CS270577B2 - Method of quinoline carboxylic acids production - Google Patents
Method of quinoline carboxylic acids production Download PDFInfo
- Publication number
- CS270577B2 CS270577B2 CS878688A CS868887A CS270577B2 CS 270577 B2 CS270577 B2 CS 270577B2 CS 878688 A CS878688 A CS 878688A CS 868887 A CS868887 A CS 868887A CS 270577 B2 CS270577 B2 CS 270577B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- group
- oxo
- cyclopropyl
- dihydro
- fluoro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 24
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical class C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title description 2
- -1 methoxy, amino, methylamino Chemical group 0.000 claims description 71
- 150000001875 compounds Chemical class 0.000 claims description 30
- 239000011541 reaction mixture Substances 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052801 chlorine Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- ISPVACVJFUIDPD-UHFFFAOYSA-N 7-chloro-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 ISPVACVJFUIDPD-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- KNEXGVPHPGXAGF-UHFFFAOYSA-N 1-cyclopropyl-6,7-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(F)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 KNEXGVPHPGXAGF-UHFFFAOYSA-N 0.000 claims description 3
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 claims description 3
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 208000024780 Urticaria Diseases 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 5
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- PCSAPCNEJUEIGU-UHFFFAOYSA-N 2,4-dichloro-5-fluoro-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(Cl)C([N+]([O-])=O)=C1Cl PCSAPCNEJUEIGU-UHFFFAOYSA-N 0.000 description 3
- BWQMAOINYNKMSK-UHFFFAOYSA-N 2,4-dichloro-5-fluoro-3-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=C(Cl)C(F)=CC(C(Cl)=O)=C1Cl BWQMAOINYNKMSK-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- NMASXYCNDJMMFR-UHFFFAOYSA-N 1-cyclopropyl-6,7,8-trifluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=C(F)C(F)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 NMASXYCNDJMMFR-UHFFFAOYSA-N 0.000 description 2
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
- ZYEWNAMVVRPNJX-UHFFFAOYSA-N 2,3,4,5-tetrafluorobenzoyl fluoride Chemical compound FC(=O)C1=CC(F)=C(F)C(F)=C1F ZYEWNAMVVRPNJX-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 2
- VZQWDTRNBPDEGB-UHFFFAOYSA-N 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=C([N+]([O-])=O)C(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 VZQWDTRNBPDEGB-UHFFFAOYSA-N 0.000 description 2
