DE2101595A1 - Neue Acylderivate des Digoxins und Verfahren zu deren Herstellung - Google Patents
Neue Acylderivate des Digoxins und Verfahren zu deren HerstellungInfo
- Publication number
- DE2101595A1 DE2101595A1 DE19712101595 DE2101595A DE2101595A1 DE 2101595 A1 DE2101595 A1 DE 2101595A1 DE 19712101595 DE19712101595 DE 19712101595 DE 2101595 A DE2101595 A DE 2101595A DE 2101595 A1 DE2101595 A1 DE 2101595A1
- Authority
- DE
- Germany
- Prior art keywords
- digoxin
- general formula
- given above
- meaning given
- digoxine
- 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.)
- Pending
Links
- 229960005156 digoxin Drugs 0.000 title claims description 44
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 title claims description 31
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 title claims description 24
- 238000000034 method Methods 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title claims description 6
- 125000002252 acyl group Chemical group 0.000 title claims 2
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical class C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 claims description 29
- 238000004519 manufacturing process Methods 0.000 claims description 11
- -1 cycloalkyl radical Chemical class 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 150000002905 orthoesters Chemical class 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 230000000707 stereoselective effect Effects 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
- 150000005840 aryl radicals Chemical class 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 claims 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 239000000829 suppository Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000011260 aqueous acid Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940085034 digoxin 0.25 mg Drugs 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 235000020094 liqueur Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- KOPMZTKUZCNGFY-UHFFFAOYSA-N 1,1,1-triethoxybutane Chemical compound CCCC(OCC)(OCC)OCC KOPMZTKUZCNGFY-UHFFFAOYSA-N 0.000 description 1
- FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical class OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229910052787 antimony Inorganic materials 0.000 description 1
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 150000001727 carbonic acid monoesters Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940096529 carboxypolymethylene Drugs 0.000 description 1
- 229940097217 cardiac glycoside Drugs 0.000 description 1
- 239000002368 cardiac glycoside Substances 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229940085080 digoxin 0.125 mg Drugs 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229960003343 ouabain Drugs 0.000 description 1
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
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- 230000009090 positive inotropic effect Effects 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
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- 238000001556 precipitation Methods 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229930002534 steroid glycoside Natural products 0.000 description 1
- 150000008143 steroidal glycosides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical group COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- 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
- A61K31/075—Ethers or acetals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (29)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712101595 DE2101595A1 (de) | 1971-01-14 | 1971-01-14 | Neue Acylderivate des Digoxins und Verfahren zu deren Herstellung |
| BG022617A BG18877A3 (bg) | 1971-01-14 | 1972-01-03 | Метод за получаване на анилинови производни на дитоксина |
| US00215666A US3804825A (en) | 1971-01-14 | 1972-01-05 | Carboxylic acyl derivatives of digoxin |
| BG019442A BG18190A3 (bg) | 1971-01-14 | 1972-01-11 | Метод за получаване на ацилови производни на дигоксина |
| HUBO1345A HU162743B (enExample) | 1971-01-14 | 1972-01-12 | |
| SE7200327A SE379048B (enExample) | 1971-01-14 | 1972-01-12 | |
| NL7200446A NL7200446A (enExample) | 1971-01-14 | 1972-01-12 | |
| PH13181A PH10692A (en) | 1971-01-14 | 1972-01-12 | Carboxylic acyl derivatives of digoxin |
| ES398804A ES398804A1 (es) | 1971-01-14 | 1972-01-12 | Procedimiento para la preparacion de nuevos derivados aci- licos de la digoxina. |
| AU37868/72A AU465777B2 (en) | 1971-01-14 | 1972-01-13 | Digoxin analogues |
| FI720070A FI51359C (fi) | 1971-01-14 | 1972-01-13 | Menetelmä digoksiinin alfa-asyylijohdannaisten valmistamiseksi. |
| PL1972152879A PL82940B1 (enExample) | 1971-01-14 | 1972-01-13 | |
| DK16872AA DK126938B (da) | 1971-01-14 | 1972-01-13 | Analogifremgangsmåde til fremstilling af α-acylderivater af digoxin. |
| CH46072A CH571025A5 (enExample) | 1971-01-14 | 1972-01-13 | |
| CA132,333A CA962665A (en) | 1971-01-14 | 1972-01-13 | Acyl derivatives of the digoxin and process for the production thereof |
| IL38550A IL38550A (en) | 1971-01-14 | 1972-01-13 | Noble history of digoxin and process for their production |
| BE778014A BE778014A (fr) | 1971-01-14 | 1972-01-13 | Nouveaux derives acyles de la digoxine et procedes de fabrication |
| CS230A CS178403B2 (enExample) | 1971-01-14 | 1972-01-13 | |
| ZA720241A ZA72241B (en) | 1971-01-14 | 1972-01-13 | Improvements relating to acyl derivatives of digoxin |
| CH720075A CH575435A5 (enExample) | 1971-01-14 | 1972-01-13 | |
| GB172972A GB1371937A (en) | 1971-01-14 | 1972-01-13 | Digoxin analogues |
| RO7271661A RO68217A (ro) | 1971-01-14 | 1972-01-14 | Procedeu pentru prepararea unor derivati de acil ai digoxinei |
| RO7200069393A RO62477A (fr) | 1971-01-14 | 1972-01-14 | Procede pour la preparation des derives d'acide du digoxine |
| IE55/72A IE36060B1 (en) | 1971-01-14 | 1972-01-14 | Acyl derivatives of digoxin |
| SU1737660A SU511015A3 (ru) | 1971-01-14 | 1972-01-14 | Способ получени ацилпроизводных дигоксина |
| FR7201256A FR2121851B1 (enExample) | 1971-01-14 | 1972-01-14 | |
| AT32772A AT317444B (de) | 1971-01-14 | 1972-01-14 | Verfahren zur Herstellung von neuen Acylderivaten des Digoxins |
| ES401836A ES401836A1 (es) | 1971-01-14 | 1972-04-17 | Procedimiento para la preparacion de nuevos derivados aci- licos de la digoxina. |
| US05/433,663 US3932626A (en) | 1971-01-14 | 1974-01-16 | Pharmaceutical compositions containing a carboxylic acyl derivative of digoxin and method of use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712101595 DE2101595A1 (de) | 1971-01-14 | 1971-01-14 | Neue Acylderivate des Digoxins und Verfahren zu deren Herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2101595A1 true DE2101595A1 (de) | 1972-07-27 |
Family
ID=5795884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19712101595 Pending DE2101595A1 (de) | 1971-01-14 | 1971-01-14 | Neue Acylderivate des Digoxins und Verfahren zu deren Herstellung |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US3804825A (enExample) |
| AT (1) | AT317444B (enExample) |
| AU (1) | AU465777B2 (enExample) |
| BE (1) | BE778014A (enExample) |
| BG (2) | BG18877A3 (enExample) |
| CA (1) | CA962665A (enExample) |
| CH (2) | CH571025A5 (enExample) |
| CS (1) | CS178403B2 (enExample) |
| DE (1) | DE2101595A1 (enExample) |
| DK (1) | DK126938B (enExample) |
| ES (2) | ES398804A1 (enExample) |
| FI (1) | FI51359C (enExample) |
| FR (1) | FR2121851B1 (enExample) |
| GB (1) | GB1371937A (enExample) |
| HU (1) | HU162743B (enExample) |
| IE (1) | IE36060B1 (enExample) |
| IL (1) | IL38550A (enExample) |
| NL (1) | NL7200446A (enExample) |
| PH (1) | PH10692A (enExample) |
| PL (1) | PL82940B1 (enExample) |
| RO (2) | RO68217A (enExample) |
| SE (1) | SE379048B (enExample) |
| SU (1) | SU511015A3 (enExample) |
| ZA (1) | ZA72241B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3987031A (en) * | 1970-12-23 | 1976-10-19 | Boehringer Ingelheim Gmbh | Acyl derivatives of proscillaridin a |
| DE2354119A1 (de) * | 1973-10-29 | 1975-05-15 | Boehringer Sohn Ingelheim | Neue orthoformiatderivate des digitoxins, verfahren zu deren herstellung sowie diese enthaltende arzneimittel |
| US3884905A (en) * | 1974-05-02 | 1975-05-20 | Interx Research Corp | Pro-drug forms of digoxin |
| US4021535A (en) * | 1975-01-14 | 1977-05-03 | Beckman Instruments, Inc. | Reagents used in the radioimmunoassay of digoxin |
| EP1202056A1 (en) * | 2000-10-30 | 2002-05-02 | Vrije Universiteit Amsterdam | Continuous-flow homogeneous bio-chemical assays based on mass spectrometric detection of known ligands |
| CN112552367B (zh) * | 2020-12-11 | 2023-06-06 | 郑州安图生物工程股份有限公司 | 一种地高辛衍生物及其制备方法 |
-
1971
- 1971-01-14 DE DE19712101595 patent/DE2101595A1/de active Pending
-
1972
- 1972-01-03 BG BG022617A patent/BG18877A3/xx unknown
- 1972-01-05 US US00215666A patent/US3804825A/en not_active Expired - Lifetime
- 1972-01-11 BG BG019442A patent/BG18190A3/xx unknown
- 1972-01-12 HU HUBO1345A patent/HU162743B/hu unknown
- 1972-01-12 NL NL7200446A patent/NL7200446A/xx unknown
- 1972-01-12 ES ES398804A patent/ES398804A1/es not_active Expired
- 1972-01-12 SE SE7200327A patent/SE379048B/xx unknown
- 1972-01-12 PH PH13181A patent/PH10692A/en unknown
- 1972-01-13 FI FI720070A patent/FI51359C/fi active
- 1972-01-13 ZA ZA720241A patent/ZA72241B/xx unknown
- 1972-01-13 DK DK16872AA patent/DK126938B/da unknown
- 1972-01-13 CH CH46072A patent/CH571025A5/xx not_active IP Right Cessation
- 1972-01-13 IL IL38550A patent/IL38550A/en unknown
- 1972-01-13 CS CS230A patent/CS178403B2/cs unknown
- 1972-01-13 PL PL1972152879A patent/PL82940B1/pl unknown
- 1972-01-13 CH CH720075A patent/CH575435A5/xx not_active IP Right Cessation
- 1972-01-13 CA CA132,333A patent/CA962665A/en not_active Expired
- 1972-01-13 AU AU37868/72A patent/AU465777B2/en not_active Expired
- 1972-01-13 GB GB172972A patent/GB1371937A/en not_active Expired
- 1972-01-13 BE BE778014A patent/BE778014A/xx unknown
- 1972-01-14 FR FR7201256A patent/FR2121851B1/fr not_active Expired
- 1972-01-14 AT AT32772A patent/AT317444B/de not_active IP Right Cessation
- 1972-01-14 IE IE55/72A patent/IE36060B1/xx unknown
- 1972-01-14 SU SU1737660A patent/SU511015A3/ru active
- 1972-01-14 RO RO7271661A patent/RO68217A/ro unknown
- 1972-01-14 RO RO7200069393A patent/RO62477A/ro unknown
- 1972-04-17 ES ES401836A patent/ES401836A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| CS178403B2 (enExample) | 1977-09-15 |
| AU3786872A (en) | 1973-07-19 |
| FI51359B (enExample) | 1976-08-31 |
| ZA72241B (en) | 1973-09-26 |
| CH571025A5 (enExample) | 1975-12-31 |
| FI51359C (fi) | 1976-12-10 |
| PH10692A (en) | 1977-08-10 |
| ES398804A1 (es) | 1974-08-16 |
| BG18190A3 (bg) | 1974-09-02 |
| NL7200446A (enExample) | 1972-07-18 |
| RO68217A (ro) | 1982-02-26 |
| IE36060L (en) | 1972-07-14 |
| HU162743B (enExample) | 1973-04-28 |
| IE36060B1 (en) | 1976-08-04 |
| SE379048B (enExample) | 1975-09-22 |
| IL38550A (en) | 1974-11-29 |
| FR2121851A1 (enExample) | 1972-08-25 |
| GB1371937A (en) | 1974-10-30 |
| PL82940B1 (enExample) | 1975-10-31 |
| IL38550A0 (en) | 1972-03-28 |
| RO62477A (fr) | 1978-03-15 |
| CH575435A5 (enExample) | 1976-05-14 |
| DK126938B (da) | 1973-09-03 |
| BG18877A3 (bg) | 1975-03-20 |
| AT317444B (de) | 1974-08-26 |
| BE778014A (fr) | 1972-07-13 |
| US3804825A (en) | 1974-04-16 |
| SU511015A3 (ru) | 1976-04-15 |
| ES401836A1 (es) | 1975-03-16 |
| AU465777B2 (en) | 1975-10-09 |
| CA962665A (en) | 1975-02-11 |
| FR2121851B1 (enExample) | 1975-10-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OHJ | Non-payment of the annual fee |