DE2710293C2 - Estramustinphosphat-Komplexverbindungen und Verfahren zur Reinigung von Estramustinphosphat oder von dessen wasserlöslichen Salzen - Google Patents
Estramustinphosphat-Komplexverbindungen und Verfahren zur Reinigung von Estramustinphosphat oder von dessen wasserlöslichen SalzenInfo
- Publication number
- DE2710293C2 DE2710293C2 DE2710293A DE2710293A DE2710293C2 DE 2710293 C2 DE2710293 C2 DE 2710293C2 DE 2710293 A DE2710293 A DE 2710293A DE 2710293 A DE2710293 A DE 2710293A DE 2710293 C2 DE2710293 C2 DE 2710293C2
- Authority
- DE
- Germany
- Prior art keywords
- estramustine phosphate
- salt
- water
- complex
- alcohol
- 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.)
- Expired
Links
- ADFOJJHRTBFFOF-RBRWEJTLSA-N estramustine phosphate Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)OP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 ADFOJJHRTBFFOF-RBRWEJTLSA-N 0.000 title claims description 69
- 229960004750 estramustine phosphate Drugs 0.000 title claims description 66
- 150000003839 salts Chemical class 0.000 title claims description 25
- 150000001875 compounds Chemical class 0.000 title claims description 21
- 238000000034 method Methods 0.000 title claims description 19
- 238000000746 purification Methods 0.000 title claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 71
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 19
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 16
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 11
- 239000011734 sodium Substances 0.000 claims description 10
- 229910052708 sodium Inorganic materials 0.000 claims description 10
- 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 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 8
- IIUMCNJTGSMNRO-VVSKJQCTSA-L estramustine sodium phosphate Chemical class [Na+].[Na+].ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)OP([O-])([O-])=O)[C@@H]4[C@@H]3CCC2=C1 IIUMCNJTGSMNRO-VVSKJQCTSA-L 0.000 claims description 7
- 239000002244 precipitate Substances 0.000 claims description 6
- 159000000000 sodium salts Chemical class 0.000 claims description 6
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 5
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 5
- 239000012535 impurity Substances 0.000 claims description 3
- 150000003222 pyridines Chemical class 0.000 claims description 2
- 229960001842 estramustine Drugs 0.000 claims 2
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 claims 2
- 230000009918 complex formation Effects 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000002425 crystallisation Methods 0.000 description 12
- 230000008025 crystallization Effects 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- QPRQEDXDYOZYLA-UHFFFAOYSA-N 2-methylbutan-1-ol Chemical compound CCC(C)CO QPRQEDXDYOZYLA-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000004817 gas chromatography Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- -1 estramustine phosphate alcohol complexes Chemical class 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- MXLMTQWGSQIYOW-UHFFFAOYSA-N 3-methyl-2-butanol Chemical compound CC(C)C(C)O MXLMTQWGSQIYOW-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- ZOCHHNOQQHDWHG-UHFFFAOYSA-N hexan-3-ol Chemical compound CCCC(O)CC ZOCHHNOQQHDWHG-UHFFFAOYSA-N 0.000 description 6
- SJWFXCIHNDVPSH-UHFFFAOYSA-N octan-2-ol Chemical compound CCCCCCC(C)O SJWFXCIHNDVPSH-UHFFFAOYSA-N 0.000 description 6
- JYVLIDXNZAXMDK-UHFFFAOYSA-N pentan-2-ol Chemical compound CCCC(C)O JYVLIDXNZAXMDK-UHFFFAOYSA-N 0.000 description 6
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- BKQICAFAUMRYLZ-UHFFFAOYSA-N 4-methylheptan-3-ol Chemical compound CCCC(C)C(O)CC BKQICAFAUMRYLZ-UHFFFAOYSA-N 0.000 description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 4
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- RZKSECIXORKHQS-UHFFFAOYSA-N n-heptane-3-ol Natural products CCCCC(O)CC RZKSECIXORKHQS-UHFFFAOYSA-N 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- TZYRSLHNPKPEFV-UHFFFAOYSA-N 2-ethyl-1-butanol Chemical compound CCC(CC)CO TZYRSLHNPKPEFV-UHFFFAOYSA-N 0.000 description 3
- CETWDUZRCINIHU-UHFFFAOYSA-N 2-heptanol Chemical compound CCCCCC(C)O CETWDUZRCINIHU-UHFFFAOYSA-N 0.000 description 3
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
- 125000005907 alkyl ester group Chemical group 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 3
- QNVRIHYSUZMSGM-UHFFFAOYSA-N hexan-2-ol Chemical compound CCCCC(C)O QNVRIHYSUZMSGM-UHFFFAOYSA-N 0.000 description 3
- 229940032007 methylethyl ketone Drugs 0.000 description 3
- KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 0.000 description 3
- DFOXKPDFWGNLJU-UHFFFAOYSA-N pinacolyl alcohol Chemical compound CC(O)C(C)(C)C DFOXKPDFWGNLJU-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 2
- BAYAKMPRFGNNFW-UHFFFAOYSA-N 2,4-dimethylpentan-3-ol Chemical compound CC(C)C(O)C(C)C BAYAKMPRFGNNFW-UHFFFAOYSA-N 0.000 description 2
- YIWUKEYIRIRTPP-UHFFFAOYSA-N 2-ethylhexan-1-ol Chemical compound CCCCC(CC)CO YIWUKEYIRIRTPP-UHFFFAOYSA-N 0.000 description 2
- XKIRHOWVQWCYBT-UHFFFAOYSA-N 3-ethylpentan-3-ol Chemical compound CCC(O)(CC)CC XKIRHOWVQWCYBT-UHFFFAOYSA-N 0.000 description 2
- HTSABYAWKQAHBT-UHFFFAOYSA-N 3-methylcyclohexanol Chemical compound CC1CCCC(O)C1 HTSABYAWKQAHBT-UHFFFAOYSA-N 0.000 description 2
- MQWCXKGKQLNYQG-UHFFFAOYSA-N 4-methylcyclohexan-1-ol Chemical compound CC1CCC(O)CC1 MQWCXKGKQLNYQG-UHFFFAOYSA-N 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000003791 organic solvent mixture Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- OBETXYAYXDNJHR-SSDOTTSWSA-M (2r)-2-ethylhexanoate Chemical compound CCCC[C@@H](CC)C([O-])=O OBETXYAYXDNJHR-SSDOTTSWSA-M 0.000 description 1
- CFYUBZHJDXXXQE-UHFFFAOYSA-N 2-ethylcyclohexan-1-ol Chemical compound CCC1CCCCC1O CFYUBZHJDXXXQE-UHFFFAOYSA-N 0.000 description 1
- NDVWOBYBJYUSMF-UHFFFAOYSA-N 2-methylcyclohexan-1-ol Chemical compound CC1CCCCC1O NDVWOBYBJYUSMF-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- YVBCULSIZWMTFY-UHFFFAOYSA-N Heptan-4-ol Chemical compound CCCC(O)CCC YVBCULSIZWMTFY-UHFFFAOYSA-N 0.000 description 1
- 238000003109 Karl Fischer titration Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- SXBRULKJHUOQCD-UHFFFAOYSA-N propanoic acid Chemical compound CCC(O)=O.CCC(O)=O SXBRULKJHUOQCD-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9451/76A GB1523035A (en) | 1976-03-10 | 1976-03-10 | Derivatives of estradiol - 17 - dihydrogen phosphates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2710293A1 DE2710293A1 (de) | 1977-09-15 |
| DE2710293C2 true DE2710293C2 (de) | 1986-06-12 |
Family
ID=9872205
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2710293A Expired DE2710293C2 (de) | 1976-03-10 | 1977-03-09 | Estramustinphosphat-Komplexverbindungen und Verfahren zur Reinigung von Estramustinphosphat oder von dessen wasserlöslichen Salzen |
Country Status (17)
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2554005B2 (ja) * | 1993-02-18 | 1996-11-13 | 株式会社パーマケム・アジア | エストラムスチンフォスフェート又はその塩類の精製方法 |
| US6040255A (en) * | 1996-06-25 | 2000-03-21 | Kimberly-Clark Worldwide, Inc. | Photostabilization package usable in nonwoven fabrics and nonwoven fabrics containing same |
| US20040072889A1 (en) * | 1997-04-21 | 2004-04-15 | Pharmacia Corporation | Method of using a COX-2 inhibitor and an alkylating-type antineoplastic agent as a combination therapy in the treatment of neoplasia |
| GB9921958D0 (en) * | 1999-09-16 | 1999-11-17 | Pharmacia & Upjohn Spa | Formulations for parenteral use of estramustine phosphate and sulfoalkylether-cyclodextrins |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3299104A (en) | 1963-04-09 | 1967-01-17 | Leo Ab | Certain steroid nu-bis-(haloethyl)-carbamates |
| GB1458372A (en) * | 1973-03-05 | 1976-12-15 | Leo Ab | Steroid carbamates and allophanates |
-
1976
- 1976-03-10 GB GB9451/76A patent/GB1523035A/en not_active Expired
-
1977
- 1977-03-03 US US05/773,911 patent/US4115414A/en not_active Expired - Lifetime
- 1977-03-03 IL IL51592A patent/IL51592A/xx unknown
- 1977-03-08 SE SE7702613A patent/SE428928B/xx not_active IP Right Cessation
- 1977-03-09 BE BE175633A patent/BE852271A/xx not_active IP Right Cessation
- 1977-03-09 DK DK103577A patent/DK156007C/da not_active IP Right Cessation
- 1977-03-09 MX MX775524U patent/MX5242E/es unknown
- 1977-03-09 AT AT157777A patent/AT355737B/de not_active IP Right Cessation
- 1977-03-09 CA CA273,564A patent/CA1083140A/en not_active Expired
- 1977-03-09 IE IE523/77A patent/IE45024B1/en unknown
- 1977-03-09 DE DE2710293A patent/DE2710293C2/de not_active Expired
- 1977-03-10 CH CH304777A patent/CH633813A5/de not_active IP Right Cessation
- 1977-03-10 LU LU76927A patent/LU76927A1/xx unknown
- 1977-03-10 FR FR7707129A patent/FR2343752A1/fr active Granted
- 1977-03-10 JP JP2550877A patent/JPS52108963A/ja active Granted
- 1977-03-10 IT IT21129/77A patent/IT1075668B/it active
- 1977-03-10 NL NL7702608A patent/NL7702608A/xx not_active Application Discontinuation
-
1979
- 1979-12-25 JP JP16774779A patent/JPS5589300A/ja active Granted
Non-Patent Citations (1)
| Title |
|---|
| NICHTS-ERMITTELT |
Also Published As
| Publication number | Publication date |
|---|---|
| US4115414A (en) | 1978-09-19 |
| MX5242E (es) | 1983-05-16 |
| FR2343752B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1978-10-20 |
| AT355737B (de) | 1980-03-25 |
| IL51592A0 (en) | 1977-05-31 |
| ATA157777A (de) | 1979-08-15 |
| GB1523035A (en) | 1978-08-31 |
| DK103577A (da) | 1977-09-11 |
| JPS5526160B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1980-07-11 |
| CA1083140A (en) | 1980-08-05 |
| CH633813A5 (de) | 1982-12-31 |
| LU76927A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1978-10-18 |
| JPS52108963A (en) | 1977-09-12 |
| JPS5589300A (en) | 1980-07-05 |
| NL7702608A (nl) | 1977-09-13 |
| DK156007C (da) | 1989-11-06 |
| SE428928B (sv) | 1983-08-01 |
| IT1075668B (it) | 1985-04-22 |
| IE45024L (en) | 1977-09-10 |
| IE45024B1 (en) | 1982-06-02 |
| FR2343752A1 (fr) | 1977-10-07 |
| IL51592A (en) | 1980-09-16 |
| DE2710293A1 (de) | 1977-09-15 |
| SE7702613L (sv) | 1977-09-11 |
| BE852271A (fr) | 1977-09-09 |
| JPS5755720B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1982-11-25 |
| DK156007B (da) | 1989-06-12 |
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