BR9807944B1 - derivados antimitóticos dos alcalóides da vinca, processo para preparar os mesmos e uso dos derivados. - Google Patents
derivados antimitóticos dos alcalóides da vinca, processo para preparar os mesmos e uso dos derivados. Download PDFInfo
- Publication number
- BR9807944B1 BR9807944B1 BRPI9807944-1A BR9807944A BR9807944B1 BR 9807944 B1 BR9807944 B1 BR 9807944B1 BR 9807944 A BR9807944 A BR 9807944A BR 9807944 B1 BR9807944 B1 BR 9807944B1
- Authority
- BR
- Brazil
- Prior art keywords
- formula
- derivatives
- see original
- compound
- original document
- Prior art date
Links
- 229940122803 Vinca alkaloid Drugs 0.000 title claims abstract description 8
- 230000002927 anti-mitotic effect Effects 0.000 title claims abstract 3
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 239000000203 mixture Substances 0.000 claims abstract description 21
- 229910021630 Antimony pentafluoride Inorganic materials 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 5
- VBVBHWZYQGJZLR-UHFFFAOYSA-I antimony pentafluoride Chemical compound F[Sb](F)(F)(F)F VBVBHWZYQGJZLR-UHFFFAOYSA-I 0.000 claims abstract description 5
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 53
- 150000001875 compounds Chemical class 0.000 claims description 46
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 14
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- -1 silver tetrafluoroborate Chemical compound 0.000 claims description 7
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 claims description 7
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000007848 Bronsted acid Substances 0.000 claims description 2
- 239000002841 Lewis acid Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 150000007517 lewis acids Chemical class 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 238000011282 treatment Methods 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000026030 halogenation Effects 0.000 claims 1
- 238000005658 halogenation reaction Methods 0.000 claims 1
- 230000007170 pathology Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 23
- 238000006243 chemical reaction Methods 0.000 abstract description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 abstract description 10
- 239000003930 superacid Substances 0.000 abstract description 10
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 abstract description 8
- 229960000922 vinflunine Drugs 0.000 abstract description 8
- ZEOVXNVKXIPWMS-UHFFFAOYSA-N 2,2-dichloropropane Chemical compound CC(C)(Cl)Cl ZEOVXNVKXIPWMS-UHFFFAOYSA-N 0.000 abstract description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 abstract description 4
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 abstract description 4
- 150000003797 alkaloid derivatives Chemical class 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract description 3
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 abstract description 2
- 150000007513 acids Chemical class 0.000 abstract 1
- 150000004820 halides Chemical class 0.000 abstract 1
- NMDYYWFGPIMTKO-HBVLKOHWSA-N vinflunine Chemical compound C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-HBVLKOHWSA-N 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 19
- 239000000047 product Substances 0.000 description 15
- NOSAJPUYIASWEH-ODOBZBQGSA-N methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-4-[(13S,15R,17R)-17-(1,1-difluoroethyl)-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate Chemical compound C([C@@H](C[C@@H](C1)C[C@@]2(C3=C(OC)C=C4N(C)[C@@H]5[C@@]6(C4=C3)CCN3CC=C[C@]([C@@H]63)([C@H]([C@]5(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)C(C)(F)F)N1CCC1=C2NC2=CC=CC=C12 NOSAJPUYIASWEH-ODOBZBQGSA-N 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- NMDYYWFGPIMTKO-KLCPSUAYSA-N vinflunine Chemical compound C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-KLCPSUAYSA-N 0.000 description 9
- 229960003048 vinblastine Drugs 0.000 description 8
- 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 7
- 239000012074 organic phase Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 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 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 238000010908 decantation Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000011975 tartaric acid Substances 0.000 description 4
- 235000002906 tartaric acid Nutrition 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 240000001829 Catharanthus roseus Species 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920006362 Teflon® Polymers 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229960002066 vinorelbine Drugs 0.000 description 3
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 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 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- YIHUEPHBPPAAHH-GBROPSEISA-N 194468-36-5 Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 YIHUEPHBPPAAHH-GBROPSEISA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 231100000632 Spindle poison Toxicity 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- WVTGEXAIVZDLCR-UHFFFAOYSA-N Vindoline Natural products CC1C2CN3CCCC14CCC5Nc6ccccc6C25C34 WVTGEXAIVZDLCR-UHFFFAOYSA-N 0.000 description 1
- BVYIPGWEDGBFSD-UHFFFAOYSA-N [C].ClCCl Chemical compound [C].ClCCl BVYIPGWEDGBFSD-UHFFFAOYSA-N 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- GKWYINOZGDHWRA-UHFFFAOYSA-N catharanthine Natural products C1C(CC)(O)CC(CC2C(=O)OC)CN1CCC1=C2NC2=CC=CC=C12 GKWYINOZGDHWRA-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000021121 meiosis Effects 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- IABOVZGENONJML-UHFFFAOYSA-N pentaazanium pentafluoride Chemical compound [F-].[F-].[F-].[F-].[F-].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+] IABOVZGENONJML-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- 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 1
- 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 1
- CXBGOBGJHGGWIE-IYJDUVQVSA-N vindoline Chemical compound CN([C@H]1[C@](O)([C@@H]2OC(C)=O)C(=O)OC)C3=CC(OC)=CC=C3[C@]11CCN3CC=C[C@]2(CC)[C@@H]13 CXBGOBGJHGGWIE-IYJDUVQVSA-N 0.000 description 1
- 238000005406 washing 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Steroid Compounds (AREA)
- Saccharide Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9704398A FR2761990B1 (fr) | 1997-04-10 | 1997-04-10 | Derives halogenes antimitotiques d'alcaloides de vinca |
| FR97/04398 | 1997-04-10 | ||
| PCT/FR1998/000730 WO1998045301A1 (fr) | 1997-04-10 | 1998-04-10 | Derives halogenes antimitotiques d'alcaloides de vinca |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR9807944A BR9807944A (pt) | 2000-03-08 |
| BR9807944B1 true BR9807944B1 (pt) | 2011-02-08 |
Family
ID=9505731
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI9807944-1A BR9807944B1 (pt) | 1997-04-10 | 1998-04-10 | derivados antimitóticos dos alcalóides da vinca, processo para preparar os mesmos e uso dos derivados. |
| BRPI9816177-6A BR9816177B1 (pt) | 1997-04-10 | 1998-04-10 | processo para preparar a 4'-desàxi-20', 20'-difluorovinblastina, e, processo para preparar a vinflunina. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI9816177-6A BR9816177B1 (pt) | 1997-04-10 | 1998-04-10 | processo para preparar a 4'-desàxi-20', 20'-difluorovinblastina, e, processo para preparar a vinflunina. |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US6127377A (https=) |
| EP (3) | EP1357125A3 (https=) |
| JP (3) | JP4401440B2 (https=) |
| AT (2) | ATE270297T1 (https=) |
| AU (1) | AU737549C (https=) |
| BR (2) | BR9807944B1 (https=) |
| CA (3) | CA2455416C (https=) |
| CY (2) | CY1111476T1 (https=) |
| DE (3) | DE69841766D1 (https=) |
| DK (2) | DK1764368T3 (https=) |
| ES (2) | ES2347878T3 (https=) |
| FR (2) | FR2761990B1 (https=) |
| LU (1) | LU91769I2 (https=) |
| PT (2) | PT975640E (https=) |
| WO (1) | WO1998045301A1 (https=) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2761990B1 (fr) * | 1997-04-10 | 1999-06-25 | Pf Medicament | Derives halogenes antimitotiques d'alcaloides de vinca |
| US6890558B2 (en) * | 2002-05-31 | 2005-05-10 | R.P. Scherer Technologies, Inc. | Oral pharmaceutical composition for soft capsules containing vinorelbine and method of treatment |
| WO2005055939A2 (en) * | 2003-12-04 | 2005-06-23 | Amr Technology, Inc. | Vinca derivatives |
| WO2005055943A2 (en) * | 2003-12-04 | 2005-06-23 | Amr Technology, Inc. | Vinorelbine derivatives |
| FR2863891B1 (fr) * | 2003-12-23 | 2006-03-24 | Pf Medicament | Composition pharmaceutique de vinflunine destinee a une administration parentale, procede de preparation et utilisation |
| US20110015221A1 (en) * | 2003-12-23 | 2011-01-20 | Pierre Fabre Medicament | Pharmaceutical composition of vinflunine which is intended for parenteral administration preparation method thereof and use of same |
| US7772177B2 (en) | 2005-05-18 | 2010-08-10 | Aegera Therapeutics, Inc. | BIR domain binding compounds |
| FR2894966B1 (fr) | 2005-12-20 | 2008-03-14 | Pierre Fabre Medicament Sa | Nouvelle forme cristalline de la vinflunine |
| AU2007250443B2 (en) | 2006-05-16 | 2013-06-13 | Pharmascience Inc. | IAP BIR domain binding compounds |
| US20080125451A1 (en) * | 2006-09-12 | 2008-05-29 | Amr Technology, Inc. | Vinorelbine derivatives |
| US8039453B2 (en) * | 2006-09-12 | 2011-10-18 | Albany Molecular Research, Inc. | Vinca derivatives |
| FR2905949B1 (fr) * | 2006-09-20 | 2008-11-21 | Pierre Fabre Medicament Sa | Derives fluores de catharanthine, leur preparation et leur utilisation comme precurseurs d'alcaloides dimeres de vinca |
| FR2910812B1 (fr) | 2006-12-29 | 2009-03-20 | Pierre Fabre Medicament Sa | Compositions pharmaceutiques injectables lyophilisees de derives hemi-synthetiques d'alcaloide de vinca stables a temperature ambiante |
| FR2912406B1 (fr) * | 2007-02-13 | 2009-05-08 | Pierre Fabre Medicament Sa | Sels cristalins anhydres de vinflunine, procede de preparation et utilisation en tant que medicament et moyen de purification de la vinflunine. |
| FR2918567B1 (fr) * | 2007-07-11 | 2012-08-03 | Pf Medicament | Composition pharmaceutique stable d'un sel hydrosoluble de vinorelbine. |
| FR2918566B1 (fr) * | 2007-07-11 | 2009-10-09 | Pierre Fabre Medicament Sa | Composition pharmaceutique stable d'un sel hydrosoluble de vinflunine. |
| US20090076055A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched vinflunine |
| DE102010020994B4 (de) * | 2010-01-27 | 2022-01-27 | Interpane Entwicklungs-Und Beratungsgesellschaft Mbh | Verfahren zur Herstellung eines beschichteten Gegenstands mit Texturätzen |
| WO2011098904A1 (en) | 2010-02-12 | 2011-08-18 | Aegera Therapeutics, Inc. | Iap bir domain binding compounds |
| WO2011103007A2 (en) * | 2010-02-22 | 2011-08-25 | The Scripps Research Institute | 10'-fluorinated vinca alkaloids provide enhanced biological activity against mdr cancer cells |
| WO2026064527A1 (en) | 2024-09-19 | 2026-03-26 | Tesseract Medicines Us, Llc | Kras-targeting covalent-induced drug conjugates comprising a tubulin inhibitor payload |
| WO2026064520A1 (en) | 2024-09-19 | 2026-03-26 | Tesseract Medicines Us, Llc | Covalent-induced drug conjugates targeting kras and comprising a tubulin inhibitor payload |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2707988B1 (fr) * | 1993-07-21 | 1995-10-13 | Pf Medicament | Nouveaux dérivés antimitotiques des alcaloïdes binaires du catharantus rosesus, leur procédé de préparation et les compositions pharmaceutiques les comprenant. |
| FR2761990B1 (fr) * | 1997-04-10 | 1999-06-25 | Pf Medicament | Derives halogenes antimitotiques d'alcaloides de vinca |
-
1997
- 1997-04-10 FR FR9704398A patent/FR2761990B1/fr not_active Expired - Lifetime
-
1998
- 1998-04-10 JP JP54247098A patent/JP4401440B2/ja not_active Expired - Lifetime
- 1998-04-10 BR BRPI9807944-1A patent/BR9807944B1/pt not_active IP Right Cessation
- 1998-04-10 PT PT98920607T patent/PT975640E/pt unknown
- 1998-04-10 DK DK06124480.2T patent/DK1764368T3/da active
- 1998-04-10 DE DE69841766T patent/DE69841766D1/de not_active Expired - Lifetime
- 1998-04-10 ES ES06124480T patent/ES2347878T3/es not_active Expired - Lifetime
- 1998-04-10 DK DK98920607T patent/DK0975640T3/da active
- 1998-04-10 DE DE69824840T patent/DE69824840T2/de not_active Expired - Lifetime
- 1998-04-10 AU AU73408/98A patent/AU737549C/en not_active Expired
- 1998-04-10 BR BRPI9816177-6A patent/BR9816177B1/pt not_active IP Right Cessation
- 1998-04-10 EP EP20030017052 patent/EP1357125A3/fr not_active Ceased
- 1998-04-10 CA CA2455416A patent/CA2455416C/fr not_active Expired - Lifetime
- 1998-04-10 EP EP98920607A patent/EP0975640B1/fr not_active Expired - Lifetime
- 1998-04-10 WO PCT/FR1998/000730 patent/WO1998045301A1/fr not_active Ceased
- 1998-04-10 ES ES98920607T patent/ES2222588T3/es not_active Expired - Lifetime
- 1998-04-10 US US09/402,678 patent/US6127377A/en not_active Expired - Lifetime
- 1998-04-10 DE DE122010000054C patent/DE122010000054I1/de active Pending
- 1998-04-10 EP EP06124480A patent/EP1764368B1/fr not_active Expired - Lifetime
- 1998-04-10 AT AT98920607T patent/ATE270297T1/de active
- 1998-04-10 AT AT06124480T patent/ATE473987T1/de active
- 1998-04-10 CA CA002286560A patent/CA2286560C/fr not_active Expired - Lifetime
- 1998-04-10 PT PT06124480T patent/PT1764368E/pt unknown
- 1998-04-10 CA CA2665949A patent/CA2665949C/fr not_active Expired - Lifetime
-
2004
- 2004-03-03 JP JP2004059502A patent/JP4307292B2/ja not_active Expired - Lifetime
-
2009
- 2009-03-11 JP JP2009058098A patent/JP2009167196A/ja active Pending
-
2010
- 2010-09-27 FR FR10C0045C patent/FR10C0045I2/fr active Active
- 2010-10-14 CY CY20101100917T patent/CY1111476T1/el unknown
- 2010-12-22 LU LU91769C patent/LU91769I2/fr unknown
- 2010-12-22 CY CY2010019C patent/CY2010019I1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BR9807944B1 (pt) | derivados antimitóticos dos alcalóides da vinca, processo para preparar os mesmos e uso dos derivados. | |
| US5620985A (en) | Antimitotic binary alkaloid derivatives from catharanthus roseus | |
| Wang et al. | Enantioselective complexation of organic ammonium ions by simple tetracyclic podand ionophores | |
| Ridge et al. | Reactions of strong bases with alkyl halides in the gas phase. New look at E2 base-induced elimination reactions without solvent participation | |
| EP3380447B1 (en) | Method for synthesizing iodo- or astatoarenes using diaryliodonium salts | |
| Zupan | Fluorination with xenon difluoride; Part IX. Reaction with phenylsubstituted sulphides | |
| Takemura et al. | Syntheses and properties of highly symmetrical cage compounds: pyridine analogs of hexa-m-xylylenetetraamine | |
| Kol et al. | Functionalization of aromatic molecules using HOF. cntdot. CH3CN and CH3OF | |
| Praly et al. | Photohalogenation of glycopyranosyl halides: an expedient route to C-1 gem dihalogenated sugars | |
| Murayama et al. | Metal-catalysed organic photoreactions. Evidence for the long-range electron-transfer mechanism in the uranyl-or iron (III)-catalysed photoreactions of olefins | |
| BRPI0411068B1 (pt) | Anchorages of colchicosides | |
| MXPA99009264A (en) | Vinca alkaloid antimitotic halogenated derivatives | |
| Mackay et al. | Structure of 1, 6-bis (p-chlorophenyl)-3, 4-diacetyl-1, 5-hexaazadiene: a compound with a highly electrophilic N-acetyl group | |
| Twum et al. | Observation by NMR of cationic Wheland-like intermediates in the deiodination of protected 1-iodonaphthalene-2, 4-diamines in acidic media | |
| ITMI941696A1 (it) | 8-fluoro-antracicline, loro processi di preparazione e composizioni farmaceutiche che le contengono | |
| WO1997042193A1 (en) | Process for the manufacture of 1-substituted-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane salts | |
| Kobzev et al. | Synthesis of pyrrolo [1, 2-d][1, 4] diazecines through an alkyne-trigged sequence of cleavage/cyclization in 1-phenylethynyl substituted pyrrolo [1, 2-a] pyrazines | |
| HU189817B (en) | Process for preparing vincristine and addition salts thereof | |
| Astruc et al. | Can t-BuOK be a good nucleophile? An ion-pairing answer. Cleavage of aryl ethers in their cationic iron complexes | |
| Roche et al. | Synthesis and structural verification of novel olefinic derivatives of bicyclo [2.2. 2] octane. Intermediates in the synthesis of bridged morphinan-like compounds | |
| JPH07110866B2 (ja) | ヴアンクリスチンの製造方法 | |
| CN116283819A (zh) | 一种异噻唑-5(2h)-亚胺类化合物的制备方法及其应用 | |
| Lundberg | Substitution reactions of 5 [alpha]-Cholestan-6 [alpha]-ols | |
| HU193318B (en) | Process for producing new bis- indol derivatives | |
| JPS6043349B2 (ja) | ヘテロ環の縮合した１，２−ジアゼピン化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B07A | Application suspended after technical examination (opinion) [chapter 7.1 patent gazette] | ||
| B06A | Patent application procedure suspended [chapter 6.1 patent gazette] | ||
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] |
Free format text: PRAZO DE VALIDADE: 10 (DEZ) ANOS CONTADOS A PARTIR DE 08/02/2011, OBSERVADAS AS CONDICOES LEGAIS. |
|
| B21A | Patent or certificate of addition expired [chapter 21.1 patent gazette] |
Free format text: PATENTE EXTINTA EM 08.02.2021 |