SK11852001A3 - Deriváty epotiólonu, spôsoby ich výroby a ich farmaceutické použitie - Google Patents

Deriváty epotiólonu, spôsoby ich výroby a ich farmaceutické použitie Download PDF

Info

Publication number: SK11852001A3
Authority: SK; Slovakia
Prior art keywords: dihydroxy; dione; ethenyl; methyl; ethyl
Prior art date: 1999-02-18

Application number

SK1185-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Ulrich Klar

Werner Skuballa

Bernd Buchmann

Wolfgang Schwede

Michael Schirner

Original Assignee

Schering Aktiengesellschaft

Priority date (The priority date 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 date listed.)

1999-02-18

Filing date

2000-02-18

Publication date

2002-04-04

1999-02-18 Priority claimed from DE19908765A external-priority patent/DE19908765A1/de

1999-11-04 Priority claimed from DE19954230A external-priority patent/DE19954230A1/de

2000-02-18 Application filed by Schering Aktiengesellschaft filed Critical Schering Aktiengesellschaft

2002-04-04 Publication of SK11852001A3 publication Critical patent/SK11852001A3/sk

Links

238000004519 manufacturing process Methods 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 335
-1 2-hydroxymethyl-4-thiazolyl radical Chemical class 0.000 claims description 212
229910052739 hydrogen Inorganic materials 0.000 claims description 82
239000001257 hydrogen Substances 0.000 claims description 73
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 50
LZWPOLSJFGLQCE-UHFFFAOYSA-N heptadecane-5,9-dione Chemical compound CCCCCCCCC(=O)CCCC(=O)CCCC LZWPOLSJFGLQCE-UHFFFAOYSA-N 0.000 claims description 39
125000000217 alkyl group Chemical group 0.000 claims description 36
GESONPPMDAXJEH-UHFFFAOYSA-N cyclohexadec-9-ene-1,5-dione Chemical compound O=C1CCCCCCC=CCCCC(=O)CCC1 GESONPPMDAXJEH-UHFFFAOYSA-N 0.000 claims description 30
125000003118 aryl group Chemical group 0.000 claims description 24
125000004430 oxygen atom Chemical group O* 0.000 claims description 23
150000003883 epothilone derivatives Chemical class 0.000 claims description 21
150000002431 hydrogen Chemical class 0.000 claims description 21
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
125000006239 protecting group Chemical group 0.000 claims description 19
125000003710 aryl alkyl group Chemical group 0.000 claims description 18
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
238000002360 preparation method Methods 0.000 claims description 15
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 15
229910052801 chlorine Inorganic materials 0.000 claims description 13
239000000460 chlorine Substances 0.000 claims description 11
229910052736 halogen Inorganic materials 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
229910052794 bromium Inorganic materials 0.000 claims description 10
229910052731 fluorine Inorganic materials 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 10
125000001309 chloro group Chemical group Cl* 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
229910052740 iodine Inorganic materials 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 8
125000001153 fluoro group Chemical group F* 0.000 claims description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
FIULGFJIHJJXMT-UHFFFAOYSA-N [C]1[N]C=CC=C1 Chemical compound [C]1[N]C=CC=C1 FIULGFJIHJJXMT-UHFFFAOYSA-N 0.000 claims description 7
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
229910002091 carbon monoxide Inorganic materials 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
239000000543 intermediate Substances 0.000 claims description 5
SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical group C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 claims description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000002252 acyl group Chemical group 0.000 claims description 4
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 3
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 claims description 3
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical group [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 claims description 3
150000003254 radicals Chemical group 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
239000000825 pharmaceutical preparation Substances 0.000 claims description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 4
150000002483 hydrogen compounds Chemical class 0.000 claims 3
125000004429 atom Chemical group 0.000 claims 1
229940079593 drug Drugs 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
LFVXJYQAKCTHIF-UHFFFAOYSA-N hexadec-13-ene-2,6-dione Chemical compound CC(CCCC(CCCCCCC=CCC)=O)=O LFVXJYQAKCTHIF-UHFFFAOYSA-N 0.000 claims 1
230000001681 protective effect Effects 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 180
239000000243 solution Substances 0.000 description 127
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 123
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 121
238000005481 NMR spectroscopy Methods 0.000 description 89
239000000203 mixture Substances 0.000 description 89
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
239000012230 colorless oil Substances 0.000 description 46
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 40
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 39
229940126062 Compound A Drugs 0.000 description 37
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 37
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 34
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 33
229910052938 sodium sulfate Inorganic materials 0.000 description 32
235000011152 sodium sulphate Nutrition 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
238000000746 purification Methods 0.000 description 27
239000012634 fragment Substances 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
239000011541 reaction mixture Substances 0.000 description 21
239000000741 silica gel Substances 0.000 description 20
229910002027 silica gel Inorganic materials 0.000 description 20
239000007983 Tris buffer Substances 0.000 description 18
239000012299 nitrogen atmosphere Substances 0.000 description 18
238000010626 work up procedure Methods 0.000 description 18
239000002904 solvent Substances 0.000 description 16
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 15
239000012074 organic phase Substances 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
229910052786 argon Inorganic materials 0.000 description 14
238000004440 column chromatography Methods 0.000 description 14
239000003921 oil Substances 0.000 description 14
238000001914 filtration Methods 0.000 description 13
238000010898 silica gel chromatography Methods 0.000 description 13
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 11
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 10
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
239000000706 filtrate Substances 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
238000005160 1H NMR spectroscopy Methods 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000012300 argon atmosphere Substances 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 9
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
239000000284 extract Substances 0.000 description 9
HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 8
210000004027 cell Anatomy 0.000 description 8
229930013356 epothilone Natural products 0.000 description 8
238000002955 isolation Methods 0.000 description 8
239000007787 solid Substances 0.000 description 8
229930012538 Paclitaxel Natural products 0.000 description 7
230000000694 effects Effects 0.000 description 7
QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[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 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 7
229960001592 paclitaxel Drugs 0.000 description 7
239000000725 suspension Substances 0.000 description 7
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 6
HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical compound 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 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
238000000034 method Methods 0.000 description 6
238000012746 preparative thin layer chromatography Methods 0.000 description 6
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
230000015572 biosynthetic process Effects 0.000 description 5
238000001816 cooling Methods 0.000 description 5
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-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
150000001299 aldehydes Chemical class 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
239000012043 crude product Substances 0.000 description 4
BEFZAMRWPCMWFJ-UHFFFAOYSA-N desoxyepothilone A Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC=CCC1C(C)=CC1=CSC(C)=N1 BEFZAMRWPCMWFJ-UHFFFAOYSA-N 0.000 description 4
BEFZAMRWPCMWFJ-QJKGZULSSA-N epothilone C Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 BEFZAMRWPCMWFJ-QJKGZULSSA-N 0.000 description 4
XOZIUKBZLSUILX-GIQCAXHBSA-N epothilone D Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 XOZIUKBZLSUILX-GIQCAXHBSA-N 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
150000004714 phosphonium salts Chemical class 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
235000019345 sodium thiosulphate Nutrition 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
PRIGFEJKMMRJSF-UHFFFAOYSA-M 1-fluoro-2,4,6-trimethylpyridin-1-ium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.CC1=CC(C)=[N+](F)C(C)=C1 PRIGFEJKMMRJSF-UHFFFAOYSA-M 0.000 description 3
OZGSEIVTQLXWRO-UHFFFAOYSA-N 2,4,6-trichlorobenzoyl chloride Chemical compound ClC(=O)C1=C(Cl)C=C(Cl)C=C1Cl OZGSEIVTQLXWRO-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
206010006187 Breast cancer Diseases 0.000 description 3
208000026310 Breast neoplasm Diseases 0.000 description 3
HIXQZXFNYOHUCV-UHFFFAOYSA-N CC(C)(C)[Si](C)(C)OC(C(O)=O)CCCCCCCCCC=CCCC=C Chemical compound CC(C)(C)[Si](C)(C)OC(C(O)=O)CCCCCCCCCC=CCCC=C HIXQZXFNYOHUCV-UHFFFAOYSA-N 0.000 description 3
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 3
BEFZAMRWPCMWFJ-JRBBLYSQSA-N Epothilone C Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C=C\C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C BEFZAMRWPCMWFJ-JRBBLYSQSA-N 0.000 description 3
XOZIUKBZLSUILX-SDMHVBBESA-N Epothilone D Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C(/C)=C/C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C XOZIUKBZLSUILX-SDMHVBBESA-N 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
239000002253 acid Substances 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
XOZIUKBZLSUILX-UHFFFAOYSA-N desoxyepothilone B Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC(C)=CCC1C(C)=CC1=CSC(C)=N1 XOZIUKBZLSUILX-UHFFFAOYSA-N 0.000 description 3
229940043279 diisopropylamine Drugs 0.000 description 3
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
230000012010 growth Effects 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
239000011630 iodine Substances 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
239000005445 natural material Substances 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
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OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
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VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 1
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230000000394 mitotic effect Effects 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
210000003887 myelocyte Anatomy 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
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210000005170 neoplastic cell Anatomy 0.000 description 1
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230000003000 nontoxic effect Effects 0.000 description 1
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JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
231100000590 oncogenic Toxicity 0.000 description 1
230000002246 oncogenic effect Effects 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
150000003057 platinum Chemical class 0.000 description 1
239000002861 polymer material Substances 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
239000012521 purified sample Substances 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
102000016914 ras Proteins Human genes 0.000 description 1
108010014186 ras Proteins Proteins 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000008844 regulatory mechanism Effects 0.000 description 1
OWPCHSCAPHNHAV-LMONGJCWSA-N rhizoxin Chemical compound C/C([C@H](OC)[C@@H](C)[C@@H]1C[C@H](O)[C@]2(C)O[C@@H]2/C=C/[C@@H](C)[C@]2([H])OC(=O)C[C@@](C2)(C[C@@H]2O[C@H]2C(=O)O1)[H])=C\C=C\C(\C)=C\C1=COC(C)=N1 OWPCHSCAPHNHAV-LMONGJCWSA-N 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
239000008259 solid foam Substances 0.000 description 1
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
229960000553 somatostatin Drugs 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
238000003756 stirring Methods 0.000 description 1
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150000003462 sulfoxides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
229960001278 teniposide Drugs 0.000 description 1
PKRMIJLZLYPANW-XXYUJHKVSA-N tert-butyl-[(z,3s)-2-chloro-5-iodo-1-(2-methyl-1,3-thiazol-4-yl)pent-1-en-3-yl]oxy-dimethylsilane Chemical compound CC1=NC(\C=C(/Cl)[C@H](CCI)O[Si](C)(C)C(C)(C)C)=CS1 PKRMIJLZLYPANW-XXYUJHKVSA-N 0.000 description 1
IAUVGQANLCITQV-ZSMUJPCHSA-N tert-butyl-[(z,3s)-2-chloro-5-iodo-1-pyridin-2-ylpent-1-en-3-yl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[C@@H](CCI)C(\Cl)=C\C1=CC=CC=N1 IAUVGQANLCITQV-ZSMUJPCHSA-N 0.000 description 1
RXJNGNPHMDNUJA-XXYUJHKVSA-N tert-butyl-[(z,3s)-2-fluoro-5-iodo-1-(2-methyl-1,3-thiazol-4-yl)pent-1-en-3-yl]oxy-dimethylsilane Chemical compound CC1=NC(\C=C(/F)[C@H](CCI)O[Si](C)(C)C(C)(C)C)=CS1 RXJNGNPHMDNUJA-XXYUJHKVSA-N 0.000 description 1
BHXMMAXWAYULQE-ZSMUJPCHSA-N tert-butyl-[(z,3s)-2-fluoro-5-iodo-1-pyridin-2-ylpent-1-en-3-yl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[C@@H](CCI)C(\F)=C\C1=CC=CC=N1 BHXMMAXWAYULQE-ZSMUJPCHSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
229960000303 topotecan Drugs 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
WIOADUFWOUUQCV-UHFFFAOYSA-N triphenylphosphanium dichloride Chemical compound [Cl-].[Cl-].C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 WIOADUFWOUUQCV-UHFFFAOYSA-N 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
238000005292 vacuum distillation 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
239000000341 volatile oil Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- 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
- C07D405/06—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 linked by a carbon chain containing only aliphatic carbon atoms
- 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
- C07D417/06—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 linked by a carbon chain containing only aliphatic carbon atoms
- 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
- 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
- C07D493/08—Bridged systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Plural Heterocyclic Compounds (AREA)
Saccharide Compounds (AREA)

