FI90234C - Menetelmä valmistaa farmakologisesti käyttökelpoisia kinatsoliinijohdannaisia - Google Patents

Menetelmä valmistaa farmakologisesti käyttökelpoisia kinatsoliinijohdannaisia Download PDF

Info

Publication number: FI90234C
Authority: FI; Finland
Prior art keywords: tetrahydro; nujol; ethyl; dioxoquinazolin; acetate
Prior art date: 1985-10-07

Application number

FI863917A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI90234B (fi

FI863917A0 (fi

FI863917L (fi

Inventor

Masashi Hashimoto

Chiyoshi Kasahara

Teruo Oku

Yoshikuni Ito

Takayuki Namiki

Kozo Sawada

Yukihisa Baba

Original Assignee

Fujisawa Pharmaceutical Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1985-10-07

Filing date

1986-09-29

Publication date

1994-01-10

1986-09-29 Application filed by Fujisawa Pharmaceutical Co filed Critical Fujisawa Pharmaceutical Co

1986-09-29 Publication of FI863917A0 publication Critical patent/FI863917A0/fi

1987-04-08 Publication of FI863917L publication Critical patent/FI863917L/fi

1993-09-30 Publication of FI90234B publication Critical patent/FI90234B/fi

1994-01-10 Application granted granted Critical

1994-01-10 Publication of FI90234C publication Critical patent/FI90234C/fi

Links

238000000034 method Methods 0.000 title claims abstract description 65
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title claims 2
150000001875 compounds Chemical class 0.000 claims abstract description 150
150000003839 salts Chemical class 0.000 claims abstract description 107
238000002360 preparation method Methods 0.000 claims abstract description 31
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 15
229910052736 halogen Inorganic materials 0.000 claims abstract description 14
150000002367 halogens Chemical class 0.000 claims abstract description 12
125000000217 alkyl group Chemical group 0.000 claims abstract description 8
125000001424 substituent group Chemical group 0.000 claims abstract description 6
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 5
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 4
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims abstract description 4
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 3
239000001257 hydrogen Substances 0.000 claims abstract description 3
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 3
229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
239000001301 oxygen Substances 0.000 claims abstract description 3
229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
125000004434 sulfur atom Chemical group 0.000 claims abstract description 3
125000002947 alkylene group Chemical group 0.000 claims abstract 2
-1 C 1 -C 6 alkoxy Inorganic materials 0.000 claims description 139
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
241000277284 Salvelinus fontinalis Species 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 abstract description 4
125000003545 alkoxy group Chemical group 0.000 abstract description 2
125000003118 aryl group Chemical group 0.000 abstract 1
239000003937 drug carrier Substances 0.000 abstract 1
125000001475 halogen functional group Chemical group 0.000 abstract 1
125000000623 heterocyclic group Chemical group 0.000 abstract 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 211
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 131
235000011054 acetic acid Nutrition 0.000 description 70
238000006243 chemical reaction Methods 0.000 description 66
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 59
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 59
239000000203 mixture Substances 0.000 description 58
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
239000002904 solvent Substances 0.000 description 38
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
239000000243 solution Substances 0.000 description 26
238000001816 cooling Methods 0.000 description 24
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000002253 acid Substances 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
238000001914 filtration Methods 0.000 description 14
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
241000700159 Rattus Species 0.000 description 13
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
229910052757 nitrogen Inorganic materials 0.000 description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 description 11
238000003756 stirring Methods 0.000 description 11
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
230000002411 adverse Effects 0.000 description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
238000010438 heat treatment Methods 0.000 description 9
238000001953 recrystallisation Methods 0.000 description 9
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 8
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
239000003814 drug Substances 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
206010012601 diabetes mellitus Diseases 0.000 description 7
229940079593 drug Drugs 0.000 description 7
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 7
150000003246 quinazolines Chemical class 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
FQUMHBXENNAXTG-UHFFFAOYSA-N 2-[7-bromo-3-[(4-bromo-2-fluorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Br)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F FQUMHBXENNAXTG-UHFFFAOYSA-N 0.000 description 6
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
239000012267 brine Substances 0.000 description 6
239000013078 crystal Substances 0.000 description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
230000002401 inhibitory effect Effects 0.000 description 6
239000002480 mineral oil Substances 0.000 description 6
235000010446 mineral oil Nutrition 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000000600 sorbitol Substances 0.000 description 6
SEOOOAKCIOZNBC-UHFFFAOYSA-N 2-[3-(naphthalen-2-ylmethyl)-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound C1=CC=CC2=CC(CN3C(=O)C4=CC=CC=C4N(C3=O)CC(=O)O)=CC=C21 SEOOOAKCIOZNBC-UHFFFAOYSA-N 0.000 description 5
SMJPLDADWFVJNR-UHFFFAOYSA-N 2-[7-chloro-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(I)C=C1F SMJPLDADWFVJNR-UHFFFAOYSA-N 0.000 description 5
QKTDABZFNMEKGF-UHFFFAOYSA-N 2-[7-chloro-3-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Cl)C(C(F)(F)F)=C1 QKTDABZFNMEKGF-UHFFFAOYSA-N 0.000 description 5
102000016912 Aldehyde Reductase Human genes 0.000 description 5
108010053754 Aldehyde reductase Proteins 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
210000003497 sciatic nerve Anatomy 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000000725 suspension Substances 0.000 description 5
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
GBMBFYYGBBVEGT-UHFFFAOYSA-N 2-[3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=C(I)C=C1F GBMBFYYGBBVEGT-UHFFFAOYSA-N 0.000 description 4
AJUXANYDJWYIDV-UHFFFAOYSA-N 2-[3-[(2-fluoro-4-iodophenyl)methyl]-7-iodo-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(I)=CC=C2C(=O)N1CC1=CC=C(I)C=C1F AJUXANYDJWYIDV-UHFFFAOYSA-N 0.000 description 4
FBKRMYUIJMDCAD-UHFFFAOYSA-N 2-[3-[(3,4-dichlorophenyl)methyl]-4-oxo-2-sulfanylidenequinazolin-1-yl]acetic acid Chemical compound S=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C(Cl)=C1 FBKRMYUIJMDCAD-UHFFFAOYSA-N 0.000 description 4
QWCDEEFYNYRJCB-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-5,7-dichloro-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC(Cl)=C2C(=O)N1CC1=CC=C(Br)C=C1F QWCDEEFYNYRJCB-UHFFFAOYSA-N 0.000 description 4
PEAGERJCSHJISQ-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-7-iodo-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(I)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F PEAGERJCSHJISQ-UHFFFAOYSA-N 0.000 description 4
SXEPCMGMVAWKLM-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-7-methoxy-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound C=1C(OC)=CC=C(C2=O)C=1N(CC(O)=O)C(=O)N2CC1=CC=C(Br)C=C1F SXEPCMGMVAWKLM-UHFFFAOYSA-N 0.000 description 4
SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 4
XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 4
YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 4
XPKRKIMKOLPWQI-UHFFFAOYSA-N 2-[6,7-dichloro-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=C(Cl)C=C2C(=O)N1CC1=CC=C(I)C=C1F XPKRKIMKOLPWQI-UHFFFAOYSA-N 0.000 description 4
LZIYHKUKOLSJIE-UHFFFAOYSA-N 2-[7-fluoro-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(F)=CC=C2C(=O)N1CC1=CC=C(I)C=C1F LZIYHKUKOLSJIE-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
150000007529 inorganic bases Chemical class 0.000 description 4
229910052742 iron Inorganic materials 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
239000007787 solid Substances 0.000 description 4
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 3
VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 3
FFFQQRPMTKDGAG-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-6,7-dichloro-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=C(Cl)C=C2C(=O)N1CC1=CC=C(Br)C=C1F FFFQQRPMTKDGAG-UHFFFAOYSA-N 0.000 description 3
GANUQUHEMPMSDL-UHFFFAOYSA-N 2-[7-chloro-3-[(3-chloro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(I)C(Cl)=C1 GANUQUHEMPMSDL-UHFFFAOYSA-N 0.000 description 3
DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
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 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
150000008041 alkali metal carbonates Chemical class 0.000 description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
150000001408 amides Chemical class 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
239000008280 blood Substances 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
HJECSYIYYIBAJP-UHFFFAOYSA-N ethyl 2-[3-[(3,4-dichlorophenyl)methyl]-2,4-bis(sulfanylidene)quinazolin-1-yl]acetate Chemical compound S=C1N(CC(=O)OCC)C2=CC=CC=C2C(=S)N1CC1=CC=C(Cl)C(Cl)=C1 HJECSYIYYIBAJP-UHFFFAOYSA-N 0.000 description 3
YKEDZMUEYGWSDX-UHFFFAOYSA-N ethyl 2-[3-[(3,4-dichlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C(Cl)=C1 YKEDZMUEYGWSDX-UHFFFAOYSA-N 0.000 description 3
FQXIRXTVFVCJFQ-UHFFFAOYSA-N ethyl 2-[3-[(4-bromo-2-fluorophenyl)methyl]-7-chloro-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F FQXIRXTVFVCJFQ-UHFFFAOYSA-N 0.000 description 3
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229910052763 palladium Inorganic materials 0.000 description 1
239000006072 paste Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000004346 phenylpentyl group Chemical group C1(=CC=CC=C1)CCCCC* 0.000 description 1
125000004344 phenylpropyl group Chemical group 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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238000001556 precipitation Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
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239000001632 sodium acetate Substances 0.000 description 1
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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
- C07D401/06—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 only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/15—Six-membered rings
- C07D285/16—Thiadiazines; Hydrogenated thiadiazines
- C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
- C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
- C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Diabetes (AREA)
Ophthalmology & Optometry (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Hematology (AREA)
Obesity (AREA)
Gastroenterology & Hepatology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Reproductive Health (AREA)
Biomedical Technology (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

FI863917A 1985-10-07 1986-09-29 Menetelmä valmistaa farmakologisesti käyttökelpoisia kinatsoliinijohdannaisia FI90234C (fi)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB8524663		1985-10-07
GB858524663A GB8524663D0 (en)	1985-10-07	1985-10-07	Quinazoline derivatives

Publications (4)

Publication Number	Publication Date
FI863917A0 FI863917A0 (fi)	1986-09-29
FI863917L FI863917L (fi)	1987-04-08
FI90234B FI90234B (fi)	1993-09-30
FI90234C true FI90234C (fi)	1994-01-10

Family

ID=10586291

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI863917A FI90234C (fi)	1985-10-07	1986-09-29	Menetelmä valmistaa farmakologisesti käyttökelpoisia kinatsoliinijohdannaisia

Country Status (23)

Country	Link
US (2)	US4734419A (2)
EP (1)	EP0218999B1 (2)
JP (3)	JPS6296476A (2)
KR (1)	KR940007270B1 (2)
CN (1)	CN1017242B (2)
AT (1)	ATE60761T1 (2)
AU (1)	AU596611B2 (2)
CA (1)	CA1289139C (2)
DE (1)	DE3677452D1 (2)
DK (1)	DK158838C (2)
ES (1)	ES2021266B3 (2)
FI (1)	FI90234C (2)
GB (1)	GB8524663D0 (2)
GR (1)	GR3001502T3 (2)
HK (1)	HK6993A (2)
HU (1)	HU196972B (2)
IE (1)	IE59309B1 (2)
IL (1)	IL80213A (2)
NO (1)	NO171785C (2)
SG (1)	SG112092G (2)
SU (1)	SU1588283A3 (2)
UA (1)	UA5562A1 (2)
ZA (1)	ZA867043B (2)

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US4931440A (en) *	1987-07-29	1990-06-05	Fujisawa Pharmaceutical Company, Ltd.	Uricosuric composition
EP0335979A4 (en) *	1987-09-16	1992-02-26	Taiho Pharmaceutical Company, Limited	Thienopyrimidine derivatives
JP2621460B2 (ja) *	1988-02-29	1997-06-18	藤沢薬品工業株式会社	利尿または降圧剤
US5324747A (en) *	1992-07-15	1994-06-28	Hoffmann-La Roche Inc.	N-substituted anilines, inhibitors of phospholipases A2
US5728704A (en) *	1992-09-28	1998-03-17	Pfizer Inc.	Substituted pyridmidines for control of diabetic complications
WO1997008131A1 (de) *	1995-08-31	1997-03-06	Clariant Gmbh	Monoester der carboxymethylenanthranilsäuren und verfahren zu ihrer herstellung
DE19532052C2 (de) *	1995-08-31	1998-11-19	Clariant Gmbh	Verfahren zur Herstellung von Chinazolinderivaten
EP0781767B1 (en) *	1995-12-26	2001-09-05	Sumitomo Chemical Company, Limited	Process for producing isatoic anhydrides
US6201121B1 (en)	1995-12-28	2001-03-13	Fuji Chemical Industry Co., Ltd.	Process for the preparation of 3-dihalobenzyl-2,4-quinazolinedione derivatives
DE69701647T2 (de) *	1996-02-01	2000-09-07	Sumitomo Chemical Co., Ltd.	Verfahren zur Herstellung von Dioxochinazolinen
DE19650975A1 (de) *	1996-12-09	1998-06-10	Basf Ag	Neue heterocyclisch substituierte Benzamide und deren Anwendung
GB2338235B (en) *	1997-04-15	2001-11-14	Csir	Appetite suppressing plant extracts
US6444816B1 (en)	1997-10-27	2002-09-03	Dr. Reddy's Research Foundation	Fused 7-oxo-pyrimidinyl compounds, preparation, composition and use thereof
WO1999038497A2 (en) *	1998-01-30	1999-08-05	R-Tech Ueno, Ltd.	Ophthalmic composition
WO2000043015A1 (fr) *	1999-01-25	2000-07-27	Fujisawa Pharmaceutical Co., Ltd.	Gouttes ophtalmologiques
JP2003516309A (ja)	1999-02-18	2003-05-13	株式会社アールテック・ウエノ	涙液分泌障害を除く外分泌障害処置剤
IL145114A0 (en) *	1999-03-09	2002-06-30	Fujisawa Pharmaceutical Co	A process for preparing a quinazoline derivative
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US6545004B1 (en) *	1999-10-27	2003-04-08	Cytokinetics, Inc.	Methods and compositions utilizing quinazolinones
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GB2363985B (en)	2000-06-30	2004-09-29	Phytopharm Plc	Extracts,compounds & pharmaceutical compositions having anti-diabetic activity and their use
EP1337272A2 (en)	2000-11-30	2003-08-27	Pfizer Products Inc.	Combination of gaba agonists and aldose reductase inhibitors
WO2002098462A1 (en) *	2001-06-01	2002-12-12	Ono Pharmaceutical Co., Ltd.	Remedies containing aldose reductase inhibitor as the active ingredient for demyelinating diseases or diseases associated with demyelination
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1985
- 1985-10-07 GB GB858524663A patent/GB8524663D0/en active Pending
1986
- 1986-09-16 ZA ZA867043A patent/ZA867043B/xx unknown
- 1986-09-16 US US06/908,005 patent/US4734419A/en not_active Expired - Lifetime
- 1986-09-23 IE IE252086A patent/IE59309B1/en not_active IP Right Cessation
- 1986-09-25 DK DK459086A patent/DK158838C/da not_active IP Right Cessation
- 1986-09-29 FI FI863917A patent/FI90234C/fi not_active IP Right Cessation
- 1986-10-02 ES ES86113559T patent/ES2021266B3/es not_active Expired - Lifetime
- 1986-10-02 DE DE8686113559T patent/DE3677452D1/de not_active Expired - Fee Related
- 1986-10-02 AT AT86113559T patent/ATE60761T1/de not_active IP Right Cessation
- 1986-10-02 EP EP86113559A patent/EP0218999B1/en not_active Expired - Lifetime
- 1986-10-02 IL IL80213A patent/IL80213A/xx not_active IP Right Cessation
- 1986-10-03 UA UA4028362A patent/UA5562A1/uk unknown
- 1986-10-03 CA CA000519759A patent/CA1289139C/en not_active Expired - Fee Related
- 1986-10-03 SU SU864028362A patent/SU1588283A3/ru active
- 1986-10-06 AU AU63589/86A patent/AU596611B2/en not_active Ceased
- 1986-10-06 JP JP61237605A patent/JPS6296476A/ja active Granted
- 1986-10-06 HU HU864192A patent/HU196972B/hu not_active IP Right Cessation
- 1986-10-06 NO NO863980A patent/NO171785C/no not_active IP Right Cessation
- 1986-10-07 CN CN86106984A patent/CN1017242B/zh not_active Expired
- 1986-10-07 KR KR86008374A patent/KR940007270B1/ko not_active Expired - Fee Related
1987
- 1987-12-08 US US07/130,297 patent/US4883800A/en not_active Expired - Lifetime
1988
- 1988-08-22 JP JP63207570A patent/JPH0794447B2/ja not_active Expired - Lifetime
- 1988-08-22 JP JP63207571A patent/JPH01125322A/ja active Granted
1991
- 1991-02-25 GR GR90401160T patent/GR3001502T3/el unknown
1992
- 1992-10-27 SG SG1120/92A patent/SG112092G/en unknown
1993
- 1993-01-28 HK HK69/93A patent/HK6993A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
HU196972B (en)	1989-02-28
DK158838C (da)	1991-01-14
FI90234B (fi)	1993-09-30
GB8524663D0 (en)	1985-11-13
FI863917A0 (fi)	1986-09-29
JPH01125322A (ja)	1989-05-17
JPH0794447B2 (ja)	1995-10-11
NO863980D0 (no)	1986-10-06
US4883800A (en)	1989-11-28
JPH01131164A (ja)	1989-05-24
KR870003998A (ko)	1987-05-06
GR3001502T3 (en)	1992-11-23
FI863917L (fi)	1987-04-08
DK158838B (da)	1990-07-23
NO171785B (no)	1993-01-25
JPS6296476A (ja)	1987-05-02
JPH05366B2 (2)	1993-01-05
DK459086D0 (da)	1986-09-25
EP0218999A3 (en)	1988-01-13
IL80213A (en)	1991-06-30
CN86106984A (zh)	1987-05-20
KR940007270B1 (en)	1994-08-12
CN1017242B (zh)	1992-07-01
DK459086A (da)	1987-04-08
EP0218999A2 (en)	1987-04-22
HUT41747A (en)	1987-05-28
DE3677452D1 (de)	1991-03-14
NO863980L (no)	1987-04-08
SU1588283A3 (ru)	1990-08-23
EP0218999B1 (en)	1991-02-06
UA5562A1 (uk)	1994-12-28
JPH0482148B2 (2)	1992-12-25
AU596611B2 (en)	1990-05-10
IE59309B1 (en)	1994-02-09
ES2021266B3 (es)	1991-11-01
HK6993A (en)	1993-02-05
CA1289139C (en)	1991-09-17
SG112092G (en)	1992-12-24
IL80213A0 (en)	1987-01-30
NO171785C (no)	1993-05-05
AU6358986A (en)	1987-04-09
IE862520L (en)	1987-04-07
US4734419A (en)	1988-03-29
ATE60761T1 (de)	1991-02-15
ZA867043B (en)	1987-07-29

Legal Events

Date	Code	Title	Description
1993-09-01	BB	Publication of examined application
2004-08-31	MM	Patent lapsed	Owner name: FUJISAWA PHARMACEUTICAL CO., LTD.

Publication	Publication Date	Title
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