NO328149B1 - Epoksy-epotilonforbindelser, fremgangsmate for deres fremstilling, deres anvendelse for fremstilling av farmasoytiske preparater og de farmasoytiske preparater. - Google Patents

Epoksy-epotilonforbindelser, fremgangsmate for deres fremstilling, deres anvendelse for fremstilling av farmasoytiske preparater og de farmasoytiske preparater. Download PDF

Info

Publication number: NO328149B1
Authority: NO; Norway
Prior art keywords: tetramethyl; dione; dihydroxy; ethenyl; oxa
Prior art date: 1999-04-30

Application number

NO20015278A

Other languages

English (en)

Norwegian (no)

Other versions

NO20015278L (no

NO20015278D0 (no

Inventor

Ulrich Klar

Werner Skuballa

Wolfgang Schwede

Rosemarie Lichtner

Bernd Buchmann

Jens Hoffmann

Original Assignee

Schering Ag

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.)

1999-04-30

Filing date

2001-10-29

Publication date

2009-12-21

1999-04-30 Priority claimed from DE19921086A external-priority patent/DE19921086A1/de

1999-11-04 Priority claimed from DE19954228A external-priority patent/DE19954228A1/de

2000-03-27 Priority claimed from DE10015836A external-priority patent/DE10015836A1/de

2001-10-29 Application filed by Schering Ag filed Critical Schering Ag

2001-10-29 Publication of NO20015278D0 publication Critical patent/NO20015278D0/no

2001-12-21 Publication of NO20015278L publication Critical patent/NO20015278L/no

2009-12-21 Publication of NO328149B1 publication Critical patent/NO328149B1/no

Links

238000000034 method Methods 0.000 title claims description 37
230000008569 process Effects 0.000 title claims description 11
238000002360 preparation method Methods 0.000 title claims description 10
239000008194 pharmaceutical composition Substances 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 308
-1 Epothilone compound Chemical class 0.000 claims description 44
239000001257 hydrogen Substances 0.000 claims description 42
229910052739 hydrogen Inorganic materials 0.000 claims description 42
LZWPOLSJFGLQCE-UHFFFAOYSA-N heptadecane-5,9-dione Chemical compound CCCCCCCCC(=O)CCCC(=O)CCCC LZWPOLSJFGLQCE-UHFFFAOYSA-N 0.000 claims description 29
150000002431 hydrogen Chemical class 0.000 claims description 25
239000012634 fragment Substances 0.000 claims description 24
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 24
125000004430 oxygen atom Chemical group O* 0.000 claims description 18
238000006243 chemical reaction Methods 0.000 claims description 17
125000006239 protecting group Chemical group 0.000 claims description 17
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 9
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125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
229910052740 iodine Inorganic materials 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 7
229910052794 bromium Inorganic materials 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
150000003254 radicals Chemical class 0.000 claims description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
HRUYBRGMRSNLNW-UHFFFAOYSA-N 6-methoxy-2-[(4-methylphenyl)methylsulfanyl]-1h-benzimidazole Chemical compound N1C2=CC(OC)=CC=C2N=C1SCC1=CC=C(C)C=C1 HRUYBRGMRSNLNW-UHFFFAOYSA-N 0.000 claims description 6
102100033616 Phospholipid-transporting ATPase ABCA1 Human genes 0.000 claims description 6
101710205202 Phospholipid-transporting ATPase ABCA1 Proteins 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 claims description 3
239000002671 adjuvant Substances 0.000 claims description 3
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239000013067 intermediate product Substances 0.000 claims description 3
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238000007363 ring formation reaction Methods 0.000 claims description 3
125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 2
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 claims description 2
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 2
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201000010099 disease Diseases 0.000 claims description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
150000004820 halides Chemical class 0.000 claims description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical group C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 claims description 2
HVZWVEKIQMJYIK-UHFFFAOYSA-N nitryl chloride Chemical compound [O-][N+](Cl)=O HVZWVEKIQMJYIK-UHFFFAOYSA-N 0.000 claims description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims 1
125000001960 7 membered carbocyclic group Chemical group 0.000 claims 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 138
238000005160 1H NMR spectroscopy Methods 0.000 description 130
239000000243 solution Substances 0.000 description 112
239000012230 colorless oil Substances 0.000 description 103
238000000746 purification Methods 0.000 description 97
238000010626 work up procedure Methods 0.000 description 91
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 70
239000000203 mixture Substances 0.000 description 46
229940126062 Compound A Drugs 0.000 description 45
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 45
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
239000002904 solvent Substances 0.000 description 29
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
238000004587 chromatography analysis Methods 0.000 description 25
239000012300 argon atmosphere Substances 0.000 description 23
238000001914 filtration Methods 0.000 description 23
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
239000000284 extract Substances 0.000 description 21
229910052938 sodium sulfate Inorganic materials 0.000 description 21
235000011152 sodium sulphate Nutrition 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
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230000015572 biosynthetic process Effects 0.000 description 17
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 16
150000003883 epothilone derivatives Chemical class 0.000 description 16
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
238000003786 synthesis reaction Methods 0.000 description 15
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
239000002585 base Substances 0.000 description 12
229930012538 Paclitaxel Natural products 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 11
229960001592 paclitaxel Drugs 0.000 description 11
239000007858 starting material Substances 0.000 description 11
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 11
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230000003647 oxidation Effects 0.000 description 10
238000007254 oxidation reaction Methods 0.000 description 10
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230000000694 effects Effects 0.000 description 9
239000002253 acid Substances 0.000 description 8
230000009471 action Effects 0.000 description 8
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
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238000005481 NMR spectroscopy Methods 0.000 description 6
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239000006260 foam Substances 0.000 description 6
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AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 5
BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
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FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
239000005445 natural material Substances 0.000 description 4
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FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
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150000003138 primary alcohols Chemical class 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
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FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
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239000004094 surface-active agent Substances 0.000 description 1
230000002195 synergetic effect Effects 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
229940063683 taxotere 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
XNSFQWWAULHCRS-XXYUJHKVSA-N tert-butyl-[(z,3s)-2-fluoro-5-iodo-1-(2-methyl-1,3-oxazol-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)=CO1 XNSFQWWAULHCRS-XXYUJHKVSA-N 0.000 description 1
FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
PCTNAMGLSYHIPL-UHFFFAOYSA-N tin(4+) tetraazide Chemical compound [Sn+4].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-] PCTNAMGLSYHIPL-UHFFFAOYSA-N 0.000 description 1
239000010936 titanium Substances 0.000 description 1
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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
210000004881 tumor cell Anatomy 0.000 description 1
230000004614 tumor growth Effects 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
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
239000000341 volatile oil Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 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
- C07D405/06—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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
- 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
- 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
- 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
- C07D405/14—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 three or more hetero rings
- 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
- 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
- C07D413/06—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 linked by a carbon chain containing only aliphatic carbon atoms
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- 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
- 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
- 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
- C07D417/14—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 three or more hetero rings
- 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)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Hematology (AREA)
Oncology (AREA)
Pain & Pain Management (AREA)
Rheumatology (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)
Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

NO20015278A 1999-04-30 2001-10-29 Epoksy-epotilonforbindelser, fremgangsmate for deres fremstilling, deres anvendelse for fremstilling av farmasoytiske preparater og de farmasoytiske preparater. NO328149B1 (no)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DE19921086A DE19921086A1 (de)	1999-04-30	1999-04-30	6-Alkenyl- und 6-Alkinyl-Epothilon Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten
DE19954228A DE19954228A1 (de)	1999-11-04	1999-11-04	6-Alkenyl-und 6-Alkinyl-Epothilon-Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten
DE10015836A DE10015836A1 (de)	2000-03-27	2000-03-27	6-Alkenyl- und 6-Alkinyl-Epothilon-Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten
PCT/IB2000/000657 WO2000066589A1 (en)	1999-04-30	2000-05-01	6-alkenyl-, 6-alkinyl- and 6-epoxy-epothilone derivatives, process for their production, and their use in pharmaceutical preparations

Publications (3)

Publication Number	Publication Date
NO20015278D0 NO20015278D0 (no)	2001-10-29
NO20015278L NO20015278L (no)	2001-12-21
NO328149B1 true NO328149B1 (no)	2009-12-21

Family

ID=27213767

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Application Number	Title	Priority Date	Filing Date
NO20015278A NO328149B1 (no)	1999-04-30	2001-10-29	Epoksy-epotilonforbindelser, fremgangsmate for deres fremstilling, deres anvendelse for fremstilling av farmasoytiske preparater og de farmasoytiske preparater.

Country Status (33)

Country	Link
EP (1)	EP1173441B1 (de)
JP (2)	JP4024003B2 (de)
KR (1)	KR100721488B1 (de)
CN (1)	CN100368415C (de)
AR (1)	AR023792A1 (de)
AT (1)	ATE440847T1 (de)
BG (1)	BG65601B1 (de)
BR (1)	BR0010190A (de)
CA (2)	CA2651653C (de)
CY (1)	CY1109768T1 (de)
CZ (1)	CZ299653B6 (de)
DE (1)	DE60042821D1 (de)
DK (1)	DK1173441T3 (de)
EA (1)	EA011502B1 (de)
EE (1)	EE05292B1 (de)
ES (1)	ES2331506T3 (de)
HK (1)	HK1046681B (de)
HR (1)	HRP20010892A2 (de)
HU (1)	HUP0201010A3 (de)
IL (1)	IL145938A0 (de)
ME (1)	MEP13908A (de)
MX (1)	MXPA01011039A (de)
NO (1)	NO328149B1 (de)
NZ (1)	NZ514989A (de)
PE (1)	PE20010116A1 (de)
PL (1)	PL210762B1 (de)
PT (1)	PT1173441E (de)
RS (1)	RS51023B (de)
SI (1)	SI1173441T1 (de)
SK (1)	SK286858B6 (de)
TW (2)	TWI280962B (de)
WO (1)	WO2000066589A1 (de)
ZA (1)	ZA200109859B (de)

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DK1483251T3 (da)	2002-03-12	2010-04-12	Bristol Myers Squibb Co	C3-cyano-epothilon-derivater
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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
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EP1559447A1 (de)	2004-01-30	2005-08-03	Institut National De La Sante Et De La Recherche Medicale (Inserm)	Verwendung von Epothilonen zur Behandlung von neuronalen Konnektivitätsdefekten wie zum Beispiel Schizophrenie und Autismus
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EP0469480A3 (en) *	1990-08-01	1993-03-10	Hoechst Aktiengesellschaft	Process for stereoselective preparation of 5-substituted delta-lactones and their use
EP1201666A3 (de) *	1997-02-25	2003-03-05	Gesellschaft für biotechnologische Forschung mbH (GBF)	Seitenkettenmodifizierte Epothilone
CA2299608A1 (en) *	1997-08-09	1999-02-18	Schering Aktiengesellschaft	New epothilone derivatives, method for producing same and their pharmaceutical use

2000
- 2000-04-28 PE PE2000000403A patent/PE20010116A1/es not_active Application Discontinuation
- 2000-04-28 AR ARP000102024A patent/AR023792A1/es active IP Right Grant
- 2000-05-01 DK DK00922826T patent/DK1173441T3/da active
- 2000-05-01 CN CNB008069786A patent/CN100368415C/zh not_active Expired - Fee Related
- 2000-05-01 ES ES00922826T patent/ES2331506T3/es not_active Expired - Lifetime
- 2000-05-01 WO PCT/IB2000/000657 patent/WO2000066589A1/en not_active Ceased
- 2000-05-01 ME MEP-139/08A patent/MEP13908A/xx unknown
- 2000-05-01 CA CA2651653A patent/CA2651653C/en not_active Expired - Fee Related
- 2000-05-01 IL IL14593800A patent/IL145938A0/xx unknown
- 2000-05-01 KR KR1020017013840A patent/KR100721488B1/ko not_active Expired - Fee Related
- 2000-05-01 NZ NZ514989A patent/NZ514989A/xx not_active IP Right Cessation
- 2000-05-01 HR HR20010892A patent/HRP20010892A2/xx not_active Application Discontinuation
- 2000-05-01 SI SI200031044T patent/SI1173441T1/sl unknown
- 2000-05-01 SK SK1551-2001A patent/SK286858B6/sk not_active IP Right Cessation
- 2000-05-01 RS YUP-776/01A patent/RS51023B/sr unknown
- 2000-05-01 EP EP00922826A patent/EP1173441B1/de not_active Expired - Lifetime
- 2000-05-01 BR BR0010190-7A patent/BR0010190A/pt not_active IP Right Cessation
- 2000-05-01 HU HU0201010A patent/HUP0201010A3/hu unknown
- 2000-05-01 EA EA200101025A patent/EA011502B1/ru not_active IP Right Cessation
- 2000-05-01 MX MXPA01011039A patent/MXPA01011039A/es active IP Right Grant
- 2000-05-01 HK HK02108204.3A patent/HK1046681B/zh not_active IP Right Cessation
- 2000-05-01 JP JP2000615619A patent/JP4024003B2/ja not_active Expired - Fee Related
- 2000-05-01 DE DE60042821T patent/DE60042821D1/de not_active Expired - Lifetime
- 2000-05-01 AT AT00922826T patent/ATE440847T1/de active
- 2000-05-01 PL PL351491A patent/PL210762B1/pl not_active IP Right Cessation
- 2000-05-01 CZ CZ20013885A patent/CZ299653B6/cs not_active IP Right Cessation
- 2000-05-01 EE EEP200100568A patent/EE05292B1/xx not_active IP Right Cessation
- 2000-05-01 PT PT00922826T patent/PT1173441E/pt unknown
- 2000-05-01 CA CA2371226A patent/CA2371226C/en not_active Expired - Fee Related
- 2000-05-18 TW TW89108133A patent/TWI280962B/zh not_active IP Right Cessation
- 2000-05-18 TW TW095145399A patent/TWI294292B/zh not_active IP Right Cessation
2001
- 2001-10-26 BG BG106053A patent/BG65601B1/bg unknown
- 2001-10-29 NO NO20015278A patent/NO328149B1/no not_active IP Right Cessation
- 2001-11-29 ZA ZA200109859A patent/ZA200109859B/xx unknown
2007
- 2007-04-11 JP JP2007104224A patent/JP4886578B2/ja not_active Expired - Fee Related
2009
- 2009-11-25 CY CY20091101237T patent/CY1109768T1/el unknown

Also Published As

Publication number	Publication date
HUP0201010A3 (en)	2005-02-28
NO20015278L (no)	2001-12-21
SK286858B6 (sk)	2009-06-05
EP1173441A1 (de)	2002-01-23
CA2371226A1 (en)	2000-11-09
ATE440847T1 (de)	2009-09-15
KR100721488B1 (ko)	2007-05-23
EP1173441B1 (de)	2009-08-26
BR0010190A (pt)	2002-01-08
PL351491A1 (en)	2003-04-22
KR20020005737A (ko)	2002-01-17
CZ299653B6 (cs)	2008-10-08
ES2331506T3 (es)	2010-01-07
CA2371226C (en)	2011-11-29
JP4886578B2 (ja)	2012-02-29
MXPA01011039A (es)	2003-06-30
BG65601B1 (bg)	2009-02-27
PL210762B1 (pl)	2012-02-29
AR023792A1 (es)	2002-09-04
PE20010116A1 (es)	2001-02-15
TWI280962B (en)	2007-05-11
HRP20010892A2 (hr)	2008-06-30
EE05292B1 (et)	2010-04-15
TWI294292B (en)	2008-03-11
MEP13908A (en)	2010-06-10
YU77601A (sh)	2005-07-19
CY1109768T1 (el)	2014-09-10
WO2000066589A1 (en)	2000-11-09
CZ20013885A3 (cs)	2002-04-17
TW200711679A (en)	2007-04-01
CA2651653C (en)	2012-02-14
HUP0201010A2 (en)	2002-08-28
CN1349534A (zh)	2002-05-15
RS51023B (sr)	2010-10-31
DE60042821D1 (de)	2009-10-08
EA011502B1 (ru)	2009-04-28
JP4024003B2 (ja)	2007-12-19
DK1173441T3 (da)	2009-12-07
EA200101025A1 (ru)	2002-06-27
SI1173441T1 (sl)	2010-01-29
BG106053A (en)	2002-05-31
JP2002543203A (ja)	2002-12-17
EE200100568A (et)	2003-02-17
CN100368415C (zh)	2008-02-13
NZ514989A (en)	2004-02-27
JP2007224038A (ja)	2007-09-06
CA2651653A1 (en)	2000-11-09
HK1046681B (zh)	2008-08-29
PT1173441E (pt)	2009-11-06
HK1046681A1 (zh)	2003-01-24
SK15512001A3 (sk)	2002-05-09
IL145938A0 (en)	2002-07-25
ZA200109859B (en)	2003-02-28
NO20015278D0 (no)	2001-10-29

Legal Events

Date	Code	Title	Description
2013-02-11	CHAD	Change of the owner's name or address (par. 44 patent law, par. patentforskriften)	Owner name: BAYER INTELLECTUAL PROPERTY GMBH, DE
2013-12-23	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
CA2371226C (en)	2011-11-29	6-alkenyl-, 6-alkinyl- and 6-epoxy-epothilone derivatives, process for their production, and their use in pharmaceutical preparations
US20030144523A1 (en)	2003-07-31	Epothilone derivatives, method for producing same and their pharmaceutical use
AU3156700A (en)	2000-09-04	16-halogen-epothilone derivatives, method for producing them and their pharmaceutical use
WO2000000485A1 (de)	2000-01-06	Epothilon-derivate, verfahren zu deren herstellung, zwischenprodukte und ihre pharmazeutische verwendung
US20100168179A1 (en)	2010-07-01	6-alkenyl-, 6-alkinyl- and 6-epoxy-epothilone derivatives, process for their production, and their use in pharmaceutical preparations
EP1276740A2 (de)	2003-01-22	Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung
KR20010094763A (ko)	2001-11-01	에포틸론 유도체, 그 제조방법 및 제약적 용도
JP2003531206A (ja)	2003-10-21	９−オキサ−エポシロン−誘導体の製造方法及び医薬的調製におけるこれらの使用
DE10015836A1 (de)	2001-10-11	6-Alkenyl- und 6-Alkinyl-Epothilon-Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten
DE19954228A1 (de)	2001-09-13	6-Alkenyl-und 6-Alkinyl-Epothilon-Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten
DE19921086A1 (de)	2000-11-02	6-Alkenyl- und 6-Alkinyl-Epothilon Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten