HUP0200529A2 - Optically pure camptothecin analogues, pharmaceutical compositions containing them and their use - Google Patents
Optically pure camptothecin analogues, pharmaceutical compositions containing them and their use Download PDFInfo
- Publication number
- HUP0200529A2 HUP0200529A2 HU0200529A HUP0200529A HUP0200529A2 HU P0200529 A2 HUP0200529 A2 HU P0200529A2 HU 0200529 A HU0200529 A HU 0200529A HU P0200529 A HUP0200529 A HU P0200529A HU P0200529 A2 HUP0200529 A2 HU P0200529A2
- Authority
- HU
- Hungary
- Prior art keywords
- ethyl
- hydroxy
- indolizino
- quinoline
- dione
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 title description 13
- 150000001875 compounds Chemical class 0.000 claims description 108
- 125000000217 alkyl group Chemical group 0.000 claims description 50
- 125000005843 halogen group Chemical group 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 101710183280 Topoisomerase Proteins 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- DARUIXPLGGGEEF-WJOKGBTCSA-N (5r)-12-decyl-5-ethyl-9-fluoro-5-hydroxy-4,5,13,15-tetrahydro-1h,3h-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione Chemical compound C12=NC3=CC(F)=CC=C3C(CCCCCCCCCC)=C2CN(C2=O)C1=CC1=C2COC(=O)C[C@]1(O)CC DARUIXPLGGGEEF-WJOKGBTCSA-N 0.000 claims description 3
- 208000030852 Parasitic disease Diseases 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- 230000009385 viral infection Effects 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 1
- 239000000047 product Substances 0.000 description 84
- 238000000034 method Methods 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 52
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 47
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 47
- 239000007787 solid Substances 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 238000002844 melting Methods 0.000 description 36
- 230000008018 melting Effects 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 239000003153 chemical reaction reagent Substances 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- 239000012265 solid product Substances 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- LGPVTNAJFDUWLF-UHFFFAOYSA-N 2-amino-4-fluorobenzoic acid Chemical compound NC1=CC(F)=CC=C1C(O)=O LGPVTNAJFDUWLF-UHFFFAOYSA-N 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 239000000284 extract Substances 0.000 description 13
- HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical compound NC1=CC=CC=C1C#N HLCPWBZNUKCSBN-UHFFFAOYSA-N 0.000 description 12
- 239000000010 aprotic solvent Substances 0.000 description 12
- -1 methoxy, ethoxy, propoxy Chemical group 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- DGOZIZVTANAGCA-UHFFFAOYSA-N 2-amino-4,5-difluorobenzoic acid Chemical compound NC1=CC(F)=C(F)C=C1C(O)=O DGOZIZVTANAGCA-UHFFFAOYSA-N 0.000 description 8
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- TWSZCEBPTKBNBR-UHFFFAOYSA-N 2-amino-4,6-difluorobenzoic acid Chemical compound NC1=CC(F)=CC(F)=C1C(O)=O TWSZCEBPTKBNBR-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 7
- 229910004298 SiO 2 Inorganic materials 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229940127093 camptothecin Drugs 0.000 description 7
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- IPOVOSHRRIJKBR-UHFFFAOYSA-N 2-ethylpropanedioyl dichloride Chemical compound CCC(C(Cl)=O)C(Cl)=O IPOVOSHRRIJKBR-UHFFFAOYSA-N 0.000 description 6
- RKFNAZGRJVNWEW-UHFFFAOYSA-N 3-cyclohexylpropanal Chemical compound O=CCCC1CCCCC1 RKFNAZGRJVNWEW-UHFFFAOYSA-N 0.000 description 6
- YGCZTXZTJXYWCO-UHFFFAOYSA-N 3-phenylpropanal Chemical compound O=CCCC1=CC=CC=C1 YGCZTXZTJXYWCO-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- KMPQYAYAQWNLME-UHFFFAOYSA-N undecanal Chemical compound CCCCCCCCCCC=O KMPQYAYAQWNLME-UHFFFAOYSA-N 0.000 description 6
- 150000002690 malonic acid derivatives Chemical class 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- MYKBYBUJCGGUDZ-XMMPIXPASA-N (5r)-5-ethyl-9,11-difluoro-5-hydroxy-12-propyl-4,5,13,15-tetrahydro-1h,3h-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione Chemical compound C12=NC3=CC(F)=CC(F)=C3C(CCC)=C2CN(C2=O)C1=CC1=C2COC(=O)C[C@]1(O)CC MYKBYBUJCGGUDZ-XMMPIXPASA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- ZFGCYWLLTGEGEY-UHFFFAOYSA-M [Br-].FC1=CC(F)=C(F)C([Mg+])=C1F Chemical compound [Br-].FC1=CC(F)=C(F)C([Mg+])=C1F ZFGCYWLLTGEGEY-UHFFFAOYSA-M 0.000 description 4
- ZZWGJRXCBZUTLD-UHFFFAOYSA-M [Br-].FC1=CC(F)=C([Mg+])C(F)=C1 Chemical compound [Br-].FC1=CC(F)=C([Mg+])C(F)=C1 ZZWGJRXCBZUTLD-UHFFFAOYSA-M 0.000 description 4
- GVCYNWARJJVWCT-UHFFFAOYSA-M [Br-].FC1=CC=CC(F)=C1[Mg+] Chemical compound [Br-].FC1=CC=CC(F)=C1[Mg+] GVCYNWARJJVWCT-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- AMQDBUIQKQUCKY-UHFFFAOYSA-M magnesium;1,2,3,4,5-pentafluorobenzene-6-ide;bromide Chemical compound [Mg+2].[Br-].FC1=[C-]C(F)=C(F)C(F)=C1F AMQDBUIQKQUCKY-UHFFFAOYSA-M 0.000 description 4
- FAANOBAJWDSCGM-UHFFFAOYSA-M magnesium;1,2,3-trifluorobenzene-5-ide;bromide Chemical compound [Mg+2].[Br-].FC1=C[C-]=CC(F)=C1F FAANOBAJWDSCGM-UHFFFAOYSA-M 0.000 description 4
- XQNUHMQSOMLVGM-UHFFFAOYSA-M magnesium;1,3-difluorobenzene-5-ide;bromide Chemical compound [Mg+2].[Br-].FC1=C[C-]=CC(F)=C1 XQNUHMQSOMLVGM-UHFFFAOYSA-M 0.000 description 4
- BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- PZBQTEAQROIDHA-RUZDIDTESA-N (5r)-12-butyl-5-ethyl-9,10-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1h,3h-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione Chemical compound C12=NC3=CC(F)=C(F)C=C3C(CCCC)=C2CN(C2=O)C1=CC1=C2COC(=O)C[C@]1(O)CC PZBQTEAQROIDHA-RUZDIDTESA-N 0.000 description 3
- MQCSQJFJJLSWSB-OAQYLSRUSA-N (5r)-5-ethyl-9,11-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1h,3h-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione Chemical compound CC[C@@]1(O)CC(=O)OCC(C2=O)=C1C=C1N2CC2=CC3=C(F)C=C(F)C=C3N=C21 MQCSQJFJJLSWSB-OAQYLSRUSA-N 0.000 description 3
- BEIVRAYQIXQZKG-UHFFFAOYSA-N 3-hydroxy-3-[2-methoxy-3-(phenylmethoxymethyl)pyridin-4-yl]pentanoic acid Chemical compound OC(=O)CC(O)(CC)C1=CC=NC(OC)=C1COCC1=CC=CC=C1 BEIVRAYQIXQZKG-UHFFFAOYSA-N 0.000 description 3
- SCJCDNUXDWFVFI-UHFFFAOYSA-N 4,4,4-trifluorobutanal Chemical compound FC(F)(F)CCC=O SCJCDNUXDWFVFI-UHFFFAOYSA-N 0.000 description 3
- DZWACSVTJIDBDB-UHFFFAOYSA-N 4,4-dimethylpentanal Chemical compound CC(C)(C)CCC=O DZWACSVTJIDBDB-UHFFFAOYSA-N 0.000 description 3
- JGEGJYXHCFUMJF-UHFFFAOYSA-N 4-methylpentanal Chemical compound CC(C)CCC=O JGEGJYXHCFUMJF-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 125000003158 alcohol group Chemical group 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical class C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- MHSXRVVAJFLXQG-GDLZYMKVSA-N (5r)-12-(2-cyclohexylethyl)-5-ethyl-9,11-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1h,3h-oxepino[3',4':6,7]indolizino [1,2-b]quinoline-3,15-dione Chemical compound C([C@]1(O)CC)C(=O)OCC(C(N2CC3=4)=O)=C1C=C2C3=NC1=CC(F)=CC(F)=C1C=4CCC1CCCCC1 MHSXRVVAJFLXQG-GDLZYMKVSA-N 0.000 description 2
- OFOSLOUHQSITBC-HHHXNRCGSA-N (5r)-12-(3,3-dimethylbutyl)-5-ethyl-9,11-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1h,3h-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione Chemical compound CC[C@@]1(O)CC(=O)OCC(C2=O)=C1C=C1N2CC2=C(CCC(C)(C)C)C3=C(F)C=C(F)C=C3N=C21 OFOSLOUHQSITBC-HHHXNRCGSA-N 0.000 description 2
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000001472 potassium tartrate Substances 0.000 description 1
- 229940111695 potassium tartrate Drugs 0.000 description 1
- 235000011005 potassium tartrates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- WPDZACQODUHYCH-UHFFFAOYSA-N propan-2-yloxycarbonyliminocarbamic acid Chemical compound CC(C)OC(=O)N=NC(O)=O WPDZACQODUHYCH-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000012128 staining reagent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- HXIUJMODSXDEDI-UHFFFAOYSA-N tert-butyl 3-hydroxy-3-[2-methoxy-3-(phenylmethoxymethyl)pyridin-4-yl]pentanoate Chemical compound CC(C)(C)OC(=O)CC(O)(CC)C1=CC=NC(OC)=C1COCC1=CC=CC=C1 HXIUJMODSXDEDI-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Claims (10)
- · ····· · « ·«··* • 4 4 » ♦ · » 9Szabadalmi igénypontok1. (I) általános képletű vegyületek, amelyek vagy az IA általános képletnek felelnek meg, amelybenRí jelentése rövidszénláncú alkilcsoport,R2, R3, R4 és R5 jelentése egymástól függetlenül hidrogénatom, halogénatom vagy -OSO2R10 csoport,R<5 jelentése hidrogénatom, egyenes vagy elágazó láncú 1-12 szénatomos alkilcsoport, mely adott esetben egy vagy több azonos vagy eltérő halogénatommal van helyettesítve, vagy rövidszénláncú hidroxialkil-, rövidszénláncú alkoxi-(rövidszénláncú)alkil-, cikloalkil-, rövidszénláncú cikloalkil-alkil-, vagy nitrocsoport, halogénatom, -(CH2)mSiR7R8R9 csoport, vagy pedig egy helyettesítetlen vagy helyettesített arilcsoport, vagy egy az arilcsoporton helyettesített vagy helyettesítetlen rövidszénláncú aralkilcsoport, amelyekben az arilcsoporthoz kapcsolódó, azonos vagy eltérő szubsztituensek: rövidszénláncú alkilcsoport, hidroxilcsoport, halogénatom, aminocsoport, rövidszénláncú alkilaminocsoport, di(rövidszénláncú alkil)aminocsoport, -CF3 vagy -OCF3 csoport,R7, R8 és R9 egymástól függetlenül rövidszénláncú alkilcsoportokat jelentenek,Rio jelentése rövidszénláncú alkilcsoport, mely adott esetben egy vagy több azonos vagy eltérő halogénatommal van helyettesítve, vagy egy arilcsoport, amely adott esetben egy vagy több azonos vagy eltérő rövidszénláncú alkilcsoporttal van helyettesítve, m értéke egy nulla és 6 közötti egész szám;azzal a kikötéssel, hogy ahol a „rövid” jelző egy alkilcsoportra vonatkozik, az legfeljebb 6 szénatomos lehet, és ha R2 jelentése hidrogénatom, akkor- Rő jelentése egyenes vagy elágazó 7-12 szénatomos alkilcsoport, -(CH2)mSiR7R8R9 csoport, vagy egy arilcsoport, amely egy vagy több azonos ··« ·» ·· ·<« • «* «· · * ·*·♦·· « 4 · * * 9 vagy eltérő szubsztituenssel van helyettesítve, mely szubsztituens di(rövidszénláncú alkil)amino- vagy -OCF3 csoport lehet, és/vagy- az R3, R4 és R5 csoportok közül legalább az egyik -OSO2R10 csoport;vagy azok addiciós sói.
- 2. Az 1. igénypont szerinti vegyületek, amelyekben Rj jelentése etilcsoport.
- 3. A 2. igénypont szerinti Ia általános képletű vegyületek, amelyek az aláb- biak egyikének felelnek meg:(5R)-5-etil-8-fhior-5-hidroxi-4,5,13,15-tetrahidro-1 H,3H-oxepino[3 ’ ,4 ’ :6,7]indolizino[ 1,2-b]kinolein-3,15-dion, (5R)-5-etil-9,l 0-difhior-5-hidroxi-12-(2-trimetilszilil-etil) -4,5,13,15-tetrahidro1 H,3H-oxepino[3 ’ ,4 ’ :6,7]indohzino[ 1,2-b]kinolein-3,15-dion, (5R)-5-etil-5-hidroxi-l 2-(2-trimetilszilil-etil)-4,5,13,15-tetrahidro-1 H,3H-oxepino[3 ’,4’ :6,7]indolizino[l ,2-b]kinolein-3,15-dion, (5R)-12-decil-5-etil-9-fluor-5-hidroxi-4,5,13,15-tetrahidro-1 H,3H-oxepino[3 ’,4’ :6,7]indolizino[l ,2-b]kinolein-3,l 5-dion, (5R)-12-decil-5-etil-9,10-difhior-5-hidroxi-4,5,13,15-tetrahidro-1 H,3H-oxepino[3 ’ ,4 ’ :6,7]indolizino[ 1,2-b]kinolein-3,15-dión, (5R)-12-decil-5-etil-9,11 -difhior-5-hidroxi-12-fenil-4,5,13,15-tetrahidro-1 H,3Hoxepino [3 ’ ,4 ’: 6,7] indolizino [ 1,2-b]kinolein-3,15-dión, (5R)-5-etil-9-fluor-5-hidroxi-12-(4-trifhiormetoxi-fenil)-4,5,13,15 -tetrahidro1H,3H-oxepino[3’,4’:6,7]indolizino[l,2-b]kinolein-3,l 5-dion, (5R)-12-(4-dimetilamino-fenil)-5-etil-9-fluor-5 -hidroxi-4,5,13,15 -tetrahidro1 H,3 H-oxepino [3 ’ ,4 ’: 6,7]indolizino [ 1,2-b]kinolein-3,15-dion, (5R)-5-etil-9-fluor-5 -hidroxi-3,15-dioxo-4,5,13,15-tetrahidro-1 H,3H-oxepino[3 ’ ,4 ’: 6,7]indolizino [ 1,2-b]kinolein-10-il-trifhiormetánszulfonát.
- 4. A 3. igénypont szerinti Ia általános képletű vegyületek, melyek az aláb- biak egyikének felelnek meg:(5R)-5-etil-9,10-difluor-5 -hidroxi-12-(2-trimetilszilil-etil)-4,5,13,15-tetrahidro1 H,3H-oxepino [3 ’ ,4 ’: 6,7] indolizino [ 1,2-b]kinolein-3,15-dion, (5R)-5-etil-5-hidroxi-12-(2-trimetilszilil-etil)-4,5,13,15-tetrahidro-1 H,3H-oxepino [3 ’ ,4 ’: 6,7] indolizino [ 1,2-b]kinolein-3,15-dion.
- 5. Az 1-4. igénypontok bármelyike szerinti IA általános képletű vegyületek vagy azok gyógyászati szempontból elfogadható sói mint gyógyszerek.
- 6. Gyógyászati kompozíció, amely hatóanyagként legalább egy az 1-4. igénypontok bármelyike szerinti vegyületet tartalmaz.
- 7. Az 1-4. igénypontok bármelyike szerinti vegyületek alkalmazása topoizomerázok, különösen az I típusú vagy a II típusú topoizomeráz gátlására használható gyógyszerek előállítására.
- 8. Az 1-4. igénypontok bármelyike szerinti vegyületek alkalmazása daganatok kezelésére használható gyógyszerek előállítására.
- 9. Az 1-4. igénypontok bármelyike szerinti vegyületek alkalmazása vírusos fertőzések vagy betegségek kezelésére használható gyógyszerek előállítására.
- 10. Az 1-4. igénypontok bármelyike szerinti vegyületek alkalmazása parazita fertőzések kezelésére használható gyógyszerek előállítására.A meghatalmazott:DANÜBIASatefaM és Védjegy Iroda Kft Dr. Gárdonyt Zoltánná suabírfaEai ügyvivő
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9902398A FR2790261B1 (fr) | 1999-02-26 | 1999-02-26 | Nouveaux analogues optiquement purs de la camptothecine et leurs procedes de preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUP0200529A2 true HUP0200529A2 (en) | 2002-06-29 |
| HUP0200529A3 HUP0200529A3 (en) | 2004-03-29 |
Family
ID=9542564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU0200529A HUP0200529A3 (en) | 1999-02-26 | 2000-02-24 | Optically pure camptothecin analogues, pharmaceutical compositions containing them and their use |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US7012079B1 (hu) |
| EP (2) | EP1338599B1 (hu) |
| JP (1) | JP2002537399A (hu) |
| KR (1) | KR20010108270A (hu) |
| CN (1) | CN1195757C (hu) |
| AR (1) | AR022740A1 (hu) |
| AT (2) | ATE353902T1 (hu) |
| AU (1) | AU772632B2 (hu) |
| BR (1) | BR0008526A (hu) |
| CA (1) | CA2364705C (hu) |
| CZ (1) | CZ20013091A3 (hu) |
| DE (2) | DE60033447T2 (hu) |
| DK (1) | DK1165565T3 (hu) |
| ES (2) | ES2200829T3 (hu) |
| FR (1) | FR2790261B1 (hu) |
| HK (1) | HK1045514B (hu) |
| HR (1) | HRP20010622A2 (hu) |
| HU (1) | HUP0200529A3 (hu) |
| IL (2) | IL144987A0 (hu) |
| MX (1) | MXPA01008658A (hu) |
| MY (1) | MY127819A (hu) |
| NO (1) | NO327260B1 (hu) |
| NZ (1) | NZ514153A (hu) |
| PL (1) | PL202393B1 (hu) |
| PT (1) | PT1165565E (hu) |
| RU (1) | RU2230745C2 (hu) |
| TW (1) | TWI268931B (hu) |
| WO (1) | WO2000050427A1 (hu) |
| ZA (1) | ZA200107738B (hu) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6207832B1 (en) | 1999-04-09 | 2001-03-27 | University Of Pittsburgh | Camptothecin analogs and methods of preparation thereof |
| US6372906B1 (en) | 2001-04-12 | 2002-04-16 | University Of Pittsburgh | Synthesis of silyl camptothecins and silyl homocamptothecins |
| US6723853B2 (en) | 2001-08-27 | 2004-04-20 | University Of Pittsburgh | Intermediates and methods of preparation of intermediates in the enantiomeric synthesis of (20R)homocamptothecins and the enantiomeric synthesis of (20R)homocamptothecins |
| AR046579A1 (es) * | 2003-11-12 | 2005-12-14 | Smithkline Beecham Corp | Compuesto cristalino de topotecan, composicion farmaceutica que lo comprende, procedimiento para prepararlo y su uso para preparar dicha composicion farmaceutica |
| CN100408582C (zh) * | 2004-02-12 | 2008-08-06 | 中国人民解放军第二军医大学 | 高喜树碱类化合物及其制备方法和用途 |
| WO2006033011A1 (en) * | 2004-09-21 | 2006-03-30 | Societe De Conseils De Recherches Et D'applications Scientifique (S.C.R.A.S.) | Novel processes for the production of useful intermediates |
| US8658894B1 (en) * | 2010-09-14 | 2014-02-25 | Cooper Technologies Company | Cover assembly for an electrical box |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3008226B2 (ja) * | 1991-01-16 | 2000-02-14 | 第一製薬株式会社 | 六環性化合物 |
| FR2757515B1 (fr) * | 1996-12-20 | 2000-05-05 | Sod Conseils Rech Applic | Formes prodrogues et nouveaux analogues de la camptothecine, leurs procedes de preparation, leur application comme medicaments et les compositions pharmaceutiques les contenant |
| EP0835258B1 (fr) * | 1995-06-21 | 2002-09-25 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Nouveaux analogues de la camptothecine, des procedes de preparation, leur application comme medicaments et les compositions pharmaceutiques les contenant |
| FR2768431B1 (fr) | 1997-08-29 | 2000-03-24 | Sod Conseils Rech Applic | Nouveaux analogues optiquement purs de la camptothecine, nouvel intermediaire de synthese optiquement pur et son procede de preparation |
| FR2757514B1 (fr) * | 1996-12-20 | 1999-02-12 | Sod Conseils Rech Applic | Nouveaux analogues de la camptothecine, des procedes de preparation, leur application comme medicaments et les compositions pharmaceutiques les contenant |
| GB9512670D0 (en) * | 1995-06-21 | 1995-08-23 | Sod Conseils Rech Applic | Camptothecin analogues |
| ES2214634T3 (es) * | 1996-08-19 | 2004-09-16 | Bionumerik Pharmaceuticals, Inc. | Derivados muy lipofilos de la camptotecina. |
| UA57757C2 (uk) * | 1996-12-20 | 2003-07-15 | Сос'Єте Де Консей Де Решерш Е Даплікасьон С'Єнтіфік (С.К.Р.А.С.) | Аналоги камптотецину, спосіб їх отримання (варіанти) і фармацевтична композиція |
| DK1017675T3 (da) * | 1997-02-14 | 2006-10-16 | Bionumerik Pharmaceuticals Inc | Stærkt lipofile camptothecinderivater |
| US6207673B1 (en) * | 1997-03-12 | 2001-03-27 | The University Of North Carolina At Chapel Hill | Covalent conjugates of topoisomerase I and topoisomerase II inhibitors |
| US6207832B1 (en) * | 1999-04-09 | 2001-03-27 | University Of Pittsburgh | Camptothecin analogs and methods of preparation thereof |
-
1999
- 1999-02-26 FR FR9902398A patent/FR2790261B1/fr not_active Expired - Fee Related
-
2000
- 2000-02-23 TW TW089103136A patent/TWI268931B/zh not_active IP Right Cessation
- 2000-02-23 MY MYPI20000660A patent/MY127819A/en unknown
- 2000-02-24 BR BR0008526-0A patent/BR0008526A/pt not_active IP Right Cessation
- 2000-02-24 EP EP03075924A patent/EP1338599B1/fr not_active Expired - Lifetime
- 2000-02-24 US US09/806,952 patent/US7012079B1/en not_active Expired - Fee Related
- 2000-02-24 CZ CZ20013091A patent/CZ20013091A3/cs unknown
- 2000-02-24 PT PT00907714T patent/PT1165565E/pt unknown
- 2000-02-24 AR ARP000100795A patent/AR022740A1/es active IP Right Grant
- 2000-02-24 JP JP2000601007A patent/JP2002537399A/ja active Pending
- 2000-02-24 AT AT03075924T patent/ATE353902T1/de not_active IP Right Cessation
- 2000-02-24 PL PL361334A patent/PL202393B1/pl not_active IP Right Cessation
- 2000-02-24 MX MXPA01008658A patent/MXPA01008658A/es unknown
- 2000-02-24 CN CNB008055513A patent/CN1195757C/zh not_active Expired - Fee Related
- 2000-02-24 DE DE60033447T patent/DE60033447T2/de not_active Expired - Lifetime
- 2000-02-24 DE DE60003170T patent/DE60003170T2/de not_active Expired - Lifetime
- 2000-02-24 AU AU29210/00A patent/AU772632B2/en not_active Ceased
- 2000-02-24 HU HU0200529A patent/HUP0200529A3/hu unknown
- 2000-02-24 AT AT00907714T patent/ATE242248T1/de active
- 2000-02-24 HK HK02107033.2A patent/HK1045514B/zh not_active IP Right Cessation
- 2000-02-24 NZ NZ514153A patent/NZ514153A/xx not_active IP Right Cessation
- 2000-02-24 WO PCT/FR2000/000461 patent/WO2000050427A1/fr not_active Ceased
- 2000-02-24 DK DK00907714T patent/DK1165565T3/da active
- 2000-02-24 CA CA2364705A patent/CA2364705C/fr not_active Expired - Fee Related
- 2000-02-24 EP EP00907714A patent/EP1165565B1/fr not_active Expired - Lifetime
- 2000-02-24 KR KR1020017010920A patent/KR20010108270A/ko not_active Ceased
- 2000-02-24 IL IL14498700A patent/IL144987A0/xx active IP Right Grant
- 2000-02-24 ES ES00907714T patent/ES2200829T3/es not_active Expired - Lifetime
- 2000-02-24 ES ES03075924T patent/ES2282564T3/es not_active Expired - Lifetime
- 2000-02-24 HR HR20010622A patent/HRP20010622A2/hr not_active Application Discontinuation
- 2000-02-24 RU RU2001126127/04A patent/RU2230745C2/ru not_active IP Right Cessation
-
2001
- 2001-08-20 IL IL144987A patent/IL144987A/en not_active IP Right Cessation
- 2001-08-24 NO NO20014117A patent/NO327260B1/no not_active IP Right Cessation
- 2001-09-19 ZA ZA200107738A patent/ZA200107738B/xx unknown
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Owner name: IPSEN PHARMA S.A.S., FR Free format text: FORMER OWNER(S): SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES (S.C.R.A.S.), FR |
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| FA9A | Lapse of provisional patent protection due to relinquishment or protection considered relinquished |