 description 2
- SKQDAKUPRAMWKY-UHFFFAOYSA-N methyl 3-ethoxy-7-methoxy-4-phenylfuro[3,2-b]indole-2-carboxylate Chemical compound C1=2C(OCC)=C(C(=O)OC)OC=2C2=CC(OC)=CC=C2N1C1=CC=CC=C1 SKQDAKUPRAMWKY-UHFFFAOYSA-N 0.000 description 2
- ODWPOBLOANXRFF-UHFFFAOYSA-N methyl 3-hydroxy-7-methoxy-4-phenylfuro[3,2-b]indole-2-carboxylate Chemical compound C1=2C(O)=C(C(=O)OC)OC=2C2=CC(OC)=CC=C2N1C1=CC=CC=C1 ODWPOBLOANXRFF-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
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- UOCRBEBVQFQIKZ-UHFFFAOYSA-N 3-methoxy-4-phenyl-n-(2h-tetrazol-5-yl)furo[3,2-b]indole-2-carboxamide Chemical compound C1=2C(OC)=C(C(=O)NC=3NN=NN=3)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 UOCRBEBVQFQIKZ-UHFFFAOYSA-N 0.000 description 1
- HORCQVXSANZLAY-UHFFFAOYSA-N 3-methoxy-4-phenylfuro[3,2-b]indole-2-carbonitrile Chemical compound C1=2C(OC)=C(C#N)OC=2C2=CC=CC=C2N1C1=CC=CC=C1 HORCQVXSANZLAY-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
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- YSVZGWAJIHWNQK-UHFFFAOYSA-N [3-(hydroxymethyl)-2-bicyclo[2.2.1]heptanyl]methanol Chemical compound C1CC2C(CO)C(CO)C1C2 YSVZGWAJIHWNQK-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
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- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- 238000010009 beating Methods 0.000 description 1
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- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
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- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
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- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
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- 238000011067 equilibration Methods 0.000 description 1
- QQXQAEWRSVZPJM-UHFFFAOYSA-N ethyl 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)=CC2=C1 QQXQAEWRSVZPJM-UHFFFAOYSA-N 0.000 description 1
- BUOMKXFHDBIKSX-UHFFFAOYSA-N ethyl 3-hydroxy-4-methylfuro[3,2-b]indole-2-carboxylate Chemical compound C12=CC=CC=C2N(C)C2=C1OC(C(=O)OCC)=C2O BUOMKXFHDBIKSX-UHFFFAOYSA-N 0.000 description 1
- NPEIRKVWYZPQHS-UHFFFAOYSA-N ethyl 3-methoxy-4-methylfuro[3,2-b]indole-2-carboxylate Chemical compound C12=CC=CC=C2N(C)C2=C1OC(C(=O)OCC)=C2OC NPEIRKVWYZPQHS-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
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- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
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- 150000007529 inorganic bases Chemical class 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
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- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- PFDAYINMOWUOHA-UHFFFAOYSA-N methyl 3,5-dimethoxy-4-phenylfuro[3,2-b]indole-2-carboxylate Chemical compound COC(=O)C1=C(C=2N(C=3C(=CC=CC=3C=2O1)OC)C1=CC=CC=C1)OC PFDAYINMOWUOHA-UHFFFAOYSA-N 0.000 description 1
- WIHCDHFIANBLMI-UHFFFAOYSA-N methyl 3-hydroxy-1-phenylindole-2-carboxylate Chemical compound COC(=O)C1=C(O)C2=CC=CC=C2N1C1=CC=CC=C1 WIHCDHFIANBLMI-UHFFFAOYSA-N 0.000 description 1
- CQVGHRNBLPXJBR-UHFFFAOYSA-N methyl 3-hydroxy-5-methoxy-1-phenylindole-2-carboxylate Chemical compound COC(=O)C1=C(O)C2=CC(OC)=CC=C2N1C1=CC=CC=C1 CQVGHRNBLPXJBR-UHFFFAOYSA-N 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- PDCGPFRWMCASKR-UHFFFAOYSA-N pyrano[3,2-b]indole Chemical class C1=COC2=C3C=CC=CC3=NC2=C1 PDCGPFRWMCASKR-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 235000011182 sodium carbonates Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 229910000859 α-Fe Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/20—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 4
- C07D265/22—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36944882A | 1982-04-19 | 1982-04-19 | |
| US36944882 | 1982-04-19 | ||
| US45612183 | 1983-01-10 | ||
| US06/456,121 US4503236A (en) | 1982-04-19 | 1983-01-10 | Antiallergic 4Hfuro[3,2-b]indoles |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI831272A0 FI831272A0 (fi) | 1983-04-15 |
| FI831272L FI831272L (fi) | 1983-10-20 |
| FI77246B FI77246B (fi) | 1988-10-31 |
| FI77246C true FI77246C (fi) | 1989-02-10 |
Family
ID=27004584
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI831272A FI77246C (fi) | 1982-04-19 | 1983-04-15 | Foerfarande foer framstaellning av antiallergiska 4h-furo/3,2-b/indoler. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4503236A (OSRAM) |
| EP (1) | EP0092380B1 (OSRAM) |
| KR (1) | KR870000933B1 (OSRAM) |
| AR (1) | AR240457A1 (OSRAM) |
| AU (1) | AU556487B2 (OSRAM) |
| CA (1) | CA1194880A (OSRAM) |
| DE (1) | DE3375396D1 (OSRAM) |
| DK (1) | DK157025C (OSRAM) |
| ES (1) | ES521563A0 (OSRAM) |
| FI (1) | FI77246C (OSRAM) |
| GR (1) | GR78343B (OSRAM) |
| HU (1) | HU191209B (OSRAM) |
| IE (1) | IE54834B1 (OSRAM) |
| IL (1) | IL68192A (OSRAM) |
| NO (1) | NO159600C (OSRAM) |
| NZ (1) | NZ203908A (OSRAM) |
| PH (1) | PH18914A (OSRAM) |
| PT (1) | PT76570B (OSRAM) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4596814A (en) * | 1983-01-10 | 1986-06-24 | Warner-Lambert Company | Tetrazolyl- and carboxamidotetrazolyl-substituted 4H-furo[3,2-b] indoles and anti-allergic use thereof |
| US4748183A (en) * | 1986-06-13 | 1988-05-31 | Warner-Lambert Company | N-1H-tetrazol-5-yl-2-thiophene carboxamides, N-1H-tetrazol-5-yl-2-pyrrole carboxamides, N-1H-tetrazol-5-yl-2-furan carboxamides, and anti-allergic and anti-inflammatory use thereof |
| JPH04217684A (ja) * | 1990-05-30 | 1992-08-07 | Shionogi & Co Ltd | アルド−ス還元酵素阻害物質 |
| GB9110625D0 (en) * | 1991-05-16 | 1991-07-03 | Glaxo Group Ltd | Chemical compounds |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1296469A (OSRAM) * | 1970-02-05 | 1972-11-15 | ||
| US4028383A (en) * | 1975-09-08 | 1977-06-07 | Warner-Lambert Company | Indolopyrones having antiallergic activity |
| DE2837236A1 (de) * | 1977-09-30 | 1979-04-05 | Warner Lambert Co | Indolopyrone und ihre verwendung |
-
1983
- 1983-01-10 US US06/456,121 patent/US4503236A/en not_active Expired - Lifetime
- 1983-03-21 IE IE612/83A patent/IE54834B1/en not_active IP Right Cessation
- 1983-03-22 IL IL68192A patent/IL68192A/xx unknown
- 1983-04-14 GR GR71084A patent/GR78343B/el unknown
- 1983-04-14 EP EP83302099A patent/EP0092380B1/en not_active Expired
- 1983-04-14 AU AU13511/83A patent/AU556487B2/en not_active Expired
- 1983-04-14 DE DE8383302099T patent/DE3375396D1/de not_active Expired
- 1983-04-15 KR KR1019830001595A patent/KR870000933B1/ko not_active Expired
- 1983-04-15 FI FI831272A patent/FI77246C/fi not_active IP Right Cessation
- 1983-04-15 PH PH28783A patent/PH18914A/en unknown
- 1983-04-18 NZ NZ203908A patent/NZ203908A/en unknown
- 1983-04-18 ES ES521563A patent/ES521563A0/es active Granted
- 1983-04-18 NO NO831364A patent/NO159600C/no not_active IP Right Cessation
- 1983-04-18 HU HU831341A patent/HU191209B/hu not_active IP Right Cessation
- 1983-04-18 DK DK169783A patent/DK157025C/da not_active IP Right Cessation
- 1983-04-19 PT PT76570A patent/PT76570B/pt unknown
- 1983-04-19 CA CA000426192A patent/CA1194880A/en not_active Expired
- 1983-04-19 AR AR292747A patent/AR240457A1/es active
Also Published As
| Publication number | Publication date |
|---|---|
| EP0092380A3 (en) | 1984-05-30 |
| FI831272L (fi) | 1983-10-20 |
| NZ203908A (en) | 1985-12-13 |
| PT76570A (en) | 1983-05-01 |
| AR240457A1 (es) | 1990-03-30 |
| KR840004432A (ko) | 1984-10-15 |
| NO159600B (no) | 1988-10-10 |
| EP0092380A2 (en) | 1983-10-26 |
| IE54834B1 (en) | 1990-02-28 |
| HU191209B (en) | 1987-01-28 |
| AU556487B2 (en) | 1986-11-06 |
| CA1194880A (en) | 1985-10-08 |
| KR870000933B1 (ko) | 1987-05-11 |
| DE3375396D1 (en) | 1988-02-25 |
| IL68192A0 (en) | 1983-06-15 |
| PH18914A (en) | 1985-11-06 |
| IE830612L (en) | 1983-10-19 |
| DK157025C (da) | 1990-03-26 |
| DK169783A (da) | 1983-10-20 |
| ES8406486A1 (es) | 1984-07-01 |
| US4503236A (en) | 1985-03-05 |
| DK157025B (da) | 1989-10-30 |
| NO831364L (no) | 1983-10-20 |
| DK169783D0 (da) | 1983-04-18 |
| EP0092380B1 (en) | 1988-01-20 |
| FI77246B (fi) | 1988-10-31 |
| FI831272A0 (fi) | 1983-04-15 |
| PT76570B (pt) | 1985-12-10 |
| NO159600C (no) | 1989-01-18 |
| GR78343B (OSRAM) | 1984-09-26 |
| AU1351183A (en) | 1983-10-27 |
| ES521563A0 (es) | 1984-07-01 |
| IL68192A (en) | 1985-11-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |
Owner name: WARNER-LAMBERT COMPANY |