SK1185-2001A 1999-02-18 2000-02-18 Deriváty epotiólonu, spôsoby ich výroby a ich farmaceutické použitie SK11852001A3 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE19908765A DE19908765A1 (de)	1999-02-18	1999-02-18	16-Halogen-Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung
DE19954230A DE19954230A1 (de)	1999-11-04	1999-11-04	16-Halogen-Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung
PCT/EP2000/001333 WO2000049021A2 (fr)	1999-02-18	2000-02-18	Derives de 16-halogeno-epothilon, leur procede de production et leur utilisation pharmaceutique

Publications (1)

Publication Number	Publication Date
SK11852001A3 true SK11852001A3 (sk)	2002-04-04

Family

ID=26052117

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1185-2001A SK11852001A3 (sk)	1999-02-18	2000-02-18	Deriváty epotiólonu, spôsoby ich výroby a ich farmaceutické použitie

Country Status (27)

Country	Link
US (3)	US6610736B1 (fr)
EP (1)	EP1150980B1 (fr)
JP (1)	JP2002537301A (fr)
KR (1)	KR100718616B1 (fr)
CN (1)	CN1209360C (fr)
AR (1)	AR022636A1 (fr)
AT (1)	ATE370946T1 (fr)
AU (1)	AU3156700A (fr)
BG (1)	BG105802A (fr)
BR (1)	BR0008331A (fr)
CA (1)	CA2361278A1 (fr)
CZ (1)	CZ20012951A3 (fr)
DE (1)	DE50014587D1 (fr)
EA (1)	EA009206B1 (fr)
EE (1)	EE200100431A (fr)
ES (1)	ES2291194T3 (fr)
HR (1)	HRP20010677A2 (fr)
HU (1)	HUP0105478A3 (fr)
IL (1)	IL144519A0 (fr)
MX (1)	MXPA01008328A (fr)
NO (1)	NO20014013L (fr)
NZ (1)	NZ513268A (fr)
PL (1)	PL349863A1 (fr)
SK (1)	SK11852001A3 (fr)
TW (1)	TWI285645B (fr)
WO (1)	WO2000049021A2 (fr)
YU (1)	YU59001A (fr)

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP4274583B2 (ja)	1996-11-18	2009-06-10	ゲゼルシャフト・フュア・ビオテクノロギッシェ・フォルシュンク・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，ｄ，ｅ及びｆ、製造と薬剤
US20050043376A1 (en) *	1996-12-03	2005-02-24	Danishefsky Samuel J.	Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6204388B1 (en) *	1996-12-03	2001-03-20	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
US6242469B1 (en)	1996-12-03	2001-06-05	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6605599B1 (en)	1997-07-08	2003-08-12	Bristol-Myers Squibb Company	Epothilone derivatives
CA2299608A1 (fr) *	1997-08-09	1999-02-18	Schering Aktiengesellschaft	Nouveaux derives d'epothilone, leur procede de fabrication et leur utilisation pharmaceutique
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
US6380395B1 (en)	1998-04-21	2002-04-30	Bristol-Myers Squibb Company	12, 13-cyclopropane epothilone derivatives
US6498257B1 (en)	1998-04-21	2002-12-24	Bristol-Myers Squibb Company	2,3-olefinic epothilone derivatives
US6518421B1 (en) *	2000-03-20	2003-02-11	Bristol-Myers Squibb Company	Process for the preparation of epothilone analogs
DE10020899A1 (de) *	2000-04-20	2001-10-25	Schering Ag	9-Oxa-Epothilon-Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten
CZ20032021A3 (cs)	2001-01-25	2004-05-12	Bristol@Myersásquibbácompany	Způsoby podávání analogů epothilonu při léčbě rakoviny
EP1353667A1 (fr)	2001-01-25	2003-10-22	Bristol-Myers Squibb Company	Formulations parenterales contenant des analogues d'epothilone
PL207720B1 (pl) *	2001-01-25	2011-01-31	Bristol Myers Squibb Co	Sposób przygotowania preparatu farmaceutycznego i jego zastosowanie, farmaceutyczny produkt oraz sposób wytwarzania kompozycji farmaceutycznej
NZ526871A (en) *	2001-01-25	2006-01-27	Bristol Myers Squibb Co	Pharmaceutical dosage forms of epothilones for oral administration
MXPA03007423A (es)	2001-02-20	2003-11-18	Bristol Myers Squibb Co	Derivados de epotilona para tratamiento de tumores refractarios.
WO2002066038A1 (fr)	2001-02-20	2002-08-29	Bristol-Myers Squibb Company	Traitement de tumeurs refractaires a l'aide de derives d'epothilone
CA2440555A1 (fr)	2001-03-14	2002-09-19	Bristol-Myers Squibb Company	Combinaison d'analogues d'epothilones et d'agents chimiotherapeutiques servant au traitement de maladies proliferatives
WO2002098868A1 (fr)	2001-06-01	2002-12-12	Bristol-Myers Squibb Company	Derives d'epothilone
WO2003026744A1 (fr) *	2001-09-25	2003-04-03	Alcon, Inc.	Utilisation d'epothilones et analogues en chirurgie ophtalmique
EP1340498A1 (fr) *	2002-03-01	2003-09-03	Schering Aktiengesellschaft	Utilisation d'épothilones dans le traitement de maladies du cerveau associées aux processus de prolifération
DK1483251T3 (da)	2002-03-12	2010-04-12	Bristol Myers Squibb Co	C3-cyano-epothilon-derivater
WO2003077903A1 (fr)	2002-03-12	2003-09-25	Bristol-Myers Squibb Company	Derives c12-cyano epothilone
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
US7649006B2 (en)	2002-08-23	2010-01-19	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
WO2004018478A2 (fr) *	2002-08-23	2004-03-04	Sloan-Kettering Institute For Cancer Research	Synthese d'epothilones, leurs intermediaires, leurs analogues et leurs utilisations
RU2462463C2 (ru) *	2002-08-23	2012-09-27	Слоан-Кеттеринг Инститьют Фор Кэнсер Рисерч	Синтез эпотилонов, их промежуточных продуктов, аналогов и их применения
KR20050053681A (ko)	2002-09-23	2005-06-08	브리스톨-마이어스 스큅 컴퍼니	에포틸론 ｂ의 제조, 분리 및 정제 방법, 및 에포틸론 ｂ의ｘ-선 결정 구조
EP1559447A1 (fr)	2004-01-30	2005-08-03	Institut National De La Sante Et De La Recherche Medicale (Inserm)	Utilisation d'epothilone pour le traitement de defauts de connectivité neuronale comme par exemple la schizophrenie et l'autisme
MX2007005763A (es) *	2004-11-18	2007-07-20	Squibb Bristol Myers Co	Perla recubierta enterica que comprende ixabepilona, y preparacion y administracion de la misma.
EP1824458A1 (fr) *	2004-11-18	2007-08-29	Bristol-Myers Squibb Company	Bille enrobee de keratine comprenant de l'epothilone ou un analogue d'epothilone, ainsi que preparation et administration de cette bille
EP1674098A1 (fr)	2004-12-23	2006-06-28	Schering Aktiengesellschaft	Formulations parenterales stables et tolérables des substances de haut réactivité ayant une solubilité basse ou inexistante dans l'eau
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
JP4954983B2 (ja)	2005-05-18	2012-06-20	ファーマサイエンス・インコーポレイテッド	Ｂｉｒドメイン結合化合物
US20070014978A1 (en) *	2005-07-18	2007-01-18	Anthony Poloso	Method of flame blocking and articles made therefrom
US8008256B2 (en) *	2006-05-01	2011-08-30	University Of Southern California	Combination therapy for treatment of cancer
SG10201407457UA (en)	2006-05-16	2014-12-30	Pharmascience Inc	Iap bir domain binding compounds
EP2065054A1 (fr) *	2007-11-29	2009-06-03	Bayer Schering Pharma Aktiengesellschaft	Combinaisons comprenant une prostaglandine et leurs utilisations
EP2070521A1 (fr)	2007-12-10	2009-06-17	Bayer Schering Pharma Aktiengesellschaft	Nanoparticules à surface modifiée
DE102007059752A1 (de)	2007-12-10	2009-06-18	Bayer Schering Pharma Aktiengesellschaft	Funktionalisierte, feste Polymernanopartikel enthaltend Epothilone
US8802394B2 (en)	2008-11-13	2014-08-12	Radu O. Minea	Method of expressing proteins with disulfide bridges with enhanced yields and activity
EP2210584A1 (fr)	2009-01-27	2010-07-28	Bayer Schering Pharma Aktiengesellschaft	Composition polymère stable comprenant un copolymère séquencé d'épothilone et amphiphile
MX340870B (es)	2010-02-12	2016-07-27	Pharmascience Inc	Compuestos de unión del dominio de repetición de inhibidores de proteínas de apoptosis de baculovirus.
AU2012356894B2 (en)	2011-12-23	2018-01-18	Araris Biotech Ltd.	Enzymatic conjugation of polypeptides
WO2014009426A2 (fr)	2012-07-13	2014-01-16	Innate Pharma	Criblage d'anticorps conjugués
EP2916872B1 (fr)	2012-11-09	2019-02-27	Innate Pharma	Etiquettes de reconnaissance pour la conjugaison à médiation par la tgase
WO2014140300A1 (fr)	2013-03-15	2014-09-18	Innate Pharma	Conjugaison d'anticorps en phase solide médiée par la tgase
WO2014202773A1 (fr)	2013-06-20	2014-12-24	Innate Pharma	Conjugaison enzymatique de polypeptides
JP6744212B2 (ja)	2013-06-21	2020-08-19	イナート・ファルマ・ソシエテ・アノニムＩｎｎａｔｅＰｈａｒｍａＰｈａｒｍａＳ．Ａ．	ポリペプチドの酵素的結合
WO2019092148A1 (fr)	2017-11-10	2019-05-16	Innate Pharma	Anticorps avec des résidus de glutamine fonctionnalisés
GB202309910D0 (en) *	2023-06-29	2023-08-16	Implexion Pharma Ab	Therpay

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2685521B2 (ja)	1988-08-05	1997-12-03	株式会社日立製作所	車両用換気装置
EP0353732A3 (fr) *	1988-08-05	1991-11-06	Ciba-Geigy Ag	Fluoro-oléfines, procédé pour leur préparation et leur utilisation
CN1053428A (zh) *	1989-12-27	1991-07-31	孟山都公司	取代吡啶化合物
US6441186B1 (en) *	1996-12-13	2002-08-27	The Scripps Research Institute	Epothilone analogs
CA2299608A1 (fr) *	1997-08-09	1999-02-18	Schering Aktiengesellschaft	Nouveaux derives d'epothilone, leur procede de fabrication et leur utilisation pharmaceutique
WO2000000485A1 (fr) *	1998-06-30	2000-01-06	Schering Aktiengesellschaft	Derives d'epothilone, leur procede de production, produits intermediaires et leur utilisation pharmaceutique
DE10020517A1 (de) *	2000-04-19	2001-10-25	Schering Ag	Neue Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung

2000
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- 2000-02-18 IL IL14451900A patent/IL144519A0/xx unknown
- 2000-02-18 CZ CZ20012951A patent/CZ20012951A3/cs unknown
- 2000-02-18 MX MXPA01008328A patent/MXPA01008328A/es active IP Right Grant
- 2000-02-18 EA EA200100826A patent/EA009206B1/ru unknown
- 2000-02-18 PL PL00349863A patent/PL349863A1/xx not_active Application Discontinuation
- 2000-02-18 HR HR20010677A patent/HRP20010677A2/hr not_active Application Discontinuation
- 2000-02-18 HU HU0105478A patent/HUP0105478A3/hu unknown
- 2000-02-18 ES ES00909205T patent/ES2291194T3/es not_active Expired - Lifetime
- 2000-02-18 CN CNB008039763A patent/CN1209360C/zh not_active Expired - Fee Related
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- 2000-02-18 AU AU31567/00A patent/AU3156700A/en not_active Abandoned
- 2000-02-18 WO PCT/EP2000/001333 patent/WO2000049021A2/fr not_active Ceased
- 2000-02-18 EP EP00909205A patent/EP1150980B1/fr not_active Expired - Lifetime
- 2000-02-18 AT AT00909205T patent/ATE370946T1/de not_active IP Right Cessation
- 2000-02-18 US US09/913,495 patent/US6610736B1/en not_active Expired - Fee Related
- 2000-02-18 BR BR0008331-3A patent/BR0008331A/pt not_active Application Discontinuation
- 2000-02-18 DE DE50014587T patent/DE50014587D1/de not_active Expired - Fee Related
- 2000-02-18 KR KR1020017010455A patent/KR100718616B1/ko not_active Expired - Fee Related
- 2000-02-18 JP JP2000599760A patent/JP2002537301A/ja active Pending
- 2000-02-18 CA CA002361278A patent/CA2361278A1/fr not_active Abandoned
- 2000-02-18 SK SK1185-2001A patent/SK11852001A3/sk unknown
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- 2000-02-21 AR ARP000100714A patent/AR022636A1/es unknown
- 2000-04-19 TW TW089102834A patent/TWI285645B/zh not_active IP Right Cessation
2001
- 2001-08-09 BG BG105802A patent/BG105802A/bg unknown
- 2001-08-17 NO NO20014013A patent/NO20014013L/no not_active Application Discontinuation
2003
- 2003-02-12 US US10/364,337 patent/US6930102B2/en not_active Expired - Fee Related
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Also Published As

Publication number	Publication date
KR100718616B1 (ko)	2007-05-16
MXPA01008328A (es)	2002-06-04
EA200100826A1 (ru)	2002-02-28
EA009206B1 (ru)	2007-12-28
NZ513268A (en)	2004-05-28
US20050187270A1 (en)	2005-08-25
CN1341115A (zh)	2002-03-20
IL144519A0 (en)	2002-05-23
PL349863A1 (en)	2002-09-23
EP1150980B1 (fr)	2007-08-22
CN1209360C (zh)	2005-07-06
KR20010102215A (ko)	2001-11-15
CZ20012951A3 (cs)	2001-11-14
ATE370946T1 (de)	2007-09-15
AU3156700A (en)	2000-09-04
NO20014013L (no)	2001-10-18
YU59001A (sh)	2005-07-19
CA2361278A1 (fr)	2000-08-24
ES2291194T3 (es)	2008-03-01
TWI285645B (en)	2007-08-21
BG105802A (bg)	2002-03-29
EE200100431A (et)	2002-12-16
NO20014013D0 (no)	2001-08-17
BR0008331A (pt)	2002-01-29
WO2000049021A2 (fr)	2000-08-24
HRP20010677A2 (en)	2005-06-30
DE50014587D1 (de)	2007-10-04
HUP0105478A3 (en)	2002-08-28
WO2000049021A3 (fr)	2000-12-28
EP1150980A2 (fr)	2001-11-07
HK1044945A1 (en)	2002-11-08
JP2002537301A (ja)	2002-11-05
AR022636A1 (es)	2002-09-04
US6930102B2 (en)	2005-08-16
US6610736B1 (en)	2003-08-26
US20040014978A1 (en)	2004-01-22
HUP0105478A2 (en)	2002-06-29

Publication	Publication Date	Title
KR100718616B1 (ko)	2007-05-16	16-할로겐-에포틸론 유도체, 그 제조 방법 및 제약학적 용도
KR100721488B1 (ko)	2007-05-23	6-알케닐-,6-알키닐- 및 6-에폭시-에포틸론 유도체, 그의제조 방법 및 제약 제제로서 그의 용도
US7407975B2 (en)	2008-08-05	Epothilone derivatives, method for producing same and their pharmaceutical use
RS59001B1 (sr)	2019-08-30	Miš sa zajedničkim lakim lancem
US20060040990A1 (en)	2006-02-23	Epothilone derivatives, process for their production, and their pharmaceutical use
AU4310300A (en)	2000-11-17	6-alkenyl-, 6-alkinyl- and 6-epoxy-epothilone derivatives, process for their production, and their use in pharmaceutical preparations
EP1282618A2 (fr)	2003-02-12	Derives de 9-oxa-epothilone, leur procede de production et leur utilisation pharmaceutique
ZA200107648B (en)	2003-01-07	16-Halogen-epothilone derivatives, method for producing them and their pharmaceutical use.
UA74542C2 (en)	2006-01-16	Epothilone 16-halogen derivatives, a pharmaceutical agent based thereon, intermediary compounds (variants)
DE10041470A1 (de)	2002-02-28	12,13-Cyclopropyl-Epothilon-Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten
AU2004200949A1 (en)	2004-04-01	16-halogen-epothilone derivatives, method for producing them and their pharmaceutical use
AU2004200948A1 (en)	2004-04-01	Epothilon derivatives, method for the production and the use thereof as pharmaceuticals
JP2009513498A (ja)	2009-04-02	エポチロンのｃ１−ｃ１５−フラグメント及びその誘導体の生成方法
DE19907480A1 (de)	2000-08-17	Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung