NO312550B1 - Piperazinderivater, fremgangsmåte for fremstilling derav, farmasöytiske preparater, fremgangsmåte for fremstilling derav,samt anvendelse av forbindelsene for fremstilling av et legemiddel - Google Patents
Piperazinderivater, fremgangsmåte for fremstilling derav, farmasöytiske preparater, fremgangsmåte for fremstilling derav,samt anvendelse av forbindelsene for fremstilling av et legemiddel Download PDFInfo
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- NO312550B1 NO312550B1 NO19940308A NO940308A NO312550B1 NO 312550 B1 NO312550 B1 NO 312550B1 NO 19940308 A NO19940308 A NO 19940308A NO 940308 A NO940308 A NO 940308A NO 312550 B1 NO312550 B1 NO 312550B1
- Authority
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- Norway
- Prior art keywords
- acid
- formula
- amidino
- cbz
- compound
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- 150000001875 compounds Chemical class 0.000 title claims description 57
- 238000000034 method Methods 0.000 title claims description 18
- 238000002360 preparation method Methods 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 5
- 239000003814 drug Substances 0.000 title description 4
- 150000004885 piperazines Chemical class 0.000 title description 4
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 3
- -1 amino compound Chemical class 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 40
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 150000002825 nitriles Chemical class 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims 2
- 229940126601 medicinal product Drugs 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 238000009833 condensation Methods 0.000 description 37
- 230000005494 condensation Effects 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 239000005711 Benzoic acid Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 229940095574 propionic acid Drugs 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 125000006239 protecting group Chemical group 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 239000000203 mixture Substances 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- JXYACYYPACQCDM-UHFFFAOYSA-N Benzyl glycinate Chemical compound NCC(=O)OCC1=CC=CC=C1 JXYACYYPACQCDM-UHFFFAOYSA-N 0.000 description 7
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- 238000007327 hydrogenolysis reaction Methods 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
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- 239000002775 capsule Substances 0.000 description 5
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- 239000007858 starting material Substances 0.000 description 5
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- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 4
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- 108010049003 Fibrinogen Proteins 0.000 description 4
- 102000008946 Fibrinogen Human genes 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
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- 238000003776 cleavage reaction Methods 0.000 description 4
- 229940012952 fibrinogen Drugs 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- QIQNEKPUOKXSSQ-UHFFFAOYSA-N 4-[[(e)-n'-phenylmethoxycarbonylcarbamimidoyl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=N)NC(=O)OCC1=CC=CC=C1 QIQNEKPUOKXSSQ-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- CCFAEQCRNBORIA-UHFFFAOYSA-N benzyl 3-[(3-aminobenzoyl)amino]propanoate Chemical compound NC1=CC=CC(C(=O)NCCC(=O)OCC=2C=CC=CC=2)=C1 CCFAEQCRNBORIA-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 238000003797 solvolysis reaction Methods 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 2
- ZNSCNEXVSYOLKX-UHFFFAOYSA-N 2-[[3-[3-(4-carbamimidoylpiperazin-1-yl)propanoylamino]benzoyl]amino]acetic acid Chemical compound C1CN(C(=N)N)CCN1CCC(=O)NC1=CC=CC(C(=O)NCC(O)=O)=C1 ZNSCNEXVSYOLKX-UHFFFAOYSA-N 0.000 description 2
- AGYXIUAGBLMBGV-UHFFFAOYSA-N 3,5-dimethylpyrazole-1-carboximidamide;nitric acid Chemical compound O[N+]([O-])=O.CC=1C=C(C)N(C(N)=N)N=1 AGYXIUAGBLMBGV-UHFFFAOYSA-N 0.000 description 2
- XFHPNOOMTXIKHP-UHFFFAOYSA-N 3-[[3-[3-(4-carbamimidoylpiperazin-1-yl)propanoylamino]benzoyl]amino]propanoic acid Chemical compound C1CN(C(=N)N)CCN1CCC(=O)NC1=CC=CC(C(=O)NCCC(O)=O)=C1 XFHPNOOMTXIKHP-UHFFFAOYSA-N 0.000 description 2
- DGXDRJRSUROHKK-UHFFFAOYSA-N 4-[[(e)-n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]amino]benzoic acid Chemical compound CC(C)(C)OC(=O)NC(=N)NC1=CC=C(C(O)=O)C=C1 DGXDRJRSUROHKK-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 150000001409 amidines Chemical class 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 229960005261 aspartic acid Drugs 0.000 description 2
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- QEXYDSARFDWBPV-UHFFFAOYSA-N benzyl 3-piperazin-1-ylpropanoate Chemical compound C=1C=CC=CC=1COC(=O)CCN1CCNCC1 QEXYDSARFDWBPV-UHFFFAOYSA-N 0.000 description 2
- LLCAGGALYNKVMZ-UHFFFAOYSA-N benzyl 4-piperazin-1-ylbutanoate Chemical compound C=1C=CC=CC=1COC(=O)CCCN1CCNCC1 LLCAGGALYNKVMZ-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
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- BQAMWLOABQRMAO-INIZCTEOSA-N dibenzyl (2s)-2-aminobutanedioate Chemical compound C([C@H](N)C(=O)OCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 BQAMWLOABQRMAO-INIZCTEOSA-N 0.000 description 2
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- 238000011065 in-situ storage Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
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- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- TVIXZLZZBKFVFK-UHFFFAOYSA-N methyl 3-[(3-aminobenzoyl)amino]propanoate Chemical compound COC(=O)CCNC(=O)C1=CC=CC(N)=C1 TVIXZLZZBKFVFK-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
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- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
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- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
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- JBSDXENZQVUCIE-UHFFFAOYSA-N 3-[3-(2-carbamimidoyl-4-phenylmethoxycarbonylpiperazin-1-yl)propanoylamino]benzoic acid Chemical compound NC(=N)C1CN(C(=O)OCC=2C=CC=CC=2)CCN1CCC(=O)NC1=CC=CC(C(O)=O)=C1 JBSDXENZQVUCIE-UHFFFAOYSA-N 0.000 description 1
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- WZCAJNQJLGEKHR-UHFFFAOYSA-N 3-[4-[4-(diaminomethylideneamino)benzoyl]piperazin-1-yl]propanoic acid Chemical compound C1=CC(NC(=N)N)=CC=C1C(=O)N1CCN(CCC(O)=O)CC1 WZCAJNQJLGEKHR-UHFFFAOYSA-N 0.000 description 1
- IKUOLOGZEGQMLN-UHFFFAOYSA-N 3-[4-[4-[[(e)-n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]amino]benzoyl]-2-oxopiperazin-1-yl]propanoic acid Chemical compound C1=CC(NC(=N)NC(=O)OC(C)(C)C)=CC=C1C(=O)N1CC(=O)N(CCC(O)=O)CC1 IKUOLOGZEGQMLN-UHFFFAOYSA-N 0.000 description 1
- NTVPLCKAVFJYBA-UHFFFAOYSA-N 3-[[3-(2-piperazin-1-ylpropanoylamino)benzoyl]amino]propanoic acid Chemical compound C=1C=CC(C(=O)NCCC(O)=O)=CC=1NC(=O)C(C)N1CCNCC1 NTVPLCKAVFJYBA-UHFFFAOYSA-N 0.000 description 1
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- QKBCHGQQPLLWKL-UHFFFAOYSA-N 3-[[3-[2-(4-carbamimidoylpiperazin-1-yl)propanoylamino]benzoyl]amino]propanoic acid Chemical compound C=1C=CC(C(=O)NCCC(O)=O)=CC=1NC(=O)C(C)N1CCN(C(N)=N)CC1 QKBCHGQQPLLWKL-UHFFFAOYSA-N 0.000 description 1
- ZQAHPPWSXZJMQO-UHFFFAOYSA-N 3-amino-3-imino-2-[[4-[(2-methylpropan-2-yl)oxycarbonyl]benzoyl]amino]propanoic acid Chemical compound CC(C)(C)OC(=O)C1=CC=C(C(=O)NC(C(N)=N)C(O)=O)C=C1 ZQAHPPWSXZJMQO-UHFFFAOYSA-N 0.000 description 1
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- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- ZTWBXCGKRKUYSY-UHFFFAOYSA-N piperazine-1-carboximidamide Chemical class NC(=N)N1CCNCC1 ZTWBXCGKRKUYSY-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 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
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-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
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/033—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Nutrition Science (AREA)
- Obesity (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4302485A DE4302485A1 (de) | 1993-01-29 | 1993-01-29 | Piperazinderivate |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO940308D0 NO940308D0 (no) | 1994-01-28 |
| NO940308L NO940308L (no) | 1994-08-01 |
| NO312550B1 true NO312550B1 (no) | 2002-05-27 |
Family
ID=6479203
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19940308A NO312550B1 (no) | 1993-01-29 | 1994-01-28 | Piperazinderivater, fremgangsmåte for fremstilling derav, farmasöytiske preparater, fremgangsmåte for fremstilling derav,samt anvendelse av forbindelsene for fremstilling av et legemiddel |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US5908843A (sk) |
| EP (1) | EP0608759B1 (sk) |
| JP (1) | JPH06271549A (sk) |
| KR (1) | KR100312539B1 (sk) |
| CN (1) | CN1056141C (sk) |
| AT (1) | ATE204570T1 (sk) |
| AU (1) | AU670649B2 (sk) |
| CA (1) | CA2114361A1 (sk) |
| CZ (1) | CZ288122B6 (sk) |
| DE (2) | DE4302485A1 (sk) |
| DK (1) | DK0608759T3 (sk) |
| ES (1) | ES2162825T3 (sk) |
| GR (1) | GR3036838T3 (sk) |
| HU (1) | HU222013B1 (sk) |
| NO (1) | NO312550B1 (sk) |
| PL (1) | PL172716B1 (sk) |
| PT (1) | PT608759E (sk) |
| RU (1) | RU2154639C2 (sk) |
| SK (1) | SK281842B6 (sk) |
| UA (1) | UA34429C2 (sk) |
| ZA (1) | ZA94615B (sk) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL115420A0 (en) | 1994-09-26 | 1995-12-31 | Zeneca Ltd | Aminoheterocyclic derivatives |
| AU1608397A (en) | 1996-02-02 | 1997-08-22 | Zeneca Limited | Heterocyclic compounds useful as pharmaceutical agents |
| GB9602166D0 (en) * | 1996-02-02 | 1996-04-03 | Zeneca Ltd | Aminoheterocyclic derivatives |
| GB9602294D0 (en) * | 1996-02-05 | 1996-04-03 | Zeneca Ltd | Heterocyclic compounds |
| AU3738597A (en) * | 1996-07-25 | 1998-02-20 | Biogen, Inc. | Molecular model for vla-4 inhibitors |
| TR199900303T2 (xx) * | 1996-08-14 | 1999-06-21 | Zeneca Limited | �kame edilmi� pirimidin t�revleri ve bunlar�n farmas�tik kullan�m�. |
| UA56197C2 (uk) | 1996-11-08 | 2003-05-15 | Зенека Лімітед | Гетероциклічні похідні |
| ATE242774T1 (de) | 1997-02-13 | 2003-06-15 | Astrazeneca Ab | Heterozyklische verbindungen die als oxido- squalen-zyklase-inhibitoren anwendung finden |
| JP2001511798A (ja) | 1997-02-13 | 2001-08-14 | ゼネカ・リミテッド | オキシド−スクアレンシクラーゼ抑制剤として有用な複素環化合物 |
| GB9715895D0 (en) | 1997-07-29 | 1997-10-01 | Zeneca Ltd | Heterocyclic compounds |
| DE19743435A1 (de) * | 1997-10-01 | 1999-04-08 | Merck Patent Gmbh | Benzamidinderivate |
| FR2781220B1 (fr) | 1998-07-17 | 2000-10-13 | Lafon Labor | Piperazinones substituees en beta |
| FR2781221B1 (fr) * | 1998-07-17 | 2000-10-13 | Lafon Labor | Piperazinones substituees en alpha |
| DE19835950A1 (de) * | 1998-08-08 | 2000-02-10 | Merck Patent Gmbh | Piperazinonderivate |
| GB9902989D0 (en) | 1999-02-11 | 1999-03-31 | Zeneca Ltd | Heterocyclic derivatives |
| CA2380218A1 (en) * | 1999-07-26 | 2001-02-01 | Santen Pharmaceutical Co., Ltd. | Novel thiazine or pyrazine derivatives |
| CN1703395A (zh) * | 2002-08-09 | 2005-11-30 | 特兰斯泰克制药公司 | 芳基和杂芳基化合物以及调节凝血的方法 |
| AU2004244982A1 (en) * | 2003-06-02 | 2004-12-16 | Georgetown University | Anti-HIV benzamide compounds |
| US20060194814A1 (en) * | 2003-06-02 | 2006-08-31 | Vassilios Papadopoulos | Benzamide compounds |
| US7208601B2 (en) * | 2003-08-08 | 2007-04-24 | Mjalli Adnan M M | Aryl and heteroaryl compounds, compositions, and methods of use |
| US7501538B2 (en) * | 2003-08-08 | 2009-03-10 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions and methods of use |
| TW200738701A (en) * | 2005-07-26 | 2007-10-16 | Du Pont | Fungicidal carboxamides |
| CA2606004A1 (en) * | 2005-08-02 | 2007-02-08 | Neurogen Corporation | Dipiperazinyl ketones and related analogues |
| MX2021007475A (es) | 2018-12-19 | 2021-08-05 | Celgene Corp | Compuestos de 3-((3-aminofenil)amino)piperidina-2,6-diona sustituida, composiciones de estos y metodos de tratamiento con estos. |
| CN113453681B (zh) | 2018-12-19 | 2024-10-11 | 细胞基因公司 | 经取代的3-((3-氨基苯基)氨基)哌啶-2，6-二酮化合物、其组合物及使用它们的治疗方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3711335A1 (de) * | 1987-04-03 | 1988-10-20 | Merck Patent Gmbh | Aminosaeurederivate |
| US5053393A (en) * | 1988-07-20 | 1991-10-01 | Monsanto Company | Novel platelet-aggregation inhibitor |
| US5084466A (en) * | 1989-01-31 | 1992-01-28 | Hoffmann-La Roche Inc. | Novel carboxamide pyridine compounds which have useful pharmaceutical utility |
| DE4007869A1 (de) * | 1990-03-13 | 1991-09-19 | Merck Patent Gmbh | Aminosaeurederivate |
| IL99537A (en) * | 1990-09-27 | 1995-11-27 | Merck & Co Inc | Fibrinogen receptor antagonists and pharmaceutical preparations containing them |
| US5294713A (en) * | 1991-08-23 | 1994-03-15 | Takeda Chemical Industries, Ltd. | 2-piperazinone compounds and their use |
| JP3719612B2 (ja) * | 1993-06-14 | 2005-11-24 | 塩野義製薬株式会社 | ヘテロ環を含有する尿素誘導体 |
-
1993
- 1993-01-29 DE DE4302485A patent/DE4302485A1/de not_active Withdrawn
- 1993-11-30 UA UA93003858A patent/UA34429C2/uk unknown
-
1994
- 1994-01-18 JP JP6003451A patent/JPH06271549A/ja active Pending
- 1994-01-19 AT AT94100709T patent/ATE204570T1/de not_active IP Right Cessation
- 1994-01-19 DK DK94100709T patent/DK0608759T3/da active
- 1994-01-19 EP EP94100709A patent/EP0608759B1/de not_active Expired - Lifetime
- 1994-01-19 PT PT94100709T patent/PT608759E/pt unknown
- 1994-01-19 ES ES94100709T patent/ES2162825T3/es not_active Expired - Lifetime
- 1994-01-19 DE DE59409833T patent/DE59409833D1/de not_active Expired - Fee Related
- 1994-01-20 SK SK68-94A patent/SK281842B6/sk unknown
- 1994-01-25 AU AU54702/94A patent/AU670649B2/en not_active Ceased
- 1994-01-25 CZ CZ1994163A patent/CZ288122B6/cs unknown
- 1994-01-25 CN CN94101127A patent/CN1056141C/zh not_active Expired - Fee Related
- 1994-01-27 CA CA002114361A patent/CA2114361A1/en not_active Abandoned
- 1994-01-28 ZA ZA94615A patent/ZA94615B/xx unknown
- 1994-01-28 KR KR1019940001512A patent/KR100312539B1/ko not_active IP Right Cessation
- 1994-01-28 HU HU9400249A patent/HU222013B1/hu not_active IP Right Cessation
- 1994-01-28 RU RU94002323/04A patent/RU2154639C2/ru not_active IP Right Cessation
- 1994-01-28 PL PL94302069A patent/PL172716B1/pl unknown
- 1994-01-28 NO NO19940308A patent/NO312550B1/no not_active IP Right Cessation
- 1994-01-31 US US08/189,385 patent/US5908843A/en not_active Expired - Fee Related
-
2001
- 2001-10-09 GR GR20010401700T patent/GR3036838T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0608759B1 (de) | 2001-08-22 |
| CZ16394A3 (en) | 1994-08-17 |
| DE4302485A1 (de) | 1994-08-04 |
| HU9400249D0 (en) | 1994-05-30 |
| HUT70042A (en) | 1995-09-28 |
| JPH06271549A (ja) | 1994-09-27 |
| DK0608759T3 (da) | 2001-12-03 |
| ES2162825T3 (es) | 2002-01-16 |
| CA2114361A1 (en) | 1994-07-30 |
| NO940308L (no) | 1994-08-01 |
| EP0608759A2 (de) | 1994-08-03 |
| RU2154639C2 (ru) | 2000-08-20 |
| DE59409833D1 (de) | 2001-09-27 |
| EP0608759A3 (de) | 1994-10-05 |
| NO940308D0 (no) | 1994-01-28 |
| SK281842B6 (sk) | 2001-08-06 |
| PL302069A1 (en) | 1994-08-08 |
| CZ288122B6 (cs) | 2001-04-11 |
| PL172716B1 (pl) | 1997-11-28 |
| US5908843A (en) | 1999-06-01 |
| KR940018372A (ko) | 1994-08-16 |
| CN1099759A (zh) | 1995-03-08 |
| SK6894A3 (en) | 1994-08-10 |
| KR100312539B1 (ko) | 2002-02-19 |
| GR3036838T3 (en) | 2002-01-31 |
| ATE204570T1 (de) | 2001-09-15 |
| PT608759E (pt) | 2002-02-28 |
| CN1056141C (zh) | 2000-09-06 |
| UA34429C2 (uk) | 2001-03-15 |
| AU5470294A (en) | 1994-08-04 |
| HU222013B1 (hu) | 2003-03-28 |
| AU670649B2 (en) | 1996-07-25 |
| ZA94615B (en) | 1994-09-13 |
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