OA11578A - Isoquinolines as urokinase inhibitors. - Google Patents
Isoquinolines as urokinase inhibitors. Download PDFInfo
- Publication number
- OA11578A OA11578A OA1200100002A OA1200100002A OA11578A OA 11578 A OA11578 A OA 11578A OA 1200100002 A OA1200100002 A OA 1200100002A OA 1200100002 A OA1200100002 A OA 1200100002A OA 11578 A OA11578 A OA 11578A
- Authority
- OA
- OAPI
- Prior art keywords
- mmol
- chloro
- guanidino
- isoquinolinyl
- sulphonyl
- Prior art date
Links
- 239000002797 plasminogen activator inhibitor Substances 0.000 title description 9
- 150000002537 isoquinolines Chemical class 0.000 title description 4
- 239000000203 mixture Substances 0.000 claims description 418
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 368
- -1 Çj. Chemical group 0.000 claims description 299
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 138
- 150000001875 compounds Chemical class 0.000 claims description 105
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 71
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 69
- 238000006243 chemical reaction Methods 0.000 claims description 55
- 229920006395 saturated elastomer Polymers 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 42
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 36
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- NILQLFBWTXNUOE-UHFFFAOYSA-N 1-aminocyclopentanecarboxylic acid Chemical compound OC(=O)C1(N)CCCC1 NILQLFBWTXNUOE-UHFFFAOYSA-N 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 17
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical group C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 15
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 15
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 13
- CXDHJGCWMIOAQP-UHFFFAOYSA-N 2-pyridin-3-yl-1,4,5,6-tetrahydropyrimidine;hydrochloride Chemical compound Cl.C1CCNC(C=2C=NC=CC=2)=N1 CXDHJGCWMIOAQP-UHFFFAOYSA-N 0.000 claims description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 10
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 229910052698 phosphorus Inorganic materials 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 7
- OSILBMSORKFRTB-UHFFFAOYSA-N isoquinolin-1-amine Chemical compound C1=CC=C2C(N)=NC=CC2=C1 OSILBMSORKFRTB-UHFFFAOYSA-N 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 6
- 239000005977 Ethylene Substances 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 claims description 4
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 4
- 125000000732 arylene group Chemical group 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000004977 cycloheptylene group Chemical group 0.000 claims description 3
- 125000004979 cyclopentylene group Chemical group 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical group C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims description 3
- 238000006073 displacement reaction Methods 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 150000001409 amidines Chemical class 0.000 claims description 2
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- 125000004976 cyclobutylene group Chemical group 0.000 claims description 2
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000005710 tetrahydropyranylene group Chemical group 0.000 claims description 2
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 10
- KHAPOCZPLRRWRN-UHFFFAOYSA-N 2-[4-chloro-7-[[1-(4-methylpiperazine-1-carbonyl)cyclopentyl]sulfamoyl]isoquinolin-1-yl]guanidine Chemical compound C1CN(C)CCN1C(=O)C1(NS(=O)(=O)C=2C=C3C(NC(N)=N)=NC=C(Cl)C3=CC=2)CCCC1 KHAPOCZPLRRWRN-UHFFFAOYSA-N 0.000 claims 1
- XSDAXWRCPTYNOD-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-2-methylpropanoic acid Chemical compound ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)NC(C)(C)C(O)=O)=CC=C21 XSDAXWRCPTYNOD-UHFFFAOYSA-N 0.000 claims 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 1
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 350
- 239000000243 solution Substances 0.000 description 347
- 239000007787 solid Substances 0.000 description 223
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 213
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 205
- 235000019439 ethyl acetate Nutrition 0.000 description 168
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 163
- 229910001868 water Inorganic materials 0.000 description 161
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 143
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- 239000000741 silica gel Substances 0.000 description 120
- 229910002027 silica gel Inorganic materials 0.000 description 120
- 229960001866 silicon dioxide Drugs 0.000 description 120
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 119
- 238000004440 column chromatography Methods 0.000 description 112
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 110
- 239000004471 Glycine Substances 0.000 description 109
- 229960002449 glycine Drugs 0.000 description 109
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 100
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 98
- 239000003921 oil Substances 0.000 description 97
- 235000019198 oils Nutrition 0.000 description 97
- 239000012267 brine Substances 0.000 description 93
- 239000002904 solvent Substances 0.000 description 87
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 76
- 229910000104 sodium hydride Inorganic materials 0.000 description 73
- 239000006185 dispersion Substances 0.000 description 70
- 229960000789 guanidine hydrochloride Drugs 0.000 description 66
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 66
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 59
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 58
- 239000007832 Na2SO4 Substances 0.000 description 56
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 56
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 56
- 229910052938 sodium sulfate Inorganic materials 0.000 description 56
- 235000011152 sodium sulphate Nutrition 0.000 description 56
- 235000019341 magnesium sulphate Nutrition 0.000 description 55
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 53
- 239000000284 extract Substances 0.000 description 53
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 50
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 49
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- 239000002244 precipitate Substances 0.000 description 41
- 238000001914 filtration Methods 0.000 description 37
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 36
- 101150041968 CDC13 gene Proteins 0.000 description 35
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 35
- 239000000725 suspension Substances 0.000 description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 34
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
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- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 28
- 229960003767 alanine Drugs 0.000 description 27
- 235000017557 sodium bicarbonate Nutrition 0.000 description 27
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 27
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 26
- 238000010992 reflux Methods 0.000 description 24
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- NLLGKNYQDQBMFW-UHFFFAOYSA-N ethyl 1-aminocyclopentane-1-carboxylate Chemical compound CCOC(=O)C1(N)CCCC1 NLLGKNYQDQBMFW-UHFFFAOYSA-N 0.000 description 22
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
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- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
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- 239000012264 purified product Substances 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 102220098903 rs878854483 Human genes 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 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
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- GSIFMMNNDXIWMR-PBHICJAKSA-N tert-butyl (1r,2s)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclohexane-1-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 GSIFMMNNDXIWMR-PBHICJAKSA-N 0.000 description 1
- DWKALJMROLTJPM-RJUBDTSPSA-N tert-butyl (1r,2s)-2-aminocyclohexane-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)[C@@H]1CCCC[C@@H]1N DWKALJMROLTJPM-RJUBDTSPSA-N 0.000 description 1
- VNLZBZBMFYNBFI-MRXNPFEDSA-N tert-butyl (2r)-1-(1,4-dichloroisoquinolin-7-yl)sulfonylpiperidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@H]1CCCCN1S(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 VNLZBZBMFYNBFI-MRXNPFEDSA-N 0.000 description 1
- DHHKPEUQJIEKOA-UHFFFAOYSA-N tert-butyl 2-[6-(nitromethyl)-6-bicyclo[3.2.0]hept-3-enyl]acetate Chemical group C1C=CC2C(CC(=O)OC(C)(C)C)(C[N+]([O-])=O)CC21 DHHKPEUQJIEKOA-UHFFFAOYSA-N 0.000 description 1
- CSOJECDGWHHWRS-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylcarbamothioyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=S)NC(=O)OC(C)(C)C CSOJECDGWHHWRS-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000011426 transformation method Methods 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- 108010065822 urokinase inhibitor Proteins 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- 229940045860 white wax Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—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
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/48—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—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
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/96—Sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/42—Radicals substituted by singly-bound nitrogen atoms having hetero atoms attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9816228.2A GB9816228D0 (en) | 1998-07-24 | 1998-07-24 | Isoquinolines |
| GBGB9908829.6A GB9908829D0 (en) | 1998-07-24 | 1999-04-16 | Isoquinolines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA11578A true OA11578A (en) | 2004-07-20 |
Family
ID=10836172
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA1200100002A OA11578A (en) | 1998-07-24 | 1999-07-15 | Isoquinolines as urokinase inhibitors. |
Country Status (39)
| Country | Link |
|---|---|
| EP (1) | EP1077945B1 (de) |
| JP (1) | JP2002521367A (de) |
| KR (1) | KR20010083137A (de) |
| CN (1) | CN1318059A (de) |
| AR (1) | AR018960A1 (de) |
| AT (1) | ATE230730T1 (de) |
| AU (1) | AU745545B2 (de) |
| BG (1) | BG105252A (de) |
| BR (1) | BR9912374A (de) |
| CA (1) | CA2337247A1 (de) |
| CO (1) | CO5080787A1 (de) |
| DE (1) | DE69904814T2 (de) |
| DK (1) | DK1077945T3 (de) |
| DZ (1) | DZ2852A1 (de) |
| EA (1) | EA200100073A1 (de) |
| EE (1) | EE200100049A (de) |
| ES (1) | ES2189434T3 (de) |
| GB (2) | GB9816228D0 (de) |
| GT (1) | GT199900116A (de) |
| HK (1) | HK1040996A1 (de) |
| HN (1) | HN1999000116A (de) |
| HR (1) | HRP20010059A2 (de) |
| HU (1) | HUP0103665A3 (de) |
| ID (1) | ID26993A (de) |
| IS (1) | IS5789A (de) |
| MA (1) | MA26664A1 (de) |
| NO (1) | NO20010400L (de) |
| OA (1) | OA11578A (de) |
| PA (1) | PA8478901A1 (de) |
| PE (1) | PE20000937A1 (de) |
| PL (1) | PL346022A1 (de) |
| PT (1) | PT1077945E (de) |
| SI (1) | SI1077945T1 (de) |
| SK (1) | SK1062001A3 (de) |
| TN (1) | TNSN99149A1 (de) |
| TR (1) | TR200100222T2 (de) |
| TW (1) | TW530049B (de) |
| UY (1) | UY25663A1 (de) |
| ZA (1) | ZA200100230B (de) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1485345B1 (de) * | 2002-03-11 | 2008-06-25 | Curacyte AG | Hemmstoffe der urokinase, ihre herstellung und verwendung |
| ES2325995T3 (es) | 2003-12-02 | 2009-09-28 | Schwarz Pharma Ag | Nueva utilizacion de compuestos peptidicos para tratamiento del dolor neuropatico central. |
| EP1604656A1 (de) | 2004-06-09 | 2005-12-14 | Schwarz Pharma Ag | Neue Verwendung von Peptidverbindungen zur Behandlung von amyotropher Lateralsklerose (ALS) |
| EP1604655A1 (de) | 2004-06-09 | 2005-12-14 | Schwarz Pharma Ag | Neue Verwendung von Peptidverbindungen zur Behandlung von Trigeminusneuralgie |
| ES2531118T5 (es) | 2006-06-15 | 2022-06-14 | Ucb Pharma Gmbh | Composición farmacéutica que comprende lacosamida y levetiracetamo para uso en el tratamiento de la epilepsia |
-
1998
- 1998-07-24 GB GBGB9816228.2A patent/GB9816228D0/en not_active Ceased
-
1999
- 1999-04-16 GB GBGB9908829.6A patent/GB9908829D0/en not_active Ceased
- 1999-07-15 AT AT99928177T patent/ATE230730T1/de not_active IP Right Cessation
- 1999-07-15 DE DE69904814T patent/DE69904814T2/de not_active Expired - Fee Related
- 1999-07-15 TR TR2001/00222T patent/TR200100222T2/xx unknown
- 1999-07-15 SK SK106-2001A patent/SK1062001A3/sk unknown
- 1999-07-15 ID IDW20010169D patent/ID26993A/id unknown
- 1999-07-15 HR HR20010059A patent/HRP20010059A2/hr not_active Application Discontinuation
- 1999-07-15 SI SI9930178T patent/SI1077945T1/xx unknown
- 1999-07-15 DK DK99928177T patent/DK1077945T3/da active
- 1999-07-15 HU HU0103665A patent/HUP0103665A3/hu unknown
- 1999-07-15 BR BR9912374-6A patent/BR9912374A/pt not_active IP Right Cessation
- 1999-07-15 PL PL99346022A patent/PL346022A1/xx not_active Application Discontinuation
- 1999-07-15 EE EEP200100049A patent/EE200100049A/xx unknown
- 1999-07-15 HK HK02102712.1A patent/HK1040996A1/zh unknown
- 1999-07-15 ES ES99928177T patent/ES2189434T3/es not_active Expired - Lifetime
- 1999-07-15 OA OA1200100002A patent/OA11578A/en unknown
- 1999-07-15 KR KR1020017000956A patent/KR20010083137A/ko not_active Ceased
- 1999-07-15 PT PT99928177T patent/PT1077945E/pt unknown
- 1999-07-15 AU AU45289/99A patent/AU745545B2/en not_active Ceased
- 1999-07-15 EP EP99928177A patent/EP1077945B1/de not_active Expired - Lifetime
- 1999-07-15 CA CA002337247A patent/CA2337247A1/en not_active Abandoned
- 1999-07-15 CN CN99809025A patent/CN1318059A/zh active Pending
- 1999-07-15 EA EA200100073A patent/EA200100073A1/ru unknown
- 1999-07-15 JP JP2000561170A patent/JP2002521367A/ja active Pending
- 1999-07-16 HN HN1999000116A patent/HN1999000116A/es unknown
- 1999-07-21 TN TNTNSN99149A patent/TNSN99149A1/fr unknown
- 1999-07-21 DZ DZ990152A patent/DZ2852A1/xx active
- 1999-07-21 MA MA25695A patent/MA26664A1/fr unknown
- 1999-07-21 PE PE1999000733A patent/PE20000937A1/es not_active Application Discontinuation
- 1999-07-22 AR ARP990103614A patent/AR018960A1/es not_active Application Discontinuation
- 1999-07-23 GT GT199900116A patent/GT199900116A/es unknown
- 1999-07-23 PA PA19998478901A patent/PA8478901A1/es unknown
- 1999-07-23 TW TW088112548A patent/TW530049B/zh active
- 1999-07-26 CO CO99047012A patent/CO5080787A1/es unknown
- 1999-08-16 UY UY25663A patent/UY25663A1/es unknown
-
2000
- 2000-12-22 IS IS5789A patent/IS5789A/is unknown
-
2001
- 2001-01-09 ZA ZA200100230A patent/ZA200100230B/en unknown
- 2001-01-23 NO NO20010400A patent/NO20010400L/no not_active Application Discontinuation
- 2001-02-14 BG BG105252A patent/BG105252A/xx unknown
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