AU2012264602B2 - Process for the production of estetrol intermediates - Google Patents
Process for the production of estetrol intermediates Download PDFInfo
- Publication number
- AU2012264602B2 AU2012264602B2 AU2012264602A AU2012264602A AU2012264602B2 AU 2012264602 B2 AU2012264602 B2 AU 2012264602B2 AU 2012264602 A AU2012264602 A AU 2012264602A AU 2012264602 A AU2012264602 A AU 2012264602A AU 2012264602 B2 AU2012264602 B2 AU 2012264602B2
- Authority
- AU
- Australia
- Prior art keywords
- compound
- formula
- group
- process according
- produce
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 71
- 230000008569 process Effects 0.000 title claims abstract description 50
- AJIPIJNNOJSSQC-NYLIRDPKSA-N estetrol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)[C@@H]4O)O)[C@@H]4[C@@H]3CCC2=C1 AJIPIJNNOJSSQC-NYLIRDPKSA-N 0.000 title claims description 21
- 229950009589 estetrol Drugs 0.000 title claims description 21
- 238000004519 manufacturing process Methods 0.000 title description 4
- 239000000543 intermediate Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 82
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 239000003795 chemical substances by application Substances 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 21
- -1 metal hydride compounds Chemical class 0.000 claims description 20
- 239000012298 atmosphere Substances 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 239000003638 chemical reducing agent Substances 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 230000003197 catalytic effect Effects 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 239000012279 sodium borohydride Substances 0.000 claims description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 8
- 150000002576 ketones Chemical class 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- 229910052987 metal hydride Inorganic materials 0.000 claims description 4
- NBWIIOQJUKRLKW-UHFFFAOYSA-N chloro(phenyl)silane Chemical compound Cl[SiH2]C1=CC=CC=C1 NBWIIOQJUKRLKW-UHFFFAOYSA-N 0.000 claims description 3
- PZABZCASVQXUET-UHFFFAOYSA-N phenylsilyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)O[SiH2]C1=CC=CC=C1 PZABZCASVQXUET-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 26
- 239000000243 solution Substances 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 17
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 229960003399 estrone Drugs 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 8
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 4
- KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 4
- 238000002657 hormone replacement therapy Methods 0.000 description 4
- 238000011065 in-situ storage Methods 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
- 239000000463 material Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- KJGLZJQPMKQFIK-UHFFFAOYSA-N methanolate;tributylstannanylium Chemical compound CCCC[Sn](CCCC)(CCCC)OC KJGLZJQPMKQFIK-UHFFFAOYSA-N 0.000 description 3
- YHLVIDQQTOMBGN-UHFFFAOYSA-N methyl prop-2-enyl carbonate Chemical group COC(=O)OCC=C YHLVIDQQTOMBGN-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 3
- KPZSTOVTJYRDIO-UHFFFAOYSA-K trichlorocerium;heptahydrate Chemical compound O.O.O.O.O.O.O.Cl[Ce](Cl)Cl KPZSTOVTJYRDIO-UHFFFAOYSA-K 0.000 description 3
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- SXFKICPVHVUTMH-YOEKFXIASA-N (8r,9s,13s,14s)-3-[tert-butyl(dimethyl)silyl]oxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-one Chemical compound C1C[C@]2(C)C(=O)CC[C@H]2[C@@H]2CCC3=CC(O[Si](C)(C)C(C)(C)C)=CC=C3[C@H]21 SXFKICPVHVUTMH-YOEKFXIASA-N 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 2
- 206010047791 Vulvovaginal dryness Diseases 0.000 description 2
- 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 2
- 125000002252 acyl group Chemical group 0.000 description 2
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 2
- FHCIILYMWWRNIZ-UHFFFAOYSA-N benzhydryl(chloro)silane Chemical compound C=1C=CC=CC=1C([SiH2]Cl)C1=CC=CC=C1 FHCIILYMWWRNIZ-UHFFFAOYSA-N 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- KWYZNESIGBQHJK-UHFFFAOYSA-N chloro-dimethyl-phenylsilane Chemical compound C[Si](C)(Cl)C1=CC=CC=C1 KWYZNESIGBQHJK-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 229910001882 dioxygen Inorganic materials 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- UIWXSTHGICQLQT-UHFFFAOYSA-N ethenyl propanoate Chemical compound CCC(=O)OC=C UIWXSTHGICQLQT-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- LSJFMTWFOIHWKQ-UHFFFAOYSA-N prop-1-en-2-yl 2-methylpropanoate Chemical compound CC(C)C(=O)OC(C)=C LSJFMTWFOIHWKQ-UHFFFAOYSA-N 0.000 description 2
- PDBWEHKCAUAROT-UHFFFAOYSA-N prop-1-en-2-yl butanoate Chemical compound CCCC(=O)OC(C)=C PDBWEHKCAUAROT-UHFFFAOYSA-N 0.000 description 2
- NLDFTWSUPLJCQD-UHFFFAOYSA-N prop-1-en-2-yl propanoate Chemical compound CCC(=O)OC(C)=C NLDFTWSUPLJCQD-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- 125000000094 2-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
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WGZCUXZFISUUPR-UHFFFAOYSA-N acetonitrile;oxolane Chemical compound CC#N.C1CCOC1 WGZCUXZFISUUPR-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- ZPVOVHKDYRROOB-UHFFFAOYSA-N benzhydrylsilyl trifluoromethanesulfonate Chemical compound C=1C=CC=CC=1C([SiH2]OS(=O)(=O)C(F)(F)F)C1=CC=CC=C1 ZPVOVHKDYRROOB-UHFFFAOYSA-N 0.000 description 1
- 230000000035 biogenic effect Effects 0.000 description 1
- JKJWYKGYGWOAHT-UHFFFAOYSA-N bis(prop-2-enyl) carbonate Chemical compound C=CCOC(=O)OCC=C JKJWYKGYGWOAHT-UHFFFAOYSA-N 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 150000002084 enol ethers Chemical class 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940106582 estrogenic substances Drugs 0.000 description 1
- JKKFKPJIXZFSSB-CBZIJGRNSA-N estrone 3-sulfate Chemical compound OS(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 JKKFKPJIXZFSSB-CBZIJGRNSA-N 0.000 description 1
- JZRGFKQYQJKGAK-UHFFFAOYSA-N ethenyl cyclohexanecarboxylate Chemical compound C=COC(=O)C1CCCCC1 JZRGFKQYQJKGAK-UHFFFAOYSA-N 0.000 description 1
- HPJNZMNSEFSQMV-UHFFFAOYSA-N ethenyl cyclopentanecarboxylate Chemical compound C=COC(=O)C1CCCC1 HPJNZMNSEFSQMV-UHFFFAOYSA-N 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- BNHFWQQYLUPDOG-UHFFFAOYSA-N lithium;1,2,2,3-tetramethylpiperidine Chemical compound [Li].CC1CCCN(C)C1(C)C BNHFWQQYLUPDOG-UHFFFAOYSA-N 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- VDCLSGXZVUDARN-UHFFFAOYSA-N molecular bromine;pyridine;hydrobromide Chemical compound Br.BrBr.C1=CC=NC=C1 VDCLSGXZVUDARN-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- AIPJCMMALQPRMK-UHFFFAOYSA-N prop-2-enyl cyclohexanecarboxylate Chemical compound C=CCOC(=O)C1CCCCC1 AIPJCMMALQPRMK-UHFFFAOYSA-N 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 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
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- LHJCZOXMCGQVDQ-UHFFFAOYSA-N tri(propan-2-yl)silyl trifluoromethanesulfonate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OS(=O)(=O)C(F)(F)F LHJCZOXMCGQVDQ-UHFFFAOYSA-N 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- STMPXDBGVJZCEX-UHFFFAOYSA-N triethylsilyl trifluoromethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F STMPXDBGVJZCEX-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0059—Estrane derivatives substituted in position 17 by a keto group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/005—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 16 (17)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161492300P | 2011-06-01 | 2011-06-01 | |
| EP11168561.6 | 2011-06-01 | ||
| EP11168561 | 2011-06-01 | ||
| US61/492,300 | 2011-06-01 | ||
| PCT/EP2012/060447 WO2012164096A1 (en) | 2011-06-01 | 2012-06-01 | Process for the production of estetrol intermediates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2012264602A1 AU2012264602A1 (en) | 2013-12-12 |
| AU2012264602B2 true AU2012264602B2 (en) | 2017-03-09 |
Family
ID=45003353
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2012264602A Active AU2012264602B2 (en) | 2011-06-01 | 2012-06-01 | Process for the production of estetrol intermediates |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US11053274B2 (enExample) |
| EP (1) | EP2714710B1 (enExample) |
| JP (2) | JP6425540B2 (enExample) |
| KR (1) | KR101994805B1 (enExample) |
| CN (2) | CN107266514A (enExample) |
| AU (1) | AU2012264602B2 (enExample) |
| BR (1) | BR112013030830B1 (enExample) |
| CA (1) | CA2835981C (enExample) |
| CY (1) | CY1118150T1 (enExample) |
| DK (1) | DK2714710T3 (enExample) |
| EA (1) | EA023991B1 (enExample) |
| ES (1) | ES2579175T3 (enExample) |
| HR (1) | HRP20160692T2 (enExample) |
| HU (1) | HUE029252T2 (enExample) |
| ME (1) | ME02454B (enExample) |
| MX (1) | MX341561B (enExample) |
| PL (1) | PL2714710T3 (enExample) |
| PT (1) | PT2714710T (enExample) |
| RS (1) | RS54880B1 (enExample) |
| SG (1) | SG195118A1 (enExample) |
| SI (1) | SI2714710T1 (enExample) |
| SM (1) | SMT201600206B (enExample) |
| WO (1) | WO2012164096A1 (enExample) |
| ZA (1) | ZA201308446B (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2012264601C1 (en) | 2011-06-01 | 2018-01-25 | Estetra Srl | Process for the production of estetrol intermediates |
| PT2714710T (pt) | 2011-06-01 | 2016-07-12 | Estetra Sprl | Processo para a produção de intermediários de estetrol |
| EP2383279A1 (en) | 2011-07-19 | 2011-11-02 | Pantarhei Bioscience B.V. | Process for the preparation of estetrol |
| EP2764008B1 (en) | 2011-10-07 | 2016-08-17 | Estetra S.P.R.L. | Process for the production of estetrol |
| HUE054589T2 (hu) | 2015-06-18 | 2021-09-28 | Estetra Sprl | Szájban diszpergálódó esztetrol tartalmú tabletta |
| MY195019A (en) | 2015-06-18 | 2023-01-03 | Estetra Sprl | Orodispersible dosage unit containing an estetrol component |
| MD3310346T2 (ro) | 2015-06-18 | 2021-06-30 | Estetra Sprl | Comprimată orodispersabilă ce conține estetrol |
| JP6866560B2 (ja) | 2015-06-18 | 2021-04-28 | エステトラ ソシエテ プリーヴ ア レスポンサビリテ リミテ | エステトロール成分を含有する口腔内崩壊性投与単位 |
| CN105837424A (zh) * | 2016-03-31 | 2016-08-10 | 常州大学 | 一种1-氯-3-甲基-3-丁烯-2-酮的合成方法 |
| KR102712911B1 (ko) | 2016-08-05 | 2024-10-04 | 에스테트라, 소시에떼 아 레스폰서빌리떼 리미떼 | 월경통 및 생리통의 관리방법 |
| JP6935766B2 (ja) | 2018-02-15 | 2021-09-15 | 日本精工株式会社 | スピンドル装置 |
| TWI801561B (zh) | 2018-04-19 | 2023-05-11 | 比利時商依思特拉私人有限責任公司 | 化合物及其用於緩解絕經相關症狀的用途 |
| JOP20200260A1 (ar) | 2018-04-19 | 2019-10-19 | Estetra Sprl | مركبات واستخداماتها للتخفيف من الأعراض المصاحبة لانقطاع الطمث |
| ES2948324R1 (es) | 2019-09-27 | 2025-09-11 | Ind Chimica Srl | Proceso para preparar (15alfa,16alfa,17beta)-estra-1,3,5(10)-trieno-3,15,16,17-tetrol monohidrato (Estetrol monohidrato) |
| IT201900021879A1 (it) | 2019-11-22 | 2021-05-22 | Ind Chimica Srl | PROCESSO PER LA PREPARAZIONE DI (15α,16α,17β)-ESTRA-1,3,5(10)-TRIENE-3,15,16,17-TETROLO (ESTETROLO) ED INTERMEDI DI DETTO PROCESSO |
| IT201900017414A1 (it) | 2019-09-27 | 2021-03-27 | Ind Chimica Srl | Processo per la preparazione di (15α,16α,17β)-estra-1,3,5(10)-triene-3,15,16,17-tetrolo (Estetrolo) ed intermedi di detto processo |
| TWI893101B (zh) | 2020-04-16 | 2025-08-11 | 比利時商埃斯特拉有限責任公司 | 具有降低之副作用之避孕組成物 |
| WO2023021026A1 (en) | 2021-08-17 | 2023-02-23 | Aspen Oss B.V. | A synthetic pathway to estra-1,3,5(10)-triene-3,15a,16a,17b-tetrol |
| ES2976651B2 (es) | 2021-10-01 | 2025-12-05 | Ind Chimica Srl | PROCESO PARA PREPARAR (15alfa,16alfa,17beta)-ESTRA-1,3,5(10)-TRIENO-3,15,16,17-TETROL (ESTETROL) Y ESTETROL MONOHIDRATO |
| AU2023428138A1 (en) | 2023-02-02 | 2025-09-04 | Industriale Chimica S.R.L. | PROCESS FOR PREPARING (15α,16α,17β)-ESTRA-1,3,5(10)-TRIENE-3,15,16,17-TETROL (ESTETROL) MONOHYDRATE |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004041839A2 (en) * | 2002-11-08 | 2004-05-21 | Pantarhei Bioscience B.V. | Synthesis of estetrol via estrone derived steroids |
| EP2383279A1 (en) * | 2011-07-19 | 2011-11-02 | Pantarhei Bioscience B.V. | Process for the preparation of estetrol |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE144266C (enExample) | ||||
| US3138588A (en) | 1962-08-24 | 1964-06-23 | American Home Prod | 17-ketals of estrone and derivatives thereof |
| US3177206A (en) | 1963-03-07 | 1965-04-06 | American Home Prod | Selective bromination of a-ring aromatic 17-ketalized steroids |
| US3433785A (en) | 1966-07-11 | 1969-03-18 | Sterling Drug Inc | 15,16-disubstituted aromatic steroids,intermediates and processes |
| US3673180A (en) | 1970-06-18 | 1972-06-27 | Merck & Co Inc | 19-nor-6,6-ethylene-20-spiroxenes |
| US4792620A (en) | 1983-10-14 | 1988-12-20 | Bp Chemicals Limited | Carbonylation catalysts |
| US4739078A (en) | 1984-02-17 | 1988-04-19 | The Upjohn Company | Use of borohydride-salt lanthanide salt reagents for stereo selective reduction of C-15-keto prostaglandin precursors |
| IE60780B1 (en) | 1987-01-23 | 1994-08-10 | Akzo Nv | New 11-aryl steroid derivatives |
| DE3710728A1 (de) | 1987-03-31 | 1988-10-13 | Schering Ag | Verfahren zur herstellung von 17(alpha)-ethinyl-17ss-hydroxy-18-methyl-4,15-estradien-3-on und die neuen zwischenprodukte fuer dieses verfahren |
| US5073374A (en) | 1988-11-30 | 1991-12-17 | Schering Corporation | Fast dissolving buccal tablet |
| US5340586A (en) | 1991-04-12 | 1994-08-23 | University Of Southern California | Methods and formulations for use in treating oophorectomized women |
| JPH07101977A (ja) | 1993-10-05 | 1995-04-18 | Kureha Chem Ind Co Ltd | ホルモン作用を軽減した新規なエストラジオール誘導体及びその増殖因子阻害剤 |
| WO1997004752A1 (en) | 1995-07-26 | 1997-02-13 | Duramed Pharmaceuticals, Inc. | Pharmaceutical compositions of conjugated estrogens and methods for their use |
| US6117446A (en) | 1999-01-26 | 2000-09-12 | Place; Virgil A. | Drug dosage unit for buccal administration of steroidal active agents |
| TW548277B (en) | 1999-07-16 | 2003-08-21 | Akzo Nobel Nv | Orally active androgens |
| US20020132801A1 (en) | 2001-01-11 | 2002-09-19 | Schering Aktiengesellschaft | Drospirenone for hormone replacement therapy |
| EP1260225A1 (en) | 2001-05-18 | 2002-11-27 | Pantarhei Bioscience B.V. | A pharmaceutical composition for use in hormone replacement therapy |
| US8048869B2 (en) | 2001-05-18 | 2011-11-01 | Pantarhei Bioscience B.V. | Pharmaceutical composition for use in hormone replacement therapy |
| DK1390042T3 (da) | 2001-05-23 | 2008-03-31 | Pantarhei Bioscience Bv | System for administration af et lægemiddel omfattende tetrahydroxyleret östrogen til anvendelse i hormonal svangerskabsforebyggelse |
| EP1390041B1 (en) | 2001-05-23 | 2009-11-25 | Pantarhei Bioscience B.V. | Drug delivery system comprising a tetrahydroxylated estrogen for use in hormonal contraception |
| WO2003018026A1 (en) | 2001-08-31 | 2003-03-06 | Pantarhei Bioscience B.V. | Use of estrogenic compounds in combination with progestogenic compounds in hormone-replacement therapy |
| CA2467222C (en) | 2001-11-15 | 2010-06-08 | Herman Jan Tijmen Coelingh Bennink | Use of estrogenic compounds in combination with progestogenic compounds in hormone-replacement therapy |
| US6723348B2 (en) | 2001-11-16 | 2004-04-20 | Ethypharm | Orodispersible tablets containing fexofenadine |
| HU227198B1 (en) | 2001-11-27 | 2010-10-28 | Richter Gedeon Nyrt | Pharmaceutical composition for emergency contraception containing levonorgestrel |
| CA2476940C (en) | 2002-02-21 | 2011-11-01 | Herman Jan Tijmen Coelingh Bennink | Pharmaceutical compositions comprising one or more steroids, one or more tetrahydrofolate components and vitamin b12 |
| US20050147670A1 (en) | 2002-05-29 | 2005-07-07 | Impax Laboratories Inc. | Oral disintegrating dosage forms |
| US7943604B2 (en) | 2002-06-11 | 2011-05-17 | Pantarhei Bioscience B.V. | Method of treating human skin and a skin care composition for use in such a method |
| CN1691947B (zh) | 2002-06-11 | 2011-11-23 | 潘塔希生物科学股份有限公司 | 雌激素成分在制备用于治疗或预防免疫介导的疾病中的应用以及包含所述雌激素成分的药物组合物 |
| CA2492287C (en) | 2002-07-12 | 2011-12-13 | Pantarhei Bioscience B.V. | Pharmaceutical composition comprising estetrol derivatives for use in cancer therapy |
| CN100528167C (zh) | 2002-10-23 | 2009-08-19 | 潘塔希生物科学股份有限公司 | 用于治疗癌症的包含雌四醇衍生物的药物组合物 |
| DK1624878T3 (da) | 2003-05-22 | 2007-01-08 | Pantarhei Bioscience Bv | Anvendelse af præparater som omfatter en östrogen komponent til behandling og forebyggelse af muskel-skelet-smerte |
| JP5268635B2 (ja) | 2005-05-26 | 2013-08-21 | アボット プロダクツ ゲゼルシャフト ミット ベシュレンクテル ハフツング | １７β−ＨＳＤ１及びＳＴＳインヒビター |
| EP2077322B1 (de) | 2005-07-25 | 2010-08-25 | RiboxX GmbH | Verfahren und Kit zur Amplifikation von heteropolymerer oder poly(C)- RNA |
| US20070048369A1 (en) | 2005-08-26 | 2007-03-01 | National Starch And Chemical Investment Holding Corporation | Mucosal delivery tablet |
| CA2636638C (en) | 2006-01-09 | 2014-02-18 | Pantarhei Bioscience B.V. | A method of treating an acute vascular disorder |
| US20070286819A1 (en) | 2006-06-08 | 2007-12-13 | Warner Chilcott Company, Inc. | Methods to administer ethinyl estradiol and prodrugs thereof with improved bioavailability |
| ES2659316T3 (es) | 2006-06-08 | 2018-03-14 | Allergan Pharmaceuticals International Limited | Procedimientos para administrar formas de dosificación sólidas de etinilestradiol y profármacos del mismo con biodisponibilidad mejorada |
| US20080113953A1 (en) | 2006-06-08 | 2008-05-15 | Warner Chilcott Company, Inc. | Methods to administer solid dosage forms of ethinyl estradiol and prodrugs thereof with improved bioavailability |
| GB0621926D0 (en) | 2006-11-03 | 2006-12-13 | Medlock Medical Ltd | Multi directional stretch tubular bandages |
| CA2670544A1 (en) | 2006-11-29 | 2008-06-05 | Wyeth | Estrogen/ serm and estrogen/ progestin bi-layer tablets |
| CA2674776A1 (en) | 2006-12-20 | 2008-07-03 | Duramed Pharmaceuticals, Inc. | Orally disintegrating solid dosage forms comprising progestin and methods of making and use thereof |
| US8236785B2 (en) | 2007-01-08 | 2012-08-07 | Pantarhei Bioscience B.V. | Method of treating or preventing infertility in a female mammal and pharmaceutical kit for use in such method |
| PE20081632A1 (es) | 2007-01-12 | 2008-12-10 | Wyeth Corp | Composiciones de tableta en tableta |
| CN102014924B (zh) | 2007-06-21 | 2012-07-18 | 潘塔希生物科学股份有限公司 | 用雌激素治疗胎粪吸入综合征 |
| WO2009011576A1 (en) | 2007-07-19 | 2009-01-22 | Pantarhei Bioscience B.V. | Treatment or prevention of hypertensive disorders of pregnancy or fetal growth retardation |
| EP2085373B8 (en) | 2007-08-31 | 2013-06-26 | National University Corporation Nagoya University | Method for producing carbonyl compound and pro-oxidant used for production of carbonyl compound |
| EP2077272A1 (en) | 2007-12-21 | 2009-07-08 | Affibody AB | Polypeptide libraries with a predetermined scaffold |
| EP2077273B1 (en) | 2007-12-31 | 2011-09-14 | Animal Technology Institute Taiwan | Methods for separating casein from soluble proteins in a composition |
| US20110250274A1 (en) | 2008-09-19 | 2011-10-13 | Shaked Ze Ev | Estriol formulations |
| DE102009007771B4 (de) | 2009-02-05 | 2012-02-16 | Bayer Schering Pharma Aktiengesellschaft | Bukkales Applikationssystem, 17α-Estradiol enthaltend |
| CN102058604A (zh) | 2009-11-17 | 2011-05-18 | 北京万全阳光医学技术有限公司 | 一种含有地诺孕素和戊酸雌二醇的药物组合物及其制备方法 |
| US9603860B2 (en) | 2010-07-28 | 2017-03-28 | Laboratorios Leon Farma Sa | Pharmaceutical compositions comprising active drugs, contraceptive kits comprising active drugs, and methods of administering the same |
| AU2012264601C1 (en) | 2011-06-01 | 2018-01-25 | Estetra Srl | Process for the production of estetrol intermediates |
| PT2714710T (pt) | 2011-06-01 | 2016-07-12 | Estetra Sprl | Processo para a produção de intermediários de estetrol |
| WO2013012326A1 (en) | 2011-07-19 | 2013-01-24 | Pantarhei Bioscience B.V. | Tablet containing dehydroepiandrosterone (dhea) |
| HRP20170797T1 (hr) | 2011-08-11 | 2017-08-11 | Estetra S.P.R.L. | Primjena estetrola kao hitnog kontraceptiva |
| NZ620897A (en) | 2011-09-16 | 2016-07-29 | Ferring Bv | A fast dissolving pharmaceutical composition |
| EP2764008B1 (en) | 2011-10-07 | 2016-08-17 | Estetra S.P.R.L. | Process for the production of estetrol |
| EP2653163A1 (en) | 2012-04-19 | 2013-10-23 | Université de Liège | Estrogenic components for use in the treatment of neurological disorders |
| US9808470B2 (en) | 2012-04-19 | 2017-11-07 | Universite De Liege | Estrogenic components for use in the treatment of neurological disorders |
| WO2014159377A1 (en) | 2013-03-14 | 2014-10-02 | Teva Women's Health, Inc. | Compositions containing tanaproget and natural estrogens |
| CA2924255C (en) | 2013-09-18 | 2022-11-22 | Crystal Pharma, S.A.U. | Process for the preparation of estetrol |
| KR102265150B1 (ko) | 2013-12-12 | 2021-06-16 | 에스테트라 에스.피.알.엘. | 에스테트롤 성분을 함유하는 구강 붕해성 고체 투여 단위 |
| MY195019A (en) | 2015-06-18 | 2023-01-03 | Estetra Sprl | Orodispersible dosage unit containing an estetrol component |
| MD3310346T2 (ro) | 2015-06-18 | 2021-06-30 | Estetra Sprl | Comprimată orodispersabilă ce conține estetrol |
| HUE054589T2 (hu) | 2015-06-18 | 2021-09-28 | Estetra Sprl | Szájban diszpergálódó esztetrol tartalmú tabletta |
| JP6866560B2 (ja) | 2015-06-18 | 2021-04-28 | エステトラ ソシエテ プリーヴ ア レスポンサビリテ リミテ | エステトロール成分を含有する口腔内崩壊性投与単位 |
-
2012
- 2012-06-01 PT PT127290542T patent/PT2714710T/pt unknown
- 2012-06-01 EP EP12729054.2A patent/EP2714710B1/en active Active
- 2012-06-01 KR KR1020137031483A patent/KR101994805B1/ko active Active
- 2012-06-01 CN CN201710354709.5A patent/CN107266514A/zh active Pending
- 2012-06-01 CN CN201280026162.1A patent/CN103703014A/zh active Pending
- 2012-06-01 RS RS20160478A patent/RS54880B1/sr unknown
- 2012-06-01 US US14/122,872 patent/US11053274B2/en active Active
- 2012-06-01 SG SG2013086681A patent/SG195118A1/en unknown
- 2012-06-01 HU HUE12729054A patent/HUE029252T2/en unknown
- 2012-06-01 SI SI201230598A patent/SI2714710T1/sl unknown
- 2012-06-01 ME MEP-2016-130A patent/ME02454B/me unknown
- 2012-06-01 JP JP2014513214A patent/JP6425540B2/ja active Active
- 2012-06-01 MX MX2013014045A patent/MX341561B/es active IP Right Grant
- 2012-06-01 AU AU2012264602A patent/AU2012264602B2/en active Active
- 2012-06-01 PL PL12729054T patent/PL2714710T3/pl unknown
- 2012-06-01 HR HRP20160692TT patent/HRP20160692T2/hr unknown
- 2012-06-01 DK DK12729054.2T patent/DK2714710T3/en active
- 2012-06-01 ES ES12729054.2T patent/ES2579175T3/es active Active
- 2012-06-01 CA CA2835981A patent/CA2835981C/en active Active
- 2012-06-01 EA EA201301316A patent/EA023991B1/ru unknown
- 2012-06-01 WO PCT/EP2012/060447 patent/WO2012164096A1/en not_active Ceased
- 2012-06-01 BR BR112013030830A patent/BR112013030830B1/pt active IP Right Grant
-
2013
- 2013-11-11 ZA ZA2013/08446A patent/ZA201308446B/en unknown
-
2016
- 2016-06-15 CY CY20161100525T patent/CY1118150T1/el unknown
- 2016-06-30 SM SM201600206T patent/SMT201600206B/it unknown
-
2017
- 2017-08-10 JP JP2017155801A patent/JP6479912B2/ja active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004041839A2 (en) * | 2002-11-08 | 2004-05-21 | Pantarhei Bioscience B.V. | Synthesis of estetrol via estrone derived steroids |
| EP2383279A1 (en) * | 2011-07-19 | 2011-11-02 | Pantarhei Bioscience B.V. | Process for the preparation of estetrol |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2012264602B2 (en) | Process for the production of estetrol intermediates | |
| AU2012264602A1 (en) | Process for the production of estetrol intermediates | |
| AU2012320423B2 (en) | Process for the production of estetrol | |
| CN103781795B (zh) | 用于制备雌四醇的方法 | |
| AU2012264601B2 (en) | Process for the production of estetrol intermediates | |
| NZ617613B2 (en) | Process for the production of estetrol intermediates | |
| HK1245281A1 (en) | Process for the production of estetrol intermediates | |
| NZ621973B2 (en) | Process for the production of estetrol | |
| HK1199882B (en) | Process for the production of estetrol | |
| NZ617591B2 (en) | Process for the production of estetrol intermediates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| PC | Assignment registered |
Owner name: MITHRA R&D SA Free format text: FORMER OWNER(S): ESTETRA S.P.R.L |
|
| PC | Assignment registered |
Owner name: ESTETRA SRL Free format text: FORMER OWNER(S): MITHRA R&D SA |