CH646715A5 - 2'-desoxy-3',5'-di-o-alkylcarbonyl-5-fluoruridin-derivate, verfahren zu ihrer herstellung und antitumormittel. - Google Patents
2'-desoxy-3',5'-di-o-alkylcarbonyl-5-fluoruridin-derivate, verfahren zu ihrer herstellung und antitumormittel. Download PDFInfo
- Publication number
- CH646715A5 CH646715A5 CH96481A CH96481A CH646715A5 CH 646715 A5 CH646715 A5 CH 646715A5 CH 96481 A CH96481 A CH 96481A CH 96481 A CH96481 A CH 96481A CH 646715 A5 CH646715 A5 CH 646715A5
- Authority
- CH
- Switzerland
- Prior art keywords
- fluorouridine
- deoxy
- benzoyl
- oil
- broad
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 81
- 150000001875 compounds Chemical class 0.000 claims description 65
- -1 benzoyl halide Chemical class 0.000 claims description 51
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 239000002246 antineoplastic agent Substances 0.000 claims description 7
- 239000000969 carrier Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 150000004665 fatty acids Chemical class 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical class O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 241000251730 Chondrichthyes Species 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 239000000243 solution Substances 0.000 description 56
- 239000003921 oil Substances 0.000 description 53
- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- 229910052739 hydrogen Inorganic materials 0.000 description 35
- 239000000203 mixture Substances 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 24
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 24
- 238000000862 absorption spectrum Methods 0.000 description 20
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 20
- 238000000921 elemental analysis Methods 0.000 description 19
- 125000003118 aryl group Chemical group 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 239000002775 capsule Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 230000000259 anti-tumor effect Effects 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 10
- 229910052731 fluorine Chemical group 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000011737 fluorine Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ATKVIWDGWAVUCC-GVDBMIGSSA-N [(2r,3s,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-hexanoyloxyoxolan-2-yl]methyl hexanoate Chemical compound C1[C@H](OC(=O)CCCCC)[C@@H](COC(=O)CCCCC)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ATKVIWDGWAVUCC-GVDBMIGSSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 150000007530 organic bases Chemical class 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 231100001274 therapeutic index Toxicity 0.000 description 6
- JQNBCSPQVSUBSR-UHFFFAOYSA-N 2,3-dimethoxybenzoyl chloride Chemical compound COC1=CC=CC(C(Cl)=O)=C1OC JQNBCSPQVSUBSR-UHFFFAOYSA-N 0.000 description 5
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 5
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 4
- SYVNVEGIRVXRQH-UHFFFAOYSA-N 3-fluorobenzoyl chloride Chemical compound FC1=CC=CC(C(Cl)=O)=C1 SYVNVEGIRVXRQH-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 230000006181 N-acylation Effects 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 231100000053 low toxicity Toxicity 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229920001592 potato starch Polymers 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 description 2
- ZRSGZIMDIHBXIN-UHFFFAOYSA-N 1,3-benzodioxole-5-carbonyl chloride Chemical compound ClC(=O)C1=CC=C2OCOC2=C1 ZRSGZIMDIHBXIN-UHFFFAOYSA-N 0.000 description 2
- GPZXFICWCMCQPF-UHFFFAOYSA-N 2-methylbenzoyl chloride Chemical compound CC1=CC=CC=C1C(Cl)=O GPZXFICWCMCQPF-UHFFFAOYSA-N 0.000 description 2
- ZJIOBDJEKDUUCI-UHFFFAOYSA-N 3,5-dimethylbenzoyl chloride Chemical compound CC1=CC(C)=CC(C(Cl)=O)=C1 ZJIOBDJEKDUUCI-UHFFFAOYSA-N 0.000 description 2
- YHOYYHYBFSYOSQ-UHFFFAOYSA-N 3-methylbenzoyl chloride Chemical compound CC1=CC=CC(C(Cl)=O)=C1 YHOYYHYBFSYOSQ-UHFFFAOYSA-N 0.000 description 2
- KMGCTFHTBKBITO-UHFFFAOYSA-N 4-butoxybenzoyl chloride Chemical compound CCCCOC1=CC=C(C(Cl)=O)C=C1 KMGCTFHTBKBITO-UHFFFAOYSA-N 0.000 description 2
- FKAPQNQLKYYUAE-UHFFFAOYSA-N 4-propoxybenzoyl chloride Chemical compound CCCOC1=CC=C(C(Cl)=O)C=C1 FKAPQNQLKYYUAE-UHFFFAOYSA-N 0.000 description 2
- OYKSQHMWDGUQSF-SDBHATRESA-N 5-fluoro-1-[(2S,3R,4S,5R)-2-hexanoyl-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C(CCCCC)(=O)[C@@]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C(=C1)F OYKSQHMWDGUQSF-SDBHATRESA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- QSJRTVJHHWSIMZ-RBZQAINGSA-N [(2r,3s,5r)-5-[5-fluoro-3-(4-methoxybenzoyl)-2,4-dioxopyrimidin-1-yl]-3-hexanoyloxyoxolan-2-yl]methyl hexanoate Chemical compound C1[C@H](OC(=O)CCCCC)[C@@H](COC(=O)CCCCC)O[C@H]1N1C(=O)N(C(=O)C=2C=CC(OC)=CC=2)C(=O)C(F)=C1 QSJRTVJHHWSIMZ-RBZQAINGSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- QGYPBOQJIFAAPD-IDTAVKCVSA-N 1-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-pentanoyloxolan-2-yl]-5-fluoropyrimidine-2,4-dione Chemical compound C(CCCC)(=O)[C@@]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C(=C1)F QGYPBOQJIFAAPD-IDTAVKCVSA-N 0.000 description 1
- RZNHSEZOLFEFGB-UHFFFAOYSA-N 2-methoxybenzoyl chloride Chemical compound COC1=CC=CC=C1C(Cl)=O RZNHSEZOLFEFGB-UHFFFAOYSA-N 0.000 description 1
- RYKZLRXDZMOBHD-ZLKJLUDKSA-N 3-(1,3-benzodioxole-5-carbonyl)-5-fluoro-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N(C(=O)C=2C=C3OCOC3=CC=2)C(=O)C(F)=C1 RYKZLRXDZMOBHD-ZLKJLUDKSA-N 0.000 description 1
- RUQIUASLAXJZIE-UHFFFAOYSA-N 3-methoxybenzoyl chloride Chemical compound COC1=CC=CC(C(Cl)=O)=C1 RUQIUASLAXJZIE-UHFFFAOYSA-N 0.000 description 1
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 1
- QMOQDXXLQFOVNP-BFHYXJOUSA-N 5-fluoro-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3-(3-methylbenzoyl)pyrimidine-2,4-dione Chemical compound CC1=CC=CC(C(=O)N2C(N([C@@H]3O[C@H](CO)[C@@H](O)C3)C=C(F)C2=O)=O)=C1 QMOQDXXLQFOVNP-BFHYXJOUSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 208000006268 Sarcoma 180 Diseases 0.000 description 1
- KMEDMLFKUSBTQC-XIDUGBJDSA-N [(2R,3R,4R,5R)-2-(5-fluoro-2,4-dioxopyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl] hexanoate Chemical compound C(CCCCC)(=O)O[C@H]1[C@@H](O[C@@H]([C@H]1O)CO)N1C(=O)NC(=O)C(=C1)F KMEDMLFKUSBTQC-XIDUGBJDSA-N 0.000 description 1
- IMWAONMKDTZRAJ-HBNTYKKESA-N [(2r,3s,5r)-3-acetyloxy-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl acetate Chemical group C1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 IMWAONMKDTZRAJ-HBNTYKKESA-N 0.000 description 1
- ORMSILZSWFIQJX-YTFSRNRJSA-N [(2r,3s,5r)-5-(3-benzoyl-5-fluoro-2,4-dioxopyrimidin-1-yl)-3-hexanoyloxyoxolan-2-yl]methyl hexanoate Chemical compound C1[C@H](OC(=O)CCCCC)[C@@H](COC(=O)CCCCC)O[C@H]1N1C(=O)N(C(=O)C=2C=CC=CC=2)C(=O)C(F)=C1 ORMSILZSWFIQJX-YTFSRNRJSA-N 0.000 description 1
- VEFLYQSOBNXVAH-PWRODBHTSA-N [(2r,3s,5r)-5-(3-benzoyl-5-fluoro-2,4-dioxopyrimidin-1-yl)-3-pentanoyloxyoxolan-2-yl]methyl pentanoate Chemical compound C1[C@H](OC(=O)CCCC)[C@@H](COC(=O)CCCC)O[C@H]1N1C(=O)N(C(=O)C=2C=CC=CC=2)C(=O)C(F)=C1 VEFLYQSOBNXVAH-PWRODBHTSA-N 0.000 description 1
- WKOCBSKQJVQFNA-RRFJBIMHSA-N [(2r,3s,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-pentanoyloxyoxolan-2-yl]methyl pentanoate Chemical compound C1[C@H](OC(=O)CCCC)[C@@H](COC(=O)CCCC)O[C@H]1N1C(=O)NC(=O)C(F)=C1 WKOCBSKQJVQFNA-RRFJBIMHSA-N 0.000 description 1
- AFHGVBAFDUCQAI-HBNTYKKESA-N [(2r,3s,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-propanoyloxyoxolan-2-yl]methyl propanoate Chemical compound C1[C@H](OC(=O)CC)[C@@H](COC(=O)CC)O[C@H]1N1C(=O)NC(=O)C(F)=C1 AFHGVBAFDUCQAI-HBNTYKKESA-N 0.000 description 1
- VHIVDCMOHLHEKL-BHDDXSALSA-N [(2r,3s,5r)-5-[3-(1,3-benzodioxole-5-carbonyl)-5-fluoro-2,4-dioxopyrimidin-1-yl]-3-pentanoyloxyoxolan-2-yl]methyl pentanoate Chemical compound C1[C@H](OC(=O)CCCC)[C@@H](COC(=O)CCCC)O[C@H]1N1C(=O)N(C(=O)C=2C=C3OCOC3=CC=2)C(=O)C(F)=C1 VHIVDCMOHLHEKL-BHDDXSALSA-N 0.000 description 1
- RMEFCUOBHVZKOD-BHDDXSALSA-N [(2r,3s,5r)-5-[3-(2,3-dimethoxybenzoyl)-5-fluoro-2,4-dioxopyrimidin-1-yl]-3-pentanoyloxyoxolan-2-yl]methyl pentanoate Chemical compound C1[C@H](OC(=O)CCCC)[C@@H](COC(=O)CCCC)O[C@H]1N1C(=O)N(C(=O)C=2C(=C(OC)C=CC=2)OC)C(=O)C(F)=C1 RMEFCUOBHVZKOD-BHDDXSALSA-N 0.000 description 1
- QNHFCYVNOQKPNZ-YTFSRNRJSA-N [(2r,3s,5r)-5-[3-(3,5-dimethylbenzoyl)-5-fluoro-2,4-dioxopyrimidin-1-yl]-3-pentanoyloxyoxolan-2-yl]methyl pentanoate Chemical compound C1[C@H](OC(=O)CCCC)[C@@H](COC(=O)CCCC)O[C@H]1N1C(=O)N(C(=O)C=2C=C(C)C=C(C)C=2)C(=O)C(F)=C1 QNHFCYVNOQKPNZ-YTFSRNRJSA-N 0.000 description 1
- FXFCSLNJBZKECR-ISJGIBHGSA-N [(2r,3s,5r)-5-[3-(4-ethoxybenzoyl)-5-fluoro-2,4-dioxopyrimidin-1-yl]-3-hexanoyloxyoxolan-2-yl]methyl hexanoate Chemical compound C1[C@H](OC(=O)CCCCC)[C@@H](COC(=O)CCCCC)O[C@H]1N1C(=O)N(C(=O)C=2C=CC(OCC)=CC=2)C(=O)C(F)=C1 FXFCSLNJBZKECR-ISJGIBHGSA-N 0.000 description 1
- SZUHTITZFWYJNY-YTFSRNRJSA-N [(2r,3s,5r)-5-[3-(4-ethoxybenzoyl)-5-fluoro-2,4-dioxopyrimidin-1-yl]-3-pentanoyloxyoxolan-2-yl]methyl pentanoate Chemical compound C1[C@H](OC(=O)CCCC)[C@@H](COC(=O)CCCC)O[C@H]1N1C(=O)N(C(=O)C=2C=CC(OCC)=CC=2)C(=O)C(F)=C1 SZUHTITZFWYJNY-YTFSRNRJSA-N 0.000 description 1
- NSKUCKGMFPULLT-BHDDXSALSA-N [(2r,3s,5r)-5-[5-fluoro-3-(2-methylbenzoyl)-2,4-dioxopyrimidin-1-yl]-3-pentanoyloxyoxolan-2-yl]methyl pentanoate Chemical compound C1[C@H](OC(=O)CCCC)[C@@H](COC(=O)CCCC)O[C@H]1N1C(=O)N(C(=O)C=2C(=CC=CC=2)C)C(=O)C(F)=C1 NSKUCKGMFPULLT-BHDDXSALSA-N 0.000 description 1
- XAKDFRLRMKUUIX-YTFSRNRJSA-N [(2r,3s,5r)-5-[5-fluoro-3-(3-fluorobenzoyl)-2,4-dioxopyrimidin-1-yl]-3-hexanoyloxyoxolan-2-yl]methyl hexanoate Chemical compound C1[C@H](OC(=O)CCCCC)[C@@H](COC(=O)CCCCC)O[C@H]1N1C(=O)N(C(=O)C=2C=C(F)C=CC=2)C(=O)C(F)=C1 XAKDFRLRMKUUIX-YTFSRNRJSA-N 0.000 description 1
- JZVFKLNGMOMDQI-GVDBMIGSSA-N [(2r,3s,5r)-5-[5-fluoro-3-(3-fluorobenzoyl)-2,4-dioxopyrimidin-1-yl]-3-propanoyloxyoxolan-2-yl]methyl propanoate Chemical compound C1[C@H](OC(=O)CC)[C@@H](COC(=O)CC)O[C@H]1N1C(=O)N(C(=O)C=2C=C(F)C=CC=2)C(=O)C(F)=C1 JZVFKLNGMOMDQI-GVDBMIGSSA-N 0.000 description 1
- AUIDJARRLHKKKP-RBZQAINGSA-N [(2r,3s,5r)-5-[5-fluoro-3-(3-methoxybenzoyl)-2,4-dioxopyrimidin-1-yl]-3-hexanoyloxyoxolan-2-yl]methyl hexanoate Chemical compound C1[C@H](OC(=O)CCCCC)[C@@H](COC(=O)CCCCC)O[C@H]1N1C(=O)N(C(=O)C=2C=C(OC)C=CC=2)C(=O)C(F)=C1 AUIDJARRLHKKKP-RBZQAINGSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- AQIHMSVIAGNIDM-UHFFFAOYSA-N benzoyl bromide Chemical compound BrC(=O)C1=CC=CC=C1 AQIHMSVIAGNIDM-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 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
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 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
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1740880A JPS56115799A (en) | 1980-02-15 | 1980-02-15 | 2'-deoxy-3',5'-di-o-alkylcarbonyl-5-fluorouridine derivative, its preparation, and antitumor agnet containing the same |
| JP11210280A JPS5735596A (en) | 1980-08-13 | 1980-08-13 | Ester derivative of deoxyfluorouridine |
| JP55126776A JPS5751000A (en) | 1980-09-11 | 1980-09-11 | Ester derivative of alkoxybenzoyldeoxyfluorouridine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH646715A5 true CH646715A5 (de) | 1984-12-14 |
Family
ID=27281812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH96481A CH646715A5 (de) | 1980-02-15 | 1981-02-13 | 2'-desoxy-3',5'-di-o-alkylcarbonyl-5-fluoruridin-derivate, verfahren zu ihrer herstellung und antitumormittel. |
Country Status (7)
| Country | Link |
|---|---|
| AT (1) | AT374203B (forum.php) |
| CH (1) | CH646715A5 (forum.php) |
| DE (1) | DE3105111A1 (forum.php) |
| ES (1) | ES8206550A1 (forum.php) |
| FR (1) | FR2476086A1 (forum.php) |
| GB (1) | GB2072164B (forum.php) |
| IT (1) | IT1210989B (forum.php) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0082668A1 (en) * | 1981-12-18 | 1983-06-29 | Beecham Group Plc | 5-(2-Halogenovinyl)-2'-deoxyuridine derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in treating viral infections |
| AU548712B2 (en) * | 1983-05-23 | 1986-01-02 | Taiho Pharmaceutical Co., Ltd. | 2:-deoxy-5-substituted uridine derivatives |
| EP0180897B1 (en) * | 1984-10-30 | 1991-08-07 | Otsuka Pharmaceutical Co., Ltd. | 5-fluorouracil derivatives |
| US4864021A (en) * | 1984-10-30 | 1989-09-05 | Otsuka Pharmaceutical Co., Ltd. | 5-fluorouracil derivatives |
| EP0247381B1 (en) * | 1986-04-30 | 1993-08-04 | Otsuka Pharmaceutical Co., Ltd. | 5-flurorouracil derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5924999B2 (ja) * | 1978-06-10 | 1984-06-13 | 富山化学工業株式会社 | 新規な５−フルオロ−２′−デオキシ−β−ウリジン誘導体の製造法 |
| JPS5535057A (en) * | 1978-09-05 | 1980-03-11 | Funai Corp | 2'-deoxy-5-fluorouridine derivative, its preparation, and antitumor agent comprising it |
-
1981
- 1981-02-12 GB GB8104375A patent/GB2072164B/en not_active Expired
- 1981-02-12 DE DE19813105111 patent/DE3105111A1/de active Granted
- 1981-02-13 AT AT0069181A patent/AT374203B/de not_active IP Right Cessation
- 1981-02-13 IT IT8119758A patent/IT1210989B/it active
- 1981-02-13 CH CH96481A patent/CH646715A5/de not_active IP Right Cessation
- 1981-02-13 ES ES499443A patent/ES8206550A1/es not_active Expired
- 1981-02-13 FR FR8102922A patent/FR2476086A1/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| GB2072164B (en) | 1983-12-21 |
| FR2476086B1 (forum.php) | 1984-01-06 |
| GB2072164A (en) | 1981-09-30 |
| ATA69181A (de) | 1983-08-15 |
| IT8119758A0 (it) | 1981-02-13 |
| DE3105111C2 (forum.php) | 1993-08-12 |
| DE3105111A1 (de) | 1981-12-24 |
| IT1210989B (it) | 1989-09-29 |
| ES499443A0 (es) | 1982-08-16 |
| ES8206550A1 (es) | 1982-08-16 |
| FR2476086A1 (fr) | 1981-08-21 |
| AT374203B (de) | 1984-03-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0316704B1 (de) | Fluorcytidinderivate, deren Herstellung und Arzneimittel, die diese Derivate enthalten | |
| DE69533277T2 (de) | Dc-89 derivat | |
| DE3852288T2 (de) | K-252-Derivate mit Antitumorwirkung und diese enthaltende Arzneimittel. | |
| DE3143219C2 (forum.php) | ||
| DE69302360T2 (de) | N-Oxycarbonyl substitutierte 5'-Deoxy-5-Fluorocytidin | |
| DE69302330T2 (de) | 2'-Deoxy-2',2'-Difluor(4-substituierte Pyrimidin)Nukleoside mit Antiviral und Antikrebs-Wirkung und Zwischenverbindung | |
| DE69523462T2 (de) | Substituierte o6-benzylguanine | |
| EP0056265B1 (de) | 5'-Ester von Pyrimidinnucleosiden mit antiviraler Wirksamkeit, Verfahren zur Herstellung und daraus hergestellte Arzneimittel | |
| DE4337609A1 (de) | Neue Pyrazincarboxamidderivate, ihre Herstellung und ihre Verwendung in Arzneimitteln | |
| DE3331808A1 (de) | Carbostyrilderivate, verfahren zu deren herstellung und arzneimittel, welche diese enthalten | |
| DE2923368C2 (forum.php) | ||
| DE69121334T2 (de) | DC-89-Derivate als Antitumor-Wirkstoffe | |
| DE2359536C2 (de) | 2,6-Diaminonebularinderivate | |
| DE69222992T2 (de) | Spicamycinderivate und deren Verwendung | |
| DE2424119A1 (de) | Mycophenolsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel | |
| DD149217A5 (de) | Verfahren zur herstellung von pyrimidonderivaten | |
| DE69817810T2 (de) | Cyanoguanidine als zellproliferation inhibitoren | |
| DE60003045T2 (de) | Heterozyclische verbindungen als angiogenese inhibitoren | |
| CH646715A5 (de) | 2'-desoxy-3',5'-di-o-alkylcarbonyl-5-fluoruridin-derivate, verfahren zu ihrer herstellung und antitumormittel. | |
| KR840001673B1 (ko) | 2'-디옥시-3', 5'-디-0-알킬카르보닐-5-플루오르우리딘 유도체 및 그의 제조방법과 이를 함유하는 항종양제 | |
| DE69405214T2 (de) | 3'-azaridino-anthracyclin-derivate | |
| DE69320875T2 (de) | Fumarsäuresalze von Chinolinderivaten zur Aufhebung von vielfacher Drogenresistenz in der Krebsbehandlung | |
| CH642668A5 (de) | 2,6-diaminonebularine, verfahren zu deren herstellung und sie enthaltende pharmazeutische praeparate. | |
| CH670091A5 (forum.php) | ||
| DD283401A5 (de) | Verfahren zur herstellung von epipodophyllotoxinglucosid-4'-acyl-derivaten |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |