ES2207983T3 - Derivados de epotilona y su uso como agentes antitumorales. - Google Patents
Derivados de epotilona y su uso como agentes antitumorales.Info
- Publication number
- ES2207983T3 ES2207983T3 ES99969216T ES99969216T ES2207983T3 ES 2207983 T3 ES2207983 T3 ES 2207983T3 ES 99969216 T ES99969216 T ES 99969216T ES 99969216 T ES99969216 T ES 99969216T ES 2207983 T3 ES2207983 T3 ES 2207983T3
- Authority
- ES
- Spain
- Prior art keywords
- formula
- compound
- lower alkyl
- alkyl
- bond
- 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
- 239000002246 antineoplastic agent Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 316
- 125000000217 alkyl group Chemical group 0.000 claims description 133
- 239000000203 mixture Substances 0.000 claims description 101
- 238000000034 method Methods 0.000 claims description 65
- 150000003254 radicals Chemical class 0.000 claims description 65
- -1 carbamoylmethyl Chemical group 0.000 claims description 64
- 238000006243 chemical reaction Methods 0.000 claims description 59
- 150000003839 salts Chemical class 0.000 claims description 58
- 239000002253 acid Substances 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 49
- 229910052799 carbon Inorganic materials 0.000 claims description 43
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- 238000002360 preparation method Methods 0.000 claims description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 150000002431 hydrogen Chemical class 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims description 35
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 34
- 125000006239 protecting group Chemical group 0.000 claims description 34
- 206010028980 Neoplasm Diseases 0.000 claims description 30
- 229910052740 iodine Inorganic materials 0.000 claims description 24
- 125000004429 atom Chemical group 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 9
- 241000282414 Homo sapiens Species 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 5
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 claims description 5
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 5
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 4
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims 3
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 186
- 239000000243 solution Substances 0.000 description 175
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 137
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 103
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 103
- 238000005160 1H NMR spectroscopy Methods 0.000 description 102
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 101
- 239000000460 chlorine Substances 0.000 description 93
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 84
- 239000002904 solvent Substances 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 74
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- 238000000746 purification Methods 0.000 description 46
- 239000003921 oil Substances 0.000 description 44
- 235000019198 oils Nutrition 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000000284 extract Substances 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- 150000001299 aldehydes Chemical class 0.000 description 28
- 238000001914 filtration Methods 0.000 description 28
- 239000000047 product Substances 0.000 description 24
- 238000001704 evaporation Methods 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 239000007864 aqueous solution Substances 0.000 description 20
- 230000008020 evaporation Effects 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 19
- 238000001816 cooling Methods 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
- 239000004480 active ingredient Substances 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
- 150000002596 lactones Chemical class 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- 239000002585 base Substances 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 239000007832 Na2SO4 Substances 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 102000029749 Microtubule Human genes 0.000 description 12
- 108091022875 Microtubule Proteins 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 229930013356 epothilone Natural products 0.000 description 9
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000006286 aqueous extract Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 239000002243 precursor Substances 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 150000003883 epothilone derivatives Chemical class 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 150000001261 hydroxy acids Chemical class 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 210000004688 microtubule Anatomy 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 230000001012 protector Effects 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 6
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 150000001336 alkenes Chemical class 0.000 description 5
- 150000008064 anhydrides Chemical class 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 150000004820 halides Chemical class 0.000 description 5
- 150000008282 halocarbons Chemical class 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 150000002430 hydrocarbons Chemical class 0.000 description 5
- 239000013067 intermediate product Substances 0.000 description 5
- GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical compound IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 description 5
- 239000000463 material Substances 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
- 230000001613 neoplastic effect Effects 0.000 description 5
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 5
- 238000007911 parenteral administration Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000006116 polymerization reaction Methods 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000000069 prophylactic effect Effects 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 4
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 4
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 4
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 4
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 241000208199 Buxus sempervirens Species 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 125000005103 alkyl silyl group Chemical group 0.000 description 4
- 150000001540 azides Chemical class 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
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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
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
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- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Silicon Polymers (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2530/98 | 1998-12-22 | ||
| CH253098 | 1998-12-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2207983T3 true ES2207983T3 (es) | 2004-06-01 |
Family
ID=4235876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99969216T Expired - Lifetime ES2207983T3 (es) | 1998-12-22 | 1999-12-20 | Derivados de epotilona y su uso como agentes antitumorales. |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6387927B1 (enExample) |
| EP (1) | EP1140944B1 (enExample) |
| JP (1) | JP2002533346A (enExample) |
| CN (1) | CN1122668C (enExample) |
| AT (1) | ATE248175T1 (enExample) |
| AU (1) | AU2795000A (enExample) |
| BR (1) | BR9916833A (enExample) |
| CA (1) | CA2352505C (enExample) |
| DE (1) | DE69910831T2 (enExample) |
| ES (1) | ES2207983T3 (enExample) |
| PT (1) | PT1140944E (enExample) |
| WO (1) | WO2000037473A1 (enExample) |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4183099B2 (ja) | 1995-11-17 | 2008-11-19 | ゲゼルシャフト・フュア・ビオテヒノロジッシェ・フォルシュング・ミット・ベシュレンクテル・ハフツング（ゲー・ベー・エフ） | エポチロンｃおよびｄ、製造法ならびに組成物 |
| WO1998022461A1 (de) | 1996-11-18 | 1998-05-28 | GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) | Epothilone c, d, e und f, deren herstellung und deren verwendung als cytostatische mittel bzw. als pflanzenschutzmittel |
| JP4579351B2 (ja) | 1996-12-03 | 2010-11-10 | スローン−ケッタリング インスティトュート フォア キャンサー リサーチ | エポチロンの合成とその中間体及びその類似物並びにその使用 |
| US6204388B1 (en) | 1996-12-03 | 2001-03-20 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US20050043376A1 (en) * | 1996-12-03 | 2005-02-24 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6605599B1 (en) | 1997-07-08 | 2003-08-12 | Bristol-Myers Squibb Company | Epothilone derivatives |
| US6365749B1 (en) | 1997-12-04 | 2002-04-02 | Bristol-Myers Squibb Company | Process for the preparation of ring-opened epothilone intermediates which are useful for the preparation of epothilone analogs |
| US6498257B1 (en) | 1998-04-21 | 2002-12-24 | Bristol-Myers Squibb Company | 2,3-olefinic epothilone derivatives |
| US6380395B1 (en) | 1998-04-21 | 2002-04-30 | Bristol-Myers Squibb Company | 12, 13-cyclopropane epothilone derivatives |
| US20020058286A1 (en) * | 1999-02-24 | 2002-05-16 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US6518421B1 (en) * | 2000-03-20 | 2003-02-11 | Bristol-Myers Squibb Company | Process for the preparation of epothilone analogs |
| US6593115B2 (en) | 2000-03-24 | 2003-07-15 | Bristol-Myers Squibb Co. | Preparation of epothilone intermediates |
| AU2001266583A1 (en) * | 2000-05-26 | 2001-12-11 | Kosan Biosciences, Inc. | Epothilone derivatives and methods for making and using the same |
| US6448281B1 (en) * | 2000-07-06 | 2002-09-10 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| UA75365C2 (en) | 2000-08-16 | 2006-04-17 | Bristol Myers Squibb Co | Epothilone analog polymorph modifications, a method for obtaining thereof (variants), a pharmaceutical composition based thereon |
| US20020128213A1 (en) * | 2000-09-25 | 2002-09-12 | Leonard Katz | Sixteen-membered macrolide compounds |
| JP2004521122A (ja) | 2001-01-25 | 2004-07-15 | ブリストル−マイヤーズ スクイブ カンパニー | エポチロン類似体の非経口製剤 |
| NZ526871A (en) | 2001-01-25 | 2006-01-27 | Bristol Myers Squibb Co | Pharmaceutical dosage forms of epothilones for oral administration |
| BRPI0206509B8 (pt) | 2001-01-25 | 2021-05-25 | R Pharm Us Operating Llc | processo para formular, para administração parenteral, um análogo de epotilona, preparação farmacêutica, processo para formar uma composição farmacêutica para administração parental, composição farmacêutica e uso de um análogo de epotilona na preparação de uma composição farmacêutica para o tratamento de câncer |
| MXPA03007423A (es) | 2001-02-20 | 2003-11-18 | Bristol Myers Squibb Co | Derivados de epotilona para tratamiento de tumores refractarios. |
| CA2438610A1 (en) | 2001-02-20 | 2002-08-29 | Francis Y. F. Lee | Treatment of refractory tumors using epothilone derivatives |
| CZ305799B6 (cs) | 2001-03-14 | 2016-03-23 | Bristol-Myers Squibb Company | Kombinace analogů epothilonu a chemoterapeutických činidel pro léčení proliferačních nemocí |
| JP2004519493A (ja) * | 2001-03-19 | 2004-07-02 | ノバルティス アクチエンゲゼルシャフト | 抗下痢剤およびエポチロンまたはエポチロン誘導体を含む組合せ剤 |
| EP1392664A4 (en) | 2001-06-01 | 2005-01-26 | Bristol Myers Squibb Co | EPOTHILONE DERIVATIVES |
| US20050032858A1 (en) * | 2001-10-03 | 2005-02-10 | Masae Takagi | Novel heterocyclic compound and anti-inflamatory agent |
| TWI341728B (en) * | 2002-01-14 | 2011-05-11 | Novartis Ag | Combinations comprising epothilones and anti-metabolites |
| TW200303202A (en) * | 2002-02-15 | 2003-09-01 | Bristol Myers Squibb Co | Method of preparation of 21-amino epothilone derivatives |
| WO2003077903A1 (en) | 2002-03-12 | 2003-09-25 | Bristol-Myers Squibb Company | C12-cyano epothilone derivatives |
| ATE452896T1 (de) | 2002-03-12 | 2010-01-15 | Bristol Myers Squibb Co | C3-cyanoepothilonderivate |
| TW200403994A (en) | 2002-04-04 | 2004-03-16 | Bristol Myers Squibb Co | Oral administration of EPOTHILONES |
| TW200400191A (en) | 2002-05-15 | 2004-01-01 | Bristol Myers Squibb Co | Pharmaceutical compositions and methods of using C-21 modified epothilone derivatives |
| US7008936B2 (en) | 2002-06-14 | 2006-03-07 | Bristol-Myers Squibb Company | Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases |
| US6921769B2 (en) | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US7649006B2 (en) * | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| CA2496477C (en) | 2002-08-23 | 2012-10-16 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| PL224879B1 (pl) | 2002-09-04 | 2017-02-28 | Pharmacopeia Drug Discovery Inc | Pirazolo [1,5-a] pirymidynowy związek, jego zastosowanie do wytwarzania leku oraz zawierająca go farmaceutyczna kompozycja |
| US8580782B2 (en) | 2002-09-04 | 2013-11-12 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as cyclin dependent kinase inhibitors |
| GB0221312D0 (en) * | 2002-09-13 | 2002-10-23 | Novartis Ag | Organic compounds |
| WO2004026254A2 (en) | 2002-09-23 | 2004-04-01 | Bristol-Myers Squibb Company | Methods for the preparation, isolation and purification of epothilone b, and x-ray crystal structures of epothilone b |
| US7112581B2 (en) | 2002-09-27 | 2006-09-26 | Nereus Pharmaceuticals, Inc. | Macrocyclic lactams |
| DE10256982A1 (de) * | 2002-12-05 | 2004-06-24 | Schering Ag | Neue Effektor-Konjugate, Verfahren zu Ihrer Herstellung und Ihre Pharmazeutische Verwendung |
| US20040146632A1 (en) * | 2003-01-23 | 2004-07-29 | Cristina Sayman | Effective multi-component penetrating and flavoring marinade |
| US20050171167A1 (en) * | 2003-11-04 | 2005-08-04 | Haby Thomas A. | Process and formulation containing epothilones and analogs thereof |
| GB0405898D0 (en) * | 2004-03-16 | 2004-04-21 | Novartis Ag | Organic compounds |
| US7122700B2 (en) * | 2004-07-30 | 2006-10-17 | Xerox Corporation | Arylamine processes |
| EP1640004A1 (en) * | 2004-09-24 | 2006-03-29 | Schering Aktiengesellschaft | Use of epothilones in the treatment of bone metastases and bone tumors or cancers |
| EP1674098A1 (en) | 2004-12-23 | 2006-06-28 | Schering Aktiengesellschaft | Stable and tolerable parental formulations of highly reactive organic drug substances with low or no solubility in water |
| JP2008536479A (ja) | 2005-02-11 | 2008-09-11 | ユニバーシティ オブ サザン カリフォルニア | ジスルフィド架橋を有するタンパク質の発現法 |
| CA2607940C (en) | 2005-05-18 | 2009-12-15 | Aegera Therapeutics Inc. | Bir domain binding compounds |
| EP1845096A1 (en) * | 2006-03-27 | 2007-10-17 | ETH Zürich | 12-Aza-epothilones, process for their preparation and their use as antiproliferative agents |
| US8008256B2 (en) * | 2006-05-01 | 2011-08-30 | University Of Southern California | Combination therapy for treatment of cancer |
| MY159563A (en) | 2006-05-16 | 2017-01-13 | Pharmascience Inc | Iap bir domain binding compounds |
| DE102007016046A1 (de) * | 2007-03-30 | 2008-10-23 | Bayer Schering Pharma Aktiengesellschaft | Verfahren zur Herstellung von Epothilonderivaten durch selektive katalytische Epoxidierung |
| EP2065054A1 (en) | 2007-11-29 | 2009-06-03 | Bayer Schering Pharma Aktiengesellschaft | Combinations comprising a prostaglandin and uses thereof |
| EP2070521A1 (en) | 2007-12-10 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Surface-modified nanoparticles |
| DE102007059752A1 (de) | 2007-12-10 | 2009-06-18 | Bayer Schering Pharma Aktiengesellschaft | Funktionalisierte, feste Polymernanopartikel enthaltend Epothilone |
| CN101519404B (zh) * | 2008-02-29 | 2016-01-20 | 唐莉 | 15环噻酮衍生物及其制备方法与应用 |
| US8802394B2 (en) | 2008-11-13 | 2014-08-12 | Radu O. Minea | Method of expressing proteins with disulfide bridges with enhanced yields and activity |
| EP2210584A1 (en) | 2009-01-27 | 2010-07-28 | Bayer Schering Pharma Aktiengesellschaft | Stable polymeric composition comprising an epothilone and an amphiphilic block copolymer |
| KR20120140658A (ko) | 2010-02-12 | 2012-12-31 | 파마사이언스 인크. | Ｉａｐ ｂｉｒ 도메인 결합 화합물 |
| US20110300150A1 (en) | 2010-05-18 | 2011-12-08 | Scott Eliasof | Compositions and methods for treatment of autoimmune and other disease |
| WO2013092998A1 (en) | 2011-12-23 | 2013-06-27 | Innate Pharma | Enzymatic conjugation of antibodies |
| US10132799B2 (en) | 2012-07-13 | 2018-11-20 | Innate Pharma | Screening of conjugated antibodies |
| EP3564259A3 (en) | 2012-11-09 | 2020-02-12 | Innate Pharma | Recognition tags for tgase-mediated conjugation |
| US10611824B2 (en) | 2013-03-15 | 2020-04-07 | Innate Pharma | Solid phase TGase-mediated conjugation of antibodies |
| WO2014202773A1 (en) | 2013-06-20 | 2014-12-24 | Innate Pharma | Enzymatic conjugation of polypeptides |
| AU2014283185B2 (en) | 2013-06-21 | 2019-05-02 | Araris Biotech Ltd. | Enzymatic conjugation of polypeptides |
| WO2019092148A1 (en) | 2017-11-10 | 2019-05-16 | Innate Pharma | Antibodies with functionalized glutamine residues |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4579351B2 (ja) * | 1996-12-03 | 2010-11-10 | スローン−ケッタリング インスティトュート フォア キャンサー リサーチ | エポチロンの合成とその中間体及びその類似物並びにその使用 |
| US6605599B1 (en) * | 1997-07-08 | 2003-08-12 | Bristol-Myers Squibb Company | Epothilone derivatives |
-
1999
- 1999-12-20 ES ES99969216T patent/ES2207983T3/es not_active Expired - Lifetime
- 1999-12-20 DE DE69910831T patent/DE69910831T2/de not_active Expired - Lifetime
- 1999-12-20 CN CN99815116A patent/CN1122668C/zh not_active Expired - Fee Related
- 1999-12-20 AT AT99969216T patent/ATE248175T1/de not_active IP Right Cessation
- 1999-12-20 CA CA002352505A patent/CA2352505C/en not_active Expired - Fee Related
- 1999-12-20 JP JP2000589543A patent/JP2002533346A/ja active Pending
- 1999-12-20 BR BR9916833-2A patent/BR9916833A/pt not_active Application Discontinuation
- 1999-12-20 EP EP99969216A patent/EP1140944B1/en not_active Expired - Lifetime
- 1999-12-20 PT PT99969216T patent/PT1140944E/pt unknown
- 1999-12-20 WO PCT/EP1999/010129 patent/WO2000037473A1/en not_active Ceased
- 1999-12-20 AU AU27950/00A patent/AU2795000A/en not_active Abandoned
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2001
- 2001-06-01 US US09/871,860 patent/US6387927B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2352505A1 (en) | 2000-06-29 |
| DE69910831T2 (de) | 2004-07-15 |
| WO2000037473A1 (en) | 2000-06-29 |
| CN1122668C (zh) | 2003-10-01 |
| AU2795000A (en) | 2000-07-12 |
| US6387927B1 (en) | 2002-05-14 |
| CA2352505C (en) | 2009-04-07 |
| BR9916833A (pt) | 2001-09-25 |
| DE69910831D1 (de) | 2003-10-02 |
| CN1332742A (zh) | 2002-01-23 |
| EP1140944A1 (en) | 2001-10-10 |
| EP1140944B1 (en) | 2003-08-27 |
| JP2002533346A (ja) | 2002-10-08 |
| ATE248175T1 (de) | 2003-09-15 |
| PT1140944E (pt) | 2004-01-30 |
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