NO327260B1 - Optisk rene camptothecin-analoger, medikament og farmasoytisk preparat inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom - Google Patents
Optisk rene camptothecin-analoger, medikament og farmasoytisk preparat inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom Download PDFInfo
- Publication number
- NO327260B1 NO327260B1 NO20014117A NO20014117A NO327260B1 NO 327260 B1 NO327260 B1 NO 327260B1 NO 20014117 A NO20014117 A NO 20014117A NO 20014117 A NO20014117 A NO 20014117A NO 327260 B1 NO327260 B1 NO 327260B1
- Authority
- NO
- Norway
- Prior art keywords
- ethyl
- indolizino
- dione
- oxepino
- hydroxy
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 87
- 229940079593 drug Drugs 0.000 title claims description 11
- 239000003814 drug Substances 0.000 title claims description 11
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 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 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 5
- 201000010099 disease Diseases 0.000 title description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 101710183280 Topoisomerase Proteins 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 238000000034 method Methods 0.000 description 195
- 239000007787 solid Substances 0.000 description 65
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
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- 239000000047 product Substances 0.000 description 46
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- -1 alkyl radical Chemical class 0.000 description 33
- 239000000243 solution Substances 0.000 description 33
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
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- 239000012429 reaction media Substances 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000002609 medium Substances 0.000 description 15
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- 239000011780 sodium chloride Substances 0.000 description 14
- 239000000284 extract Substances 0.000 description 13
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 239000000010 aprotic solvent Substances 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
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- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 238000001914 filtration Methods 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
- 239000012047 saturated solution 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
- 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
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 238000002360 preparation method Methods 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
- 229940127093 camptothecin Drugs 0.000 description 7
- 210000004027 cell Anatomy 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
- 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
- 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
- 229910052786 argon Inorganic materials 0.000 description 6
- 125000003118 aryl group Chemical group 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
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- 239000002253 acid Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
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- 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
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- 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
- 238000010992 reflux Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- KMPQYAYAQWNLME-UHFFFAOYSA-N undecanal Chemical compound CCCCCCCCCCC=O KMPQYAYAQWNLME-UHFFFAOYSA-N 0.000 description 4
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
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- 125000004435 hydrogen atom Chemical group [H]* 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
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- 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
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- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
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- 150000002148 esters Chemical class 0.000 description 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
- ULBLITMQCMVRMY-UHFFFAOYSA-N ethyl 2,4-dichloroquinoline-3-carboxylate Chemical compound C1=CC=CC2=C(Cl)C(C(=O)OCC)=C(Cl)N=C21 ULBLITMQCMVRMY-UHFFFAOYSA-N 0.000 description 1
- AQDSJAXDYWKFRB-UHFFFAOYSA-N ethyl 2-chloro-5-fluoroquinoline-3-carboxylate Chemical compound C1=CC=C2N=C(Cl)C(C(=O)OCC)=CC2=C1F AQDSJAXDYWKFRB-UHFFFAOYSA-N 0.000 description 1
- HNWQMBKFXFOBLR-UHFFFAOYSA-N ethyl 4-benzyl-2-oxo-1h-quinoline-3-carboxylate Chemical compound C12=CC=CC=C2NC(=O)C(C(=O)OCC)=C1CC1=CC=CC=C1 HNWQMBKFXFOBLR-UHFFFAOYSA-N 0.000 description 1
- ORJPWYNMEHWCEE-UHFFFAOYSA-N ethyl 5-fluoro-2-oxo-1h-quinoline-3-carboxylate Chemical compound C1=CC=C2NC(=O)C(C(=O)OCC)=CC2=C1F ORJPWYNMEHWCEE-UHFFFAOYSA-N 0.000 description 1
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- 238000007429 general method Methods 0.000 description 1
- ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 229910000360 iron(III) sulfate Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
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- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- WJGVYRMMIIWBAU-UHFFFAOYSA-M magnesium;2-methylbutane;bromide Chemical compound [Mg+2].[Br-].CC(C)C[CH2-] WJGVYRMMIIWBAU-UHFFFAOYSA-M 0.000 description 1
- LWLPYZUDBNFNAH-UHFFFAOYSA-M magnesium;butane;bromide Chemical compound [Mg+2].[Br-].CCC[CH2-] LWLPYZUDBNFNAH-UHFFFAOYSA-M 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- DTKMKZYEOXZPQZ-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=C[C-]=C1 DTKMKZYEOXZPQZ-UHFFFAOYSA-M 0.000 description 1
- SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 1
- JFWSITPEDQPZNZ-UHFFFAOYSA-M magnesium;tert-butylbenzene;bromide Chemical compound [Mg+2].[Br-].CC(C)(C)C1=CC=[C-]C=C1 JFWSITPEDQPZNZ-UHFFFAOYSA-M 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- IVKNUIVDQMARCO-UHFFFAOYSA-N oxazin-4-one Chemical compound O=C1C=CON=C1 IVKNUIVDQMARCO-UHFFFAOYSA-N 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 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
- 229920006316 polyvinylpyrrolidine Polymers 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
- 230000035755 proliferation Effects 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
- 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
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 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
- 150000003254 radicals Chemical class 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 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
- 239000002356 single layer Substances 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
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 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
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 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
- 210000001550 testis Anatomy 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| 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 |
| PCT/FR2000/000461 WO2000050427A1 (fr) | 1999-02-26 | 2000-02-24 | Analogues optiquement purs de la camptothecine |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20014117D0 NO20014117D0 (no) | 2001-08-24 |
| NO20014117L NO20014117L (no) | 2001-10-11 |
| NO327260B1 true NO327260B1 (no) | 2009-05-25 |
Family
ID=9542564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20014117A NO327260B1 (no) | 1999-02-26 | 2001-08-24 | Optisk rene camptothecin-analoger, medikament og farmasoytisk preparat inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US7012079B1 (hr) |
| EP (2) | EP1165565B1 (hr) |
| JP (1) | JP2002537399A (hr) |
| KR (1) | KR20010108270A (hr) |
| CN (1) | CN1195757C (hr) |
| AR (1) | AR022740A1 (hr) |
| AT (2) | ATE353902T1 (hr) |
| AU (1) | AU772632B2 (hr) |
| BR (1) | BR0008526A (hr) |
| CA (1) | CA2364705C (hr) |
| CZ (1) | CZ20013091A3 (hr) |
| DE (2) | DE60033447T2 (hr) |
| DK (1) | DK1165565T3 (hr) |
| ES (2) | ES2200829T3 (hr) |
| FR (1) | FR2790261B1 (hr) |
| HK (1) | HK1045514B (hr) |
| HR (1) | HRP20010622A2 (hr) |
| HU (1) | HUP0200529A3 (hr) |
| IL (2) | IL144987A0 (hr) |
| MX (1) | MXPA01008658A (hr) |
| MY (1) | MY127819A (hr) |
| NO (1) | NO327260B1 (hr) |
| NZ (1) | NZ514153A (hr) |
| PL (1) | PL202393B1 (hr) |
| PT (1) | PT1165565E (hr) |
| RU (1) | RU2230745C2 (hr) |
| TW (1) | TWI268931B (hr) |
| WO (1) | WO2000050427A1 (hr) |
| ZA (1) | ZA200107738B (hr) |
Families Citing this family (6)
| 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 |
| 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 |
| EP1794127A1 (en) * | 2004-09-21 | 2007-06-13 | Société de Conseils de Recherches et d'Applications Scientifiques ( S.C.R.A.S.) | Novel processes for the production of useful intermediates |
| US8575484B1 (en) | 2010-09-14 | 2013-11-05 | Cooper Technologies Company | Adjustable-depth ring assembly and method of installation |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9512670D0 (en) * | 1995-06-21 | 1995-08-23 | Sod Conseils Rech Applic | Camptothecin analogues |
| 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 |
| 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 |
| PT835258E (pt) * | 1995-06-21 | 2003-02-28 | Sod Conseils Rech Applic | Novos analogos de camptotecina, processos para a sua preparacao, sua utilizacao como farmacos e composicoes farmaceuticas que os contem |
| 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 |
| BR9711319B1 (pt) * | 1996-08-19 | 2009-08-11 | derivados de camptotecina altamente lipofìlicos. | |
| 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 |
| ATE329903T1 (de) * | 1997-02-14 | 2006-07-15 | Bionumerik Pharmaceuticals Inc | Hochgradig lipophile camptothecin-derivate |
| 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 MY MYPI20000660A patent/MY127819A/en unknown
- 2000-02-23 TW TW089103136A patent/TWI268931B/zh not_active IP Right Cessation
- 2000-02-24 BR BR0008526-0A patent/BR0008526A/pt not_active IP Right Cessation
- 2000-02-24 EP EP00907714A patent/EP1165565B1/fr not_active Expired - Lifetime
- 2000-02-24 CN CNB008055513A patent/CN1195757C/zh not_active Expired - Fee Related
- 2000-02-24 ES ES00907714T patent/ES2200829T3/es not_active Expired - Lifetime
- 2000-02-24 MX MXPA01008658A patent/MXPA01008658A/es unknown
- 2000-02-24 WO PCT/FR2000/000461 patent/WO2000050427A1/fr not_active Application Discontinuation
- 2000-02-24 HU HU0200529A patent/HUP0200529A3/hu unknown
- 2000-02-24 DK DK00907714T patent/DK1165565T3/da active
- 2000-02-24 US US09/806,952 patent/US7012079B1/en not_active Expired - Fee Related
- 2000-02-24 KR KR1020017010920A patent/KR20010108270A/ko not_active Application Discontinuation
- 2000-02-24 IL IL14498700A patent/IL144987A0/xx active IP Right Grant
- 2000-02-24 RU RU2001126127/04A patent/RU2230745C2/ru not_active IP Right Cessation
- 2000-02-24 AT AT03075924T patent/ATE353902T1/de not_active IP Right Cessation
- 2000-02-24 AR ARP000100795A patent/AR022740A1/es active IP Right Grant
- 2000-02-24 ES ES03075924T patent/ES2282564T3/es not_active Expired - Lifetime
- 2000-02-24 EP EP03075924A patent/EP1338599B1/fr not_active Expired - Lifetime
- 2000-02-24 AU AU29210/00A patent/AU772632B2/en not_active Ceased
- 2000-02-24 PT PT00907714T patent/PT1165565E/pt unknown
- 2000-02-24 CA CA2364705A patent/CA2364705C/fr not_active Expired - Fee Related
- 2000-02-24 CZ CZ20013091A patent/CZ20013091A3/cs unknown
- 2000-02-24 PL PL361334A patent/PL202393B1/pl not_active IP Right Cessation
- 2000-02-24 JP JP2000601007A patent/JP2002537399A/ja active Pending
- 2000-02-24 AT AT00907714T patent/ATE242248T1/de active
- 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 NZ NZ514153A patent/NZ514153A/xx not_active IP Right Cessation
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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
- 2001-08-24 HR HR20010622A patent/HRP20010622A2/hr not_active Application Discontinuation
- 2001-09-19 ZA ZA200107738A patent/ZA200107738B/xx unknown
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2002
- 2002-09-26 HK HK02107033.2A patent/HK1045514B/zh not_active IP Right Cessation
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