CA2466975A1 - Macrolides - Google Patents
Macrolides Download PDFInfo
- Publication number
- CA2466975A1 CA2466975A1 CA002466975A CA2466975A CA2466975A1 CA 2466975 A1 CA2466975 A1 CA 2466975A1 CA 002466975 A CA002466975 A CA 002466975A CA 2466975 A CA2466975 A CA 2466975A CA 2466975 A1 CA2466975 A1 CA 2466975A1
- Authority
- CA
- Canada
- Prior art keywords
- amino
- oxo
- dihydro
- dcm
- cyclopropyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003120 macrolide antibiotic agent Substances 0.000 title abstract description 5
- 229940041033 macrolides Drugs 0.000 title abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 25
- 241000282414 Homo sapiens Species 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 239000012453 solvate Substances 0.000 claims abstract description 9
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 241001465754 Metazoa Species 0.000 claims abstract description 6
- 230000000699 topical effect Effects 0.000 claims abstract description 6
- 230000009885 systemic effect Effects 0.000 claims abstract description 5
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 5
- 238000011321 prophylaxis Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 297
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 129
- -1 C1-4thioalkyl Chemical group 0.000 claims description 100
- 229960002626 clarithromycin Drugs 0.000 claims description 90
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 79
- 229960004099 azithromycin Drugs 0.000 claims description 54
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 49
- 238000006243 chemical reaction Methods 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
- 229960005224 roxithromycin Drugs 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 229910052731 fluorine Chemical group 0.000 claims description 5
- 239000011737 fluorine Chemical group 0.000 claims description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- 101100240518 Caenorhabditis elegans nhr-12 gene Proteins 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 673
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 624
- 239000000543 intermediate Substances 0.000 description 307
- 239000000243 solution Substances 0.000 description 216
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 133
- 239000000203 mixture Substances 0.000 description 132
- 239000002904 solvent Substances 0.000 description 127
- 239000011541 reaction mixture Substances 0.000 description 125
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 102
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 92
- 239000003480 eluent Substances 0.000 description 83
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
- 238000003818 flash chromatography Methods 0.000 description 69
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- 239000012043 crude product Substances 0.000 description 60
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 55
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 55
- 229910017974 NH40H Inorganic materials 0.000 description 54
- 238000005160 1H NMR spectroscopy Methods 0.000 description 52
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 52
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 50
- 239000012074 organic phase Substances 0.000 description 50
- 239000000725 suspension Substances 0.000 description 48
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 43
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 40
- 239000008346 aqueous phase Substances 0.000 description 37
- 239000012267 brine Substances 0.000 description 37
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 34
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 34
- 229960003276 erythromycin Drugs 0.000 description 33
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 28
- 238000005481 NMR spectroscopy Methods 0.000 description 27
- 239000007864 aqueous solution Substances 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- 239000012044 organic layer Substances 0.000 description 25
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- 239000012047 saturated solution Substances 0.000 description 20
- 239000013058 crude material Substances 0.000 description 19
- 229920006395 saturated elastomer Polymers 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- 235000019253 formic acid Nutrition 0.000 description 18
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 17
- 239000000284 extract Substances 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 17
- 239000011347 resin Substances 0.000 description 17
- 229920005989 resin Polymers 0.000 description 17
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- 238000000935 solvent evaporation Methods 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 229920000642 polymer Polymers 0.000 description 15
- 239000012300 argon atmosphere Substances 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- 238000011068 loading method Methods 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229960001866 silicon dioxide Drugs 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000012948 isocyanate Substances 0.000 description 12
- 150000002513 isocyanates Chemical class 0.000 description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 11
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 8
- 150000002431 hydrogen Chemical group 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 238000001556 precipitation Methods 0.000 description 8
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 239000000460 chlorine Chemical group 0.000 description 7
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 150000005826 halohydrocarbons Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 239000012452 mother liquor Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 241000193996 Streptococcus pyogenes Species 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 5
- 229940093499 ethyl acetate Drugs 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000012746 preparative thin layer chromatography Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-UHFFFAOYSA-N 0.000 description 4
- ISPVACVJFUIDPD-UHFFFAOYSA-N 7-chloro-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 ISPVACVJFUIDPD-UHFFFAOYSA-N 0.000 description 4
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 150000001804 chlorine Chemical class 0.000 description 4
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000011200 topical administration Methods 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- LPZQLDFBCCDBTK-UHFFFAOYSA-N 7-(2-aminobutylamino)-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)C=2C=C(F)C(NCC(N)CC)=CC=2N1C1CC1 LPZQLDFBCCDBTK-UHFFFAOYSA-N 0.000 description 3
- 101150041968 CDC13 gene Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241000588655 Moraxella catarrhalis Species 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 3
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- IWQJEAWVHIBCDP-UHFFFAOYSA-N 1-cyclopropyl-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid Chemical compound C12=CC(N3CCNCC3)=CC=C2C(=O)C(C(=O)O)=CN1C1CC1 IWQJEAWVHIBCDP-UHFFFAOYSA-N 0.000 description 2
- MVQFCFAEKDIPMH-UHFFFAOYSA-N 6-(2-aminoethylamino)-7-chloro-1-cyclopropylquinolin-4-one Chemical compound C1=C(Cl)C(NCCN)=CC(C(C=C2)=O)=C1N2C1CC1 MVQFCFAEKDIPMH-UHFFFAOYSA-N 0.000 description 2
- PISYZMAJMMQIRQ-UHFFFAOYSA-N 7-chloro-1-cyclopropyl-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(Cl)=CC=C2C(=O)C(C(=O)O)=CN1C1CC1 PISYZMAJMMQIRQ-UHFFFAOYSA-N 0.000 description 2
- UEZCMDFHCHWUFM-UHFFFAOYSA-N 7-chloro-1-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(Cl)C=C2N(C)C=C(C(O)=O)C(=O)C2=C1 UEZCMDFHCHWUFM-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
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- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
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- 125000002883 imidazolyl group Chemical group 0.000 description 1
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- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
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- 239000002324 mouth wash Substances 0.000 description 1
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- 239000003208 petroleum Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
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- 239000003380 propellant Substances 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
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- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
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- 239000002453 shampoo Substances 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
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- 150000003892 tartrate salts Chemical class 0.000 description 1
- XKXIQBVKMABYQJ-UHFFFAOYSA-M tert-butyl carbonate Chemical compound CC(C)(C)OC([O-])=O XKXIQBVKMABYQJ-UHFFFAOYSA-M 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
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- 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)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0127349.9A GB0127349D0 (en) | 2001-11-14 | 2001-11-14 | Macrolides |
| GB0127349.9 | 2001-11-14 | ||
| PCT/GB2002/005101 WO2003042228A1 (en) | 2001-11-14 | 2002-11-13 | Macrolides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2466975A1 true CA2466975A1 (en) | 2003-05-22 |
Family
ID=9925777
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002466975A Abandoned CA2466975A1 (en) | 2001-11-14 | 2002-11-13 | Macrolides |
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|---|---|
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| EP (1) | EP1453846B1 (cg-RX-API-DMAC7.html) |
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| CN (1) | CN1307194C (cg-RX-API-DMAC7.html) |
| AR (1) | AR037371A1 (cg-RX-API-DMAC7.html) |
| AT (1) | ATE362479T1 (cg-RX-API-DMAC7.html) |
| BR (1) | BR0214132A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2466975A1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE60220180T2 (cg-RX-API-DMAC7.html) |
| EA (1) | EA007433B1 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2287332T3 (cg-RX-API-DMAC7.html) |
| GB (1) | GB0127349D0 (cg-RX-API-DMAC7.html) |
| HR (1) | HRP20040433A2 (cg-RX-API-DMAC7.html) |
| HU (1) | HUP0402225A3 (cg-RX-API-DMAC7.html) |
| IL (1) | IL161710A0 (cg-RX-API-DMAC7.html) |
| PL (1) | PL371472A1 (cg-RX-API-DMAC7.html) |
| RS (1) | RS41904A (cg-RX-API-DMAC7.html) |
| UA (1) | UA77210C2 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2003042228A1 (cg-RX-API-DMAC7.html) |
| ZA (1) | ZA200403684B (cg-RX-API-DMAC7.html) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6995143B2 (en) * | 2002-02-28 | 2006-02-07 | Basilea Pharmaceutica Ag | Macrolides with antibacterial activity |
| US7135573B2 (en) | 2002-05-13 | 2006-11-14 | Enanta Pharmaceuticals, Inc. | Processes for the preparation of O-(6-Pyrazol-1-yl-pyridin-3-ylmethyl)-hydroxylamine |
| US7910558B2 (en) | 2002-05-13 | 2011-03-22 | Enanta Pharmaceuticals, Inc. | Bridged macrocyclic compounds and processes for the preparation thereof |
| US7022679B2 (en) | 2002-05-13 | 2006-04-04 | Enanta Pharmaceuticals, Inc. | Processes for the preparation of 6-11 bicyclic erythromycin derivatives |
| US6764998B1 (en) | 2003-06-18 | 2004-07-20 | Enanta Pharmaceuticals, Inc. | 6,11-4C-bicyclic 9a-azalide derivatives |
| KR20040107525A (ko) * | 2002-05-14 | 2004-12-20 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 치환된 퀴놀론 카르복실산, 이들의 유도체, 그의 작용부위 및 용도 |
| AR043050A1 (es) | 2002-09-26 | 2005-07-13 | Rib X Pharmaceuticals Inc | Compuestos heterociclicos bifuncionales y metodos para preparar y usar los mismos |
| GB0225384D0 (en) | 2002-10-31 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| US6645941B1 (en) | 2003-03-26 | 2003-11-11 | Enanta Pharmaceuticals, Inc. | 6,11-3C-bicyclic 9a-azalide derivatives |
| ATE348837T1 (de) * | 2003-05-13 | 2007-01-15 | Glaxo Group Ltd | Neue 14- und 15-gliedrige ringverbindungen |
| GB0310980D0 (en) * | 2003-05-13 | 2003-06-18 | Glaxo Group Ltd | Novel compounds |
| GB0310984D0 (en) * | 2003-05-13 | 2003-06-18 | Glaxo Group Ltd | Novel compounds |
| GB0310979D0 (en) * | 2003-05-13 | 2003-06-18 | Glaxo Group Ltd | Novel compounds |
| GB0310986D0 (en) * | 2003-05-13 | 2003-06-18 | Glaxo Group Ltd | Novel compounds |
| WO2005030227A1 (en) | 2003-09-23 | 2005-04-07 | Enanta Pharmaceuticals, Inc. | 9a, 11-3C-BICYCLIC 9a-AZALIDE DERIVATIVES |
| WO2005070113A2 (en) | 2004-01-09 | 2005-08-04 | Enanta Pharmaceuticals, Inc. | 9n-substituted 6-11 bicyclic erythromycin derivatives |
| US8202843B2 (en) | 2004-02-27 | 2012-06-19 | Rib-X Pharmaceuticals, Inc. | Macrocyclic compounds and methods of making and using the same |
| EP1756134A1 (en) * | 2004-05-06 | 2007-02-28 | GlaxoSmithKline istrazivacki centar Zagreb d.o.o. | Carbamate linked macrolides useful for the treatment of microbial infections |
| JP2007536371A (ja) * | 2004-05-06 | 2007-12-13 | グラクソスミスクライン・イストラジヴァッキ・センタル・ザグレブ・ドルズバ・ゼー・オメイェノ・オドゴヴォルノスティオ | 微生物感染症の治療に有用なエステル結合マクロライド |
| WO2006047167A2 (en) * | 2004-10-21 | 2006-05-04 | Janssen Pharmaceutica, N.V. | 9 alkyl and 9 alkylidenyl 6-0 alkyl-11, 12 carbamate ketolide antimicrobials |
| GB0424959D0 (en) * | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| GB0424951D0 (en) * | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| GB0424958D0 (en) * | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| GB0424961D0 (en) * | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| WO2008017696A1 (en) * | 2006-08-09 | 2008-02-14 | Basilea Pharmaceutica Ag | New macrolides useful against inflammatory and allergic disseases |
| CN101541331A (zh) | 2006-08-24 | 2009-09-23 | 沃克哈特研究中心 | 具有抗微生物活性的新颖大环内酯和酮内酯 |
| KR101617897B1 (ko) | 2008-02-08 | 2016-05-03 | 바실리어 파마슈티카 아게 | 신규 마크로라이드 및 그의 용도 |
| EP2435460B1 (en) | 2009-05-27 | 2015-01-07 | Wockhardt Limited | Ketolide compounds having antimicrobial activity |
| CN103384676B (zh) | 2010-12-09 | 2016-02-03 | 沃克哈特有限公司 | 酮内酯化合物 |
| CA2826174A1 (en) * | 2011-01-31 | 2012-08-09 | Meiji Seika Pharma Co., Ltd. | Novel macrolide derivative |
| CN103619849B (zh) | 2011-03-01 | 2016-05-25 | 沃克哈特有限公司 | 酮内酯中间体的制备方法 |
| CN119060110A (zh) * | 2023-05-30 | 2024-12-03 | 北京理工大学 | 一种红霉素衍生物及其制备方法和应用 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0126344A2 (en) | 1983-05-20 | 1984-11-28 | Abbott Laboratories | Tripeptide esters of therapeutic agents |
| US4742049A (en) * | 1986-06-04 | 1988-05-03 | Abbott Laboratories | Semisynthetic erythromycin antibiotics |
| AU623764B2 (en) * | 1989-03-28 | 1992-05-21 | Abbott Laboratories | Erythromycin derivatives |
| CA2064634C (en) * | 1991-04-04 | 1998-08-04 | James V. Heck | 9-deoxo-8a-aza-8a-homoerythromycin a derivatives modified at the 4"- and8a-positions |
| BR9708929A (pt) | 1996-05-07 | 1999-08-03 | Abbott Lab | Composto composição farmacêutica e processos para controlar uma infecção bacteriana em um mamífero e para preparar compostos de macrólidos |
| EP0895999A1 (en) * | 1997-08-06 | 1999-02-10 | Pfizer Products Inc. | C-4" substituted macrolide antibiotics |
| US6262030B1 (en) * | 1998-11-03 | 2001-07-17 | Pfizer Inc. | Erythromycin derivatives |
| EP1180110A1 (en) | 1999-05-24 | 2002-02-20 | Pfizer Products Inc. | 13-methyl-erythromycin derivatives |
| WO2001014397A1 (en) | 1999-08-24 | 2001-03-01 | Abbott Laboratories | 9a-azalides with antibacterial activity |
| US6946446B2 (en) * | 2000-02-24 | 2005-09-20 | Abbott Laboratories | Anti-infective agents useful against multidrug-resistant strains of bacteria |
| WO2001063539A2 (en) | 2000-02-24 | 2001-08-30 | Abbott Laboratories | Anti-infective agents useful against multidrug-resistant strains of bacteria |
| JP2002173498A (ja) | 2000-09-27 | 2002-06-21 | Hokuriku Seiyaku Co Ltd | エリスロマイシン誘導体 |
| GB0025688D0 (en) * | 2000-10-19 | 2000-12-06 | Glaxo Group Ltd | Macrolides |
-
2001
- 2001-11-14 GB GBGB0127349.9A patent/GB0127349D0/en not_active Ceased
-
2002
- 2002-11-13 EA EA200400536A patent/EA007433B1/ru not_active IP Right Cessation
- 2002-11-13 US US10/495,413 patent/US7202221B2/en not_active Expired - Fee Related
- 2002-11-13 AR ARP020104364A patent/AR037371A1/es unknown
- 2002-11-13 PL PL02371472A patent/PL371472A1/xx not_active Application Discontinuation
- 2002-11-13 BR BR0214132-9A patent/BR0214132A/pt not_active IP Right Cessation
- 2002-11-13 RS YU41904A patent/RS41904A/sr unknown
- 2002-11-13 CN CNB028270452A patent/CN1307194C/zh not_active Expired - Fee Related
- 2002-11-13 DE DE60220180T patent/DE60220180T2/de not_active Expired - Fee Related
- 2002-11-13 IL IL16171002A patent/IL161710A0/xx unknown
- 2002-11-13 HU HU0402225A patent/HUP0402225A3/hu unknown
- 2002-11-13 HR HR20040433A patent/HRP20040433A2/hr not_active Application Discontinuation
- 2002-11-13 CA CA002466975A patent/CA2466975A1/en not_active Abandoned
- 2002-11-13 ES ES02779670T patent/ES2287332T3/es not_active Expired - Lifetime
- 2002-11-13 WO PCT/GB2002/005101 patent/WO2003042228A1/en not_active Ceased
- 2002-11-13 JP JP2003544063A patent/JP2005515978A/ja active Pending
- 2002-11-13 EP EP02779670A patent/EP1453846B1/en not_active Expired - Lifetime
- 2002-11-13 UA UA20040503313A patent/UA77210C2/uk unknown
- 2002-11-13 AT AT02779670T patent/ATE362479T1/de not_active IP Right Cessation
-
2004
- 2004-05-13 ZA ZA200403684A patent/ZA200403684B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL161710A0 (en) | 2004-09-27 |
| UA77210C2 (en) | 2006-11-15 |
| RS41904A (sr) | 2006-10-27 |
| GB0127349D0 (en) | 2002-01-02 |
| AR037371A1 (es) | 2004-11-03 |
| ZA200403684B (en) | 2005-09-13 |
| ES2287332T3 (es) | 2007-12-16 |
| EP1453846A1 (en) | 2004-09-08 |
| DE60220180D1 (de) | 2007-06-28 |
| HUP0402225A3 (en) | 2006-01-30 |
| HUP0402225A2 (hu) | 2005-02-28 |
| EA007433B1 (ru) | 2006-10-27 |
| EA200400536A1 (ru) | 2004-12-30 |
| JP2005515978A (ja) | 2005-06-02 |
| CN1612888A (zh) | 2005-05-04 |
| CN1307194C (zh) | 2007-03-28 |
| PL371472A1 (en) | 2005-06-13 |
| HRP20040433A2 (en) | 2005-04-30 |
| DE60220180T2 (de) | 2008-01-17 |
| BR0214132A (pt) | 2004-09-14 |
| ATE362479T1 (de) | 2007-06-15 |
| US7202221B2 (en) | 2007-04-10 |
| US20050080025A1 (en) | 2005-04-14 |
| EP1453846B1 (en) | 2007-05-16 |
| WO2003042228A1 (en) | 2003-05-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |