CH671578A5 - - Google Patents
Download PDFInfo
- Publication number
- CH671578A5 CH671578A5 CH1091/87A CH109187A CH671578A5 CH 671578 A5 CH671578 A5 CH 671578A5 CH 1091/87 A CH1091/87 A CH 1091/87A CH 109187 A CH109187 A CH 109187A CH 671578 A5 CH671578 A5 CH 671578A5
- Authority
- CH
- Switzerland
- Prior art keywords
- compound
- fluorouracil
- formula
- reaction
- benzoyloxy
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 87
- 239000000203 mixture Substances 0.000 claims description 25
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical class FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 10
- WTSKMKRYHATLLL-UHFFFAOYSA-N (6-benzoyloxy-3-cyanopyridin-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=2C(=CC=C(OC(=O)C=3C=CC=CC=3)N=2)C#N)=C1 WTSKMKRYHATLLL-UHFFFAOYSA-N 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 239000002516 radical scavenger Substances 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 30
- 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 20
- 229940079593 drug Drugs 0.000 description 16
- 239000003814 drug Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- -1 1-propoxymethyl Chemical group 0.000 description 14
- 206010028980 Neoplasm Diseases 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 239000000843 powder Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 231100001274 therapeutic index Toxicity 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
- 229920002472 Starch Polymers 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
- 230000037396 body weight Effects 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- OLRJXMHANKMLTD-UHFFFAOYSA-N silyl Chemical compound [SiH3] OLRJXMHANKMLTD-UHFFFAOYSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 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 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229960002949 fluorouracil Drugs 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
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 238000006884 silylation reaction Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 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 3
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 3
- 239000005995 Aluminium silicate Substances 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 235000012211 aluminium silicate Nutrition 0.000 description 3
- 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 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000012876 carrier material Substances 0.000 description 3
- 229940110456 cocoa butter Drugs 0.000 description 3
- 235000019868 cocoa butter Nutrition 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 235000019786 weight gain Nutrition 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
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-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
- 229910000019 calcium carbonate Inorganic materials 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
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 238000007493 shaping process 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
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 230000001875 tumorinhibitory effect Effects 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-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
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-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
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-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
- 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 1
- 229920001817 Agar Polymers 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920001543 Laminarin Polymers 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
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 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
- 229920001800 Shellac Polymers 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 208000009916 Yoshida Sarcoma Diseases 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000012055 enteric layer Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 125000005456 glyceride group Chemical group 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
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- DBTMGCOVALSLOR-VPNXCSTESA-N laminarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1O[C@@H]1[C@@H](O)C(O[C@H]2[C@@H]([C@@H](CO)OC(O)[C@@H]2O)O)O[C@H](CO)[C@H]1O DBTMGCOVALSLOR-VPNXCSTESA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- XRPITCBWOUOJTH-UHFFFAOYSA-N n,n-diethylpyridin-2-amine Chemical compound CCN(CC)C1=CC=CC=N1 XRPITCBWOUOJTH-UHFFFAOYSA-N 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
- 231100001090 no gastrointestinal toxicity Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 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
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH671578A5 true CH671578A5 (cg-RX-API-DMAC7.html) | 1989-09-15 |
Family
ID=27288338
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1091/87A CH671578A5 (cg-RX-API-DMAC7.html) | 1986-07-25 | 1987-03-23 |
Country Status (10)
| Country | Link |
|---|---|
| KR (2) | KR950009857B1 (cg-RX-API-DMAC7.html) |
| CH (1) | CH671578A5 (cg-RX-API-DMAC7.html) |
| DE (1) | DE3709699C2 (cg-RX-API-DMAC7.html) |
| DK (1) | DK169520B1 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2004904A6 (cg-RX-API-DMAC7.html) |
| FR (1) | FR2605006B1 (cg-RX-API-DMAC7.html) |
| GB (1) | GB2192880B (cg-RX-API-DMAC7.html) |
| IT (1) | IT1207785B (cg-RX-API-DMAC7.html) |
| NL (1) | NL194043C (cg-RX-API-DMAC7.html) |
| SE (1) | SE464303B (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2010312594B2 (en) * | 2009-10-27 | 2013-06-20 | Delta-Fly Pharma, Inc. | Novel 5-fluorouracil derivative |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4864021A (en) * | 1984-10-30 | 1989-09-05 | Otsuka Pharmaceutical Co., Ltd. | 5-fluorouracil derivatives |
| NL194430C (nl) | 1989-01-05 | 2002-04-04 | Otsuka Pharma Co Ltd | Niet-injecteerbaar farmaceutisch preparaat met anti-kankerwerking. |
| EP0489181B1 (en) * | 1990-07-19 | 1996-10-02 | Otsuka Pharmaceutical Co., Ltd. | Solid preparation |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3588103T2 (de) * | 1984-10-30 | 1996-10-17 | Otsuka Pharma Co Ltd | 5-Fluorouracil-Derivate |
| 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 NL NL8700742A patent/NL194043C/nl not_active IP Right Cessation
- 1987-03-30 IT IT8705150A patent/IT1207785B/it active
- 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
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2010312594B2 (en) * | 2009-10-27 | 2013-06-20 | Delta-Fly Pharma, Inc. | Novel 5-fluorouracil derivative |
| RU2503673C2 (ru) * | 2009-10-27 | 2014-01-10 | Дельта-Флай Фарма, Инк. | Новое производное 5-фторурацила |
Also Published As
| Publication number | Publication date |
|---|---|
| DK133387D0 (da) | 1987-03-16 |
| ES2004904A6 (es) | 1989-02-16 |
| KR950009857B1 (ko) | 1995-08-29 |
| NL194043B (nl) | 2001-01-02 |
| KR950011394B1 (ko) | 1995-10-02 |
| SE8701118D0 (sv) | 1987-03-18 |
| DE3709699A1 (de) | 1988-02-04 |
| FR2605006B1 (fr) | 1990-01-12 |
| GB2192880A (en) | 1988-01-27 |
| NL8700742A (nl) | 1988-02-16 |
| IT8705150A0 (it) | 1987-03-30 |
| KR880001635A (ko) | 1988-04-25 |
| DK169520B1 (da) | 1994-11-21 |
| KR880001630A (ko) | 1988-04-25 |
| GB2192880B (en) | 1990-05-09 |
| DK133387A (da) | 1988-01-26 |
| IT1207785B (it) | 1989-06-01 |
| NL194043C (nl) | 2001-05-03 |
| GB8706972D0 (en) | 1987-04-29 |
| SE8701118L (sv) | 1988-01-26 |
| SE464303B (sv) | 1991-04-08 |
| FR2605006A1 (fr) | 1988-04-15 |
| DE3709699C2 (de) | 1996-09-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE3781845T2 (de) | Benzimidazol-derivate. | |
| CH637928A5 (de) | Verfahren zur herstellung von pyrrolidinverbindungen. | |
| DE2455423C3 (de) | 28.11.73 Japan 132796-73 26.04.74 Japan 46617-74 In 1-Stellung acylierte 5-Fluoruracile und Arzneimittel aus diesen Verbindungen und üblichen inerten Bindemitteln oder Trägermaterialien | |
| DE2165962C2 (de) | 4-Hydroxy-6-arylpyrimidine | |
| DE69430587T2 (de) | Pyrimidin-acyclonukleosid-derivate | |
| DE69126469T2 (de) | Pyrimidin-Nukleosid-Derivate und antivirale Mittel, die diese Derivate als aktiven Bestandteil enthalten | |
| CH634567A5 (de) | Verfahren zur herstellung von uracilderivaten. | |
| DE3855520T2 (de) | Methode zur Verbesserung des Schlafes | |
| CH636862A5 (de) | In 2-stellung substituierte 5-hydroxy-1h-imidazol-4-carboxamidderivate, ihre salze und verfahren zu ihrer herstellung. | |
| DE4424714A1 (de) | Neue chemische Verbindung, ihre Herstellung und ihre Verwendung als Arnzneistoff | |
| CH671578A5 (cg-RX-API-DMAC7.html) | ||
| DE3940021C2 (de) | Adenosin-Derivate, deren Herstellung und Verwendung | |
| CH643830A5 (de) | Bis-moranolin-derivate. | |
| DE2459629C3 (de) | Pyrimidinoaminoäthylergolin-Derivate, Verfahren zu ihrer Herstellung und pharmazeutisches Mittel | |
| CH637646A5 (de) | Analgetisch wirksame triazindione, herstellungsverfahren und pharmazeutische zusammensetzungen. | |
| DE3587912T2 (de) | Amid-Derivate und die als aktive Substanz enthaltende 5-Lipoxygenase-Inhibitoren. | |
| DE3879378T2 (de) | Amid-verbindungen. | |
| DE2838837C3 (de) | 4-Hydroxyisophthalsäure-bis-picolylamide, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel | |
| DE69019807T2 (de) | Pyrimidindionderivate, Verfahren zu deren Herstellung und diese enthaltende antiarrhythmische Mittel. | |
| DE2403786A1 (de) | Neue derivate der cumarine | |
| DE3239719C2 (de) | Uracil-Derivate, Verfahren zu ihrer Herstellung und dieselben enthaltende pharmazeutische Zusammensetzungen | |
| DE2843136C3 (de) | 6-O-Mono- und 1,6-O-Di-acylierte 2-[3-(2-Chloräthyl)-3-nitroscureido]-2-desoxy-D-glukopyranosen sowie Gemische aus 1,3,6-O-Tri und 1,4,6-O-Tri-acylierten 2-[3-(2-Chloräthyl)-3-nitrosoureido]-2-desoxy-D-glukopyranosen | |
| DE3889167T2 (de) | Pyridinon-Derivate und diese enthaltende fungizide Zusammenstellungen für die Landwirtschaft und Gartenbau. | |
| EP0113911B1 (de) | Pyrido-triazolochinazoline, ihre Herstellung und Verwendung | |
| DE2834698C2 (de) | Verfahren zur Herstellung von N&darr;1&darr;-(2-Tetrahydrofuryl)-uracil und dessen 5-substituierten Derivaten |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |