SK279525B6 - Xantínové deriváty, spôsob ich výroby, farmaceutic - Google Patents
Xantínové deriváty, spôsob ich výroby, farmaceutic Download PDFInfo
- Publication number
- SK279525B6 SK279525B6 SK7197-89A SK719789A SK279525B6 SK 279525 B6 SK279525 B6 SK 279525B6 SK 719789 A SK719789 A SK 719789A SK 279525 B6 SK279525 B6 SK 279525B6
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- Slovakia
- Prior art keywords
- formula
- alkyl
- group
- compound
- substituted
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- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 238000000034 method Methods 0.000 title claims abstract description 43
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 230000008569 process Effects 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 72
- -1 tetrahydropyran-4-yl Chemical group 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 229940075420 xanthine Drugs 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- RUHGOZFOVBMWOO-UHFFFAOYSA-N 8-(3-oxocyclopentyl)-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1CCC(=O)C1 RUHGOZFOVBMWOO-UHFFFAOYSA-N 0.000 claims description 9
- 229910004013 NO 2 Inorganic materials 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- NRECPLZNMXAXRH-UHFFFAOYSA-N 8-(3-hydroxycyclopentyl)-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1CCC(O)C1 NRECPLZNMXAXRH-UHFFFAOYSA-N 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 150000001940 cyclopentanes Chemical group 0.000 claims description 5
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Chemical group C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 5
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Chemical group C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 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 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 4
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000002829 reductive effect Effects 0.000 claims description 4
- 238000003747 Grignard reaction Methods 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 3
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 claims description 3
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 abstract description 8
- 239000002126 C01EB10 - Adenosine Substances 0.000 abstract description 4
- 229960005305 adenosine Drugs 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 208000014644 Brain disease Diseases 0.000 abstract 1
- 230000003412 degenerative effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 100
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- 239000000203 mixture Substances 0.000 description 53
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 239000013078 crystal Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 150000001299 aldehydes Chemical class 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 150000001298 alcohols Chemical class 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000005984 hydrogenation reaction Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 5
- 239000004367 Lipase Substances 0.000 description 5
- 108090001060 Lipase Proteins 0.000 description 5
- 102000004882 Lipase Human genes 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 235000019421 lipase Nutrition 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000006798 ring closing metathesis reaction Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 230000027455 binding Effects 0.000 description 4
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 4
- 239000000920 calcium hydroxide Substances 0.000 description 4
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 230000009935 nitrosation Effects 0.000 description 4
- 238000007034 nitrosation reaction Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- SVMBOONGPUFHRA-UHFFFAOYSA-N 5,6-diamino-1,3-dipropylpyrimidine-2,4-dione Chemical compound CCCN1C(N)=C(N)C(=O)N(CCC)C1=O SVMBOONGPUFHRA-UHFFFAOYSA-N 0.000 description 3
- JSAVMACNWUUICZ-UHFFFAOYSA-N 5-(2,6-dioxo-1,3-dipropyl-7h-purin-8-yl)furan-2-carbaldehyde Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1=CC=C(C=O)O1 JSAVMACNWUUICZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
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- RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 description 2
- WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 description 2
- QCZZSANNLWPGEA-UHFFFAOYSA-N 1-(4-phenylphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C1=CC=CC=C1 QCZZSANNLWPGEA-UHFFFAOYSA-N 0.000 description 2
- CWKXDPPQCVWXAG-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Chemical compound O1CCOC2=CC(C=O)=CC=C21 CWKXDPPQCVWXAG-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 2
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 2
- BBTNLADSUVOPPN-UHFFFAOYSA-N 5,6-diaminouracil Chemical class NC=1NC(=O)NC(=O)C=1N BBTNLADSUVOPPN-UHFFFAOYSA-N 0.000 description 2
- IHFUYEBTRLHPDC-UHFFFAOYSA-N 5-(2,6-dioxo-1,3-dipropyl-7h-purin-8-yl)furan-2-carboxylic acid Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1=CC=C(C(O)=O)O1 IHFUYEBTRLHPDC-UHFFFAOYSA-N 0.000 description 2
- QMKJOZVQZBJSEC-UHFFFAOYSA-N 6-amino-1-benzylpyrimidine-2,4-dione Chemical compound NC1=CC(=O)NC(=O)N1CC1=CC=CC=C1 QMKJOZVQZBJSEC-UHFFFAOYSA-N 0.000 description 2
- 102000055025 Adenosine deaminases Human genes 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000069665 Crenosoma striatum Species 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
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- 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
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
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- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
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- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
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- 239000012279 sodium borohydride Substances 0.000 description 2
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- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
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- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Steroid Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3843117A DE3843117A1 (de) | 1988-12-22 | 1988-12-22 | Neue xanthinderivate mit adenosin-antagonistischer wirkung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK719789A3 SK719789A3 (en) | 1998-12-02 |
| SK279525B6 true SK279525B6 (sk) | 1998-12-02 |
Family
ID=6369764
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK7197-89A SK279525B6 (sk) | 1988-12-22 | 1989-12-19 | Xantínové deriváty, spôsob ich výroby, farmaceutic |
Country Status (32)
| Country | Link |
|---|---|
| US (4) | US5175291A (cs) |
| EP (1) | EP0374808B1 (cs) |
| JP (1) | JP2565576B2 (cs) |
| KR (1) | KR0165666B1 (cs) |
| AT (1) | ATE136897T1 (cs) |
| BG (1) | BG61669B2 (cs) |
| BR (1) | BR1100527A (cs) |
| CA (1) | CA2006387C (cs) |
| CZ (1) | CZ286230B6 (cs) |
| DD (1) | DD290421A5 (cs) |
| DE (3) | DE3843117A1 (cs) |
| DK (1) | DK652689A (cs) |
| ES (1) | ES2086313T3 (cs) |
| FI (1) | FI96513C (cs) |
| GR (1) | GR3019733T3 (cs) |
| HR (1) | HRP940724A2 (cs) |
| HU (1) | HU218674B (cs) |
| IE (1) | IE74205B1 (cs) |
| IL (1) | IL92829A (cs) |
| MX (1) | MX9203618A (cs) |
| NO (1) | NO173502C (cs) |
| NZ (1) | NZ231901A (cs) |
| PH (2) | PH31107A (cs) |
| PL (1) | PL162877B1 (cs) |
| PT (1) | PT92658B (cs) |
| RU (1) | RU2057752C1 (cs) |
| SG (1) | SG46380A1 (cs) |
| SI (1) | SI8912423B (cs) |
| SK (1) | SK279525B6 (cs) |
| UA (1) | UA26427A (cs) |
| YU (1) | YU47934B (cs) |
| ZA (1) | ZA899881B (cs) |
Families Citing this family (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3843117A1 (de) * | 1988-12-22 | 1990-06-28 | Boehringer Ingelheim Kg | Neue xanthinderivate mit adenosin-antagonistischer wirkung |
| JPH06102662B2 (ja) * | 1989-09-01 | 1994-12-14 | 協和醗酵工業株式会社 | キサンチン誘導体 |
| US5290782A (en) * | 1989-09-01 | 1994-03-01 | Kyowa Hakko Kogyo Co., Ltd. | Xanthine derivatives |
| US5047534A (en) * | 1990-03-26 | 1991-09-10 | Merrell Dow Pharmaceuticals Inc. | Selective adenosine receptor agents |
| EP0459702A1 (en) * | 1990-05-29 | 1991-12-04 | Zeneca Limited | Azole Derivatives |
| DE4019892A1 (de) * | 1990-06-22 | 1992-01-02 | Boehringer Ingelheim Kg | Neue xanthinderivate |
| CA2061544A1 (en) * | 1991-02-25 | 1992-08-26 | Fumio Suzuki | Xanthine compounds |
| GB9111131D0 (en) * | 1991-05-23 | 1991-07-17 | Ici Plc | Heterocyclic compounds |
| GB9111130D0 (en) * | 1991-05-23 | 1991-07-17 | Ici Plc | Azole derivatives |
| EP0541120B1 (en) * | 1991-11-08 | 1999-05-26 | Kyowa Hakko Kogyo Co., Ltd. | Xanthine derivatives for the treatment of dementia |
| IT1260444B (it) * | 1992-01-24 | 1996-04-09 | Mario Brufani | Derivati della 8-(1-amminocicloalchil)1,3-dialchilxantina, procedimenbto di preparazione e loro composizioni farmaceutiche antidepressive, nootropiche e psicostimolanti |
| EP0556778A3 (en) * | 1992-02-17 | 1993-11-24 | Kyowa Hakko Kogyo Kk | Xanthine derivatives |
| CA2093403C (en) * | 1992-04-08 | 1999-08-10 | Fumio Suzuki | Therapeutic agent for parkinson's disease |
| US5484920A (en) * | 1992-04-08 | 1996-01-16 | Kyowa Hakko Kogyo Co., Ltd. | Therapeutic agent for Parkinson's disease |
| WO1994003173A1 (de) * | 1992-08-01 | 1994-02-17 | Boehringer Ingelheim Kg | Verwendung von 8-(3-oxocyclopentyl)-1,3-dipropyl-7h-purin-2,6-dion zur symptomatischen behandlung der zystischen fibrose |
| TW252044B (cs) * | 1992-08-10 | 1995-07-21 | Boehringer Ingelheim Kg | |
| US5288721A (en) * | 1992-09-22 | 1994-02-22 | Cell Therapeutics, Inc. | Substituted epoxyalkyl xanthines |
| JP2613355B2 (ja) * | 1992-09-28 | 1997-05-28 | 協和醗酵工業株式会社 | パーキンソン氏病治療剤 |
| US5877179A (en) * | 1992-09-29 | 1999-03-02 | The United States Of America As Represented By The Department Of Health And Human Services | Xanthines for identifying CFTR--binding compounds useful for activating chloride conductance in animal cells |
| DE4236331A1 (de) * | 1992-10-28 | 1994-05-05 | Boehringer Ingelheim Kg | Synergistische Kombination |
| AU6087894A (en) * | 1993-01-14 | 1994-08-15 | Cell Therapeutics, Inc. | Acetal or ketal substituted therapeutic compounds |
| AU680241B2 (en) * | 1993-02-26 | 1997-07-24 | Merrell Pharmaceuticals Inc. | Xanthine derivatives as adenosine A1 receptor antagonists |
| WO1994025462A1 (en) * | 1993-05-03 | 1994-11-10 | The United States Of America, Represented By The | 8-substituted 1,3,7-trialkyl-xanthine derivatives as a2-selective adenosine receptor antagonists |
| DE4316576A1 (de) * | 1993-05-18 | 1994-11-24 | Boehringer Ingelheim Kg | Verbessertes Verfahren zur Herstellung von 1,3-Dipropyl-8-(3-Oxocyclopentyl)-xanthin |
| US5736528A (en) * | 1993-10-28 | 1998-04-07 | University Of Florida Research Foundation, Inc. | N6 -(epoxynorborn-2-yl) adenosines as A1 adenosine receptor agonists |
| US5446046A (en) * | 1993-10-28 | 1995-08-29 | University Of Florida Research Foundation | A1 adenosine receptor agonists and antagonists as diuretics |
| JP3769737B2 (ja) * | 1994-03-30 | 2006-04-26 | 味の素株式会社 | シクロプロパン誘導体及びその製造法 |
| US5591776A (en) * | 1994-06-24 | 1997-01-07 | Euro-Celtique, S.A. | Pheynl or benzyl-substituted rolipram-based compounds for and method of inhibiting phosphodiesterase IV |
| CA2206804C (en) * | 1994-12-13 | 2002-03-19 | Euro-Celtique, S.A. | Trisubstituted thioxanthines |
| WO1996018399A1 (en) * | 1994-12-13 | 1996-06-20 | Euro-Celtique, S.A. | Aryl thioxanthines |
| US5864037A (en) * | 1996-06-06 | 1999-01-26 | Euro-Celtique, S.A. | Methods for the synthesis of chemical compounds having PDE-IV inhibitory activity |
| US5789416B1 (en) * | 1996-08-27 | 1999-10-05 | Cv Therapeutics Inc | N6 mono heterocyclic substituted adenosine derivatives |
| US5786360A (en) | 1996-11-19 | 1998-07-28 | Link Technology Incorporated | A1 adenosine receptor antagonists |
| DE69834500T2 (de) * | 1997-09-05 | 2007-05-03 | Kyowa Hakko Kogyo Co., Ltd. | Xanthinderivative zur behandlung von hirnischämie |
| US6248746B1 (en) | 1998-01-07 | 2001-06-19 | Euro-Celtique S.A. | 3-(arylalkyl) xanthines |
| DE19816857A1 (de) * | 1998-04-16 | 1999-10-21 | Boehringer Ingelheim Pharma | Neue unsymmetrisch substituierte Xanthin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| AU754094B2 (en) * | 1998-06-01 | 2002-11-07 | Astellas Pharma Inc. | Remedies for male sterility |
| AU4980999A (en) | 1998-07-10 | 2000-02-01 | United States Of America, Represented By The Secretary, Department Of Health And Human Services, The | A3 adenosine receptor antagonists |
| US6025362A (en) * | 1998-08-31 | 2000-02-15 | Fukunaga; Atsuo F. | Uses of xanthine compounds |
| US6576619B2 (en) | 1999-05-24 | 2003-06-10 | Cv Therapeutics, Inc. | Orally active A1 adenosine receptor agonists |
| US6545002B1 (en) | 1999-06-01 | 2003-04-08 | University Of Virginia Patent Foundation | Substituted 8-phenylxanthines useful as antagonists of A2B adenosine receptors |
| CZ20021615A3 (cs) * | 1999-11-12 | 2002-08-14 | Biogen, Inc. | Antagonisty adenosinového receptoru, způsoby jejich přípravy a způsoby jejich pouľití |
| ES2323357T3 (es) * | 1999-11-12 | 2009-07-14 | Biogen Idec Ma Inc. | Policicloalquilpurinas como antagonistas del receptor de adenosina. |
| WO2001051490A1 (en) | 2000-01-14 | 2001-07-19 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Methanocarba cycloalkyl nucleoside analogues |
| US20020115635A1 (en) * | 2001-02-21 | 2002-08-22 | Pnina Fishman | Modulation of GSK-3beta activity and its different uses |
| US20080318983A1 (en) * | 2001-11-09 | 2008-12-25 | Rao Kalla | A2b adenosine receptor antagonists |
| US7125993B2 (en) * | 2001-11-09 | 2006-10-24 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| US6977300B2 (en) * | 2001-11-09 | 2005-12-20 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| US7317017B2 (en) * | 2002-11-08 | 2008-01-08 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| US6825349B2 (en) * | 2001-11-09 | 2004-11-30 | Cv Therapeutics Inc. | A2B adenosine receptor antagonists |
| WO2004009594A2 (en) * | 2002-07-19 | 2004-01-29 | Aryx Therapeutics | Xanthine derivatives having adenosine a1-receptor antagonist properties |
| US7202252B2 (en) | 2003-02-19 | 2007-04-10 | Endacea, Inc. | A1 adenosine receptor antagonists |
| US20040229901A1 (en) * | 2003-02-24 | 2004-11-18 | Lauren Otsuki | Method of treatment of disease using an adenosine A1 receptor antagonist |
| US20060293312A1 (en) * | 2003-04-25 | 2006-12-28 | Howard Dittrich | Method of improved diuresis in individuals with impaired renal function |
| BRPI0409699A (pt) * | 2003-04-25 | 2006-04-18 | Novacardia Inc | métodos de indução do efeito diurético, de indução, manutenção ou restauração do efeito diurético de diurético não modificador de adenosina, de manutenção, restauração ou melhoria da função renal em paciente, de indução de diurese, de prevenção do inìcio de deficiência renal em paciente com sobrecarga de fluidos ou chf, de tratamento de paciente que sofre de chf e de melhoria dos resultados globais da saúde, composição farmacêutica e seus usos |
| ES2311759T3 (es) * | 2003-05-06 | 2009-02-16 | Cv Therapeutics, Inc. | Derivados de xantina como antagonistas del receptor a2b de adenosina. |
| US7247639B2 (en) * | 2003-06-06 | 2007-07-24 | Endacea, Inc. | A1 adenosine receptor antagonists |
| JP2007506804A (ja) * | 2003-06-09 | 2007-03-22 | エンダセア， インコーポレイテッド | Ａ１アデノシンレセプターアンタゴニスト |
| TW200507882A (en) * | 2003-07-17 | 2005-03-01 | Kyowa Hakko Kogyo Kk | Solid formulations |
| RU2357969C2 (ru) * | 2003-08-25 | 2009-06-10 | АДЕНОЗАЙН ТЕРАПЬЮТИКС, ЭлЭлСи | Новые замещенные 8-гетероарилксантины и фармацевтическая композиция на их основе |
| US6847249B1 (en) * | 2003-10-09 | 2005-01-25 | Analog Devices, Inc. | Highest available voltage selector circuit |
| BRPI0509753A (pt) * | 2004-04-16 | 2007-10-16 | Novacardia Inc | composição farmacêutica e método de tratamento de doença cardiovascular |
| PT1789053E (pt) * | 2004-09-01 | 2012-08-09 | Gilead Sciences Inc | Método de cicatrização de feridas utilizando antagonistas dos receptores de adenosina a2b |
| EP2035009A1 (en) * | 2006-06-16 | 2009-03-18 | Novacardia, Inc. | Prolonged improvement of renal function comprising infrequent administration of an aa1ra |
| US8193200B2 (en) | 2007-01-04 | 2012-06-05 | University Of Virginia Patent Foundation | Antagonists of A2B adenosine receptors for treatment of inflammatory bowel disease |
| WO2008121893A1 (en) * | 2007-03-29 | 2008-10-09 | Novacardia, Inc. | Methods of treating heart failure and renal dysfunction in individuals with an adenosine a1 receptor antagonist |
| WO2008121882A1 (en) * | 2007-03-29 | 2008-10-09 | Novacardia, Inc. | Improved methods of administration of adenosine a1 receptor antagonists |
| WO2009118759A2 (en) * | 2008-03-26 | 2009-10-01 | Advinus Therapeutics Pvt. Ltd., | Heterocyclic compounds as adenosine receptor antagonist |
| US8129862B2 (en) * | 2009-10-23 | 2012-03-06 | Analog Devices, Inc. | Scalable highest available voltage selector circuit |
| US8796290B2 (en) | 2009-11-09 | 2014-08-05 | Advinus Therapeutics Limited | Substituted fused pyrimidine compounds, its preparation and uses thereof |
| EP2507241A1 (en) | 2009-12-02 | 2012-10-10 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Methanocarba adenosine derivatives and dendrimer conjugates thereof |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1201997A (en) * | 1967-08-04 | 1970-08-12 | Yissum Res Dev Co | New substituted purines and purine derivatives |
| US3624216A (en) * | 1970-06-25 | 1971-11-30 | Abbott Lab | 8-substituted theophyllines as anti-inflammatory agents |
| US3624215A (en) * | 1970-06-25 | 1971-11-30 | Abbott Lab | 8-substituted theophyllines as anti-anxiety agents |
| DE3028273A1 (de) * | 1980-07-25 | 1982-02-25 | Fa. Dr. Willmar Schwabe, 7500 Karlsruhe | Durch purinbasen substituierte 1.4;3.6-dianhydro-hexit-nitrate |
| ES8401072A1 (es) * | 1982-11-23 | 1983-12-16 | Faes | Procedimiento de preparacion de un nuevo espirodecano. |
| US4593095A (en) * | 1983-02-18 | 1986-06-03 | The Johns Hopkins University | Xanthine derivatives |
| US4548939A (en) * | 1984-10-01 | 1985-10-22 | Janssen Pharmaceutica N. V. | 1H-Indol-3-yl containing 1,3-dimethyl-1H-purine-2,6-diones |
| US4755517A (en) * | 1986-07-31 | 1988-07-05 | Warner-Lambert Company | Derivatives of xanthine, pharmaceutical compositions and methods of use therefor |
| US5175290A (en) * | 1988-09-16 | 1992-12-29 | Marion Merrell Dow Inc. | 8-(oxo-substituted cycloalkyl)xanthines |
| DE3843117A1 (de) * | 1988-12-22 | 1990-06-28 | Boehringer Ingelheim Kg | Neue xanthinderivate mit adenosin-antagonistischer wirkung |
| JPH06102662B2 (ja) * | 1989-09-01 | 1994-12-14 | 協和醗酵工業株式会社 | キサンチン誘導体 |
| US5290782A (en) * | 1989-09-01 | 1994-03-01 | Kyowa Hakko Kogyo Co., Ltd. | Xanthine derivatives |
| US4957921A (en) * | 1989-12-06 | 1990-09-18 | Warner-Lambert Company | Substituted cyclohexanols as central nervous system agents |
| EP0541120B1 (en) * | 1991-11-08 | 1999-05-26 | Kyowa Hakko Kogyo Co., Ltd. | Xanthine derivatives for the treatment of dementia |
-
1988
- 1988-12-22 DE DE3843117A patent/DE3843117A1/de not_active Ceased
- 1988-12-22 DE DE8817122U patent/DE8817122U1/de not_active Expired - Lifetime
-
1989
- 1989-12-19 CZ CS19897197A patent/CZ286230B6/cs not_active IP Right Cessation
- 1989-12-19 ES ES89123412T patent/ES2086313T3/es not_active Expired - Lifetime
- 1989-12-19 AT AT89123412T patent/ATE136897T1/de not_active IP Right Cessation
- 1989-12-19 EP EP89123412A patent/EP0374808B1/de not_active Expired - Lifetime
- 1989-12-19 SK SK7197-89A patent/SK279525B6/sk unknown
- 1989-12-19 DE DE58909657T patent/DE58909657D1/de not_active Expired - Fee Related
- 1989-12-19 SG SG1996003965A patent/SG46380A1/en unknown
- 1989-12-20 DD DD89335983A patent/DD290421A5/de not_active IP Right Cessation
- 1989-12-20 FI FI896117A patent/FI96513C/fi not_active IP Right Cessation
- 1989-12-20 NZ NZ231901A patent/NZ231901A/en unknown
- 1989-12-20 PL PL28287889A patent/PL162877B1/pl unknown
- 1989-12-20 SI SI8912423A patent/SI8912423B/sl unknown
- 1989-12-20 YU YU242389A patent/YU47934B/sh unknown
- 1989-12-21 KR KR1019890019085A patent/KR0165666B1/ko not_active Expired - Fee Related
- 1989-12-21 NO NO895168A patent/NO173502C/no not_active IP Right Cessation
- 1989-12-21 PH PH39764A patent/PH31107A/en unknown
- 1989-12-21 CA CA002006387A patent/CA2006387C/en not_active Expired - Fee Related
- 1989-12-21 DK DK652689A patent/DK652689A/da not_active Application Discontinuation
- 1989-12-21 IL IL9282989A patent/IL92829A/en active IP Right Grant
- 1989-12-21 IE IE414789A patent/IE74205B1/en not_active IP Right Cessation
- 1989-12-21 PT PT92658A patent/PT92658B/pt not_active IP Right Cessation
- 1989-12-21 ZA ZA899881A patent/ZA899881B/xx unknown
- 1989-12-21 UA UA5011448A patent/UA26427A/uk unknown
- 1989-12-21 HU HU736/89A patent/HU218674B/hu not_active IP Right Cessation
- 1989-12-22 JP JP1334668A patent/JP2565576B2/ja not_active Expired - Lifetime
-
1991
- 1991-04-25 US US07/691,193 patent/US5175291A/en not_active Expired - Fee Related
-
1992
- 1992-05-07 RU SU925011448A patent/RU2057752C1/ru active
- 1992-06-26 MX MX9203618A patent/MX9203618A/es unknown
- 1992-07-10 PH PH44630A patent/PH31111A/en unknown
-
1993
- 1993-07-27 US US08/097,478 patent/US5532368A/en not_active Expired - Fee Related
-
1994
- 1994-02-08 BG BG098441A patent/BG61669B2/bg unknown
- 1994-10-21 HR HRP-2423/89A patent/HRP940724A2/hr not_active Application Discontinuation
-
1995
- 1995-05-30 US US08/454,452 patent/US5696124A/en not_active Expired - Fee Related
-
1996
- 1996-04-23 GR GR960401119T patent/GR3019733T3/el unknown
- 1996-06-14 US US08/663,417 patent/US5688802A/en not_active Expired - Fee Related
-
1997
- 1997-05-13 BR BR1100527-0A patent/BR1100527A/pt active IP Right Grant
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