NL194043C - 5-Fluoruracilderivaat, alsmede een dergelijk derivaat omvattend farmaceutisch preparaat met kankerbestrijdende werking. - Google Patents
5-Fluoruracilderivaat, alsmede een dergelijk derivaat omvattend farmaceutisch preparaat met kankerbestrijdende werking. Download PDFInfo
- Publication number
- NL194043C NL194043C NL8700742A NL8700742A NL194043C NL 194043 C NL194043 C NL 194043C NL 8700742 A NL8700742 A NL 8700742A NL 8700742 A NL8700742 A NL 8700742A NL 194043 C NL194043 C NL 194043C
- Authority
- NL
- Netherlands
- Prior art keywords
- compound
- fluorouracil
- derivative
- reaction
- benzoyloxy
- Prior art date
Links
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical class FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 title claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 230000001093 anti-cancer Effects 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 72
- 239000003814 drug Substances 0.000 claims description 22
- 230000000052 comparative effect Effects 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 12
- WTSKMKRYHATLLL-UHFFFAOYSA-N (6-benzoyloxy-3-cyanopyridin-2-yl) 3-[3-(ethoxymethyl)-5-fluoro-2,6-dioxopyrimidine-1-carbonyl]benzoate Chemical group O=C1N(COCC)C=C(F)C(=O)N1C(=O)C1=CC=CC(C(=O)OC=2C(=CC=C(OC(=O)C=3C=CC=CC=3)N=2)C#N)=C1 WTSKMKRYHATLLL-UHFFFAOYSA-N 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products 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 claims 2
- 229920002472 Starch Polymers 0.000 claims 2
- 239000008101 lactose Substances 0.000 claims 2
- 235000019359 magnesium stearate Nutrition 0.000 claims 2
- 239000008107 starch Substances 0.000 claims 2
- 235000019698 starch Nutrition 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 206010028980 Neoplasm Diseases 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 229940086542 triethylamine Drugs 0.000 description 9
- 230000037396 body weight Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 231100001274 therapeutic index Toxicity 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- OUAPULXYUWUOHW-UHFFFAOYSA-N 1-(ethoxymethyl)-5-fluoropyrimidine-2,4-dione Chemical compound CCOCN1C=C(F)C(=O)NC1=O OUAPULXYUWUOHW-UHFFFAOYSA-N 0.000 description 5
- -1 6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl-benzoyl Chemical group 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- ZMHTVXJNUMQQNZ-UHFFFAOYSA-N (5-cyano-6-oxo-1h-pyridin-2-yl) benzoate Chemical compound C1=C(C#N)C(O)=NC(OC(=O)C=2C=CC=CC=2)=C1 ZMHTVXJNUMQQNZ-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
- 238000002513 implantation Methods 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 230000001629 suppression Effects 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CYHIRKZFRGZIEO-UHFFFAOYSA-N (5-cyano-6-trimethylsilyloxypyridin-2-yl) benzoate Chemical compound C1=C(C#N)C(O[Si](C)(C)C)=NC(OC(=O)C=2C=CC=CC=2)=C1 CYHIRKZFRGZIEO-UHFFFAOYSA-N 0.000 description 2
- BFHKYHMCIAMQIN-UHFFFAOYSA-N 2-hydroxy-6-oxo-1h-pyridine-3-carbonitrile Chemical compound OC=1NC(=O)C=CC=1C#N BFHKYHMCIAMQIN-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 241000978776 Senegalia senegal Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- FDQSRULYDNDXQB-UHFFFAOYSA-N benzene-1,3-dicarbonyl chloride Chemical compound ClC(=O)C1=CC=CC(C(Cl)=O)=C1 FDQSRULYDNDXQB-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 238000000975 co-precipitation Methods 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- HRKNFPDVXODMID-UHFFFAOYSA-N (4-benzoyloxy-5-chloropyridin-2-yl) 3-[3-(ethoxymethyl)-5-fluoro-2,6-dioxopyrimidine-1-carbonyl]benzoate Chemical compound O=C1N(COCC)C=C(F)C(=O)N1C(=O)C1=CC=CC(C(=O)OC=2N=CC(Cl)=C(OC(=O)C=3C=CC=CC=3)C=2)=C1 HRKNFPDVXODMID-UHFFFAOYSA-N 0.000 description 1
- XUVWYVIPRYKTHS-UHFFFAOYSA-N (6-benzoyloxy-3-cyanopyridin-2-yl) 3-[5-fluoro-3-(methoxymethyl)-2,6-dioxopyrimidine-1-carbonyl]benzoate Chemical compound O=C1N(COC)C=C(F)C(=O)N1C(=O)C1=CC=CC(C(=O)OC=2C(=CC=C(OC(=O)C=3C=CC=CC=3)N=2)C#N)=C1 XUVWYVIPRYKTHS-UHFFFAOYSA-N 0.000 description 1
- IPIIRGQQLHQBQZ-UHFFFAOYSA-N (6-benzoyloxy-3-cyanopyridin-2-yl) 3-carbonochloridoylbenzoate Chemical compound C(C1=CC=CC=C1)(=O)OC1=CC=C(C(=N1)OC(=O)C=1C=C(C(=O)Cl)C=CC1)C#N IPIIRGQQLHQBQZ-UHFFFAOYSA-N 0.000 description 1
- OZJCXPFKYXJALL-UHFFFAOYSA-N (6-benzoyloxy-3-cyanopyridin-2-yl) 4-[3-(ethoxymethyl)-5-fluoro-2,6-dioxopyrimidine-1-carbonyl]benzoate Chemical compound O=C1N(COCC)C=C(F)C(=O)N1C(=O)C1=CC=C(C(=O)OC=2C(=CC=C(OC(=O)C=3C=CC=CC=3)N=2)C#N)C=C1 OZJCXPFKYXJALL-UHFFFAOYSA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- 208000006268 Sarcoma 180 Diseases 0.000 description 1
- WFWLQNSHRPWKFK-UHFFFAOYSA-N Tegafur Chemical compound O=C1NC(=O)C(F)=CN1C1OCCC1 WFWLQNSHRPWKFK-UHFFFAOYSA-N 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 208000009916 Yoshida Sarcoma Diseases 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Chemical group 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 231100001090 no gastrointestinal toxicity Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17646486 | 1986-07-25 | ||
| JP17646486 | 1986-07-25 | ||
| JP61181027A JPS63301880A (ja) | 1985-09-03 | 1986-07-30 | ５−フルオロウラシル誘導体 |
| JP18102786 | 1986-07-30 | ||
| JP62034161A JPS63201127A (ja) | 1987-02-17 | 1987-02-17 | ５−フルオロウラシル誘導体を含有する制癌剤 |
| JP3416187 | 1987-02-17 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NL8700742A NL8700742A (nl) | 1988-02-16 |
| NL194043B NL194043B (nl) | 2001-01-02 |
| NL194043C true NL194043C (nl) | 2001-05-03 |
Family
ID=27288338
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8700742A NL194043C (nl) | 1986-07-25 | 1987-03-30 | 5-Fluoruracilderivaat, alsmede een dergelijk derivaat omvattend farmaceutisch preparaat met kankerbestrijdende werking. |
Country Status (10)
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4864021A (en) * | 1984-10-30 | 1989-09-05 | Otsuka Pharmaceutical Co., Ltd. | 5-fluorouracil derivatives |
| KR0133555B1 (ko) | 1989-01-05 | 1998-04-23 | 오오쓰까 아끼히꼬 | 5-플루오로우라실계 화합물에 기인한 염증의 발생을 억제할 수 있는 비-주사제 형태의 항암조성물 |
| ES2093106T3 (es) * | 1990-07-19 | 1996-12-16 | Otsuka Pharma Co Ltd | Preparacion solida. |
| EP2495243B1 (en) | 2009-10-27 | 2016-12-28 | Delta-Fly Pharma, Inc. | Novel 5-fluorouracil derivative |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0180897B1 (en) * | 1984-10-30 | 1991-08-07 | Otsuka Pharmaceutical Co., Ltd. | 5-fluorouracil derivatives |
| JPS61114739A (ja) * | 1984-11-08 | 1986-06-02 | Mitsubishi Rayon Co Ltd | 不飽和カルボン酸製造用触媒の調製法 |
-
1987
- 1987-03-16 DK DK133387A patent/DK169520B1/da not_active IP Right Cessation
- 1987-03-18 ES ES8700756A patent/ES2004904A6/es not_active Expired
- 1987-03-18 SE SE8701118A patent/SE464303B/sv not_active IP Right Cessation
- 1987-03-23 CH CH1091/87A patent/CH671578A5/de not_active IP Right Cessation
- 1987-03-24 GB GB8706972A patent/GB2192880B/en not_active Expired - Fee Related
- 1987-03-25 DE DE3709699A patent/DE3709699C2/de not_active Expired - Fee Related
- 1987-03-30 KR KR1019870002961A patent/KR950009857B1/ko not_active Expired - Fee Related
- 1987-03-30 IT IT8705150A patent/IT1207785B/it active
- 1987-03-30 NL NL8700742A patent/NL194043C/nl not_active IP Right Cessation
- 1987-03-31 FR FR878704500A patent/FR2605006B1/fr not_active Expired - Fee Related
- 1987-07-01 KR KR1019870006895A patent/KR950011394B1/ko not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DK133387D0 (da) | 1987-03-16 |
| GB2192880A (en) | 1988-01-27 |
| DE3709699A1 (de) | 1988-02-04 |
| SE464303B (sv) | 1991-04-08 |
| GB8706972D0 (en) | 1987-04-29 |
| ES2004904A6 (es) | 1989-02-16 |
| NL8700742A (nl) | 1988-02-16 |
| FR2605006A1 (fr) | 1988-04-15 |
| SE8701118D0 (sv) | 1987-03-18 |
| IT1207785B (it) | 1989-06-01 |
| NL194043B (nl) | 2001-01-02 |
| GB2192880B (en) | 1990-05-09 |
| CH671578A5 (enrdf_load_stackoverflow) | 1989-09-15 |
| FR2605006B1 (fr) | 1990-01-12 |
| IT8705150A0 (it) | 1987-03-30 |
| DK133387A (da) | 1988-01-26 |
| DK169520B1 (da) | 1994-11-21 |
| KR950011394B1 (ko) | 1995-10-02 |
| KR880001635A (ko) | 1988-04-25 |
| SE8701118L (sv) | 1988-01-26 |
| KR880001630A (ko) | 1988-04-25 |
| KR950009857B1 (ko) | 1995-08-29 |
| DE3709699C2 (de) | 1996-09-05 |
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| Date | Code | Title | Description |
|---|---|---|---|
| BA | A request for search or an international-type search has been filed | ||
| BB | A search report has been drawn up | ||
| BC | A request for examination has been filed | ||
| V1 | Lapsed because of non-payment of the annual fee |
Effective date: 20061001 |