CA2556915A1 - Epothilone derivatives - Google Patents
Epothilone derivatives Download PDFInfo
- Publication number
- CA2556915A1 CA2556915A1 CA002556915A CA2556915A CA2556915A1 CA 2556915 A1 CA2556915 A1 CA 2556915A1 CA 002556915 A CA002556915 A CA 002556915A CA 2556915 A CA2556915 A CA 2556915A CA 2556915 A1 CA2556915 A1 CA 2556915A1
- Authority
- CA
- Canada
- Prior art keywords
- solution
- mmol
- compound
- dione
- dimethyl
- 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.)
- Abandoned
Links
- 150000003883 epothilone derivatives Chemical class 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 58
- 150000003839 salts Chemical class 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- BNEVSCPIBMLZGL-UHFFFAOYSA-N 14-(1,2-dimethylbenzimidazol-5-yl)-6,10-dihydroxy-5,7,9,9-tetramethyl-13-oxabicyclo[14.1.0]heptadecane-8,12-dione Chemical compound O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC2CC2CC1C1=CC=C(N(C)C(C)=N2)C2=C1 BNEVSCPIBMLZGL-UHFFFAOYSA-N 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- BNEVSCPIBMLZGL-PYGHBYHZSA-N (1r,5s,6s,7r,10s,14s,16s)-14-(1,2-dimethylbenzimidazol-5-yl)-6,10-dihydroxy-5,7,9,9-tetramethyl-13-oxabicyclo[14.1.0]heptadecane-8,12-dione Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@@H]2C[C@H]2C[C@H]1C1=CC=C(N(C)C(C)=N2)C2=C1 BNEVSCPIBMLZGL-PYGHBYHZSA-N 0.000 claims description 2
- MNOKJZZTHUGFGO-CCEYBZCHSA-N (3e,7r,8s,9s,13e,16s)-16-(1,2-dimethylbenzimidazol-5-yl)-8-hydroxy-5,5,7,9-tetramethyl-1-oxacyclohexadeca-3,13-diene-2,6-dione Chemical compound O1C(=O)\C=C\C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C=C\C[C@H]1C1=CC=C(N(C)C(C)=N2)C2=C1 MNOKJZZTHUGFGO-CCEYBZCHSA-N 0.000 claims description 2
- RJXSMHWBBLJKLY-WPNDJVSTSA-N (4s,7r,8s,9s,13e,16s)-16-(1,2-dimethylbenzimidazol-5-yl)-4,8-dihydroxy-5,5,7,9-tetramethyl-1-oxacyclohexadec-13-ene-2,6-dione 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]1C1=CC=C(N(C)C(C)=N2)C2=C1 RJXSMHWBBLJKLY-WPNDJVSTSA-N 0.000 claims description 2
- NAVCAXWTHIGRRQ-HWDUUENNSA-N (7r,8s,9s,13e,16s)-16-(1,2-dimethylbenzimidazol-5-yl)-8-hydroxy-5,5,7,9-tetramethyl-1-oxacyclohexadec-13-ene-2,6-dione Chemical compound O1C(=O)CCC(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C=C\C[C@H]1C1=CC=C(N(C)C(C)=N2)C2=C1 NAVCAXWTHIGRRQ-HWDUUENNSA-N 0.000 claims description 2
- PIUCYHQFEORJGM-UHFFFAOYSA-N 14-(1,2-dimethylbenzimidazol-5-yl)-6,10-dihydroxy-5,7,9,9-tetramethyl-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione Chemical compound O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC2OC2CC1C1=CC=C(N(C)C(C)=N2)C2=C1 PIUCYHQFEORJGM-UHFFFAOYSA-N 0.000 claims description 2
- PINYKHFDYGYNDE-UHFFFAOYSA-N 14-(1,2-dimethylbenzimidazol-5-yl)-6-hydroxy-5,7,9,9-tetramethyl-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione Chemical compound O1C(=O)CCC(C)(C)C(=O)C(C)C(O)C(C)CCCC2OC2CC1C1=CC=C(N(C)C(C)=N2)C2=C1 PINYKHFDYGYNDE-UHFFFAOYSA-N 0.000 claims description 2
- RJXSMHWBBLJKLY-UHFFFAOYSA-N 16-(1,2-dimethylbenzimidazol-5-yl)-4,8-dihydroxy-5,5,7,9-tetramethyl-1-oxacyclohexadec-13-ene-2,6-dione Chemical compound O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC=CCC1C1=CC=C(N(C)C(C)=N2)C2=C1 RJXSMHWBBLJKLY-UHFFFAOYSA-N 0.000 claims description 2
- NAVCAXWTHIGRRQ-UHFFFAOYSA-N 16-(1,2-dimethylbenzimidazol-5-yl)-8-hydroxy-5,5,7,9-tetramethyl-1-oxacyclohexadec-13-ene-2,6-dione Chemical compound O1C(=O)CCC(C)(C)C(=O)C(C)C(O)C(C)CCCC=CCC1C1=CC=C(N(C)C(C)=N2)C2=C1 NAVCAXWTHIGRRQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
- IOIXMMLLEZLNPS-BIOQQELPSA-N (1s,3s,10r,11s,12s,16r)-11-hydroxy-8,8,10,12,16-pentamethyl-3-[(e)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione 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)CCC(=O)O1)O)C)=C\C1=CSC(C)=N1 IOIXMMLLEZLNPS-BIOQQELPSA-N 0.000 claims 1
- GEYOFQZSFIWPPK-BQYTYRMFSA-N (1s,3s,10r,11s,12s,16r)-3-(1,2-dimethylbenzimidazol-5-yl)-11-hydroxy-8,8,10,12,16-pentamethyl-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione Chemical compound O1C(=O)CCC(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@H]1C1=CC=C(N(C)C(C)=N2)C2=C1 GEYOFQZSFIWPPK-BQYTYRMFSA-N 0.000 claims 1
- KSVJJYLXVPYGKF-VQOFAXPZSA-N (1s,5s,6s,7r,10e,14s,16s)-14-(1,2-dimethylbenzimidazol-5-yl)-6-hydroxy-5,7,9,9-tetramethyl-13,17-dioxabicyclo[14.1.0]heptadec-10-ene-8,12-dione Chemical compound O1C(=O)\C=C\C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@@H]2O[C@H]2C[C@H]1C1=CC=C(N(C)C(C)=N2)C2=C1 KSVJJYLXVPYGKF-VQOFAXPZSA-N 0.000 claims 1
- PIUCYHQFEORJGM-CMNJRJKDSA-N (1s,5s,6s,7r,10s,14s,16s)-14-(1,2-dimethylbenzimidazol-5-yl)-6,10-dihydroxy-5,7,9,9-tetramethyl-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@@H]2O[C@H]2C[C@H]1C1=CC=C(N(C)C(C)=N2)C2=C1 PIUCYHQFEORJGM-CMNJRJKDSA-N 0.000 claims 1
- PINYKHFDYGYNDE-RFPOXKJFSA-N (1s,5s,6s,7r,14s,16s)-14-(1,2-dimethylbenzimidazol-5-yl)-6-hydroxy-5,7,9,9-tetramethyl-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione Chemical compound O1C(=O)CCC(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@@H]2O[C@H]2C[C@H]1C1=CC=C(N(C)C(C)=N2)C2=C1 PINYKHFDYGYNDE-RFPOXKJFSA-N 0.000 claims 1
- PVDJHOFZNQMBSV-GANQCTJWSA-N (7r,8s,9s,13z,16s)-16-(1,2-dimethylbenzimidazol-5-yl)-8-hydroxy-5,5,7,9,13-pentamethyl-1-oxacyclohexadec-13-ene-2,6-dione Chemical compound O1C(=O)CCC(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C1=CC=C(N(C)C(C)=N2)C2=C1 PVDJHOFZNQMBSV-GANQCTJWSA-N 0.000 claims 1
- OFFMAOLMRZZNAE-CHZUWRTOSA-N (7r,8s,9s,13z,16s)-8-hydroxy-5,5,7,9,13-pentamethyl-16-[(e)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadec-13-ene-2,6-dione Chemical compound O1C(=O)CCC(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 OFFMAOLMRZZNAE-CHZUWRTOSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 252
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 240
- 239000000243 solution Substances 0.000 description 153
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 90
- 239000011541 reaction mixture Substances 0.000 description 60
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 59
- 238000003818 flash chromatography Methods 0.000 description 56
- 239000000203 mixture Substances 0.000 description 53
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
- 238000005481 NMR spectroscopy Methods 0.000 description 45
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- 239000012044 organic layer Substances 0.000 description 38
- 238000000746 purification Methods 0.000 description 38
- 229910001868 water Inorganic materials 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 238000003756 stirring Methods 0.000 description 29
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 25
- 235000019341 magnesium sulphate Nutrition 0.000 description 25
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 21
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 20
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000008346 aqueous phase Substances 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
- 101150041968 CDC13 gene Proteins 0.000 description 16
- 238000004809 thin layer chromatography Methods 0.000 description 15
- 238000010908 decantation Methods 0.000 description 14
- 239000012153 distilled water Substances 0.000 description 14
- 239000012047 saturated solution Substances 0.000 description 14
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 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 12
- GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical compound IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 238000001035 drying Methods 0.000 description 10
- 239000012043 crude product Substances 0.000 description 9
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 7
- -1 alkyl radical Chemical class 0.000 description 7
- VZSXFJPZOCRDPW-UHFFFAOYSA-N carbanide;trioxorhenium Chemical compound [CH3-].O=[Re](=O)=O VZSXFJPZOCRDPW-UHFFFAOYSA-N 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- TVZDIFXOIOIPJG-UHFFFAOYSA-N 2,3,4-trichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C(Cl)=C1Cl TVZDIFXOIOIPJG-UHFFFAOYSA-N 0.000 description 6
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 239000004809 Teflon Substances 0.000 description 6
- 229920006362 Teflon® Polymers 0.000 description 6
- 150000001336 alkenes Chemical class 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 229910000085 borane Inorganic materials 0.000 description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 description 6
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 6
- 238000010791 quenching Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 229950007035 homocamfin Drugs 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 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 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229930013356 epothilone Natural products 0.000 description 4
- 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 4
- LZWPOLSJFGLQCE-UHFFFAOYSA-N heptadecane-5,9-dione Chemical compound CCCCCCCCC(=O)CCCC(=O)CCCC LZWPOLSJFGLQCE-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 238000002560 therapeutic procedure Methods 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 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229910021554 Chromium(II) chloride Inorganic materials 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229930091371 Fructose Natural products 0.000 description 3
- 239000005715 Fructose Substances 0.000 description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229940123237 Taxane Drugs 0.000 description 3
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- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0405898.8 | 2004-03-16 | ||
| GBGB0405898.8A GB0405898D0 (en) | 2004-03-16 | 2004-03-16 | Organic compounds |
| PCT/EP2005/002756 WO2005090335A1 (en) | 2004-03-16 | 2005-03-15 | Epothilone derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2556915A1 true CA2556915A1 (en) | 2005-09-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002556915A Abandoned CA2556915A1 (en) | 2004-03-16 | 2005-03-15 | Epothilone derivatives |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7825141B2 (enExample) |
| EP (3) | EP1730138A1 (enExample) |
| JP (1) | JP2007529455A (enExample) |
| KR (1) | KR20070006773A (enExample) |
| CN (2) | CN101805328A (enExample) |
| AU (1) | AU2005223325B2 (enExample) |
| BR (1) | BRPI0508874A (enExample) |
| CA (1) | CA2556915A1 (enExample) |
| GB (1) | GB0405898D0 (enExample) |
| RU (1) | RU2006136089A (enExample) |
| WO (1) | WO2005090335A1 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102007016046A1 (de) * | 2007-03-30 | 2008-10-23 | Bayer Schering Pharma Aktiengesellschaft | Verfahren zur Herstellung von Epothilonderivaten durch selektive katalytische Epoxidierung |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1440973A3 (de) | 1995-11-17 | 2004-10-20 | Gesellschaft für biotechnologische Forschung mbH (GBF) | Epothilonderivate, Herstellung und Mittel |
| DE19751027A1 (de) | 1996-11-20 | 1998-05-28 | Degussa | Arylsubstituierte aminoacylierte Phosphonsäuren und deren Halbester |
| US6441186B1 (en) | 1996-12-13 | 2002-08-27 | The Scripps Research Institute | Epothilone analogs |
| US6380394B1 (en) * | 1996-12-13 | 2002-04-30 | The Scripps Research Institute | Epothilone analogs |
| IL135590A (en) | 1997-12-04 | 2003-09-17 | Bristol Myers Squibb Co | Process for the reduction of oxiranyl epothilones to olefinic epothilones |
| FR2775187B1 (fr) | 1998-02-25 | 2003-02-21 | Novartis Ag | Utilisation de l'epothilone b pour la fabrication d'une preparation pharmaceutique antiproliferative et d'une composition comprenant l'epothilone b comme agent antiproliferatif in vivo |
| DE19856128A1 (de) | 1998-12-04 | 2000-06-15 | Volkswagen Ag | Verfahren und Einrichtung zum Lesen von Navigationsdaten |
| AU2795000A (en) * | 1998-12-22 | 2000-07-12 | Novartis Ag | Epothilone derivatives and their use as antitumor agents |
| SK287200B6 (sk) | 1999-02-22 | 2010-03-08 | Gesellschaft Fuer Biotechnologische Forschung Mbh (Gbf) | C-21 modifikované epotilóny, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a použitie |
| BR0212107A (pt) | 2001-08-23 | 2004-08-24 | Novartis Ag | Análogos da ciclopropil e da ciclobutil epotilona |
| DK1483251T3 (da) | 2002-03-12 | 2010-04-12 | Bristol Myers Squibb Co | C3-cyano-epothilon-derivater |
| AU2003266961A1 (en) | 2002-08-02 | 2004-02-25 | Novartis Ag | Epothilone derivatives |
-
2004
- 2004-03-16 GB GBGB0405898.8A patent/GB0405898D0/en not_active Ceased
-
2005
- 2005-03-15 EP EP05716085A patent/EP1730138A1/en not_active Withdrawn
- 2005-03-15 CN CN201010150615A patent/CN101805328A/zh active Pending
- 2005-03-15 EP EP10180401A patent/EP2301940A1/en not_active Withdrawn
- 2005-03-15 CA CA002556915A patent/CA2556915A1/en not_active Abandoned
- 2005-03-15 CN CN2005800069311A patent/CN1926133B/zh not_active Expired - Fee Related
- 2005-03-15 KR KR1020067018936A patent/KR20070006773A/ko not_active Withdrawn
- 2005-03-15 WO PCT/EP2005/002756 patent/WO2005090335A1/en not_active Ceased
- 2005-03-15 RU RU2006136089/04A patent/RU2006136089A/ru not_active Application Discontinuation
- 2005-03-15 JP JP2007503276A patent/JP2007529455A/ja not_active Withdrawn
- 2005-03-15 EP EP10160012A patent/EP2213670A3/en not_active Withdrawn
- 2005-03-15 BR BRPI0508874-7A patent/BRPI0508874A/pt not_active IP Right Cessation
- 2005-03-15 US US10/591,921 patent/US7825141B2/en not_active Expired - Fee Related
- 2005-03-15 AU AU2005223325A patent/AU2005223325B2/en not_active Ceased
-
2010
- 2010-09-21 US US12/886,819 patent/US20110009459A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20110009459A1 (en) | 2011-01-13 |
| CN1926133B (zh) | 2010-06-23 |
| EP2213670A3 (en) | 2010-11-24 |
| BRPI0508874A (pt) | 2007-09-04 |
| EP2301940A1 (en) | 2011-03-30 |
| CN101805328A (zh) | 2010-08-18 |
| EP2213670A2 (en) | 2010-08-04 |
| AU2005223325B2 (en) | 2009-09-10 |
| RU2006136089A (ru) | 2008-04-27 |
| WO2005090335A1 (en) | 2005-09-29 |
| US20080114040A1 (en) | 2008-05-15 |
| CN1926133A (zh) | 2007-03-07 |
| JP2007529455A (ja) | 2007-10-25 |
| GB0405898D0 (en) | 2004-04-21 |
| KR20070006773A (ko) | 2007-01-11 |
| US7825141B2 (en) | 2010-11-02 |
| EP1730138A1 (en) | 2006-12-13 |
| AU2005223325A1 (en) | 2005-09-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |