HU181431B - Process for preparing derivatives of 4-desacetil-vincaleukoblastine-3-carbohydrazide with anticarcinogen activity - Google Patents
Process for preparing derivatives of 4-desacetil-vincaleukoblastine-3-carbohydrazide with anticarcinogen activity Download PDFInfo
- Publication number
- HU181431B HU181431B HU79EI850A HUEI000850A HU181431B HU 181431 B HU181431 B HU 181431B HU 79EI850 A HU79EI850 A HU 79EI850A HU EI000850 A HUEI000850 A HU EI000850A HU 181431 B HU181431 B HU 181431B
- Authority
- HU
- Hungary
- Prior art keywords
- vincaleucoblastin
- desacetyl
- preparation
- deacetyl
- carbohydrazide
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 230000000694 effects Effects 0.000 title description 5
- 239000003005 anticarcinogenic agent Substances 0.000 title 1
- 238000002360 preparation method Methods 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims description 41
- 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 claims description 32
- -1 β-hydroxyethyl Chemical group 0.000 claims description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- JYZVAJRSNNFELK-UHFFFAOYSA-N 1-amino-3-(ethylamino)urea Chemical compound CCNNC(=O)NN JYZVAJRSNNFELK-UHFFFAOYSA-N 0.000 claims description 5
- 125000001118 alkylidene group Chemical group 0.000 claims description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- RNPNUQAIHFZXIU-UHFFFAOYSA-N 1,3-diamino-1-methylurea Chemical compound CN(N)C(=O)NN RNPNUQAIHFZXIU-UHFFFAOYSA-N 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 3
- CTWQVURGXYSHGO-UHFFFAOYSA-N 1-acetyl-1,3-diaminourea Chemical compound CC(=O)N(N)C(=O)NN CTWQVURGXYSHGO-UHFFFAOYSA-N 0.000 claims description 2
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 claims description 2
- RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 claims 1
- VYSYZMNJHYOXGN-UHFFFAOYSA-N ethyl n-aminocarbamate Chemical compound CCOC(=O)NN VYSYZMNJHYOXGN-UHFFFAOYSA-N 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 15
- 239000007858 starting material Substances 0.000 abstract description 6
- 239000002246 antineoplastic agent Substances 0.000 abstract description 4
- 229940034982 antineoplastic agent Drugs 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- 239000000243 solution Substances 0.000 description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- 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 description 23
- 231100000331 toxic Toxicity 0.000 description 21
- 230000002588 toxic effect Effects 0.000 description 21
- 239000000843 powder Substances 0.000 description 16
- 239000003814 drug Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 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 10
- 239000000047 product Substances 0.000 description 9
- 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 9
- 229960004528 vincristine Drugs 0.000 description 9
- 229930013930 alkaloid Natural products 0.000 description 8
- 229960003048 vinblastine Drugs 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 239000000908 ammonium hydroxide Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical class NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- RJDCTBHUIPNXEC-UHFFFAOYSA-N 1,3-diamino-1-benzoylurea Chemical compound NNC(=O)N(N)C(=O)C1=CC=CC=C1 RJDCTBHUIPNXEC-UHFFFAOYSA-N 0.000 description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 3
- 206010006007 bone sarcoma Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 208000025036 lymphosarcoma Diseases 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
- IMNRCDZAQJOHKM-UHFFFAOYSA-N 1,3-diamino-1-ethylurea Chemical compound C(C)N(N)C(=O)NN IMNRCDZAQJOHKM-UHFFFAOYSA-N 0.000 description 2
- WOELNAUJYBMEIS-UHFFFAOYSA-N 1-acetamido-3-aminourea Chemical compound CC(=O)NNC(=O)NN WOELNAUJYBMEIS-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- CTODJDOCNIIUTR-UHFFFAOYSA-N Vincadioline Natural products CCC1(O)CC2CN(CCc3c([nH]c4ccccc34)C(C2)(C(=O)OC)c5cc6c(cc5OC)N(C)C7(O)C(O)(C(OC(=O)C)C8(CC)C=CCN9CCC67C89)C(=O)OC)C1 CTODJDOCNIIUTR-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- CFFPQBHLZWTYAQ-UHFFFAOYSA-N 2-hydrazinylethyl acetate Chemical compound CC(=O)OCCNN CFFPQBHLZWTYAQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 240000001829 Catharanthus roseus Species 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
- LPGWZGMPDKDHEP-GKWAKPNHSA-N Leurosine 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@]6(CC)O[C@@H]6[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C LPGWZGMPDKDHEP-GKWAKPNHSA-N 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 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 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- OWAQXCQNWNJICI-UHFFFAOYSA-N benzene;chloroform Chemical compound ClC(Cl)Cl.C1=CC=CC=C1 OWAQXCQNWNJICI-UHFFFAOYSA-N 0.000 description 1
- XOTUWBDDKYVWMF-UHFFFAOYSA-N benzene;chloroform;n,n-diethylethanamine Chemical compound ClC(Cl)Cl.C1=CC=CC=C1.CCN(CC)CC XOTUWBDDKYVWMF-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 239000003039 volatile agent Substances 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/899,032 US4166810A (en) | 1978-04-20 | 1978-04-20 | Derivatives of 4-desacetyl VLB C-3 carboxyhydrazide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU181431B true HU181431B (en) | 1983-07-28 |
Family
ID=25410402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU79EI850A HU181431B (en) | 1978-04-20 | 1979-04-19 | Process for preparing derivatives of 4-desacetil-vincaleukoblastine-3-carbohydrazide with anticarcinogen activity |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US4166810A (enExample) |
| EP (1) | EP0005051B1 (enExample) |
| JP (1) | JPS54141798A (enExample) |
| AR (1) | AR228940A1 (enExample) |
| AT (1) | AT369010B (enExample) |
| AU (1) | AU527109B2 (enExample) |
| BE (1) | BE875652A (enExample) |
| BG (3) | BG33294A3 (enExample) |
| CA (1) | CA1097629A (enExample) |
| CH (1) | CH643269A5 (enExample) |
| CS (3) | CS218585B2 (enExample) |
| DD (1) | DD143075A5 (enExample) |
| DE (1) | DE2964130D1 (enExample) |
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Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4322351A (en) * | 1980-08-25 | 1982-03-30 | Eli Lilly And Company | Antineoplastic 4'-formylamino and 4'-acetylamino VLB, and derivatives thereof |
| US4596676A (en) * | 1983-03-30 | 1986-06-24 | Lilly Industries Limited | Bifunctional ester derivatives of 4-desacetyl indole-dihydroindole alkaloids |
| US4675400A (en) * | 1985-06-17 | 1987-06-23 | Eli Lilly And Company | Bifunctional derivatives of 4-desacetyl indole-dihydroindole alkaloids |
| US4667030A (en) * | 1985-06-17 | 1987-05-19 | Eli Lilly And Company | Hydrazide succinimide derivatives of antineoplastic indole-dihydroindole alkaloids |
| US4801688A (en) * | 1986-05-27 | 1989-01-31 | Eli Lilly And Company | Hydrazone immunoglobulin conjugates |
| US5043340A (en) * | 1990-04-03 | 1991-08-27 | Eli Lilly And Company | Derivatives of 4-desacetyl VLB C-3 carboxhydrazide |
| US5043336A (en) * | 1990-04-03 | 1991-08-27 | Eli Lilly And Company | Cyclic imide derivatives of 4-desacetyl VLB c-3 carboxhydrazide |
| WO2002085908A1 (en) | 2001-04-24 | 2002-10-31 | Purdue Research Foundation | Folate mimetics and folate-receptor binding conjugates thereof |
| CA2484640C (en) * | 2002-05-15 | 2012-01-17 | Endocyte, Inc. | Vitamin-mitomycin conjugates |
| JP5576007B2 (ja) | 2003-01-27 | 2014-08-20 | エンドサイト・インコーポレイテッド | ビタミン受容体結合性薬剤送達結合体 |
| JP5149620B2 (ja) * | 2004-07-23 | 2013-02-20 | エンドサイト，インコーポレイテッド | ２価リンカーおよびその結合体 |
| WO2006101845A2 (en) * | 2005-03-16 | 2006-09-28 | Endocyte, Inc. | Synthesis and purification of pteroic acid and conjugates thereof |
| JP2009504783A (ja) | 2005-08-19 | 2009-02-05 | エンドサイト，インコーポレイテッド | ビンカアルカロイド、類似体および誘導体のリガンド結合体 |
| EP2374480A3 (en) | 2005-08-19 | 2013-05-01 | Endocyte, Inc. | Mutli-drug ligand conjugates |
| US20100087370A1 (en) * | 2007-02-14 | 2010-04-08 | The General Hospital Corporation | Modulation of nitric oxide signaling to normalize tumor vasculature |
| US20100104626A1 (en) * | 2007-02-16 | 2010-04-29 | Endocyte, Inc. | Methods and compositions for treating and diagnosing kidney disease |
| NZ580132A (en) * | 2007-03-14 | 2012-11-30 | Endocyte Inc | Binding ligand linked drug delivery conjugates of tubulysins to vitamins |
| CN104383553A (zh) | 2007-06-25 | 2015-03-04 | 恩多塞特公司 | 含有亲水性间隔区接头的共轭物 |
| US9877965B2 (en) | 2007-06-25 | 2018-01-30 | Endocyte, Inc. | Vitamin receptor drug delivery conjugates for treating inflammation |
| WO2009055562A1 (en) * | 2007-10-25 | 2009-04-30 | Endocyte, Inc. | Tubulysins and processes for preparing |
| ES2574032T3 (es) * | 2009-09-07 | 2016-06-14 | Nipro Patch Co., Ltd. | Preparación absorbible por vía transdérmica |
| US10080805B2 (en) | 2012-02-24 | 2018-09-25 | Purdue Research Foundation | Cholecystokinin B receptor targeting for imaging and therapy |
| US20140080175A1 (en) | 2012-03-29 | 2014-03-20 | Endocyte, Inc. | Processes for preparing tubulysin derivatives and conjugates thereof |
| JP2015536323A (ja) | 2012-10-16 | 2015-12-21 | エンドサイト・インコーポレイテッドＥｎｄｏｃｙｔｅ， Ｉｎｃ． | 非天然アミノ酸を含む薬物送達結合体および使用方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3097137A (en) * | 1960-05-19 | 1963-07-09 | Canadian Patents Dev | Vincaleukoblastine |
| US3205220A (en) * | 1961-10-26 | 1965-09-07 | Lilly Co Eli | Leurosidine and leurocristine and their production |
| US3392173A (en) * | 1964-03-09 | 1968-07-09 | Lilly Co Eli | Novel acyl derivatives of desacetyl-vincaleukoblastine and processes for their preparation |
| US3370057A (en) * | 1964-04-27 | 1968-02-20 | Lilly Co Eli | Leurosine |
| US3387001A (en) * | 1964-10-19 | 1968-06-04 | Lilly Co Eli | Novel aminoacyl esters of desacetyl vincaleukoblastine |
| US3887565A (en) * | 1974-05-06 | 1975-06-03 | Lilly Co Eli | Vincadioline |
| US3890325A (en) * | 1974-05-15 | 1975-06-17 | Lilly Co Eli | Leurocolombine |
| US3954773A (en) * | 1974-11-21 | 1976-05-04 | Eli Lilly And Company | 4-Desacetoxyvinblastine |
| US3944554A (en) * | 1975-01-09 | 1976-03-16 | Eli Lilly And Company | 4-Desacetoxy-3-hydroxyvinblastine |
| IL48685A (en) | 1975-01-09 | 1980-03-31 | Lilly Co Eli | Amides of vincadioline and vinblastine |
| US4029663A (en) * | 1975-07-10 | 1977-06-14 | Eli Lilly And Company | Dimeric anhydro-vinca derivatives |
| US4115388A (en) * | 1977-03-30 | 1978-09-19 | Eli Lilly And Company | 3'-Oxygenated derivatives of 4'-deoxy VLB "A" and "B" and related 1-formyl compounds |
-
1978
- 1978-04-20 US US05/899,032 patent/US4166810A/en not_active Expired - Lifetime
-
1979
- 1979-04-17 JP JP4715279A patent/JPS54141798A/ja active Granted
- 1979-04-17 PT PT69496A patent/PT69496A/pt unknown
- 1979-04-17 PH PH23391A patent/PH14163A/en unknown
- 1979-04-18 BE BE1/9358A patent/BE875652A/xx unknown
- 1979-04-18 GB GB7913460A patent/GB2019396B/en not_active Expired
- 1979-04-18 RO RO79102377A patent/RO81037A/ro unknown
- 1979-04-18 AU AU46097/79A patent/AU527109B2/en not_active Ceased
- 1979-04-18 AT AT0291279A patent/AT369010B/de not_active IP Right Cessation
- 1979-04-18 LU LU81166A patent/LU81166A1/xx unknown
- 1979-04-18 EG EG238/79A patent/EG14867A/xx active
- 1979-04-18 RO RO79102376A patent/RO81114A/ro unknown
- 1979-04-18 GR GR58950A patent/GR69987B/el unknown
- 1979-04-18 YU YU00931/79A patent/YU93179A/xx unknown
- 1979-04-18 RO RO7997290A patent/RO80084A/ro unknown
- 1979-04-18 EP EP79300638A patent/EP0005051B1/en not_active Expired
- 1979-04-18 DE DE7979300638T patent/DE2964130D1/de not_active Expired
- 1979-04-18 NZ NZ190213A patent/NZ190213A/xx unknown
- 1979-04-19 CA CA325,844A patent/CA1097629A/en not_active Expired
- 1979-04-19 PL PL1979215011A patent/PL119416B1/pl unknown
- 1979-04-19 CS CS807546A patent/CS218585B2/cs unknown
- 1979-04-19 ES ES479754A patent/ES479754A1/es not_active Expired
- 1979-04-19 FR FR7909874A patent/FR2423495A1/fr active Granted
- 1979-04-19 ZA ZA791856A patent/ZA791856B/xx unknown
- 1979-04-19 PL PL21591179A patent/PL215911A1/xx unknown
- 1979-04-19 PL PL1979230538A patent/PL125470B1/pl unknown
- 1979-04-19 ES ES479753A patent/ES479753A1/es not_active Expired
- 1979-04-19 FI FI791286A patent/FI791286A7/fi not_active Application Discontinuation
- 1979-04-19 HU HU79EI850A patent/HU181431B/hu not_active IP Right Cessation
- 1979-04-19 DK DK160679A patent/DK147484C/da not_active IP Right Cessation
- 1979-04-19 CH CH370779A patent/CH643269A5/fr not_active IP Right Cessation
- 1979-04-19 CS CS792678A patent/CS218583B2/cs unknown
- 1979-04-19 CS CS807545A patent/CS218584B2/cs unknown
- 1979-04-20 SU SU792925606A patent/SU1225490A3/ru active
- 1979-04-20 BG BG043323A patent/BG33294A3/xx unknown
- 1979-04-20 BG BG056470A patent/BG33297A3/xx unknown
- 1979-04-20 SU SU792759650A patent/SU893135A3/ru active
- 1979-04-20 BG BG056469A patent/BG33296A3/xx unknown
- 1979-04-20 DD DD79212369A patent/DD143075A5/de unknown
- 1979-04-20 AR AR276248A patent/AR228940A1/es active
- 1979-04-29 IL IL57168A patent/IL57168A/xx unknown
- 1979-08-08 IE IE795/79A patent/IE48213B1/en unknown
-
1980
- 1980-05-26 SU SU802925605A patent/SU1061698A3/ru active
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |