MXPA04004607A - Agentes de venenos de topoisomerasa solubilizados. - Google Patents
Agentes de venenos de topoisomerasa solubilizados.Info
- Publication number
- MXPA04004607A MXPA04004607A MXPA04004607A MXPA04004607A MXPA04004607A MX PA04004607 A MXPA04004607 A MX PA04004607A MX PA04004607 A MXPA04004607 A MX PA04004607A MX PA04004607 A MXPA04004607 A MX PA04004607A MX PA04004607 A MXPA04004607 A MX PA04004607A
- Authority
- MX
- Mexico
- Prior art keywords
- compound
- substituted
- alkyl
- groups
- formula
- Prior art date
Links
- 231100000614 poison Toxicity 0.000 title description 11
- 239000002574 poison Substances 0.000 title description 11
- 101710183280 Topoisomerase Proteins 0.000 title description 10
- 239000003795 chemical substances by application Substances 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 178
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 24
- 201000011510 cancer Diseases 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- -1 piperazino ring Chemical group 0.000 claims description 52
- 125000000623 heterocyclic group Chemical group 0.000 claims description 30
- 229910003827 NRaRb Inorganic materials 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 241000124008 Mammalia Species 0.000 claims description 15
- 229910052705 radium Inorganic materials 0.000 claims description 15
- 229910052701 rubidium Inorganic materials 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 12
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 230000000844 anti-bacterial effect Effects 0.000 claims description 9
- 230000000843 anti-fungal effect Effects 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 229940121375 antifungal agent Drugs 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 7
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 230000000507 anthelmentic effect Effects 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 230000000842 anti-protozoal effect Effects 0.000 claims description 5
- 239000003904 antiprotozoal agent Substances 0.000 claims description 5
- 230000012010 growth Effects 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000006413 ring segment Chemical group 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
- 230000000840 anti-viral effect Effects 0.000 claims description 3
- 230000005907 cancer growth Effects 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 238000001727 in vivo Methods 0.000 claims description 3
- 230000003381 solubilizing effect Effects 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 238000011161 development Methods 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 238000013160 medical therapy Methods 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims 3
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 3
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 1
- 125000005907 alkyl ester group Chemical group 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 11
- 230000008569 process Effects 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 102000003915 DNA Topoisomerases Human genes 0.000 description 10
- 108090000323 DNA Topoisomerases Proteins 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 7
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000010494 dissociation reaction Methods 0.000 description 6
- 230000005593 dissociations Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- 125000004104 aryloxy group Chemical group 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 5
- 125000005553 heteroaryloxy group Chemical group 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 150000001204 N-oxides Chemical class 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000830681 Homo sapiens DNA topoisomerase 1 Proteins 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 239000000921 anthelmintic agent Substances 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 238000002784 cytotoxicity assay Methods 0.000 description 3
- 231100000263 cytotoxicity test Toxicity 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 125000004470 heterocyclooxy group Chemical group 0.000 description 3
- 102000056859 human TOP1 Human genes 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 2
- MSLYUFAHRVRLKU-UHFFFAOYSA-N 7,10,15-trihydroxypentacyclo[10.7.1.02,11.03,8.016,20]icosa-1,3(8),4,6,10,12(20),13,15,18-nonaene-9,17-dione Chemical compound Oc1ccc2c3c(O)c(=O)c4c(O)cccc4c3c3ccc(=O)c1c23 MSLYUFAHRVRLKU-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 235000019800 disodium phosphate Nutrition 0.000 description 2
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 150000003014 phosphoric acid esters Chemical class 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- CGFVUVWMYIHGHS-UHFFFAOYSA-N saintopin Chemical compound C1=C(O)C=C2C=C(C(=O)C=3C(=C(O)C=C(C=3)O)C3=O)C3=C(O)C2=C1O CGFVUVWMYIHGHS-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
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- 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
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- 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
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- 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
- A61P31/10—Antimycotics
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- 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
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Saccharide Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Paper (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33269201P | 2001-11-14 | 2001-11-14 | |
| PCT/US2002/036475 WO2003051289A2 (en) | 2001-11-14 | 2002-11-14 | Solubilized topoisomerase poison agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA04004607A true MXPA04004607A (es) | 2004-09-10 |
Family
ID=23299415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA04004607A MXPA04004607A (es) | 2001-11-14 | 2002-11-14 | Agentes de venenos de topoisomerasa solubilizados. |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US6987109B2 (https=) |
| EP (1) | EP1453507B1 (https=) |
| JP (1) | JP4789414B2 (https=) |
| KR (1) | KR20040088466A (https=) |
| AT (1) | ATE424200T1 (https=) |
| AU (1) | AU2002365161B2 (https=) |
| CA (1) | CA2467279A1 (https=) |
| DE (1) | DE60231426D1 (https=) |
| MX (1) | MXPA04004607A (https=) |
| WO (1) | WO2003051289A2 (https=) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1453812B1 (en) * | 2001-11-14 | 2008-08-20 | Rutgers, The State University | Cytotoxic agents |
| MXPA04004607A (es) * | 2001-11-14 | 2004-09-10 | Univ Rutgers | Agentes de venenos de topoisomerasa solubilizados. |
| DE60235287D1 (de) * | 2001-11-14 | 2010-03-25 | Univ Rutgers | Löslich gemachte topoisomerase-gifte |
| AU2002364953A1 (en) * | 2001-11-14 | 2003-06-17 | Edmond J. Lavoie | Topoisomerase poison agents |
| AU2003268075A1 (en) * | 2002-08-09 | 2004-02-25 | Edmond J. Lavoie | Nitro and amino substituted dibenzonaphthyridines as topoisomerase agents |
| US6992088B2 (en) * | 2002-08-09 | 2006-01-31 | Rutgers, The State University Of New Jersey | Nitro and amino substituted heterocycles as topoisomerase I targeting agents |
| US6989387B2 (en) * | 2002-08-09 | 2006-01-24 | Rutgers, The State University Of New Jersey | Nitro and amino substituted topoisomerase agents |
| CA2510337C (en) * | 2002-11-12 | 2013-01-08 | Rutgers, The State University Of New Jersey | Topoisomerase-targeting agents |
| EP1646388A4 (en) | 2003-05-12 | 2007-04-18 | Purdue Research Foundation | CYTOTOXIC INDENO AND ISOINDOLOISOCHINOLONE |
| US7495100B2 (en) | 2004-05-07 | 2009-02-24 | Purdue Research Foundation | Synthesis of indenoisoquinolines |
| DK2403856T3 (da) | 2009-03-06 | 2013-04-08 | Univ Rutgers | Methylendioxybenzo[i]phenanthridinderivater anvendt til behandling af cancer |
| WO2010127363A1 (en) | 2009-05-01 | 2010-11-04 | Rutgers, The State University Of New Jersey | Toposiomerase inhibitors |
| CN102993094B (zh) * | 2011-09-08 | 2014-07-23 | 中国石油大学(北京) | 一种四氢喹啉衍生物的合成方法 |
| US11091498B2 (en) | 2016-04-04 | 2021-08-17 | Rutgers, The State University Of New Jersey | Topoisomerase poisons |
Family Cites Families (45)
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| US2981731A (en) * | 1961-04-25 | Acridine derivatives | ||
| US2985661A (en) * | 1956-02-06 | 1961-05-23 | American Cyanamid Co | Preparation of 2(omicron-aminophenyl)-benzimidazole |
| US2915523A (en) * | 1956-12-03 | 1959-12-01 | Parke Davis & Co | Benzacridine compounds |
| US3272707A (en) | 1964-07-17 | 1966-09-13 | Smith Kline French Lab | Pharmaceutical compositions and methods for their use |
| CH420044A (de) * | 1964-09-01 | 1967-03-15 | Ciba Geigy | Verwendung von neuen Azol-Derivaten als optische Aufheller für textile organische Materialien |
| US3267107A (en) * | 1964-09-17 | 1966-08-16 | American Home Prod | 3-(4'-5'-methylenedioxy-phenyl)-7, 8-dimethoxy-1, 2, 3, 4,-tetrahydroisoquinolines |
| US3849561A (en) * | 1964-10-20 | 1974-11-19 | S Naruto | Anti-peptic ulcer substance from corydalis tubers |
| US3272107A (en) * | 1965-04-23 | 1966-09-13 | Geo Space Corp | Radial vane shutter |
| DE1670684A1 (de) * | 1966-04-01 | 1970-12-03 | Hoechst Ag | Verfahren zur Herstellung von basisch substituierten Bis-benzimidazol-derivaten |
| US3542782A (en) * | 1967-03-15 | 1970-11-24 | Sandoz Ag | 5,6-dihydro-8h-isoquino(1,2-b)quinazolines |
| JPS4942700A (https=) * | 1972-08-25 | 1974-04-22 | ||
| US3912740A (en) * | 1974-02-28 | 1975-10-14 | Us Health | Method for the preparation of oxygenated benzo{8 c{9 phenanthridine compounds |
| PT73763B (fr) | 1981-10-01 | 1983-10-26 | Quatrum Empresa Nacional De Qu | Procede pour la preparation de nouveaux epoxides d'alkaloides benzofenantridiniques et de compositions pharmaceutiques qui les contiennent |
| US5153178A (en) * | 1982-05-14 | 1992-10-06 | Maroko Peter R | Compositions and method of treatment for improving circulatory performance |
| US4761417A (en) * | 1982-05-14 | 1988-08-02 | Maroko Peter R | Compounds, compositions and method of treatments for improving circulatory performance |
| IE55519B1 (en) | 1982-05-14 | 1990-10-10 | Maroko Peter R | Use of a protoberberine alkaloid and composition containing same |
| US4980344A (en) * | 1982-05-14 | 1990-12-25 | Maroko Peter R | Compositions for improving circulatory performance |
| US4749708A (en) * | 1982-05-14 | 1988-06-07 | Maroko Peter R | Composition for improving circulatory performance |
| JPS61130289A (ja) * | 1984-11-29 | 1986-06-18 | Ss Pharmaceut Co Ltd | １３−プロピルベルベリンの塩 |
| FR2595356B1 (fr) * | 1986-03-05 | 1991-05-24 | Pasteur Strasbourg Universite | Derives des nitro ou aminobenzyltetrahydroisoquinoleines, procedes d'obtention, compositions pharmaceutiques les contenant, proprietes pharmacologiques et applications |
| US5244903A (en) * | 1987-03-31 | 1993-09-14 | Research Triangle Institute | Camptothecin analogs as potent inhibitors of topoisomerase I |
| SU1530628A1 (ru) | 1987-11-20 | 1989-12-23 | Ленинградский Технологический Институт Им.Ленсовета | Тригидрохлорид 2-[2-фенил-5(6)-бензимидазолил]-N-(3-диметиламинопропил)-5(6)-бензимидазолкарбоксамида в качестве флуоресцентного красител дл исследовани ДНК |
| US5106863A (en) * | 1990-03-26 | 1992-04-21 | Ortho Pharmaceutical Corporation | Substituted imidazole and pyridine derivatives |
| US5135934A (en) * | 1990-07-06 | 1992-08-04 | Du Pont Merck Pharmaceutical Company | 3-phenyl-5,6-dihydrobenz(c) acridine-7-carboxylic acids and related compounds as immunosuppressive agents |
| US5126351A (en) * | 1991-01-24 | 1992-06-30 | Glaxo Inc. | Antitumor compounds |
| US5223506A (en) * | 1991-06-04 | 1993-06-29 | Glaxo Inc. | Cyclic antitumor compounds |
| US5428040A (en) * | 1993-08-31 | 1995-06-27 | The Du Pont Merck Pharmaceutical Company | Carbocyclic fused-ring quinolinecarboxylic acids useful as immunosuppressive agents |
| CA2150235A1 (en) * | 1993-09-28 | 1995-04-06 | Fumio Suzuki | A novel tetracyclic compound |
| US5807874A (en) * | 1995-05-17 | 1998-09-15 | Rutgers, The State University Of New Jersey | Trisbenzimidazoles useful as topoisomerase I inhibitors |
| NZ307959A (en) | 1995-05-17 | 1998-08-26 | Univ Rutgers | Substituted tribenzimidazole derivatives where the substituent can be aryl or heteroaryl and medicaments |
| US5767142A (en) * | 1996-03-20 | 1998-06-16 | Rutgers, The State University Of New Jersey | Trisbenzimidazoles useful as topoisomerase I inhibitors |
| ES2161442T3 (es) | 1996-02-12 | 2001-12-01 | Univ Rutgers | Analogos de coralina como inhibidores de topoisomerasa. |
| US5770617A (en) | 1996-03-20 | 1998-06-23 | Rutgers, The State University Of New Jersey | Terbenzimidazoles useful as antifungal agents |
| JP2001501197A (ja) * | 1996-09-23 | 2001-01-30 | ルトガーズ，ザ ステイト ユニバーシティ オブ ニュージャージー | 抗―腫瘍剤としての置換された複素環式化合物類 |
| US6140328A (en) * | 1997-12-12 | 2000-10-31 | Rutgers, The State University Of New Jersey | Heterocyclic cytotoxic agents |
| CA2347100C (en) | 1998-10-14 | 2010-12-14 | Purdue Research Foundation | Novel indenoisoquinolines as antineoplastic agents |
| US6740650B2 (en) * | 1999-10-29 | 2004-05-25 | Rutgers, The State University Of New Jersey | Heterocyclic cytotoxic agents |
| WO2001032631A2 (en) * | 1999-10-29 | 2001-05-10 | Rutgers, The State University Of New Jerey | Heterocyclic cytotoxic agents |
| DE60235287D1 (de) * | 2001-11-14 | 2010-03-25 | Univ Rutgers | Löslich gemachte topoisomerase-gifte |
| MXPA04004607A (es) * | 2001-11-14 | 2004-09-10 | Univ Rutgers | Agentes de venenos de topoisomerasa solubilizados. |
| AU2002364953A1 (en) * | 2001-11-14 | 2003-06-17 | Edmond J. Lavoie | Topoisomerase poison agents |
| EP1453812B1 (en) * | 2001-11-14 | 2008-08-20 | Rutgers, The State University | Cytotoxic agents |
| US6989387B2 (en) * | 2002-08-09 | 2006-01-24 | Rutgers, The State University Of New Jersey | Nitro and amino substituted topoisomerase agents |
| US6992088B2 (en) * | 2002-08-09 | 2006-01-31 | Rutgers, The State University Of New Jersey | Nitro and amino substituted heterocycles as topoisomerase I targeting agents |
| AU2003268075A1 (en) * | 2002-08-09 | 2004-02-25 | Edmond J. Lavoie | Nitro and amino substituted dibenzonaphthyridines as topoisomerase agents |
-
2002
- 2002-11-14 MX MXPA04004607A patent/MXPA04004607A/es active IP Right Grant
- 2002-11-14 AT AT02803313T patent/ATE424200T1/de not_active IP Right Cessation
- 2002-11-14 JP JP2003552222A patent/JP4789414B2/ja not_active Expired - Fee Related
- 2002-11-14 AU AU2002365161A patent/AU2002365161B2/en not_active Ceased
- 2002-11-14 KR KR10-2004-7007453A patent/KR20040088466A/ko not_active Withdrawn
- 2002-11-14 DE DE60231426T patent/DE60231426D1/de not_active Expired - Lifetime
- 2002-11-14 EP EP02803313A patent/EP1453507B1/en not_active Expired - Lifetime
- 2002-11-14 CA CA002467279A patent/CA2467279A1/en not_active Abandoned
- 2002-11-14 WO PCT/US2002/036475 patent/WO2003051289A2/en not_active Ceased
-
2004
- 2004-05-14 US US10/846,951 patent/US6987109B2/en not_active Expired - Lifetime
-
2005
- 2005-08-24 US US11/210,457 patent/US20060058306A1/en not_active Abandoned
-
2010
- 2010-05-28 US US12/789,750 patent/US20100240664A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1453507B1 (en) | 2009-03-04 |
| US6987109B2 (en) | 2006-01-17 |
| AU2002365161A1 (en) | 2003-06-30 |
| CA2467279A1 (en) | 2003-06-26 |
| WO2003051289A2 (en) | 2003-06-26 |
| JP2005511762A (ja) | 2005-04-28 |
| US20060058306A1 (en) | 2006-03-16 |
| EP1453507A2 (en) | 2004-09-08 |
| ATE424200T1 (de) | 2009-03-15 |
| US20100240664A1 (en) | 2010-09-23 |
| KR20040088466A (ko) | 2004-10-16 |
| JP4789414B2 (ja) | 2011-10-12 |
| EP1453507A4 (en) | 2005-06-08 |
| AU2002365161B2 (en) | 2008-07-03 |
| US20050009826A1 (en) | 2005-01-13 |
| DE60231426D1 (de) | 2009-04-16 |
| WO2003051289A3 (en) | 2003-12-11 |
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