CH648320A5 - Cytostatische verbindungen, verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel. - Google Patents
Cytostatische verbindungen, verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel. Download PDFInfo
- Publication number
- CH648320A5 CH648320A5 CH5313/81A CH531381A CH648320A5 CH 648320 A5 CH648320 A5 CH 648320A5 CH 5313/81 A CH5313/81 A CH 5313/81A CH 531381 A CH531381 A CH 531381A CH 648320 A5 CH648320 A5 CH 648320A5
- Authority
- CH
- Switzerland
- Prior art keywords
- vinblastine
- desmethyl
- group
- general formula
- carbon atoms
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 38
- 238000000034 method Methods 0.000 title claims description 17
- 230000001085 cytostatic effect Effects 0.000 title description 6
- 239000000824 cytostatic agent Substances 0.000 title description 3
- 229940126601 medicinal product Drugs 0.000 title 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 44
- 229960003048 vinblastine Drugs 0.000 claims description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 39
- -1 isobutoxymethyl Chemical group 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 15
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 15
- 229940117975 chromium trioxide Drugs 0.000 claims description 14
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 239000011541 reaction mixture Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 8
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 claims description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 6
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims 3
- 239000004480 active ingredient Substances 0.000 claims 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000003463 adsorbent Substances 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- RVCKCEDKBVEEHL-UHFFFAOYSA-N 2,3,4,5,6-pentachlorobenzyl alcohol Chemical compound OCC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl RVCKCEDKBVEEHL-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 230000016507 interphase Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229930013930 alkaloid Natural products 0.000 description 4
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 230000031864 metaphase Effects 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- KDQAABAKXDWYSZ-PNYVAJAMSA-N vinblastine sulfate Chemical compound OS(O)(=O)=O.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 KDQAABAKXDWYSZ-PNYVAJAMSA-N 0.000 description 4
- 229960004982 vinblastine sulfate Drugs 0.000 description 4
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 4
- 229960004528 vincristine Drugs 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- 150000003797 alkaloid derivatives Chemical class 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 230000011278 mitosis Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical class [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 230000031016 anaphase Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 150000007524 organic acids Chemical group 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- FFRFGVHNKJYNOV-DOVUUNBWSA-N 3',4'-Anhydrovinblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C=C(C2)CC)N2CCC2=C1NC1=CC=CC=C21 FFRFGVHNKJYNOV-DOVUUNBWSA-N 0.000 description 1
- DMHIJUVUPKCGLJ-UHFFFAOYSA-N 3-ethyl-2-methylpentan-3-ol Chemical compound CCC(O)(CC)C(C)C DMHIJUVUPKCGLJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000008342 Leukemia P388 Diseases 0.000 description 1
- JXLYSJRDGCGARV-PJXZDTQASA-N Leurosidine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-PJXZDTQASA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 241000208181 Pelargonium Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 238000004816 paper chromatography Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000001875 tumorinhibitory effect Effects 0.000 description 1
- KDQAABAKXDWYSZ-JKDPCDLQSA-N vincaleukoblastine sulfate Chemical compound OS(O)(=O)=O.C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 KDQAABAKXDWYSZ-JKDPCDLQSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/04—Dimeric indole alkaloids, e.g. vincaleucoblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU802562A HU181745B (en) | 1980-10-22 | 1980-10-22 | Process for producing new vinblastin and leurosidin derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH648320A5 true CH648320A5 (de) | 1985-03-15 |
Family
ID=10960005
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH5313/81A CH648320A5 (de) | 1980-10-22 | 1981-08-17 | Cytostatische verbindungen, verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel. |
Country Status (15)
| Country | Link |
|---|---|
| JP (1) | JPS5772992A (en, 2012) |
| AT (1) | AT376678B (en, 2012) |
| BE (1) | BE889989A (en, 2012) |
| CA (1) | CA1174672A (en, 2012) |
| CH (1) | CH648320A5 (en, 2012) |
| DE (1) | DE3132476A1 (en, 2012) |
| ES (1) | ES505310A0 (en, 2012) |
| FR (1) | FR2492384B1 (en, 2012) |
| GB (1) | GB2086378B (en, 2012) |
| HU (1) | HU181745B (en, 2012) |
| IL (1) | IL63593A0 (en, 2012) |
| IT (1) | IT1138154B (en, 2012) |
| NL (1) | NL8103844A (en, 2012) |
| SE (1) | SE442116B (en, 2012) |
| SU (1) | SU1053757A3 (en, 2012) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU193318B (en) * | 1985-06-12 | 1987-09-28 | Richter Gedeon Vegyeszet | Process for producing new bis- indol derivatives |
| HU198074B (en) * | 1985-06-12 | 1989-07-28 | Richter Gedeon Vegyeszet | Process for producing new bis-indole derivatives and pharmaceutical compositions comprising these compounds |
| JPH0321210U (en, 2012) * | 1989-07-11 | 1991-03-01 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3899493A (en) * | 1972-12-29 | 1975-08-12 | Richter Gedeon Vegyeszet | Chromic acid oxidation of vinblastine sulfate to form vincristine |
| HU178706B (en) * | 1979-04-23 | 1982-06-28 | Richter Gedeon Vegyeszet | Process for preparing bis-indole alkaloids and acid addition salts thereof |
| JPS56128643A (en) * | 1980-03-13 | 1981-10-08 | Sintokogio Ltd | Vertical flaskless type molding machine |
-
1980
- 1980-10-22 HU HU802562A patent/HU181745B/hu not_active IP Right Cessation
-
1981
- 1981-08-17 NL NL8103844A patent/NL8103844A/nl not_active Application Discontinuation
- 1981-08-17 IT IT23540/81A patent/IT1138154B/it active
- 1981-08-17 GB GB8125029A patent/GB2086378B/en not_active Expired
- 1981-08-17 IL IL63593A patent/IL63593A0/xx unknown
- 1981-08-17 JP JP56128642A patent/JPS5772992A/ja active Granted
- 1981-08-17 CA CA000383978A patent/CA1174672A/en not_active Expired
- 1981-08-17 CH CH5313/81A patent/CH648320A5/de not_active IP Right Cessation
- 1981-08-17 BE BE0/205691A patent/BE889989A/fr not_active IP Right Cessation
- 1981-08-17 ES ES505310A patent/ES505310A0/es active Granted
- 1981-08-17 DE DE3132476A patent/DE3132476A1/de active Granted
- 1981-08-17 AT AT0358681A patent/AT376678B/de not_active IP Right Cessation
- 1981-08-17 SU SU813320101A patent/SU1053757A3/ru active
- 1981-08-17 FR FR8115835A patent/FR2492384B1/fr not_active Expired
- 1981-08-17 SE SE8104877A patent/SE442116B/sv not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SU1053757A3 (ru) | 1983-11-07 |
| IT1138154B (it) | 1986-09-17 |
| ES8300777A1 (es) | 1982-12-01 |
| SE8104877L (sv) | 1982-04-23 |
| ATA358681A (de) | 1984-05-15 |
| DE3132476A1 (de) | 1982-06-09 |
| GB2086378A (en) | 1982-05-12 |
| BE889989A (fr) | 1982-02-17 |
| FR2492384B1 (fr) | 1986-04-04 |
| DE3132476C2 (en, 2012) | 1991-04-18 |
| JPH0161118B2 (en, 2012) | 1989-12-27 |
| IT8123540A0 (it) | 1981-08-17 |
| SE442116B (sv) | 1985-12-02 |
| AT376678B (de) | 1984-12-27 |
| CA1174672A (en) | 1984-09-18 |
| HU181745B (en) | 1983-11-28 |
| JPS5772992A (en) | 1982-05-07 |
| ES505310A0 (es) | 1982-12-01 |
| NL8103844A (nl) | 1982-05-17 |
| FR2492384A1 (fr) | 1982-04-23 |
| GB2086378B (en) | 1984-07-25 |
| IL63593A0 (en) | 1981-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CH648037A5 (de) | Imidazo-rifamycin-derivate mit antibakterieller wirksamkeit. | |
| DE2263100C2 (de) | 5,5-Dimethyl-8-(3-methyl-2-octyl)-10-[4-(piperidino)-butyryloxy]-2-(2-propinyl)-1,2,3,4-tetrahydro-5H-[1]-benzopyrano[3,4-d]pyridin, Verfahren zu dessen Herstellung und die Verbindung enthaltende Arzneimittel | |
| DE3132475C2 (en, 2012) | ||
| DE2929760C2 (en, 2012) | ||
| CH648320A5 (de) | Cytostatische verbindungen, verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel. | |
| DE3035259C2 (de) | Cephalosporinverbindungen, Verfahren zu deren Herstellung und Arzneimittel, welche diese enthalten | |
| DE2632118A1 (de) | Apovincaminolester und verfahren zu deren herstellung | |
| DE2244265A1 (de) | Neue imidazolderivate, ihre herstellung und die medizinischen zusammensetzungen, die sie enthalten | |
| AT234699B (de) | Verfahren zur Herstellung von neuen Sulfanilamidochinazolinderivaten und von deren Metallsalzen | |
| DE2221939B2 (de) | 2-(3-Pyridazinyl)-3-(4-methylpiperazino-carbonyloxy)-1-isoindolinonderivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzungen | |
| DE2422430C3 (de) | Derivate der Secalonsäure D, Verfahren zu ihrer Herstellung und ihre Verwendung bei der Bekämpfung von Tumoren | |
| AT270630B (de) | Verfahren zur Herstellung von neuen Pyrrolinderivaten und ihren Salzen | |
| AT371457B (de) | Verfahren zur herstellung von neuen 6-substituierten pyranon-verbindungen | |
| AT314537B (de) | Verfahren zur Herstellung von neuen 1,3,4,9b-Tetrahydro-2H-indeno[1,2-c]pyridinen und ihren Säureadditionssalzen | |
| DE2202518A1 (de) | O-Ester von ara-Cytidin und Verfahren zu ihrer Herstellung | |
| AT278831B (de) | Verfahren zur herstellung neuer 4-acyl-3,4-dihydro-2(1h)-chinoxalinonderivate | |
| CH422803A (de) | Verfahren zur Herstellung von 2-substituierten 4-Sulfanilamidochinazolinen | |
| CH494242A (de) | Verfahren zur Herstellung von neuen Estern der 10-Piperazino-10,11-dihydrodibenzo (b,f)thiepin-Reihe | |
| DE2500692C3 (de) | Derivate des 4-Amidoalkylen-4'oxy diphenyle | |
| AT359509B (de) | Verfahren zur herstellung von neuen 3-di-n- -propylacetoxybenzodiazepin-2-onen | |
| DE2536387A1 (de) | Pyrido(3,2-e)-as-triazinderivate, solche enthaltende arzneimittel sowie verfahren zur herstellung derselben | |
| DE2642598A1 (de) | Neue isoindolinderivate, deren herstellung und diese enthaltende zusammensetzungen | |
| DE1225658B (de) | Verfahren zur Herstellung von Cumarinderivaten | |
| CH517746A (de) | Verfahren zur Herstellung neuer Indenopyridinderivate | |
| CH615424A5 (en) | Process for the preparation of novel 6-substituted 9-methoxy-1-phenazinecarboxylic acids and their alkyl esters |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |