NO310684B1 - 1-metylkarbapenemderivater og farmasöytisk preparat inneholdende disse - Google Patents
1-metylkarbapenemderivater og farmasöytisk preparat inneholdende disse Download PDFInfo
- Publication number
- NO310684B1 NO310684B1 NO19982873A NO982873A NO310684B1 NO 310684 B1 NO310684 B1 NO 310684B1 NO 19982873 A NO19982873 A NO 19982873A NO 982873 A NO982873 A NO 982873A NO 310684 B1 NO310684 B1 NO 310684B1
- Authority
- NO
- Norway
- Prior art keywords
- nitrobenzyloxycarbonyl
- methyl
- denotes
- pyrrolidin
- ylcarbonyl
- Prior art date
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- YKMONJZIUAOVEM-GDVGLLTNSA-N (5S)-4-methyl-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical class CC1C=CN2[C@H]1CC2=O YKMONJZIUAOVEM-GDVGLLTNSA-N 0.000 title claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- -1 phenylene- Chemical class 0.000 claims description 112
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 150000002148 esters Chemical group 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 208000035473 Communicable disease Diseases 0.000 claims description 7
- 238000001727 in vivo Methods 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 239000004615 ingredient Substances 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- NARVIWMVBMUEOG-UHFFFAOYSA-N prop-1-en-2-ol Chemical group CC(O)=C NARVIWMVBMUEOG-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- AURGXAAPSXABQV-VZRURGHZSA-N (5S)-3-[5-[3-[2-(diaminomethylideneamino)propanoylamino]azetidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CC(O)C1[C@H]2C(C)C(SC3CNC(C3)C(=O)N3CC(C3)NC(=O)C(C)NC(N)=N)=C(N2C1=O)C(O)=O AURGXAAPSXABQV-VZRURGHZSA-N 0.000 claims description 2
- SIOTXAXQMYMRSW-XRKGJLGJSA-N (5S)-3-[5-[3-[[2-(diaminomethylideneamino)acetyl]-methylamino]pyrrolidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N(C(=N)N)CC(=O)N(C)C1CN(CC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C SIOTXAXQMYMRSW-XRKGJLGJSA-N 0.000 claims description 2
- KEDAXBWZURNCHS-XRKGJLGJSA-N (5S)-3-[5-[3-[[2-(diaminomethylideneamino)acetyl]amino]pyrrolidine-1-carbonyl]-1-methylpyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CC(O)C1[C@H]2C(C)C(SC3CC(N(C)C3)C(=O)N3CCC(C3)NC(=O)CNC(N)=N)=C(N2C1=O)C(O)=O KEDAXBWZURNCHS-XRKGJLGJSA-N 0.000 claims description 2
- VSVDGUIRMVQXNP-BOFZDKAQSA-N (5S)-3-[5-[3-[[2-(diaminomethylideneamino)acetyl]amino]pyrrolidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical group CC(O)C1[C@H]2C(C)C(SC3CNC(C3)C(=O)N3CCC(C3)NC(=O)CNC(N)=N)=C(N2C1=O)C(O)=O VSVDGUIRMVQXNP-BOFZDKAQSA-N 0.000 claims description 2
- QKIOFYJUUDPEND-XRKGJLGJSA-N (5S)-3-[5-[3-[[2-[carbamimidoyl(methyl)amino]acetyl]amino]pyrrolidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CN(C(=N)N)CC(=O)NC1CN(CC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C QKIOFYJUUDPEND-XRKGJLGJSA-N 0.000 claims description 2
- CAOOCJBOEODUAN-CIFATLAASA-N (5S)-3-[5-[3-[[4-(diaminomethylideneamino)-3-hydroxybutanoyl]amino]azetidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N(C(=N)N)CC(CC(=O)NC1CN(C1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C)O CAOOCJBOEODUAN-CIFATLAASA-N 0.000 claims description 2
- 125000000783 acetimidoyl group Chemical group C(C)(=N)* 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 description 355
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 283
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 249
- 238000000862 absorption spectrum Methods 0.000 description 241
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 230
- 239000000243 solution Substances 0.000 description 193
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 192
- 239000000203 mixture Substances 0.000 description 187
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 171
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 164
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- 101150041968 CDC13 gene Proteins 0.000 description 149
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 118
- 238000003756 stirring Methods 0.000 description 98
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 88
- 230000002829 reductive effect Effects 0.000 description 85
- 239000000126 substance Substances 0.000 description 85
- 238000001816 cooling Methods 0.000 description 82
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 82
- 238000001704 evaporation Methods 0.000 description 80
- 230000008020 evaporation Effects 0.000 description 80
- 238000006243 chemical reaction Methods 0.000 description 79
- 239000000843 powder Substances 0.000 description 72
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 68
- 238000000746 purification Methods 0.000 description 65
- 239000002904 solvent Substances 0.000 description 55
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 52
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 49
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- 238000004587 chromatography analysis Methods 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 36
- 229910002027 silica gel Inorganic materials 0.000 description 36
- 239000003054 catalyst Substances 0.000 description 34
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 34
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
- 238000005984 hydrogenation reaction Methods 0.000 description 30
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 28
- 238000000034 method Methods 0.000 description 28
- JQWUEVPNOSPHNN-OALUTQOASA-N (2s,4s)-4-[(4-methoxyphenyl)methylsulfanyl]-1-[(4-nitrophenyl)methoxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CS[C@@H]1CN(C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)[C@H](C(O)=O)C1 JQWUEVPNOSPHNN-OALUTQOASA-N 0.000 description 27
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 24
- YLXDRUQODCBMGR-BWGZFRQBSA-N (4R,5R,6S)-3-diphenylphosphoryloxy-6-[(1R)-1-hydroxyethyl]-4-methyl-4-[(4-nitrophenyl)methyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C[C@H]([C@@H]1[C@@H]2[C@@](C(=C(N2C1=O)C(=O)O)OP(=O)(C3=CC=CC=C3)C4=CC=CC=C4)(C)CC5=CC=C(C=C5)[N+](=O)[O-])O YLXDRUQODCBMGR-BWGZFRQBSA-N 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 239000001257 hydrogen Substances 0.000 description 22
- 229910052739 hydrogen Inorganic materials 0.000 description 22
- 125000006239 protecting group Chemical group 0.000 description 21
- IXHQGIFAPSNAKV-UHFFFAOYSA-N (4-nitrophenyl)methyl n-[n'-[3-(azetidin-3-ylamino)-3-oxopropyl]-n-[(4-nitrophenyl)methoxycarbonyl]carbamimidoyl]carbamate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC([N+](=O)[O-])=CC=C1COC(=O)NC(NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)=NCCC(=O)NC1CNC1 IXHQGIFAPSNAKV-UHFFFAOYSA-N 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 239000012267 brine Substances 0.000 description 18
- 239000007864 aqueous solution Substances 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
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- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 12
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- DMKZERWLEGTECU-PIYXRGFCSA-N (4-nitrophenyl)methyl (4r,5r,6s)-3-diphenylphosphoryloxy-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)=O)[C@H](O)C)OP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 DMKZERWLEGTECU-PIYXRGFCSA-N 0.000 description 10
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- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 9
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 9
- 238000000605 extraction Methods 0.000 description 9
- ZZMUNSYAVBLAPC-UHFFFAOYSA-N (4-nitrophenyl)methyl n-[[(4-nitrophenyl)methoxycarbonylamino]-pyrazol-1-ylmethylidene]carbamate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)NC(N1N=CC=C1)=NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 ZZMUNSYAVBLAPC-UHFFFAOYSA-N 0.000 description 8
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- WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical class C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 description 7
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- CMIBWIAICVBURI-ZETCQYMHSA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1 CMIBWIAICVBURI-ZETCQYMHSA-N 0.000 description 6
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- AHSQPICSVCRVKP-NRAUDTLTSA-N (4-nitrophenyl)methyl (2s,4s)-2-[3-[[(2s)-2-[bis[(4-nitrophenyl)methoxycarbonylamino]methylideneamino]propanoyl]amino]azetidine-1-carbonyl]-4-sulfanylpyrrolidine-1-carboxylate Chemical compound N([C@@H](C)C(=O)NC1CN(C1)C(=O)[C@H]1N(C[C@@H](S)C1)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)C(=NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 AHSQPICSVCRVKP-NRAUDTLTSA-N 0.000 description 3
- BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical class OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 3
- LVGIUOZGDVZIMK-UHFFFAOYSA-N 1-sulfanylpyrrolidine Chemical class SN1CCCC1 LVGIUOZGDVZIMK-UHFFFAOYSA-N 0.000 description 3
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- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- NGHMEZWZOZEZOH-UHFFFAOYSA-N silicic acid;hydrate Chemical compound O.O[Si](O)(O)O NGHMEZWZOZEZOH-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000019385 spermaceti wax Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- CMIBWIAICVBURI-SSDOTTSWSA-N tert-butyl (3r)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](N)C1 CMIBWIAICVBURI-SSDOTTSWSA-N 0.000 description 1
- RMAALMHOFBOFNU-VIFPVBQESA-N tert-butyl (3s)-3-(3-aminopropanoylamino)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](NC(=O)CCN)C1 RMAALMHOFBOFNU-VIFPVBQESA-N 0.000 description 1
- UZSHWEBDTXOVOL-HNNXBMFYSA-N tert-butyl (3s)-3-[3-[[amino-[(4-nitrophenyl)methoxycarbonylamino]methylidene]amino]propanoylamino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1NC(=O)CCNC(=N)NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 UZSHWEBDTXOVOL-HNNXBMFYSA-N 0.000 description 1
- GBECUHSLMXGJID-QFIPXVFZSA-N tert-butyl (3s)-3-[4-[bis[(4-nitrophenyl)methoxycarbonylamino]methylideneamino]butanoylamino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1NC(=O)CCCN=C(NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 GBECUHSLMXGJID-QFIPXVFZSA-N 0.000 description 1
- ZUBUNWFHEQCHKF-NQIIRXRSSA-N tert-butyl (3s)-3-[[(2r)-2-[bis[(4-nitrophenyl)methoxycarbonylamino]methylideneamino]propanoyl]amino]pyrrolidine-1-carboxylate Chemical compound N([C@H](C)C(=O)N[C@@H]1CN(CC1)C(=O)OC(C)(C)C)=C(NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 ZUBUNWFHEQCHKF-NQIIRXRSSA-N 0.000 description 1
- XLSZZKBUIAYNFS-BDAKNGLRSA-N tert-butyl (3s)-3-[[(2r)-2-aminopropanoyl]amino]pyrrolidine-1-carboxylate Chemical compound C[C@@H](N)C(=O)N[C@H]1CCN(C(=O)OC(C)(C)C)C1 XLSZZKBUIAYNFS-BDAKNGLRSA-N 0.000 description 1
- UEJTZRMNIYRNPA-HNNXBMFYSA-N tert-butyl (3s)-3-[[2-(diaminomethylideneamino)acetyl]-[(4-nitrophenyl)methoxycarbonyl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1N(C(=O)CN=C(N)N)C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 UEJTZRMNIYRNPA-HNNXBMFYSA-N 0.000 description 1
- LGYQZWUIXIXWBE-NRFANRHFSA-N tert-butyl (3s)-3-[[2-[[n,n'-bis[(4-nitrophenyl)methoxycarbonyl]carbamimidoyl]-methylamino]acetyl]amino]pyrrolidine-1-carboxylate Chemical compound C=1C=C([N+]([O-])=O)C=CC=1COC(=O)NC(=NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)N(C)CC(=O)N[C@H]1CCN(C(=O)OC(C)(C)C)C1 LGYQZWUIXIXWBE-NRFANRHFSA-N 0.000 description 1
- OMCHNYOABGXXAK-FQEVSTJZSA-N tert-butyl (3s)-3-[[2-[bis[(4-nitrophenyl)methoxycarbonylamino]methylideneamino]acetyl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1NC(=O)CN=C(NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 OMCHNYOABGXXAK-FQEVSTJZSA-N 0.000 description 1
- NFEGNISFSSLEGU-UHFFFAOYSA-N tert-butyl 2-diethoxyphosphorylacetate Chemical compound CCOP(=O)(OCC)CC(=O)OC(C)(C)C NFEGNISFSSLEGU-UHFFFAOYSA-N 0.000 description 1
- GEPCTPKWCUMXPX-UHFFFAOYSA-N tert-butyl 3-(3-aminopropanoylamino)azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(NC(=O)CCN)C1 GEPCTPKWCUMXPX-UHFFFAOYSA-N 0.000 description 1
- RMFCZOCFGKSIGP-UHFFFAOYSA-N tert-butyl 3-(4-aminobutanoylamino)azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(NC(=O)CCCN)C1 RMFCZOCFGKSIGP-UHFFFAOYSA-N 0.000 description 1
- GXVXEWBILOZCRQ-UHFFFAOYSA-N tert-butyl 3-[(2-aminoacetyl)amino]azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(NC(=O)CN)C1 GXVXEWBILOZCRQ-UHFFFAOYSA-N 0.000 description 1
- OVYJSQJLWNYYBN-UHFFFAOYSA-N tert-butyl 3-[(4-amino-4-hydroxybutanoyl)amino]azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(NC(=O)CCC(N)O)C1 OVYJSQJLWNYYBN-UHFFFAOYSA-N 0.000 description 1
- RNGRCOWFOVQZRR-KRWDZBQOSA-N tert-butyl 3-[[(2s)-2-[bis[(4-nitrophenyl)methoxycarbonylamino]methylideneamino]propanoyl]amino]azetidine-1-carboxylate Chemical compound N([C@@H](C)C(=O)NC1CN(C1)C(=O)OC(C)(C)C)C(=NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 RNGRCOWFOVQZRR-KRWDZBQOSA-N 0.000 description 1
- SCMAJDWSVMGYOO-UHFFFAOYSA-N tert-butyl 3-[[2-[bis[(4-nitrophenyl)methoxycarbonylamino]methylideneamino]acetyl]amino]azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1NC(=O)CNC(NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)=NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 SCMAJDWSVMGYOO-UHFFFAOYSA-N 0.000 description 1
- RKLKFOLWXBYABA-UHFFFAOYSA-N tert-butyl 3-[[4-[bis[(4-nitrophenyl)methoxycarbonylamino]methylideneamino]-3-hydroxybutanoyl]amino]azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(C1)NC(=O)CC(O)CNC(NC(=O)OCC1=CC=C(C=C1)[N+]([O-])=O)=NC(=O)OCC1=CC=C(C=C1)[N+]([O-])=O RKLKFOLWXBYABA-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 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
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/10—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D477/12—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6
- C07D477/16—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6 with hetero atoms or carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 3
- C07D477/20—Sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP33313595 | 1995-12-21 | ||
JP30894096 | 1996-11-20 | ||
PCT/JP1996/003726 WO1997023483A1 (en) | 1995-12-21 | 1996-12-20 | 1-methylcarbapenem derivatives |
Publications (3)
Publication Number | Publication Date |
---|---|
NO982873D0 NO982873D0 (no) | 1998-06-19 |
NO982873L NO982873L (no) | 1998-08-21 |
NO310684B1 true NO310684B1 (no) | 2001-08-13 |
Family
ID=26565749
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19982873A NO310684B1 (no) | 1995-12-21 | 1998-06-19 | 1-metylkarbapenemderivater og farmasöytisk preparat inneholdende disse |
Country Status (18)
Country | Link |
---|---|
US (1) | US6090802A (zh) |
EP (1) | EP0882728B1 (zh) |
KR (1) | KR100386993B1 (zh) |
CN (1) | CN1095843C (zh) |
AT (1) | ATE223411T1 (zh) |
AU (1) | AU711135B2 (zh) |
CA (1) | CA2241092C (zh) |
CZ (1) | CZ298246B6 (zh) |
DE (1) | DE69623497T2 (zh) |
DK (1) | DK0882728T3 (zh) |
ES (1) | ES2181927T3 (zh) |
HK (1) | HK1015766A1 (zh) |
HU (1) | HUP9901376A3 (zh) |
MX (1) | MX9805023A (zh) |
NO (1) | NO310684B1 (zh) |
NZ (1) | NZ324447A (zh) |
PT (1) | PT882728E (zh) |
WO (1) | WO1997023483A1 (zh) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR9807187A (pt) | 1997-02-07 | 2000-01-25 | Kyoto Pharma Ind | Composto de carbapenem, seu uso e composto intermediário para o mesmo |
DE69932927D1 (de) | 1998-05-01 | 2006-10-05 | Kyoto Pharma Ind | Cabapenemderivate, ihre anwendung und ihre zwischenprodukte |
AU1415500A (en) * | 1998-12-07 | 2000-06-26 | Sankyo Company Limited | 1-methylcarbapenem derivatives |
US7041660B2 (en) | 1999-07-06 | 2006-05-09 | Sankyo Company, Limited | Crystalline 1-methylcarbapenem derivatives |
TWI250160B (en) | 1999-07-06 | 2006-03-01 | Sankyo Co | Crystalline 1-methylcarbapenem compound |
US6531594B2 (en) * | 2000-08-24 | 2003-03-11 | Mitsubishi Chemical Corporation | Process for producing 1H-3-aminopyrrolidine and derivatives thereof |
DK1338596T3 (da) * | 2000-11-20 | 2006-04-18 | Sankyo Co | Fremgangsmåde til fremstilling af antibakterielt middel af carbapenemtypen |
EP1398314A4 (en) * | 2001-05-21 | 2004-10-20 | Kyoto Pharma Ind | CARBAPENEM CONNECTION |
JP4619655B2 (ja) | 2001-09-14 | 2011-01-26 | ハイ・ポイント・ファーマスーティカルズ、エルエルシー | 新規アミノアゼチジン、−ピロリジンおよび−ピペリジン誘導体 |
US6673829B2 (en) | 2001-09-14 | 2004-01-06 | Novo Nordisk A/S | Aminoazetidine,-pyrrolidine and -piperidine derivatives |
CA2644316A1 (en) * | 2003-08-25 | 2005-03-03 | Sankyo Company Limited | Crystal of 1-methyl carbapenem compound |
KR20070112464A (ko) * | 2005-03-22 | 2007-11-26 | 다이이찌 산쿄 가부시키가이샤 | 1-알킬피롤리딘 구조를 갖는 카르바페넴 유도체의 제조방법 |
TW200639176A (en) * | 2005-05-13 | 2006-11-16 | Sankyo Co | Crystal of 1-methyl carbapenem compound |
DK2231667T3 (da) | 2008-01-18 | 2013-12-16 | Merck Sharp & Dohme | Beta-lactamase-hæmmere |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1283906C (en) * | 1983-05-09 | 1991-05-07 | Makoto Sunagawa | .beta.-LACTAM COMPOUNDS AND PRODUCTION THEREOF |
CA1281720C (en) * | 1984-11-08 | 1991-03-19 | Makoto Sunagawa | Carbapenem compounds and production thereof |
JPS62155279A (ja) * | 1984-11-08 | 1987-07-10 | Sumitomo Pharmaceut Co Ltd | 新規なβ−ラクタム化合物 |
JP3005045B2 (ja) * | 1990-02-14 | 2000-01-31 | 住友製薬株式会社 | 新規なβ―ラクタム化合物及びその製造法 |
TW198034B (zh) * | 1990-03-27 | 1993-01-11 | Manyu Seiyaku Kk | |
US5712267A (en) * | 1991-06-04 | 1998-01-27 | Sankyo Company,. Limited | Carbapenem derivatives, their preparation and their use as antibiotics |
CZ167792A3 (en) * | 1991-06-04 | 1995-12-13 | Sankyo Co | 1-methylcarbapenem derivatives process of their preparation and use |
JP3048196B2 (ja) * | 1991-06-20 | 2000-06-05 | 第一製薬株式会社 | カルバペネム誘導体 |
CZ290002B6 (cs) * | 1992-03-11 | 2002-05-15 | Sankyo Company Limited | Antimikrobiální karbapenemové deriváty, způsob výroby a farmaceutický prostředek |
JP3411589B2 (ja) * | 1992-05-11 | 2003-06-03 | 第一製薬株式会社 | カルバペネム誘導体 |
JP3344662B2 (ja) * | 1992-09-14 | 2002-11-11 | 三共株式会社 | カルバペネム−3−カルボン酸誘導体 |
JPH06199860A (ja) * | 1992-09-16 | 1994-07-19 | Sankyo Co Ltd | カルバペネム誘導体 |
AU4912393A (en) * | 1993-06-15 | 1994-12-22 | Dong Kook Pharmaceutical Co., Ltd. | 1-beta-methyl-2-thiolic carbapenem derivatives |
GB9320816D0 (en) * | 1993-10-08 | 1993-12-01 | Fujisawa Pharmaceutical Co | Novel compounds |
DE69714841T2 (de) * | 1996-04-26 | 2003-05-28 | Sankyo Co | Ein 1-methylcarbapenem-derivat |
-
1996
- 1996-12-20 CA CA002241092A patent/CA2241092C/en not_active Expired - Fee Related
- 1996-12-20 KR KR10-1998-0704250A patent/KR100386993B1/ko not_active IP Right Cessation
- 1996-12-20 CN CN96180077A patent/CN1095843C/zh not_active Expired - Fee Related
- 1996-12-20 DK DK96942592T patent/DK0882728T3/da active
- 1996-12-20 HU HU9901376A patent/HUP9901376A3/hu unknown
- 1996-12-20 DE DE69623497T patent/DE69623497T2/de not_active Expired - Lifetime
- 1996-12-20 EP EP96942592A patent/EP0882728B1/en not_active Expired - Lifetime
- 1996-12-20 CZ CZ0191898A patent/CZ298246B6/cs not_active IP Right Cessation
- 1996-12-20 ES ES96942592T patent/ES2181927T3/es not_active Expired - Lifetime
- 1996-12-20 PT PT96942592T patent/PT882728E/pt unknown
- 1996-12-20 AU AU11718/97A patent/AU711135B2/en not_active Ceased
- 1996-12-20 AT AT96942592T patent/ATE223411T1/de active
- 1996-12-20 WO PCT/JP1996/003726 patent/WO1997023483A1/ja active IP Right Grant
- 1996-12-20 NZ NZ324447A patent/NZ324447A/xx not_active IP Right Cessation
-
1998
- 1998-06-12 US US09/095,925 patent/US6090802A/en not_active Expired - Fee Related
- 1998-06-19 NO NO19982873A patent/NO310684B1/no not_active IP Right Cessation
- 1998-06-19 MX MX9805023A patent/MX9805023A/es active IP Right Grant
-
1999
- 1999-02-15 HK HK99100666A patent/HK1015766A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
CA2241092C (en) | 2004-04-27 |
ATE223411T1 (de) | 2002-09-15 |
NZ324447A (en) | 1999-08-30 |
HUP9901376A3 (en) | 2000-03-28 |
ES2181927T3 (es) | 2003-03-01 |
MX9805023A (es) | 1998-11-30 |
CN1209130A (zh) | 1999-02-24 |
CA2241092A1 (en) | 1997-07-03 |
NO982873L (no) | 1998-08-21 |
HUP9901376A2 (hu) | 1999-08-30 |
HK1015766A1 (en) | 1999-10-22 |
CZ298246B6 (cs) | 2007-08-01 |
EP0882728B1 (en) | 2002-09-04 |
AU711135B2 (en) | 1999-10-07 |
PT882728E (pt) | 2002-11-29 |
CN1095843C (zh) | 2002-12-11 |
NO982873D0 (no) | 1998-06-19 |
DK0882728T3 (da) | 2003-01-06 |
DE69623497T2 (de) | 2003-05-28 |
US6090802A (en) | 2000-07-18 |
KR100386993B1 (ko) | 2003-12-18 |
AU1171897A (en) | 1997-07-17 |
EP0882728A4 (en) | 1999-03-24 |
EP0882728A1 (en) | 1998-12-09 |
KR19990071960A (ko) | 1999-09-27 |
WO1997023483A1 (en) | 1997-07-03 |
DE69623497D1 (de) | 2002-10-10 |
CZ191898A3 (cs) | 1998-09-16 |
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