JPS6256151B2 - - Google Patents
Info
- Publication number
- JPS6256151B2 JPS6256151B2 JP17127183A JP17127183A JPS6256151B2 JP S6256151 B2 JPS6256151 B2 JP S6256151B2 JP 17127183 A JP17127183 A JP 17127183A JP 17127183 A JP17127183 A JP 17127183A JP S6256151 B2 JPS6256151 B2 JP S6256151B2
- Authority
- JP
- Japan
- Prior art keywords
- oxo
- dihydroquinoline
- carboxylic acid
- mixture
- acid
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- DTYLXDLAOLOTKT-UHFFFAOYSA-N 1,4-dihydroquinoline-3-carboxylic acid Chemical class C1=CC=C2CC(C(=O)O)=CNC2=C1 DTYLXDLAOLOTKT-UHFFFAOYSA-N 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 150000001875 compounds Chemical class 0.000 description 37
- 239000000203 mixture Substances 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 31
- 239000002904 solvent Substances 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 238000002844 melting Methods 0.000 description 25
- 230000008018 melting Effects 0.000 description 25
- 238000000921 elemental analysis Methods 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- 239000002244 precipitate Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 239000013078 crystal Substances 0.000 description 18
- -1 phosphoric acid Chemical class 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- 238000001914 filtration Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- ILNJBIQQAIIMEY-UHFFFAOYSA-N 4-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CN=C21 ILNJBIQQAIIMEY-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- NZAUVXCUULSKDI-UHFFFAOYSA-N 2,3,4-trifluoro-n-propan-2-ylaniline Chemical compound CC(C)NC1=CC=C(F)C(F)=C1F NZAUVXCUULSKDI-UHFFFAOYSA-N 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000588722 Escherichia Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 231100000111 LD50 Toxicity 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- YBEOYBKKSWUSBR-UHFFFAOYSA-N ethyl 4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OCC)=CNC2=C1 YBEOYBKKSWUSBR-UHFFFAOYSA-N 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 230000027939 micturition Effects 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 150000004885 piperazines Chemical class 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 2
- OPELDSFLVQSDPM-UHFFFAOYSA-N 1,2,5-trifluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=C2C(C(=C(N(C2=CC=C1)F)F)C(=O)O)=O OPELDSFLVQSDPM-UHFFFAOYSA-N 0.000 description 1
- ARHYWWAJZDAYDJ-UHFFFAOYSA-N 1,2-dimethylpiperazine Chemical compound CC1CNCCN1C ARHYWWAJZDAYDJ-UHFFFAOYSA-N 0.000 description 1
- XJDDLMJULQGRLU-UHFFFAOYSA-N 1,3-dioxane-4,6-dione Chemical compound O=C1CC(=O)OCO1 XJDDLMJULQGRLU-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YHRXPOLYCUTZAM-UHFFFAOYSA-N 1-ethyl-6,8-difluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 YHRXPOLYCUTZAM-UHFFFAOYSA-N 0.000 description 1
- PXZDLINBBKAIPK-UHFFFAOYSA-N 1-ethyl-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 PXZDLINBBKAIPK-UHFFFAOYSA-N 0.000 description 1
- DPVAPRQGOBTQFA-UHFFFAOYSA-N 1-ethyl-7-(4-ethyl-3-methylpiperazin-1-yl)-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)N(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2CC DPVAPRQGOBTQFA-UHFFFAOYSA-N 0.000 description 1
- WRDGNXCXTDDYBZ-UHFFFAOYSA-N 2,3,4-trifluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1F WRDGNXCXTDDYBZ-UHFFFAOYSA-N 0.000 description 1
- WWYFHDNQGVTJJJ-UHFFFAOYSA-N 2-cyclohexylpiperazine Chemical compound C1CCCCC1C1NCCNC1 WWYFHDNQGVTJJJ-UHFFFAOYSA-N 0.000 description 1
- DXOHZOPKNFZZAD-UHFFFAOYSA-N 2-ethylpiperazine Chemical compound CCC1CNCCN1 DXOHZOPKNFZZAD-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- JSGVZVOGOQILFM-UHFFFAOYSA-N 3-methoxy-1-butanol Chemical compound COC(C)CCO JSGVZVOGOQILFM-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- MJZVWVHWFGBYPM-UHFFFAOYSA-N 6,8-difluoro-1-methyl-7-(3-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid Chemical compound C1CNC(C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C)C2=C1F MJZVWVHWFGBYPM-UHFFFAOYSA-N 0.000 description 1
- AZDZRTMODXHCJO-UHFFFAOYSA-N 6,8-difluoro-7-(3-methylpiperazin-1-yl)-4-oxo-1-propan-2-ylquinoline-3-carboxylic acid Chemical compound FC1=C2N(C(C)C)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 AZDZRTMODXHCJO-UHFFFAOYSA-N 0.000 description 1
- KCEJQAATYWQMMQ-UHFFFAOYSA-N 6-fluoro-4-oxo-1h-quinoline-3-carboxylic acid Chemical class C1=C(F)C=C2C(=O)C(C(=O)O)=CNC2=C1 KCEJQAATYWQMMQ-UHFFFAOYSA-N 0.000 description 1
- ZCYKSNZFXQZOLV-UHFFFAOYSA-N 7-(3,4-dimethylpiperazin-1-yl)-1-ethyl-6,8-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)C(C)C1 ZCYKSNZFXQZOLV-UHFFFAOYSA-N 0.000 description 1
- TXNIGKVRKAHETQ-UHFFFAOYSA-N 7-(3,4-dimethylpiperazin-1-yl)-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)C(C)C1 TXNIGKVRKAHETQ-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- AUNMIRGSKUNPAQ-UHFFFAOYSA-N CCCN1C=C(C(=O)C2=CC(=C(C=C21)N3CCNC(C3)C)F)C(=O)O Chemical compound CCCN1C=C(C(=O)C2=CC(=C(C=C21)N3CCNC(C3)C)F)C(=O)O AUNMIRGSKUNPAQ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- WVHBHPATSLQXGC-UHFFFAOYSA-N benzene;ethanol Chemical compound CCO.C1=CC=CC=C1 WVHBHPATSLQXGC-UHFFFAOYSA-N 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
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- LNNAIKLYSCYPOG-UHFFFAOYSA-N ethyl 1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylate Chemical compound FC=1C=C2C(=O)C(C(=O)OCC)=CN(CC)C2=C(F)C=1N1CCNC(C)C1 LNNAIKLYSCYPOG-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 235000019233 fast yellow AB Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229910001389 inorganic alkali salt Inorganic materials 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 1
- 229960001180 norfloxacin Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- JOHZPMXAZQZXHR-UHFFFAOYSA-N pipemidic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCNCC1 JOHZPMXAZQZXHR-UHFFFAOYSA-N 0.000 description 1
- 229960001732 pipemidic acid Drugs 0.000 description 1
- BRYCUMKDWMEGMK-UHFFFAOYSA-N piperazine-2-carboxamide Chemical compound NC(=O)C1CNCCN1 BRYCUMKDWMEGMK-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (27)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17127183A JPS6064979A (ja) | 1983-09-19 | 1983-09-19 | ７−ピペラジン置換−６−フルオロ−４−オキソ−１，４−ジヒドロキノリン−３−カルボン酸誘導体 |
| ZA847059A ZA847059B (en) | 1983-09-19 | 1984-09-07 | A 6-fluoro-1,4-dihydro-4-oxo-7-substituted piperazinylquinoline-3-carboxylic acid derivative and the method for preparing the same |
| AU32984/84A AU553415B2 (en) | 1983-09-19 | 1984-09-12 | 6-fluoro-1-4-dihydro-4-oxo-7-substituted piperazinyl- quinoline-3-carboxylic acids |
| KR1019840005625A KR870001016B1 (ko) | 1983-09-19 | 1984-09-15 | 6-플루오로-1,4-디히드로-4-옥소-7-치환 피페라지닐퀴놀린-3-카르복실산 유도체의 제조방법 |
| AT84111035T ATE34573T1 (de) | 1983-09-19 | 1984-09-15 | Ein 6-fluor-1,4-dihydro-4-oxo-7 substituiertes piperazinylchinolin-3-carbonsaeure-derivat und ein verfahren zu seiner herstellung. |
| EP84111035A EP0140116B1 (en) | 1983-09-19 | 1984-09-15 | A 6-fluoro-1,4-dihydro-4-oxo-7-substituted piperazinyl-quinoline-3-carboxylic acid derivative and the method for preparing the same |
| DE19843433924 DE3433924A1 (de) | 1983-09-19 | 1984-09-15 | 6-fluoro-1,4-dihydro-4-oxo-7-substituierte piperazinyl-chinolin-3-carbonsaeure-derivate und verfahren zu ihrer herstellung |
| FI843620A FI80033C (fi) | 1983-09-19 | 1984-09-17 | Foerfarande foer framstaellning av farmakologiskt vaerdefulla 6-fluor-1,4-dihydro-4-oxo-7-substituerat piperazinylkinolin-3-karboxylderivat. foer dess framstaellning. |
| US06/651,423 US4528287A (en) | 1983-09-19 | 1984-09-17 | 6-Fluoro-1, 4-dihydro-4-oxo-7-substituted piperazinylquinoline-3-carboxylic acids and the method for preparing the same |
| HU843498A HU193226B (en) | 1983-09-19 | 1984-09-18 | Process for preparing 6-fluoro-1,4-dihydro-4-oxo-7-substituted-piperazinyl-quinoline-3-carboxylic acid derivatives |
| UA3799807A UA6324A1 (uk) | 1983-09-19 | 1984-09-18 | Спосіб одержання похідних 6-фтор-1, дігідро-4-оксо-7-заміщений піперазінілхінолін-3-карбонової кислоти або їх фармацевтично прийнятних солей |
| ES536004A ES8604565A1 (es) | 1983-09-19 | 1984-09-18 | Un derivado de acido 6-fluor-1, 4-dihidro-4-oxo-7-piperazinil-quinolin sustituido-3-carboxilico |
| DK445084A DK157997C (da) | 1983-09-19 | 1984-09-18 | 6-fluor-1,4-dihydro-4-oxo-7-substituerede piperazinylquinolin-3-carboxylsyrederivater og deres farmakologisk acceptable salte samt farmaceutiske sammensaetninger til brug ved behandling af bakterielle sygdomme |
| SI8411603A SI8411603A8 (sl) | 1983-09-19 | 1984-09-18 | Postopek za pripravo derivatov 6-fluoro-1.4-dihidro-4-okso-7-substituiranih piperazinil - kinolin-3-karboksilnih kislin |
| SU843799807A SU1694063A3 (ru) | 1983-09-19 | 1984-09-18 | Способ получени производных 6-фтор-1,4-дигидро-4-оксо-7-замещенной пиперазинилхинолин-3-карбоновой кислоты или их фармацевтически приемлемых солей |
| FR8414294A FR2555584B1 (fr) | 1983-09-19 | 1984-09-18 | Derives de l'acide fluoro-6-dihydro-1,4-oxo-4-piperazinyl substitue-7-quinoline-carboxylique-3 et procede pour leur preparation et compositions pharmaceutiques a action anti-bacteriennes a base desdits derives |
| YU1603/84A YU45204B (en) | 1983-09-19 | 1984-09-18 | Process for making derivatives of 6-fluoro-1,4-dihydro-4-oxo-7-substituted piperazinyle-quinoline-3-carboxilic acid |
| CA000463652A CA1238638A (en) | 1983-09-19 | 1984-09-19 | 6-fluoro-1, 4-dihydro-4-oxo-7-substituted piperazinyl- quinoline-3-carboxylic acid derivative and the method for preparing the same |
| ES545756A ES8609303A1 (es) | 1983-09-19 | 1985-07-31 | Un procedimiento para la preparacion de un derivado de acido6-fluor-1,4-dihidro-4-oxo-7-piperazinilquinolin sustituido-3-carboxilico |
| SI8611958A SI8611958A8 (sl) | 1983-09-19 | 1986-11-17 | Postopek za pripravo derivatov 6-flu0r0-1,4-dihidr0-4-0ks0-7-substituiranih piperazinil-kinolin-3-karboksilnih kislin |
| YU195886A YU45379B (en) | 1983-09-19 | 1986-11-17 | Process for obtaining derivatives of 6-fluoro-1,4-dihydro-4-oxo-7-substituted-piperazinyl-quinolin-3-carboxilic acid |
| HK621/91A HK62191A (en) | 1983-09-19 | 1991-08-08 | A 6-fluoro-1,4-dihydro-4-oxo-7-substituted piperazinyl-quinoline-3-carboxylic acid derivative and the method for preparing the same |
| HRP-1958/86A HRP930652B1 (en) | 1983-09-19 | 1993-04-01 | Process for the preparation of 6-fluoro-1,4-didydro-4-oyo-7-substituted piperazinyl-quinoline-3-carboxylic acid derivative |
| HRP-1603/84A HRP930651B1 (en) | 1983-09-19 | 1993-04-01 | Process for the preparation of 6-fluoro-1,4-dihydro-4-oxo-7-substituted piperazinyl-quinoline-3-carboxylic acid derivative |
| LTRP1004A LT2516B (lt) | 1983-09-19 | 1993-09-20 | Aciskai priimtinu drusku gavimo budas 6-fluoro-1,4-dihidro-4-okso-7-pakeistos piperazinilchinolin-3-karbonines rugsties dariniu ar ju farm |
| LV931192A LV5500A3 (lv) | 1983-09-19 | 1993-11-11 | Panemiens 6-fluor-1,4-dihidro-4-osko-7-(aizvietotas piperazino)-hinolin-3-karbonskabes atvasinajumu vai to farmaceitiski pienemamo salu iegusanai |
| GEAP19942165A GEP19981255B (en) | 1983-09-19 | 1994-09-07 | Method of obtaining derivatives of 6-fluorine-1,4-dihydro-oxo-7-substituted by piperazinylquinoline or pharmaceutically acceptable salts thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17127183A JPS6064979A (ja) | 1983-09-19 | 1983-09-19 | ７−ピペラジン置換−６−フルオロ−４−オキソ−１，４−ジヒドロキノリン−３−カルボン酸誘導体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6064979A JPS6064979A (ja) | 1985-04-13 |
| JPS6256151B2 true JPS6256151B2 (da) | 1987-11-24 |
Family
ID=15920228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17127183A Granted JPS6064979A (ja) | 1983-09-19 | 1983-09-19 | ７−ピペラジン置換−６−フルオロ−４−オキソ−１，４−ジヒドロキノリン−３−カルボン酸誘導体 |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS6064979A (da) |
| YU (1) | YU45379B (da) |
| ZA (1) | ZA847059B (da) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4694669B2 (ja) | 1999-03-17 | 2011-06-08 | 第一三共株式会社 | 医薬組成物 |
-
1983
- 1983-09-19 JP JP17127183A patent/JPS6064979A/ja active Granted
-
1984
- 1984-09-07 ZA ZA847059A patent/ZA847059B/xx unknown
-
1986
- 1986-11-17 YU YU195886A patent/YU45379B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6064979A (ja) | 1985-04-13 |
| YU45379B (en) | 1992-05-28 |
| ZA847059B (en) | 1985-04-24 |
| YU195886A (en) | 1987-10-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR870001016B1 (ko) | 6-플루오로-1,4-디히드로-4-옥소-7-치환 피페라지닐퀴놀린-3-카르복실산 유도체의 제조방법 | |
| JPS5845426B2 (ja) | 置換キノリンカルボン酸誘導体 | |
| GB2057440A (en) | Quinoline carboxylic acid derivatives | |
| FI77855C (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 6-fluor-1,4-dihydro-4-oxo-3- kinolinkarboxylsyraderivat. | |
| HU199821B (en) | Process for production of derivatives of in 8 position substituated quinoline carbonic acid and medical compositions containing them | |
| DK150071B (da) | Analogifremgangsmaade til fremstilling af imidazoquinoliner eller salte deraf | |
| JPS59101467A (ja) | ６，７−ジヒドロ−８−（イミダゾ−ル−１−イル）−５−メチル−１−オキソ−１Ｈ，５Ｈ−ベンゾ〔ｉｊ〕キノリジン−２−カルボン酸およびその誘導体 | |
| JP2693988B2 (ja) | キノリンカルボン酸誘導体の製造方法 | |
| JPH0717608B2 (ja) | ６−アルコキシキノロンカルボン酸誘導体 | |
| JPS6256151B2 (da) | ||
| JP2003529601A (ja) | 抗ウイルス剤としての４−オキソ−１，４−ジヒドロ［１，８］ナフチリジン−３−カルボキサミド | |
| JPS63196580A (ja) | キノリン−３−カルボン酸誘導体 | |
| JPS63132885A (ja) | キノリン−３−カルボン酸誘導体 | |
| JP2621292B2 (ja) | 抗菌化合物 | |
| JPH02174784A (ja) | イソチアゾロキノリン誘導体 | |
| JPH0376316B2 (da) | ||
| JPS606684A (ja) | ７−ホモピペラジン置換−６，８−ジフルオロ−４−オキソ−１，４−ジヒドロキノリン−３−カルボン酸誘導体 | |
| JPS6185381A (ja) | １−エチル−６，８−ジフルオロ−１，４−ジヒドロ−４−オキソ−７−ピペラジニルキノリン−３−カルボン酸誘導体の製造法 | |
| EP0221541A2 (en) | Quinolonecarboxylic acid derivatives and their preparation | |
| JPS6270370A (ja) | キノロンカルボン酸誘導体およびその製造方法 | |
| JPH05112554A (ja) | 新規なキノロンカルボン酸誘導体 | |
| JPS63196579A (ja) | キノリン−３−カルボン酸誘導体 | |
| JPS615075A (ja) | ６−フルオロ−１，４−ジヒドロ−４−オキソ−７−置換ピペラジニルキノリン−３−カルボン酸誘導体 | |
| JPS6028964A (ja) | ７−ピペラジン又はホモピペラジン置換−１−イソプロピル−６−フルオロ−４−オキソ−１，４−ジヒドロキノリン−３−カルボン酸誘導体 | |
| JPS61218584A (ja) | キノリン−３−カルボン酸誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Year of fee payment: 21 Free format text: PAYMENT UNTIL: 20081124 |
|
| EXPY | Cancellation because of completion of term |