KR20070006773A - 에포틸론 유도체 - Google Patents
에포틸론 유도체 Download PDFInfo
- Publication number
- KR20070006773A KR20070006773A KR1020067018936A KR20067018936A KR20070006773A KR 20070006773 A KR20070006773 A KR 20070006773A KR 1020067018936 A KR1020067018936 A KR 1020067018936A KR 20067018936 A KR20067018936 A KR 20067018936A KR 20070006773 A KR20070006773 A KR 20070006773A
- Authority
- KR
- South Korea
- Prior art keywords
- mmol
- solution
- dione
- dimethyl
- benzoimidazol
- 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.)
- Withdrawn
Links
- 150000003883 epothilone derivatives Chemical class 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- -1 1,2-dimethyl-1H-benzoimidazol-5-yl Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 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 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 238000002360 preparation method 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
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 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
- 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 description 2
- 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 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
- 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 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
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- 239000000243 solution Substances 0.000 description 157
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 141
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 74
- 239000011541 reaction mixture Substances 0.000 description 57
- 238000003818 flash chromatography Methods 0.000 description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 239000000203 mixture Substances 0.000 description 49
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 239000012044 organic layer Substances 0.000 description 38
- 238000000746 purification Methods 0.000 description 34
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- 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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical compound IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000008346 aqueous phase Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 239000012230 colorless oil Substances 0.000 description 16
- 239000012043 crude product Substances 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 14
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 14
- 238000010908 decantation Methods 0.000 description 14
- 206010028980 Neoplasm Diseases 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 150000001299 aldehydes Chemical class 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000012153 distilled water Substances 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- JCWIWBWXCVGEAN-UHFFFAOYSA-L cyclopentyl(diphenyl)phosphane;dichloropalladium;iron Chemical compound [Fe].Cl[Pd]Cl.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1 JCWIWBWXCVGEAN-UHFFFAOYSA-L 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 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 7
- 239000011734 sodium Substances 0.000 description 7
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 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
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 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
- 238000004458 analytical method Methods 0.000 description 6
- 229910000085 borane Inorganic materials 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 229930013356 epothilone Natural products 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 4
- 0 C[C@@](CCCC(*)=CCC(*)*)[C@@]([C@](C)(CC(C)(C)C(*)CC(*)=O)C=O)N=O Chemical compound C[C@@](CCCC(*)=CCC(*)*)[C@@]([C@](C)(CC(C)(C)C(*)CC(*)=O)C=O)N=O 0.000 description 4
- 229910004844 Na2B4O7.10H2O Inorganic materials 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 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
- 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
- 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
- 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 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 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
- 241000699670 Mus sp. Species 0.000 description 3
- 229940123237 Taxane Drugs 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
- 229910052786 argon Inorganic materials 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
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- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0405898.8A GB0405898D0 (en) | 2004-03-16 | 2004-03-16 | Organic compounds |
| GB0405898.8 | 2004-03-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20070006773A true KR20070006773A (ko) | 2007-01-11 |
Family
ID=32117793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020067018936A Withdrawn KR20070006773A (ko) | 2004-03-16 | 2005-03-15 | 에포틸론 유도체 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7825141B2 (enExample) |
| EP (3) | EP2213670A3 (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 |
|---|---|---|---|---|
| JP4183099B2 (ja) * | 1995-11-17 | 2008-11-19 | ゲゼルシャフト・フュア・ビオテヒノロジッシェ・フォルシュング・ミット・ベシュレンクテル・ハフツング（ゲー・ベー・エフ） | エポチロンｃおよびｄ、製造法ならびに組成物 |
| DE19751027A1 (de) | 1996-11-20 | 1998-05-28 | Degussa | Arylsubstituierte aminoacylierte Phosphonsäuren und deren Halbester |
| US6380394B1 (en) | 1996-12-13 | 2002-04-30 | The Scripps Research Institute | Epothilone analogs |
| US6441186B1 (en) * | 1996-12-13 | 2002-08-27 | The Scripps Research Institute | Epothilone analogs |
| JP4434484B2 (ja) | 1997-12-04 | 2010-03-17 | ブリストル−マイヤーズ スクイブ カンパニー | オキシラニルエポチロン化合物のオレフィン性エポチロン化合物への還元法 |
| 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 |
| ES2207983T3 (es) * | 1998-12-22 | 2004-06-01 | Novartis Ag | Derivados de epotilona y su uso como agentes antitumorales. |
| US6262094B1 (en) | 1999-02-22 | 2001-07-17 | Bristol-Myers Squibb Company | C-21 modified epothilones |
| WO2003018002A2 (en) | 2001-08-23 | 2003-03-06 | Novartis Ag | Cyclopropyl and cyclobutyl epothilone analogs |
| ATE452896T1 (de) | 2002-03-12 | 2010-01-15 | Bristol Myers Squibb Co | C3-cyanoepothilonderivate |
| ES2297189T3 (es) | 2002-08-02 | 2008-05-01 | Novartis Ag | Derivados de epotilona. |
-
2004
- 2004-03-16 GB GBGB0405898.8A patent/GB0405898D0/en not_active Ceased
-
2005
- 2005-03-15 AU AU2005223325A patent/AU2005223325B2/en not_active Ceased
- 2005-03-15 WO PCT/EP2005/002756 patent/WO2005090335A1/en not_active Ceased
- 2005-03-15 CN CN201010150615A patent/CN101805328A/zh active Pending
- 2005-03-15 KR KR1020067018936A patent/KR20070006773A/ko not_active Withdrawn
- 2005-03-15 EP EP10160012A patent/EP2213670A3/en not_active Withdrawn
- 2005-03-15 JP JP2007503276A patent/JP2007529455A/ja not_active Withdrawn
- 2005-03-15 US US10/591,921 patent/US7825141B2/en not_active Expired - Fee Related
- 2005-03-15 EP EP10180401A patent/EP2301940A1/en not_active Withdrawn
- 2005-03-15 EP EP05716085A patent/EP1730138A1/en not_active Withdrawn
- 2005-03-15 RU RU2006136089/04A patent/RU2006136089A/ru not_active Application Discontinuation
- 2005-03-15 CN CN2005800069311A patent/CN1926133B/zh not_active Expired - Fee Related
- 2005-03-15 BR BRPI0508874-7A patent/BRPI0508874A/pt not_active IP Right Cessation
- 2005-03-15 CA CA002556915A patent/CA2556915A1/en not_active Abandoned
-
2010
- 2010-09-21 US US12/886,819 patent/US20110009459A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| RU2006136089A (ru) | 2008-04-27 |
| US20080114040A1 (en) | 2008-05-15 |
| CA2556915A1 (en) | 2005-09-29 |
| CN101805328A (zh) | 2010-08-18 |
| EP2213670A3 (en) | 2010-11-24 |
| EP1730138A1 (en) | 2006-12-13 |
| AU2005223325A1 (en) | 2005-09-29 |
| GB0405898D0 (en) | 2004-04-21 |
| US20110009459A1 (en) | 2011-01-13 |
| EP2213670A2 (en) | 2010-08-04 |
| CN1926133A (zh) | 2007-03-07 |
| BRPI0508874A (pt) | 2007-09-04 |
| AU2005223325B2 (en) | 2009-09-10 |
| EP2301940A1 (en) | 2011-03-30 |
| US7825141B2 (en) | 2010-11-02 |
| WO2005090335A1 (en) | 2005-09-29 |
| CN1926133B (zh) | 2010-06-23 |
| JP2007529455A (ja) | 2007-10-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20060915 Patent event code: PA01051R01D Comment text: International Patent Application |
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| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |