SE442116B - Sett att framstella cytostatiska foreningar innefattande derivat av vinblastin och leurosidin jemte farmaceutiska beredningar derav - Google Patents
Sett att framstella cytostatiska foreningar innefattande derivat av vinblastin och leurosidin jemte farmaceutiska beredningar deravInfo
- Publication number
- SE442116B SE442116B SE8104877A SE8104877A SE442116B SE 442116 B SE442116 B SE 442116B SE 8104877 A SE8104877 A SE 8104877A SE 8104877 A SE8104877 A SE 8104877A SE 442116 B SE442116 B SE 442116B
- Authority
- SE
- Sweden
- Prior art keywords
- compound
- general formula
- ethyl
- carbon atoms
- alkyl group
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 54
- 230000001085 cytostatic effect Effects 0.000 title claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 title claims 2
- 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 title description 16
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical class 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 title description 12
- 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 title 1
- JXLYSJRDGCGARV-KSNABSRWSA-N ac1l29ym 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-KSNABSRWSA-N 0.000 title 1
- 239000000824 cytostatic agent Substances 0.000 title 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 17
- -1 β-ethyl Chemical group 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 239000011541 reaction mixture Substances 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 229940117975 chromium trioxide Drugs 0.000 claims description 8
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 8
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 229960003048 vinblastine Drugs 0.000 description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical class CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000000908 ammonium hydroxide Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 230000016507 interphase Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 4
- 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 4
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 4
- 230000001476 alcoholic effect Effects 0.000 description 4
- 229930013930 alkaloid Natural products 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 229960004528 vincristine 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
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 4
- 229960004355 vindesine Drugs 0.000 description 4
- HHJUWIANJFBDHT-KOTLKJBCSA-N vindesine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(N)=O)N4C)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 HHJUWIANJFBDHT-KOTLKJBCSA-N 0.000 description 4
- 150000003797 alkaloid derivatives Chemical class 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 231100001231 less toxic Toxicity 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 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
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- 230000031016 anaphase Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000011097 chromatography purification Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 230000031864 metaphase Effects 0.000 description 2
- 230000011278 mitosis Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 230000001769 paralizing effect Effects 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
- 241000894007 species Species 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 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 2
- 229960004982 vinblastine sulfate Drugs 0.000 description 2
- ZHYZQXUYZJNEHD-CLFYSBASSA-N (2z)-3,7-dimethylocta-2,6-dienoic acid Chemical compound CC(C)=CCC\C(C)=C/C(O)=O ZHYZQXUYZJNEHD-CLFYSBASSA-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
- TYGUTURXHKSOBP-UHFFFAOYSA-N 10-bromo-5,12-dihydroindolo[2,3-g]carbazole-2,3-diol Chemical compound C1=C(Br)C=C2NC3=C(C4=C(C=C(C(=C4)O)O)N4)C4=CC=C3C2=C1 TYGUTURXHKSOBP-UHFFFAOYSA-N 0.000 description 1
- 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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000235503 Glomus Species 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000009232 chiropractic Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000009399 inbreeding Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 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
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 230000001875 tumorinhibitory effect Effects 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 (2)
| Publication Number | Publication Date |
|---|---|
| SE8104877L SE8104877L (sv) | 1982-04-23 |
| SE442116B true SE442116B (sv) | 1985-12-02 |
Family
ID=10960005
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8104877A SE442116B (sv) | 1980-10-22 | 1981-08-17 | Sett att framstella cytostatiska foreningar innefattande derivat av vinblastin och leurosidin jemte farmaceutiska beredningar derav |
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 |
| CH648320A5 (de) | 1985-03-15 |
| FR2492384B1 (fr) | 1986-04-04 |
| DE3132476C2 (en, 2012) | 1991-04-18 |
| JPH0161118B2 (en, 2012) | 1989-12-27 |
| IT8123540A0 (it) | 1981-08-17 |
| 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 |
|---|---|---|
| US4307100A (en) | Nor bis-indole compounds usable as medicaments | |
| US4769453A (en) | Bis-indolic compounds | |
| EP0313874B1 (en) | Disulfur analogs of LL-E33288 antitumor agents | |
| Katritzky et al. | The chemistry of N-substituted benzotriazoles. Part 2. Reactions of benzotriazole with aldehydes and aldehyde derivatives. 1-(α-Hydroxyalkyl)-, 1-(α-alkoxyalkyl)-, and 1-(α-acyloxyalkyl) benzotriazoles | |
| Guang‐Fu et al. | Syntheses and properties of new herbicidal 2‐arylthio‐l, 2, 4‐triazolo [l, 5‐a] pyrimidine derivatives | |
| NO154013B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive sesquiterpenderivater. | |
| Coffen et al. | A short synthesis of aromatic analogs of the aranotins | |
| US4410459A (en) | Process for preparation of cytostatic compounds | |
| SE442116B (sv) | Sett att framstella cytostatiska foreningar innefattande derivat av vinblastin och leurosidin jemte farmaceutiska beredningar derav | |
| KR880001284B1 (ko) | 아지노 리파마이신 화합물의 제조방법 | |
| RU2169149C2 (ru) | Соединения со структурой камптотецина, способы их получения, фармацевтические композиции | |
| US3663579A (en) | Dimeric steroid-21-alkyl-carbonates and process for their manufacture | |
| Ohkawa et al. | Studies on the Metabolites of Cochliobolus miyabeanus: Part I. Ophiobolosin A and Ophiobolosin B | |
| US4347249A (en) | Class of seco bis-indolic compounds which can be used as drugs and a process for the preparation thereof | |
| ARATA et al. | Studies on 1-Azabicyclo Compounds. XXII. Stereochemistry of 9a-Substituted Quinolizidine Methiodides | |
| SE436036B (sv) | Analogiforfarande for framstellning av oxazolidindionderivat av vinkaalkaloider | |
| Plescia et al. | Studies on the synthesis of heterocyclic compounds. Part II. Action of phosphorus oxychloride on N‐Methyl‐N‐1‐phenyl‐3‐methylpyrazol‐5‐yl)‐2‐acetamidobenzamide | |
| JPS6216489A (ja) | ビンブラスチン型ビスインド−ルのニトロ誘導体 | |
| US4486592A (en) | 9-Carbamoylfluorene derivatives | |
| US2140480A (en) | 3-keto-d-pentonic acid lactone and process for the manufacture of same | |
| US3998822A (en) | Morpholino containing pyrido (3,4-d) pyridazines | |
| Sako | Syntheses of Pyridazine Derivatives. IV. Halogenopyridazine 1-Oxides | |
| CH638814A5 (fr) | 4-desacetoxy-4alpha-hydroxyindole-dihydroindols et leur preparation. | |
| EP4417603A1 (en) | Method for preparing benzofuran derivative | |
| US4233224A (en) | Coriolin derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| NAL | Patent in force |
Ref document number: 8104877-9 Format of ref document f/p: F |
|
| NUG | Patent has lapsed |
Ref document number: 8104877-9 Format of ref document f/p: F |