ES2253371T3 - Procedimiento para la preparacion y la purificacion de maitansinoides que contienen tiol. - Google Patents
Procedimiento para la preparacion y la purificacion de maitansinoides que contienen tiol.Info
- Publication number
- ES2253371T3 ES2253371T3 ES01926594T ES01926594T ES2253371T3 ES 2253371 T3 ES2253371 T3 ES 2253371T3 ES 01926594 T ES01926594 T ES 01926594T ES 01926594 T ES01926594 T ES 01926594T ES 2253371 T3 ES2253371 T3 ES 2253371T3
- Authority
- ES
- Spain
- Prior art keywords
- maitansinol
- methyl
- maitansinoid
- alanine
- procedure according
- 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.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 72
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 238000000746 purification Methods 0.000 title claims description 28
- 150000002148 esters Chemical class 0.000 claims abstract description 49
- 150000003573 thiols Chemical class 0.000 claims abstract description 48
- 239000011541 reaction mixture Substances 0.000 claims abstract description 41
- 230000002829 reductive effect Effects 0.000 claims abstract description 39
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 33
- -1 lithium trimethoxyaluminium hydride Chemical class 0.000 claims abstract description 33
- 229910010199 LiAl Inorganic materials 0.000 claims abstract description 13
- 230000007062 hydrolysis Effects 0.000 claims abstract description 13
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 183
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 69
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 54
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 51
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 24
- 238000004587 chromatography analysis Methods 0.000 claims description 19
- 239000000741 silica gel Substances 0.000 claims description 19
- 229910002027 silica gel Inorganic materials 0.000 claims description 19
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 17
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 claims description 16
- 230000009467 reduction Effects 0.000 claims description 16
- 238000005886 esterification reaction Methods 0.000 claims description 15
- 230000032050 esterification Effects 0.000 claims description 13
- 239000003960 organic solvent Substances 0.000 claims description 13
- 238000000926 separation method Methods 0.000 claims description 13
- 239000000872 buffer Substances 0.000 claims description 12
- 239000000377 silicon dioxide Substances 0.000 claims description 12
- 235000004279 alanine Nutrition 0.000 claims description 11
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 11
- 239000012298 atmosphere Substances 0.000 claims description 10
- FNDFHKWOXMMFIM-ZETCQYMHSA-N (2s)-2-[acetyl(methyl)amino]-2-methyl-3-sulfanylpropanedithioic acid Chemical compound CC(=O)N(C)[C@@](C)(CS)C(S)=S FNDFHKWOXMMFIM-ZETCQYMHSA-N 0.000 claims description 9
- 238000004440 column chromatography Methods 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000012062 aqueous buffer Substances 0.000 claims description 6
- 235000005074 zinc chloride Nutrition 0.000 claims description 6
- 239000011592 zinc chloride Substances 0.000 claims description 6
- MRIUCSDUNONTSR-QMMMGPOBSA-N (2s)-2-[acetyl(methyl)amino]-2-methyl-4-sulfanylbutanedithioic acid Chemical compound CC(=O)N(C)[C@](C)(C(S)=S)CCS MRIUCSDUNONTSR-QMMMGPOBSA-N 0.000 claims description 5
- 238000012746 preparative thin layer chromatography Methods 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 150000004678 hydrides Chemical class 0.000 claims description 3
- ANAFTYVSHCSQPP-UHFFFAOYSA-N lithium;trimethoxyalumane Chemical compound [Li].CO[Al](OC)OC ANAFTYVSHCSQPP-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- UAEJRRZPRZCUBE-UHFFFAOYSA-N trimethoxyalumane Chemical compound [Al+3].[O-]C.[O-]C.[O-]C UAEJRRZPRZCUBE-UHFFFAOYSA-N 0.000 claims description 2
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 claims 2
- 239000000499 gel Substances 0.000 claims 2
- 239000000337 buffer salt Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 128
- 239000000243 solution Substances 0.000 description 79
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 46
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 22
- 239000003814 drug Substances 0.000 description 22
- GDFAOVXKHJXLEI-VKHMYHEASA-N N-methyl-L-alanine Chemical class C[NH2+][C@@H](C)C([O-])=O GDFAOVXKHJXLEI-VKHMYHEASA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 229940079593 drug Drugs 0.000 description 20
- DVOOXRTYGGLORL-VKHMYHEASA-N (2r)-2-(methylamino)-3-sulfanylpropanoic acid Chemical compound CN[C@@H](CS)C(O)=O DVOOXRTYGGLORL-VKHMYHEASA-N 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- 229910052786 argon Inorganic materials 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- GDFAOVXKHJXLEI-UHFFFAOYSA-N L-N-Boc-N-methylalanine Natural products CNC(C)C(O)=O GDFAOVXKHJXLEI-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 15
- 238000006722 reduction reaction Methods 0.000 description 15
- 125000002228 disulfide group Chemical group 0.000 description 14
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 12
- XYONNSVDNIRXKZ-UHFFFAOYSA-N S-methyl methanethiosulfonate Chemical compound CSS(C)(=O)=O XYONNSVDNIRXKZ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 12
- 239000011261 inert gas Substances 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 239000011230 binding agent Substances 0.000 description 11
- 201000011510 cancer Diseases 0.000 description 11
- OPQNCARIZFLNLF-JBHFWYGFSA-N ansamitocin P3 Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)C(C)C)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 OPQNCARIZFLNLF-JBHFWYGFSA-N 0.000 description 10
- 239000000562 conjugate Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 9
- 239000012300 argon atmosphere Substances 0.000 description 9
- 231100000433 cytotoxic Toxicity 0.000 description 9
- 230000001472 cytotoxic effect Effects 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- OPQNCARIZFLNLF-UHFFFAOYSA-N ansamitocin P-3 Natural products CN1C(=O)CC(OC(=O)C(C)C)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)C=CC=C(C)CC2=CC(OC)=C(Cl)C1=C2 OPQNCARIZFLNLF-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 8
- 229960000975 daunorubicin Drugs 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 7
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 7
- 239000007832 Na2SO4 Substances 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 125000003107 substituted aryl group Chemical group 0.000 description 7
- PHMDDWYPVDXMNL-BYPYZUCNSA-N (2s)-2-(methylamino)-4-sulfanylbutanoic acid Chemical compound CN[C@H](C(O)=O)CCS PHMDDWYPVDXMNL-BYPYZUCNSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- GCIZMJUHGHGRNW-UHFFFAOYSA-N 5-sulfanylpentanoic acid Chemical compound OC(=O)CCCCS GCIZMJUHGHGRNW-UHFFFAOYSA-N 0.000 description 5
- GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
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- 230000014759 maintenance of location Effects 0.000 description 5
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- 239000008057 potassium phosphate buffer Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 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 4
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000006298 dechlorination reaction Methods 0.000 description 4
- 150000002019 disulfides Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229910052734 helium Inorganic materials 0.000 description 4
- 239000001307 helium Substances 0.000 description 4
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 4
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- 238000000338 in vitro Methods 0.000 description 4
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- 239000012047 saturated solution Substances 0.000 description 4
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 4
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- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
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- BPOPGHPHBCLJOK-UHFFFAOYSA-N butanedithioic acid Chemical compound CCCC(S)=S BPOPGHPHBCLJOK-UHFFFAOYSA-N 0.000 description 3
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- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 2
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- 230000032258 transport Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Transplantation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US641348 | 2000-08-18 | ||
| US09/641,348 US6333410B1 (en) | 2000-08-18 | 2000-08-18 | Process for the preparation and purification of thiol-containing maytansinoids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2253371T3 true ES2253371T3 (es) | 2006-06-01 |
Family
ID=24571977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01926594T Expired - Lifetime ES2253371T3 (es) | 2000-08-18 | 2001-04-26 | Procedimiento para la preparacion y la purificacion de maitansinoides que contienen tiol. |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US6333410B1 (OSRAM) |
| EP (1) | EP1313738B1 (OSRAM) |
| JP (1) | JP4922535B2 (OSRAM) |
| AT (1) | ATE313545T1 (OSRAM) |
| AU (1) | AU763107B2 (OSRAM) |
| CA (2) | CA2373554C (OSRAM) |
| DE (1) | DE60116113T2 (OSRAM) |
| DK (1) | DK1313738T3 (OSRAM) |
| ES (1) | ES2253371T3 (OSRAM) |
| WO (1) | WO2002016368A1 (OSRAM) |
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- 2000-08-18 US US09/641,348 patent/US6333410B1/en not_active Ceased
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2001
- 2001-04-26 WO PCT/US2001/010816 patent/WO2002016368A1/en not_active Ceased
- 2001-04-26 ES ES01926594T patent/ES2253371T3/es not_active Expired - Lifetime
- 2001-04-26 DE DE60116113T patent/DE60116113T2/de not_active Expired - Lifetime
- 2001-04-26 AU AU53118/01A patent/AU763107B2/en not_active Expired
- 2001-04-26 CA CA2373554A patent/CA2373554C/en not_active Expired - Lifetime
- 2001-04-26 JP JP2002521468A patent/JP4922535B2/ja not_active Expired - Lifetime
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- 2001-04-26 CA CA2678754A patent/CA2678754C/en not_active Expired - Lifetime
- 2001-04-26 EP EP01926594A patent/EP1313738B1/en not_active Expired - Lifetime
- 2001-04-26 AT AT01926594T patent/ATE313545T1/de active
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| AU763107B2 (en) | 2003-07-10 |
| EP1313738A4 (en) | 2005-01-19 |
| AU5311801A (en) | 2002-03-04 |
| CA2678754C (en) | 2013-08-27 |
| CA2373554A1 (en) | 2002-02-28 |
| ATE313545T1 (de) | 2006-01-15 |
| CA2373554C (en) | 2011-02-15 |
| EP1313738B1 (en) | 2005-12-21 |
| DK1313738T3 (da) | 2006-05-01 |
| EP1313738A1 (en) | 2003-05-28 |
| DE60116113T2 (de) | 2006-07-27 |
| JP2004506738A (ja) | 2004-03-04 |
| JP4922535B2 (ja) | 2012-04-25 |
| DE60116113D1 (de) | 2006-01-26 |
| WO2002016368A1 (en) | 2002-02-28 |
| CA2678754A1 (en) | 2002-02-28 |
| USRE39151E1 (en) | 2006-06-27 |
| US6333410B1 (en) | 2001-12-25 |
| HK1056357A1 (en) | 2004-02-13 |
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