DE2145476A1 - Neue cardenolidglykoside - Google Patents
Neue cardenolidglykosideInfo
- Publication number
- DE2145476A1 DE2145476A1 DE2145476A DE2145476A DE2145476A1 DE 2145476 A1 DE2145476 A1 DE 2145476A1 DE 2145476 A DE2145476 A DE 2145476A DE 2145476 A DE2145476 A DE 2145476A DE 2145476 A1 DE2145476 A1 DE 2145476A1
- Authority
- DE
- Germany
- Prior art keywords
- acid
- lower alkyl
- hydrogen atom
- reaction
- alkyl radical
- 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
- 239000002253 acid Substances 0.000 claims description 29
- 229960005156 digoxin Drugs 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 239000012442 inert solvent Substances 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- -1 cardenolide glycosides Chemical class 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 230000002378 acidificating effect Effects 0.000 claims description 8
- 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 claims description 8
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 claims description 7
- 239000002841 Lewis acid Substances 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 238000004587 chromatography analysis Methods 0.000 claims description 5
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 150000001350 alkyl halides Chemical class 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 4
- 238000005804 alkylation reaction Methods 0.000 claims description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 4
- 239000004327 boric acid Substances 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 4
- 150000008050 dialkyl sulfates Chemical class 0.000 claims description 4
- 150000007517 lewis acids Chemical class 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- 125000002723 alicyclic group Chemical group 0.000 claims description 3
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 3
- 239000011260 aqueous acid Substances 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 239000012024 dehydrating agents Substances 0.000 claims description 3
- 150000002500 ions Chemical class 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000000707 stereoselective effect Effects 0.000 claims description 3
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000009826 distribution Methods 0.000 claims description 2
- 229930182470 glycoside Natural products 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 238000007142 ring opening reaction Methods 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 2
- QVQLCTNNEUAWMS-UHFFFAOYSA-N barium oxide Chemical compound [Ba]=O QVQLCTNNEUAWMS-UHFFFAOYSA-N 0.000 claims 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims 2
- TYYDXNISHGVDGA-UHFFFAOYSA-N Corotoxigenin Natural products CC12CCC3C(CCC4CC(O)CCC34C=O)C1CCC2C5=CC(=O)OC5 TYYDXNISHGVDGA-UHFFFAOYSA-N 0.000 claims 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims 1
- 229910001863 barium hydroxide Inorganic materials 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- 238000005342 ion exchange Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products 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 15
- 239000000243 solution Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000000829 suppository Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229960003304 acetyldigoxin Drugs 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000013543 active substance Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 3
- MGVYFNHJWXJYBE-UHFFFAOYSA-N alpha-Acetyl-digoxin Natural products CC1OC(CC(O)C1O)OC2C(O)CC(OC3C(C)OC(CC3OC(=O)C)OC4CCC5(C)C(CCC6C5CCC7(C)C(C(O)CC67O)C8=CC(=O)OC8)C4)OC2C MGVYFNHJWXJYBE-UHFFFAOYSA-N 0.000 description 3
- 229910000365 copper sulfate Inorganic materials 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 239000012153 distilled water Substances 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
- 150000003254 radicals Chemical class 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 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 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 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
- 238000005907 ketalization reaction Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 235000020094 liqueur Nutrition 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 description 1
- KOPMZTKUZCNGFY-UHFFFAOYSA-N 1,1,1-triethoxybutane Chemical compound CCCC(OCC)(OCC)OCC KOPMZTKUZCNGFY-UHFFFAOYSA-N 0.000 description 1
- MWUDABUKTZAZCX-UHFFFAOYSA-N 1,1-diethoxycyclohexane Chemical compound CCOC1(OCC)CCCCC1 MWUDABUKTZAZCX-UHFFFAOYSA-N 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-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
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- HWKJSYYYURVNQU-DXJNJSHLSA-N acetyldigoxin Chemical compound C1[C@H](OC(C)=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 HWKJSYYYURVNQU-DXJNJSHLSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940057847 polyethylene glycol 600 Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (24)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BE788669D BE788669A (fr) | 1971-09-11 | Nouveaux cardenolide-glucosides | |
| DE2145476A DE2145476A1 (de) | 1971-09-11 | 1971-09-11 | Neue cardenolidglykoside |
| JP47085226A JPS4834869A (pm) | 1971-09-11 | 1972-08-25 | |
| SU1824419A SU421185A3 (pm) | 1971-09-11 | 1972-08-30 | |
| CH1670675A CH574457A5 (pm) | 1971-09-11 | 1972-09-06 | |
| AT766872A AT319480B (de) | 1971-09-11 | 1972-09-07 | Verfahren zur Herstellung von neuen Cardenolidglykosiden |
| AT1061773*7A AT329193B (de) | 1971-09-11 | 1972-09-07 | Verfahren zur herstellung von neuen cardenolidglykosiden |
| GB4188972A GB1363033A (en) | 1971-09-11 | 1972-09-08 | Derivatives of 22-fluoro-digoxins |
| DK446272AA DK129345B (da) | 1971-09-11 | 1972-09-08 | Analogifremgangsmåde til fremstilling af 22-fluor-3'''-acyldigoxiner. |
| ZA726154A ZA726154B (en) | 1971-09-11 | 1972-09-08 | Improvements relating to cardiac glycosides |
| BG023519A BG19145A3 (bg) | 1971-09-11 | 1972-09-08 | Метод за получаване на карденолидни гликозиди |
| FI722482A FI49425C (fi) | 1971-09-11 | 1972-09-08 | Menetelmä uusien sydänglykosideihin kuuluvien, 3'''-asemassa asyloituj en 22-fluoridigoksiini-johdannaisten valmistamiseksi |
| CA151,243A CA979425A (en) | 1971-09-11 | 1972-09-08 | Cardiac glycosides |
| DD165553A DD99164A5 (pm) | 1971-09-11 | 1972-09-08 | |
| BG021352A BG19144A3 (bg) | 1971-09-11 | 1972-09-08 | Метод за получаване на карденолидни гликозиди |
| IL40328A IL40328A (en) | 1971-09-11 | 1972-09-08 | 22-fluorodigoxins,their preparation and pharmaceutical compositions containing them |
| BG023520A BG19146A3 (bg) | 1971-09-11 | 1972-09-08 | Метод за получаване на нови карденолидни гликозиди |
| ES406542A ES406542A1 (es) | 1971-09-11 | 1972-09-09 | Procedimiento para la preparacion de nuevos cardenolidgli- cosidos. |
| NL7212308A NL7212308A (pm) | 1971-09-11 | 1972-09-11 | |
| CS6214A CS171172B2 (pm) | 1971-09-11 | 1972-09-11 | |
| RO7200072194A RO62337A (fr) | 1971-09-11 | 1972-09-11 | Procede pour la preparation des derives de 22-fluor-digoxine |
| AU46531/72A AU473516B2 (en) | 1971-09-11 | 1972-09-11 | Derivatives of 22-fluoro-digoxins |
| FR7232137A FR2154490B1 (pm) | 1971-09-11 | 1972-09-11 | |
| HUTO887A HU164161B (pm) | 1971-09-11 | 1972-09-11 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2145476A DE2145476A1 (de) | 1971-09-11 | 1971-09-11 | Neue cardenolidglykoside |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2145476A1 true DE2145476A1 (de) | 1973-03-22 |
Family
ID=5819270
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2145476A Pending DE2145476A1 (de) | 1971-09-11 | 1971-09-11 | Neue cardenolidglykoside |
Country Status (21)
| Country | Link |
|---|---|
| JP (1) | JPS4834869A (pm) |
| AT (2) | AT319480B (pm) |
| AU (1) | AU473516B2 (pm) |
| BE (1) | BE788669A (pm) |
| BG (3) | BG19144A3 (pm) |
| CA (1) | CA979425A (pm) |
| CH (1) | CH574457A5 (pm) |
| CS (1) | CS171172B2 (pm) |
| DD (1) | DD99164A5 (pm) |
| DE (1) | DE2145476A1 (pm) |
| DK (1) | DK129345B (pm) |
| ES (1) | ES406542A1 (pm) |
| FI (1) | FI49425C (pm) |
| FR (1) | FR2154490B1 (pm) |
| GB (1) | GB1363033A (pm) |
| HU (1) | HU164161B (pm) |
| IL (1) | IL40328A (pm) |
| NL (1) | NL7212308A (pm) |
| RO (1) | RO62337A (pm) |
| SU (1) | SU421185A3 (pm) |
| ZA (1) | ZA726154B (pm) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5424777A (en) * | 1977-07-23 | 1979-02-24 | Yunikon Shiyoukai Kk | Soil disinfecting apparatus using warm water |
| JPS57152828A (en) * | 1981-03-16 | 1982-09-21 | Engei Gijutsu Center Kk | Cultivation in greenhouse |
| 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 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BG17306A3 (bg) * | 1969-06-10 | 1973-07-25 | Dr. Karl Thomae Gmbh | Метод за получаване на нови карденолид-гликозиди |
| RO60624A (pm) * | 1970-03-05 | 1976-07-15 |
-
0
- BE BE788669D patent/BE788669A/xx unknown
-
1971
- 1971-09-11 DE DE2145476A patent/DE2145476A1/de active Pending
-
1972
- 1972-08-25 JP JP47085226A patent/JPS4834869A/ja active Pending
- 1972-08-30 SU SU1824419A patent/SU421185A3/ru active
- 1972-09-06 CH CH1670675A patent/CH574457A5/xx not_active IP Right Cessation
- 1972-09-07 AT AT766872A patent/AT319480B/de active
- 1972-09-07 AT AT1061773*7A patent/AT329193B/de not_active IP Right Cessation
- 1972-09-08 BG BG021352A patent/BG19144A3/xx unknown
- 1972-09-08 BG BG023520A patent/BG19146A3/xx unknown
- 1972-09-08 BG BG023519A patent/BG19145A3/xx unknown
- 1972-09-08 GB GB4188972A patent/GB1363033A/en not_active Expired
- 1972-09-08 DD DD165553A patent/DD99164A5/xx unknown
- 1972-09-08 FI FI722482A patent/FI49425C/fi active
- 1972-09-08 DK DK446272AA patent/DK129345B/da unknown
- 1972-09-08 CA CA151,243A patent/CA979425A/en not_active Expired
- 1972-09-08 ZA ZA726154A patent/ZA726154B/xx unknown
- 1972-09-08 IL IL40328A patent/IL40328A/en unknown
- 1972-09-09 ES ES406542A patent/ES406542A1/es not_active Expired
- 1972-09-11 AU AU46531/72A patent/AU473516B2/en not_active Expired
- 1972-09-11 FR FR7232137A patent/FR2154490B1/fr not_active Expired
- 1972-09-11 CS CS6214A patent/CS171172B2/cs unknown
- 1972-09-11 RO RO7200072194A patent/RO62337A/ro unknown
- 1972-09-11 NL NL7212308A patent/NL7212308A/xx unknown
- 1972-09-11 HU HUTO887A patent/HU164161B/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RO62337A (fr) | 1977-10-15 |
| DK129345B (da) | 1974-09-30 |
| AT319480B (de) | 1974-12-27 |
| AU473516B2 (en) | 1976-06-24 |
| ES406542A1 (es) | 1975-09-16 |
| BE788669A (fr) | 1973-03-12 |
| DK129345C (pm) | 1975-02-17 |
| IL40328A0 (en) | 1972-11-28 |
| SU421185A3 (pm) | 1974-03-25 |
| CH574457A5 (pm) | 1976-04-15 |
| FI49425B (pm) | 1975-02-28 |
| NL7212308A (pm) | 1973-03-13 |
| BG19144A3 (bg) | 1975-04-30 |
| ATA1061773A (de) | 1975-07-15 |
| CA979425A (en) | 1975-12-09 |
| BG19145A3 (bg) | 1975-04-30 |
| CS171172B2 (pm) | 1976-10-29 |
| ZA726154B (en) | 1974-05-29 |
| HU164161B (pm) | 1973-12-28 |
| FI49425C (fi) | 1975-06-10 |
| AU4653172A (en) | 1974-03-21 |
| DD99164A5 (pm) | 1973-07-20 |
| JPS4834869A (pm) | 1973-05-22 |
| BG19146A3 (bg) | 1975-04-30 |
| GB1363033A (en) | 1974-08-14 |
| IL40328A (en) | 1976-01-30 |
| FR2154490A1 (pm) | 1973-05-11 |
| FR2154490B1 (pm) | 1975-10-31 |
| AT329193B (de) | 1976-04-26 |
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