SE459809B - Bensokinolizin-karboxylsyraderivat och foerfarande foer framstaellning daerav - Google Patents
Bensokinolizin-karboxylsyraderivat och foerfarande foer framstaellning daeravInfo
- Publication number
- SE459809B SE459809B SE8400853A SE8400853A SE459809B SE 459809 B SE459809 B SE 459809B SE 8400853 A SE8400853 A SE 8400853A SE 8400853 A SE8400853 A SE 8400853A SE 459809 B SE459809 B SE 459809B
- Authority
- SE
- Sweden
- Prior art keywords
- carboxylic acid
- compound
- dihydro
- oxo
- fluoro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title 1
- 239000002253 acid Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 claims description 4
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- PECXKIKQYLSGGA-UHFFFAOYSA-N 7-fluoro-12-methyl-8-[4-[(4-nitrophenyl)methyl]piperazin-1-yl]-4-oxo-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13)-tetraene-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)CCC3=C1N(CC1)CCN1CC1=CC=C([N+]([O-])=O)C=C1 PECXKIKQYLSGGA-UHFFFAOYSA-N 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 241001148470 aerobic bacillus Species 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 5
- IAKNLKLKKBPMHN-UHFFFAOYSA-N 4h-quinolizine-2-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CCN21 IAKNLKLKKBPMHN-UHFFFAOYSA-N 0.000 description 4
- 241000606125 Bacteroides Species 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- -1 1-piperazinyl Chemical group 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- MHWLWQUZZRMNGJ-UHFFFAOYSA-N nalidixic acid Chemical compound C1=C(C)N=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MHWLWQUZZRMNGJ-UHFFFAOYSA-N 0.000 description 3
- 229960000210 nalidixic acid Drugs 0.000 description 3
- 229960001180 norfloxacin Drugs 0.000 description 3
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 1
- 208000020154 Acnes Diseases 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- 241000606215 Bacteroides vulgatus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101100328888 Caenorhabditis elegans col-36 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241000186588 Erysipelatoclostridium ramosum Species 0.000 description 1
- 241000186394 Eubacterium Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000605909 Fusobacterium Species 0.000 description 1
- 241000605952 Fusobacterium necrophorum Species 0.000 description 1
- 241000605975 Fusobacterium varium Species 0.000 description 1
- 206010017914 Gastroenteritis salmonella Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000206591 Peptococcus Species 0.000 description 1
- 241001135215 Prevotella bivia Species 0.000 description 1
- 241000588767 Proteus vulgaris Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical compound [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
459 809 a 2 U'| 10 15 20 25 30 f o F coon HZN-Q-CHT-N' i: \ J \__/ cn3 Förening [I] Detaljerad beskrivning av uppfinningen: Förening [I] enligt föreliggande uppfinning har ett imponeran- de brett spektrum när det gäller antibakteriell aktivitet mot både gram-negativa och gram-positiva aeroba bakterier och gram-negativa och gram-positiva obligat anaeroba bakterier.
Därför âr föreningen [I] praktiskt effektiv som antibakteri- ellt medel. tillämpbart som nya mediciner att administreras för behandling av humana sjukdomar och även tillämpbart som läkemedel för fiskar och djur samt som jordbrukskemikalier.
Föreningarna enligt föreliggande uppfinning framställes från 8-[4-(4-nitrobensyl)-l-piperaziyl]-9-fluoro-6.7-dihydro-5-metyl- 1-oxo-1H.SH-benso[ijJkinolizin-2-karboxylsyra (händanefte förkortad som förening [II]) genom reduktion t.ex reduktion med väte i r _ katalytisk närvaro av katalysatorer såsom palladium, nickel och platina eller reduktion med metaller såsom zink. tenn. järn och aluminiumamalgam eller reduktion med metall- joner såsom tenn(II)jon och järn(II)jon. t.ex. i form av salter och företrädesvis katalytisk reduktion t-ex. med väte ' 1 närvaro av palladíum på träkol i ättíksyra under normalt tryck vid rumstemperatur. 10 15 20 25 30 35 3 459 'ÖÛ9 F coon H O /-\ I --Å-) förening ¿_l_/ ZN CflzïN N N L\//L*CH 3 Förening [II] Dessutom är föreningen [II]. utgångsmaterialet. även en ny förening och framställes t.ex. med följande metod. Föreningen [II] framställes genom omsättning av 9-fluoro-6.7-dihydro-5- -metyl-l-oxo~8-(1-piperazinyl)-lH.SH-benso[ij]kinolizin-2-karb- oxylsyra (hädanefter förkortad som förening [III]) eller dess syraadditíonssalter med p-nítrobensylhalogenid, företrädesvis bromid eller klorid (hädanefter förkortad som förening [IV]) i ett lämpligt lösningsmedel såsom t.ex. N.N-dimetylformamid vid en temperatur från rumstemperatur till använda lösningsmedels kokpunkter. företrädesvis i närvaro av en syraacceptor såsom trietylamin.
O F ü COOH | _ " ' II HN/ \N \N J, O2N_©_ CHZX ___-_) förening Å _7 H3 Förening [III] Förening [IV] Beskrivning av föredragna utföringsformer: Föreliggande uppfinning förstås bättre av följande beskrivning av föredragna utföríngsformer. 459 809 4 10 15 20 25 30 35 'Föreningen [II] (0.7l Exempel 1: Framställning av 8-[4-(4-nitrobensyl)-1 -6,7-dihydro-5 -piperaziny1]-9-fluoro- -metyl-1-oxo-lH.SH-benso[íj]kínolizin-2-karboxyl- syra (förening [II]).
En blandning av 9-fluoro-6,7-díhydro-5-metyl-8-(1-piper- azinyl)-1-oxo-1H.SH-benso[ij]xinolizin-2-karboxylsyra (före- ning [III]). hydroklorid (1,1 g). p-nitrobensylbromid (före- ning [IV]) (l.87 g) och trietylamin (1.46 g) i N.N-dimety1- formamid (50 ml) vârmdes under omrörning vid 80-90°C under 10 timmar. Efter indunstning av lösníngsmedlet sattes vatten till återstoden. och vattenblandningen extraherades med kloro- form. Kloroformskiktet torkades över vattenfritt natriumsulfat och índunstades till torrhet. återstoden omkristallíserades ur en blandning av N.N-dímetylformamid och etanol (2:l) och gav 0.83 g (utbyte: 60%) av 8-[4-(4-nitrobensyl)-1-piperazinyl]- -9-fluoro-6.7-dihydro-5-metyl-1-oxo-lH.5H-benso[ij]kino1izín-2- -karboxylsyra (förening [II]) som blekgula nålar. smp. 230-233°c (sönderfall).
C H N 62.49 5.24 11.66 62.59 5.11 11.82 Anal. beräknat för CZSHZSFNÅOS funnet Exempel 2: Framställning av 8-[4-(4-aminobensyl)-1 -6,7-díhydro-5-metyl-1-oxo-lH.SH syra (förening [I]). -piperazinyl]-9-fluoro- -benso[ij]kino1izin-2-karboxyl- g). blandad med 102 palladium på träkol (25 ml) hydrerades med den beräknade normalt tryck vid rumstemperatur. Sedan väte tagitsfupp filtrerades palladíumet och fíltratet koncentrerades till torrhet. återsto- den upplöstes i (0.2 g) och âttiksyra volymen av väte under den beräknade volymen på träkol. en liten mängd vatten och neutraliserades med 10 15 20 s 459 809 10% natriumhydroxílösning. Den resulterande fällningen uppsam- lades. torkades och renades genom kolonnkromatografi på sili- kagel med användning av en blandning av Kloroform och etanol (l0:l) som framkallande lösningsmedel. Den renade produkten omkristalliserades ur etanol och gav 0.25 g (utbyte: 37.12) 8-[4-(4-aminobensyl)-1-piperazinyl]-9-fluoro-6.7-dihydro-5-metyl -l-oxo-lH.SH-benso[íj]kino1izin-2-karboxylsyra (förening [I]) som blekgula nålar. smp. 215,5-2l7.5°C (sönderfall).
C H N Anal. beräknat för C25H27FN4O3. .l/BHZO 65.77 6.11 12.27 funnet 65.92 5.93 12.21 Experiment 1: Den antibakteriella aktiviteten hos förening [I] enligt före- liggande uppfinning analyserades med standardutspädningsmeto- den på agar mot aeroba bakterier och obligat anaeroba bakteri- er (Chemotherapy Vol. 22. nr 6. sid 1126-1128 (1974): Vo. 27. nr 3. sid 559-560 (1979)). Resultaten visas i tabell 1 och tabell 2. 10 15 20 25 459 809 s Tabell L Antíbakteríell aktivitet mot aeroba bakterier Organísmer Gram Minsta ínhíberande koncentration (/ug/ml) Förening NA NFLX (I) Bacíllus subtílis PCI219 + 0.05 6.25 0.20 Staphylococcus aureus 209P + 0.05 100 0.78 Streptococcus pyoqenes IID692 + 0.20 >l00 3.13 Streptococcus pyogenes S-8 + 0.10 >l00 1.56 Streptococcus faecalis IID682 + 0.39 >l00 3.13 Escheríchía coli NIHJ JC-2 - 0,20 3,13 0.05 Escheríchía coli ATCC10536 - 0.20 3.13 0.05 Proteus vulgaris IF03167 - 0,78 3,13 0,05 Salmmonella enterítídís IID604 - 1.56 12.5 0.10 Shígella sonneí IID969 - 0.39 1.56 0.05 Pseudomonas aerugínosa V-1 - 12.5 100 0.78 Pseudomonas aeruginosa IFO12689 - 25 >l00 1.56 NA: nalídixinsyra ' _ hydrxn-3-karbonsyra NFLX: norfloxacin piperazinyl)-3-kinolinkarboxylsyra 1-ety1-T,4-dihydro-7-metyl-4-oxo-1,8-naft- 1-etyl-6-fluoro-1,4-dihydro-4-oxo-7-(1- 10 15 20 25 30 35 459 8Ü9 Tabell 2 Antibakteríell aktivitet mot anaeroba bakterier Organismer Gram Minsta inhiberande køncentratíon (/ug/nl) Förening NA NFLX (I) Bacteroides fragilis GM7000 - 1.56 >25 >25 Bacteroides fragilís 0558 - 0.78 >25 >25 Bacteroides dístasonis 8503 - 3.13 >25 12.5 Bacteroídes thetaiotaomícron 0661 _ 6.25 >25 >25 Bacteroídes vulgatus - 0.78 >25 >25 Bacteroides bivius _ 1.56 >25 >25 Bacteroides melanínogenícus GAIOAIO - 0.78 >25 6.25 Fusobacterium necrophorum S-45 _ 0.20 >25 3,13 Fusobacteríum varium - 12.5 >25 >25 Fusobacteríum nucleatum _ 1.56 >25 25 Eubacterium límosum + 3.13 25 6.25 Propionihacteríum acnes 11828 + 3.13 >25 1.56 Peptococcus maggnus + 0,20 >25 1.56 Clostridium difficile + 12.5 >25 >25 Clostrídium perfríngens + 0,39 12,5 1,56 Clostrídium ramosum + 1.56 >25 >25 NA: nalídixinsyra NFLX: norfloxacin Såsom framgår av tabell 1 och tabell 2 år föreningen [I] mer aktiv än nalídíxínsyra och norfloxacin mot obligat anaeroba bakterier (både gram-negativa och gram-positiva bakterier) och gram-positiva aeroba bakterier och nalídíxínsyra mot gram- 459 809 a -positiva aeroba bakterier. såsom illustreras ovan har före- liggande föreningar avsevärt bredare potenta antíbakteriella Spektra mot både aeroba och oblígat anaeroba bakterier och är epecíellt effektiva som antibakteríella medel.
Claims (3)
1. 8-[4-(4-amínobensyl)-1-piperazínyll-9-f1uoro-6.7-díhydrø- -5-metyl-1-oxo-1H.SH-bensolíj]kíno1ízín-2-karboxylsyra. hydra- ter och syraaddítíonssalter därav.
2. 8-[4-(4-nitrobensyl)-1-piperazínyl]-9-f1uoro-6.7-dihydro- -5-metyl-1-oxo-1H.SH-benso[íj}kio1izín-2-karboxylsyra och syraadditíonssalter därav enligt krav 1.
3. Förfarande för framställning av 8-[4-(4-amínobensyl)-1~ -píperazínyl]-9-fluoro-6.7-díhydro-5-metyl-1-oxo-1H.EH-benso[íj] kiolízín-2-karboxylsyxa. hyörat och syraadditionssalter äärav. k ä n n e t e c k n a t av att man reducerar 8-[4-(4-nitro- bensyl)-1-píperazínyl]-9-fluoro-6.7-díhydro-5-metyl-1~oxo-lH,SH- benso[ij]kínolízin-2-karboxylsyra eller syraadóítíonssalter därav.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58028135A JPS59155381A (ja) | 1983-02-22 | 1983-02-22 | ベンゾキノリジンカルボン酸誘導体及びその製造法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| SE8400853D0 SE8400853D0 (sv) | 1984-02-17 |
| SE8400853L SE8400853L (sv) | 1984-08-23 |
| SE459809B true SE459809B (sv) | 1989-08-07 |
Family
ID=12240322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8400853A SE459809B (sv) | 1983-02-22 | 1984-02-17 | Bensokinolizin-karboxylsyraderivat och foerfarande foer framstaellning daerav |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4599418A (sv) |
| JP (1) | JPS59155381A (sv) |
| KR (1) | KR900001547B1 (sv) |
| AU (2) | AU2457884A (sv) |
| CA (1) | CA1225091A (sv) |
| DE (1) | DE3406235C2 (sv) |
| ES (1) | ES529962A0 (sv) |
| FR (1) | FR2541278B1 (sv) |
| GB (2) | GB8404223D0 (sv) |
| IT (1) | IT1173336B (sv) |
| SE (1) | SE459809B (sv) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4472405A (en) * | 1982-11-12 | 1984-09-18 | Riker Laboratories, Inc. | Antimicrobial 6,7-dihydro-5,8-dimethyl-9 fluoro-1-oxo-1H, 5H-benzo (ij) quinolizine-2-carboxylic acid and derivatives |
| JPH08775B2 (ja) * | 1986-05-22 | 1996-01-10 | 協和醗酵工業株式会社 | 魚類のパスツレラ属細菌性類結節症治療剤 |
| US7247642B2 (en) * | 1999-05-07 | 2007-07-24 | Wockhardt Limited | Antibacterial optically pure benzoquinolizine carboxylic acids, processes, compositions and methods of treatment |
| US6750224B1 (en) | 1999-05-07 | 2004-06-15 | Wockhardt Limited | Antibacterial optically pure benzoquinolizine carboxylic acids, processes, compositions and methods of treatment |
| US6514986B2 (en) | 2000-11-22 | 2003-02-04 | Wockhardt Limited | Chiral fluoroquinolone arginine salt forms |
| US6608078B2 (en) | 2000-05-08 | 2003-08-19 | Wockhardt Limited | Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment |
| US7098219B2 (en) | 2000-08-01 | 2006-08-29 | Wockhart Limited | Inhibitors of cellular efflux pumps of microbes |
| US6964966B2 (en) | 2001-04-25 | 2005-11-15 | Wockhardt Limited | Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments |
| US6878713B2 (en) * | 2001-04-25 | 2005-04-12 | Wockhardt Limited | Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments |
| US7217696B2 (en) * | 2002-02-28 | 2007-05-15 | A & D Bioscience, Inc. | Glycuronamides, glycosides and orthoester glycosides of fluoxetine, analogs and uses thereof |
| WO2003079980A2 (en) * | 2002-03-19 | 2003-10-02 | A & D Bioscience, Inc. | Caboxylic acid glycuronides, glycosamides and glycosides of quinolones, penicillins, analogs, and uses thereof |
| US20050255038A1 (en) * | 2002-04-12 | 2005-11-17 | A And D Bioscience, Inc. | Conjugates comprising cancer cell specific ligands, a sugar and diagnostic agents and uses thereof |
| US20050153928A1 (en) * | 2002-05-07 | 2005-07-14 | Holick Michael F. | Conjugates comprising a central nervous system-active drug linked to glucuronic acid or glucosamine through an amide bond and uses thereof |
| US6664267B1 (en) * | 2002-05-28 | 2003-12-16 | Wockhardt Limited | Crystalline fluoroquinolone arginine salt form |
| US20050215487A1 (en) * | 2002-06-27 | 2005-09-29 | Holick Michael F | Conjugates comprising an nsaid and a sugar and uses thereof |
| EP1660495B1 (en) | 2003-09-04 | 2007-07-11 | Wockhardt Limited | Benzoquinolizine-2-carboxylic acid arginine salt tetrahydrate |
| EP3328856A2 (en) * | 2015-07-28 | 2018-06-06 | Vyome Biosciences Pvt. Ltd. | Antibacterial therapeutics and prophylactics |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4416884A (en) * | 1978-04-12 | 1983-11-22 | Otsuka Pharmaceutical Co., Ltd. | Piperazinylbenzoheterocyclic compounds |
| JPS6019910B2 (ja) * | 1979-10-11 | 1985-05-18 | 大塚製薬株式会社 | ベンゾ〔ｉｊ〕キノリジン−２−カルボン酸誘導体及びその製造法 |
| JPS5630964A (en) * | 1979-08-22 | 1981-03-28 | Kyorin Pharmaceut Co Ltd | Novel substituted quinolinecarboxylic acid and its preparation |
| NO156828C (no) * | 1980-11-10 | 1987-12-02 | Otsuka Pharma Co Ltd | Analogifremgangsm te for fremstilling av antibakterielt virksomme benzoheterocykliske forbindelser. |
| PT74145B (en) * | 1980-12-18 | 1983-05-30 | Otsuka Pharma Co Ltd | Process for preparing benzoheterocyclic compounds |
| JPS57145862A (en) * | 1981-03-06 | 1982-09-09 | Kyorin Pharmaceut Co Ltd | Quinolinecarboxylic acid derivative |
-
1983
- 1983-02-22 JP JP58028135A patent/JPS59155381A/ja active Granted
-
1984
- 1984-02-14 AU AU24578/84A patent/AU2457884A/en not_active Abandoned
- 1984-02-17 SE SE8400853A patent/SE459809B/sv not_active IP Right Cessation
- 1984-02-17 GB GB848404223A patent/GB8404223D0/en active Pending
- 1984-02-20 FR FR8402530A patent/FR2541278B1/fr not_active Expired
- 1984-02-21 DE DE3406235A patent/DE3406235C2/de not_active Expired - Lifetime
- 1984-02-21 CA CA000447876A patent/CA1225091A/en not_active Expired
- 1984-02-21 US US06/581,957 patent/US4599418A/en not_active Expired - Lifetime
- 1984-02-22 IT IT19740/84A patent/IT1173336B/it active
- 1984-02-22 AU AU24832/84A patent/AU559156B2/en not_active Expired
- 1984-02-22 GB GB08404691A patent/GB2138806B/en not_active Expired
- 1984-02-22 KR KR1019840000865A patent/KR900001547B1/ko not_active Expired
- 1984-02-22 ES ES529962A patent/ES529962A0/es active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| KR900001547B1 (ko) | 1990-03-12 |
| GB2138806B (en) | 1986-05-21 |
| GB2138806A (en) | 1984-10-31 |
| DE3406235A1 (de) | 1984-10-11 |
| GB8404691D0 (en) | 1984-03-28 |
| SE8400853D0 (sv) | 1984-02-17 |
| DE3406235C2 (de) | 1994-12-22 |
| AU2483284A (en) | 1984-08-30 |
| AU559156B2 (en) | 1987-02-26 |
| US4599418A (en) | 1986-07-08 |
| ES8600274A1 (es) | 1985-10-01 |
| AU2457884A (en) | 1984-08-30 |
| FR2541278A1 (fr) | 1984-08-24 |
| KR840007878A (ko) | 1984-12-11 |
| IT1173336B (it) | 1987-06-24 |
| SE8400853L (sv) | 1984-08-23 |
| IT8419740A0 (it) | 1984-02-22 |
| GB8404223D0 (en) | 1984-03-21 |
| JPH0412268B2 (sv) | 1992-03-04 |
| ES529962A0 (es) | 1985-10-01 |
| JPS59155381A (ja) | 1984-09-04 |
| FR2541278B1 (fr) | 1986-09-26 |
| CA1225091A (en) | 1987-08-04 |
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