- ZHFGWIOLVRSZNQ-UHFFFAOYSA-N 8-chloro-1-cyclopropyl-6,7-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=C(Cl)C(F)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 ZHFGWIOLVRSZNQ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- QMLVECGLEOSESV-RYUDHWBXSA-N Danofloxacin Chemical compound C([C@@H]1C[C@H]2CN1C)N2C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 QMLVECGLEOSESV-RYUDHWBXSA-N 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- DIOIOSKKIYDRIQ-UHFFFAOYSA-N ciprofloxacin hydrochloride Chemical compound Cl.C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 DIOIOSKKIYDRIQ-UHFFFAOYSA-N 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical compound NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 239000011775 sodium fluoride Substances 0.000 description 2
- 235000013024 sodium fluoride Nutrition 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- NSMWYRLQHIXVAP-OLQVQODUSA-N (2r,5s)-2,5-dimethylpiperazine Chemical compound C[C@H]1CN[C@H](C)CN1 NSMWYRLQHIXVAP-OLQVQODUSA-N 0.000 description 1
- IFNWESYYDINUHV-PHDIDXHHSA-N (2r,6r)-2,6-dimethylpiperazine Chemical compound C[C@@H]1CNC[C@@H](C)N1 IFNWESYYDINUHV-PHDIDXHHSA-N 0.000 description 1
- NSMWYRLQHIXVAP-WDSKDSINSA-N (2s,5s)-2,5-dimethylpiperazine Chemical compound C[C@H]1CN[C@@H](C)CN1 NSMWYRLQHIXVAP-WDSKDSINSA-N 0.000 description 1
- IFNWESYYDINUHV-OLQVQODUSA-N (2s,6r)-2,6-dimethylpiperazine Chemical compound C[C@H]1CNC[C@@H](C)N1 IFNWESYYDINUHV-OLQVQODUSA-N 0.000 description 1
- ARHYWWAJZDAYDJ-UHFFFAOYSA-N 1,2-dimethylpiperazine Chemical compound CC1CNCCN1C ARHYWWAJZDAYDJ-UHFFFAOYSA-N 0.000 description 1
- BDGJUVBOIQSLOE-UHFFFAOYSA-N 1,3-dichloro-2,4-difluoro-5-(fluoromethyl)benzene Chemical compound FCC1=CC(Cl)=C(F)C(Cl)=C1F BDGJUVBOIQSLOE-UHFFFAOYSA-N 0.000 description 1
- JXWCOCIEGOAZOG-UHFFFAOYSA-N 1,5-dichloro-2-fluoro-4-methylbenzene Chemical compound CC1=CC(F)=C(Cl)C=C1Cl JXWCOCIEGOAZOG-UHFFFAOYSA-N 0.000 description 1
- ANHDTIZJXXMRCV-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC=CC=C2C(=O)C(C(=O)O)=CN1C1=CC=C(F)C=C1F ANHDTIZJXXMRCV-UHFFFAOYSA-N 0.000 description 1
- MSSDTZLYNMFTKN-UHFFFAOYSA-N 1-Piperazinecarboxaldehyde Chemical compound O=CN1CCNCC1 MSSDTZLYNMFTKN-UHFFFAOYSA-N 0.000 description 1
- ITXLERDKFZOJPO-UHFFFAOYSA-N 1-cyclopropyl-6,8-difluoro-7-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-oxoquinoline-3-carboxylic acid Chemical compound CN1CC2CC1CN2C(C=1F)=C(F)C=C(C(C(C(O)=O)=C2)=O)C=1N2C1CC1 ITXLERDKFZOJPO-UHFFFAOYSA-N 0.000 description 1
- JNUTUHAUMNUZAG-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-4-oxo-7-(5-prop-2-ynyl-2,5-diazabicyclo[2.2.2]octan-2-yl)quinoline-3-carboxylic acid Chemical compound C12=CC(N3C4CCC(N(C4)CC#C)C3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 JNUTUHAUMNUZAG-UHFFFAOYSA-N 0.000 description 1
- QMLVECGLEOSESV-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-7-(5-methyl-2-aza-5-azoniabicyclo[2.2.1]heptan-2-yl)-4-oxoquinoline-3-carboxylate Chemical compound CN1CC2CC1CN2C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 QMLVECGLEOSESV-UHFFFAOYSA-N 0.000 description 1
- WBAZKXNBWFVTFI-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-7-(5-methyl-2-aza-5-azoniabicyclo[2.2.2]octan-2-yl)-4-oxoquinoline-3-carboxylate Chemical compound CN1CC2CCC1CN2C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 WBAZKXNBWFVTFI-UHFFFAOYSA-N 0.000 description 1
- BDXOBBWCDGYVPB-UHFFFAOYSA-N 1-cyclopropyl-7-(1,4-diazabicyclo[3.2.1]octan-4-yl)-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1(CC1)N1C=C(C(C2=CC(=C(C(=C12)C)N1CCN2CCC1C2)F)=O)C(=O)O BDXOBBWCDGYVPB-UHFFFAOYSA-N 0.000 description 1
- YEGBYBZWOAXYLK-UHFFFAOYSA-N 1-cyclopropyl-7-(2,5-diazabicyclo[2.2.2]octan-2-yl)-6,8-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=C(F)C(N3C4CCC(NC4)C3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 YEGBYBZWOAXYLK-UHFFFAOYSA-N 0.000 description 1
- JGNYZYABUWGSJV-UHFFFAOYSA-N 1-cyclopropyl-7-(2,5-diazabicyclo[2.2.2]octan-2-yl)-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(N3C4CCC(NC4)C3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 JGNYZYABUWGSJV-UHFFFAOYSA-N 0.000 description 1
- WGCYRFWNGRMRJA-ZIEKVONGSA-N 1-ethylpiperazine Chemical class CCN1CCN[13CH2][13CH2]1 WGCYRFWNGRMRJA-ZIEKVONGSA-N 0.000 description 1
- SFKRXQKJTIYUAG-UHFFFAOYSA-N 2,3,4,5-tetrafluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(F)=C1F SFKRXQKJTIYUAG-UHFFFAOYSA-N 0.000 description 1
- XWCKIXLTBNGIHV-UHFFFAOYSA-N 2,3,4,5-tetrafluorobenzoyl chloride Chemical compound FC1=CC(C(Cl)=O)=C(F)C(F)=C1F XWCKIXLTBNGIHV-UHFFFAOYSA-N 0.000 description 1
- RIZUCYSQUWMQLX-UHFFFAOYSA-N 2,3-dimethylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1C RIZUCYSQUWMQLX-UHFFFAOYSA-N 0.000 description 1
- KZCWJHUTTSVCRO-UHFFFAOYSA-N 2,4-dichloro-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(Cl)C=C1Cl KZCWJHUTTSVCRO-UHFFFAOYSA-N 0.000 description 1
- RPZXUSJCSDQNTE-UHFFFAOYSA-N 2,4-dichloro-5-fluorobenzoyl chloride Chemical compound FC1=CC(C(Cl)=O)=C(Cl)C=C1Cl RPZXUSJCSDQNTE-UHFFFAOYSA-N 0.000 description 1
- IFNWESYYDINUHV-UHFFFAOYSA-N 2,6-dimethylpiperazine Chemical compound CC1CNCC(C)N1 IFNWESYYDINUHV-UHFFFAOYSA-N 0.000 description 1
- BYYCSTYYULCJLQ-UHFFFAOYSA-N 2-(2-methylpropyl)piperazine Chemical compound CC(C)CC1CNCCN1 BYYCSTYYULCJLQ-UHFFFAOYSA-N 0.000 description 1
- DXOHZOPKNFZZAD-UHFFFAOYSA-N 2-ethylpiperazine Chemical compound CCC1CNCCN1 DXOHZOPKNFZZAD-UHFFFAOYSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 description 1
- HJBIXRKZHZQGKZ-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 HJBIXRKZHZQGKZ-UHFFFAOYSA-N 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
- HBCSNWKQNPKIHK-UHFFFAOYSA-N 2-propan-2-ylpiperazine Chemical compound CC(C)C1CNCCN1 HBCSNWKQNPKIHK-UHFFFAOYSA-N 0.000 description 1
- FNJWLOHHZVGUIX-UHFFFAOYSA-N 2-propylpiperazine Chemical compound CCCC1CNCCN1 FNJWLOHHZVGUIX-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- MHTQOWXOYVNDMH-UHFFFAOYSA-N 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1=CC(F)=C(F)C(Cl)=C1F MHTQOWXOYVNDMH-UHFFFAOYSA-N 0.000 description 1
- RMBZGFRPRFOSCD-UHFFFAOYSA-N 3-(cyclopropylamino)prop-2-enoic acid Chemical compound OC(=O)C=CNC1CC1 RMBZGFRPRFOSCD-UHFFFAOYSA-N 0.000 description 1
- IEDMMCZBIKXEJP-UHFFFAOYSA-N 3-chloro-2,4,5-trifluorobenzoyl chloride Chemical compound FC1=CC(C(Cl)=O)=C(F)C(Cl)=C1F IEDMMCZBIKXEJP-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- UJSLOZAVHMSQNG-UHFFFAOYSA-N 4-oxo-3h-quinoline-3-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC=C2C(=O)C(C(=O)O)C=NC2=C1 UJSLOZAVHMSQNG-UHFFFAOYSA-N 0.000 description 1
- PTHNNGVSMMURMJ-UHFFFAOYSA-N 5,6-dihydrobenzo[h]quinoline-2-carboxylic acid Chemical compound N1=C(C=CC=2CCC3=C(C1=2)C=CC=C3)C(=O)O PTHNNGVSMMURMJ-UHFFFAOYSA-N 0.000 description 1
- HDPODBQAFOAFJY-UHFFFAOYSA-N 5-chloro-2,3,4-trifluorobenzoyl fluoride Chemical compound FC(=O)C1=CC(Cl)=C(F)C(F)=C1F HDPODBQAFOAFJY-UHFFFAOYSA-N 0.000 description 1
- YDCABRFIMRVMGF-UHFFFAOYSA-N 6,8-dichloro-1-cyclopropyl-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid Chemical compound C12=C(Cl)C(N3CCNCC3)=C(Cl)C=C2C(=O)C(C(=O)O)=CN1C1CC1 YDCABRFIMRVMGF-UHFFFAOYSA-N 0.000 description 1
- UMJMPQGMWKLZEC-UHFFFAOYSA-N 6,8-dichloro-1-cyclopropyl-7-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=C(Cl)C(F)=C(Cl)C=C2C(=O)C(C(=O)O)=CN1C1CC1 UMJMPQGMWKLZEC-UHFFFAOYSA-N 0.000 description 1
- KWJDQEWXENHGMW-UHFFFAOYSA-N 6-chloro-1-cyclopropyl-7,8-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=C(F)C(F)=C(Cl)C=C2C(=O)C(C(=O)O)=CN1C1CC1 KWJDQEWXENHGMW-UHFFFAOYSA-N 0.000 description 1
- RQBLLVJGAAWYEN-UHFFFAOYSA-N 6-chloro-1-cyclopropyl-8-fluoro-4-oxo-7-(4-propan-2-ylpiperazin-1-yl)quinoline-3-carboxylic acid Chemical compound C1CN(C(C)C)CCN1C1=C(Cl)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F RQBLLVJGAAWYEN-UHFFFAOYSA-N 0.000 description 1
- URLFJCGEAZUVFK-UHFFFAOYSA-N 6-chloro-1-cyclopropyl-8-fluoro-7-[3-(4-methoxyphenyl)piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1NCCN(C=2C(=C3C(C(C(C(O)=O)=CN3C3CC3)=O)=CC=2Cl)F)C1 URLFJCGEAZUVFK-UHFFFAOYSA-N 0.000 description 1
- LHZDPJRHQVYKPA-UHFFFAOYSA-N 7-(2-aza-5-azoniabicyclo[2.2.1]heptan-2-yl)-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(N3C4CC(NC4)C3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 LHZDPJRHQVYKPA-UHFFFAOYSA-N 0.000 description 1
- DFACKXMBSZDJTQ-UHFFFAOYSA-N 7-(5-benzyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(N3C4CC(N(C4)CC=4C=CC=CC=4)C3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 DFACKXMBSZDJTQ-UHFFFAOYSA-N 0.000 description 1
- SUVHVMBUDRXNKI-UHFFFAOYSA-N 8-chloro-1-cyclopropyl-6-fluoro-4-oxo-7-(3-phenylpiperazin-1-yl)quinoline-3-carboxylic acid Chemical compound C12=C(Cl)C(N3CC(NCC3)C=3C=CC=CC=3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 SUVHVMBUDRXNKI-UHFFFAOYSA-N 0.000 description 1
- MVXLDPRRAAVKTB-UHFFFAOYSA-N 8-chloro-1-cyclopropyl-6-fluoro-4-oxo-7-piperidin-1-ylquinoline-3-carboxylic acid Chemical compound C12=C(Cl)C(N3CCCCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MVXLDPRRAAVKTB-UHFFFAOYSA-N 0.000 description 1
- FZMLPRJNWFWIIK-UHFFFAOYSA-N 8-chloro-1-cyclopropyl-7-(4-ethyl-3-oxopiperazin-1-yl)-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(=O)N(CC)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1Cl FZMLPRJNWFWIIK-UHFFFAOYSA-N 0.000 description 1
- OASCSOIVISTYGS-UHFFFAOYSA-N 8-chloro-1-cyclopropyl-7-[3-(3,4-dimethoxyphenyl)piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC=C1C1NCCN(C=2C(=C3C(C(C(C(O)=O)=CN3C3CC3)=O)=CC=2F)Cl)C1 OASCSOIVISTYGS-UHFFFAOYSA-N 0.000 description 1
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 description 1
- CCKMPJCQCAUMLM-UHFFFAOYSA-N C12=C(Cl)C(N3C4CN(C4)CC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 Chemical compound C12=C(Cl)C(N3C4CN(C4)CC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 CCKMPJCQCAUMLM-UHFFFAOYSA-N 0.000 description 1
- OGYCESUAAKCZKZ-UHFFFAOYSA-N C1C(N2)CC(O)CC2CN1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 Chemical compound C1C(N2)CC(O)CC2CN1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 OGYCESUAAKCZKZ-UHFFFAOYSA-N 0.000 description 1
- ISOXNKJOELNAKZ-UHFFFAOYSA-N CC(CCCCC)C1=NC2=CC=CC=C2C=C1C(=O)O Chemical compound CC(CCCCC)C1=NC2=CC=CC=C2C=C1C(=O)O ISOXNKJOELNAKZ-UHFFFAOYSA-N 0.000 description 1
- UIUMVYUNAMACHR-UHFFFAOYSA-N CCC(CCCCC)C=1N(C2=CC=C(C=C2C(C1C(=O)O)=O)F)C1CC1 Chemical compound CCC(CCCCC)C=1N(C2=CC=C(C=C2C(C1C(=O)O)=O)F)C1CC1 UIUMVYUNAMACHR-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- MOVMCBGQQLGROS-UHFFFAOYSA-N Cl.C1(CC1)N1C=C(C(C2=CC(=C(C=C12)N1CCN2CCC1C2)F)=O)C(=O)O Chemical compound Cl.C1(CC1)N1C=C(C(C2=CC(=C(C=C12)N1CCN2CCC1C2)F)=O)C(=O)O MOVMCBGQQLGROS-UHFFFAOYSA-N 0.000 description 1
- GKKZMYDNDDMXSE-UHFFFAOYSA-N Ethyl 3-oxo-3-phenylpropanoate Chemical class CCOC(=O)CC(=O)C1=CC=CC=C1 GKKZMYDNDDMXSE-UHFFFAOYSA-N 0.000 description 1
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- GYIWFHXWLCXGQO-UHFFFAOYSA-N barium(2+);ethanolate Chemical compound [Ba+2].CC[O-].CC[O-] GYIWFHXWLCXGQO-UHFFFAOYSA-N 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- QGPKADBNRMWEQR-UHFFFAOYSA-N clinafloxacin Chemical compound C1C(N)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1Cl QGPKADBNRMWEQR-UHFFFAOYSA-N 0.000 description 1
- 230000004665 defense response Effects 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- ZKBBUZRGPULIRN-UHFFFAOYSA-N diethyl 2,2-diethylpropanedioate Chemical compound CCOC(=O)C(CC)(CC)C(=O)OCC ZKBBUZRGPULIRN-UHFFFAOYSA-N 0.000 description 1
- UMCIIIXCSXZJNZ-UHFFFAOYSA-N diethyl 2-(2,4-dichloro-5-fluoro-3-nitrobenzoyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C(=O)C1=CC(F)=C(Cl)C([N+]([O-])=O)=C1Cl UMCIIIXCSXZJNZ-UHFFFAOYSA-N 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- GCJYPXZGQIYKRF-UHFFFAOYSA-N ethyl 2-(3,5-dichloro-2,4-difluorobenzoyl)-3-ethoxyprop-2-enoate Chemical compound CCOC=C(C(=O)OCC)C(=O)C1=CC(Cl)=C(F)C(Cl)=C1F GCJYPXZGQIYKRF-UHFFFAOYSA-N 0.000 description 1
- BNEXAOCXYOUGIB-UHFFFAOYSA-N ethyl 2-(5-chloro-2,3,4-trifluorobenzoyl)-3-(cyclopropylamino)prop-2-enoate Chemical compound C=1C(Cl)=C(F)C(F)=C(F)C=1C(=O)C(C(=O)OCC)=CNC1CC1 BNEXAOCXYOUGIB-UHFFFAOYSA-N 0.000 description 1
- KOPFQNRNKNWYHK-UHFFFAOYSA-N ethyl 2-(5-chloro-2,3,4-trifluorobenzoyl)-3-ethoxyprop-2-enoate Chemical compound CCOC=C(C(=O)OCC)C(=O)C1=CC(Cl)=C(F)C(F)=C1F KOPFQNRNKNWYHK-UHFFFAOYSA-N 0.000 description 1
- JIVWQBJMHFWMKG-UHFFFAOYSA-N ethyl 3-(2,4-dichloro-5-fluoro-3-nitrophenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=CC(F)=C(Cl)C([N+]([O-])=O)=C1Cl JIVWQBJMHFWMKG-UHFFFAOYSA-N 0.000 description 1
- VIAZYLXGWMAOOA-UHFFFAOYSA-N ethyl 3-(3,5-dichloro-2,4-difluorophenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=CC(Cl)=C(F)C(Cl)=C1F VIAZYLXGWMAOOA-UHFFFAOYSA-N 0.000 description 1
- UCFRMVIODHQKQP-UHFFFAOYSA-N ethyl 3-(cyclopropylamino)-2-(3,5-dichloro-2,4-difluorobenzoyl)prop-2-enoate Chemical compound C=1C(Cl)=C(F)C(Cl)=C(F)C=1C(=O)C(C(=O)OCC)=CNC1CC1 UCFRMVIODHQKQP-UHFFFAOYSA-N 0.000 description 1
- ITQFPVUDTFABDH-UHFFFAOYSA-N ethyl 3-ethoxyprop-2-enoate Chemical compound CCOC=CC(=O)OCC ITQFPVUDTFABDH-UHFFFAOYSA-N 0.000 description 1
- FCGILORQEAHNMB-UHFFFAOYSA-N ethyl 6,8-dichloro-1-cyclopropyl-7-fluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=C(Cl)C(F)=C(Cl)C=C2C(=O)C(C(=O)OCC)=CN1C1CC1 FCGILORQEAHNMB-UHFFFAOYSA-N 0.000 description 1
- UUAYWVOLZVLIAX-UHFFFAOYSA-N ethyl 6-chloro-1-cyclopropyl-7,8-difluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=C(F)C(F)=C(Cl)C=C2C(=O)C(C(=O)OCC)=CN1C1CC1 UUAYWVOLZVLIAX-UHFFFAOYSA-N 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- OQCUGPQOZNYIMV-UHFFFAOYSA-N pyrrolidin-3-ylmethanamine Chemical compound NCC1CCNC1 OQCUGPQOZNYIMV-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- CESKLHVYGRFMFP-UHFFFAOYSA-N sulfonmethane Chemical compound CCS(=O)(=O)C(C)(C)S(=O)(=O)CC CESKLHVYGRFMFP-UHFFFAOYSA-N 0.000 description 1
- UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- C07D471/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Diaphragms For Electromechanical Transducers (AREA)
- Optical Fibers, Optical Fiber Cores, And Optical Fiber Bundles (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19863641312 DE3641312A1 (de) | 1986-12-03 | 1986-12-03 | Verfahren zur herstellung von chinolincarbonsaeuren |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS868887A2 CS868887A2 (en) | 1989-11-14 |
| CS270577B2 true CS270577B2 (en) | 1990-07-12 |
Family
ID=6315377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS878688A CS270577B2 (en) | 1986-12-03 | 1987-11-30 | Method of quinoline carboxylic acids production |
Country Status (25)
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN166416B (enrdf_load_html_response) * | 1985-09-18 | 1990-05-05 | Pfizer | |
| AU5449590A (en) * | 1989-04-28 | 1990-11-29 | Daiichi Pharmaceutical Co., Ltd. | Anti-hiv drug |
| FI921475A7 (fi) * | 1989-10-06 | 1992-04-03 | Pfizer | 1,4-dihydro-4-okso-3-kinoliinijohdannaisia selektiivisesti toksisina n isäkkään antibakteerisina aineina |
| US5385913A (en) * | 1989-10-06 | 1995-01-31 | Pfizer Inc. | 1,4-dihydro-4-oxo-3-quinoline derivatives as selectively toxic mammalian antibacterial agents |
| JP2613139B2 (ja) * | 1990-07-19 | 1997-05-21 | エスエス製薬 株式会社 | キノロンカルボン酸誘導体 |
| ES2050613B1 (es) * | 1992-10-16 | 1996-03-16 | Iteve S A | Nuevo procedimiento para la preparacion de derivados del acido 1-ciclopropil-3-quinolincarboxilico. |
| US6034100A (en) * | 1993-03-10 | 2000-03-07 | Otsuka Pharmaceutical Co., Ltd. | Method for inhibiting cytokine secretion |
| AU6421898A (en) * | 1997-03-25 | 1998-10-20 | Sankyo Company Limited | Anti-fiv agent |
| KR100454750B1 (ko) * | 2002-06-20 | 2004-11-03 | 삼성에스디아이 주식회사 | 유기 전계 발광 소자용 청색 발광 화합물 및 이를 사용한유기 전계 발광 소자 |
| DK1666477T3 (da) | 2003-09-10 | 2013-07-29 | Kyorin Seiyaku Kk | 7-(4-trisubstitueret 3-cyclopropylaminomethyl-1- pyrrolidinyl)-quinoloncarboxylsyre-derivat |
| US8222407B2 (en) | 2007-05-24 | 2012-07-17 | Kyorin Pharmaceutical Co., Ltd. | Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in substituent at 14-position |
| CN101671302B (zh) * | 2008-12-30 | 2011-03-30 | 广东海康兽药有限公司 | 禽畜用抗菌药恩诺沙星的生产工艺 |
| CN101899044B (zh) * | 2010-08-16 | 2012-07-18 | 常州市勇毅生物药业有限公司 | 吉米沙星主环化合物的合成方法 |
| CN113912540A (zh) * | 2021-12-15 | 2022-01-11 | 山东国邦药业有限公司 | 一种1-环丙基-6,7-二氟-1,4-二氢-4-氧代-3-喹啉甲酸的合成方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5365887A (en) * | 1976-11-22 | 1978-06-12 | Kyorin Seiyaku Kk | Substituted quinoline*arboxylate and process for preparing same |
| DE2656574A1 (de) * | 1976-12-10 | 1978-06-15 | Schering Ag | Neue 1,6-naphthyridincarbonsaeurederivate und verfahren zu ihrer herstellung |
| JPS53141286A (en) * | 1977-05-16 | 1978-12-08 | Kyorin Seiyaku Kk | Novel substituted quinolinecarboxylic acid |
| JPS5845426B2 (ja) * | 1978-09-29 | 1983-10-08 | 杏林製薬株式会社 | 置換キノリンカルボン酸誘導体 |
| DE3142854A1 (de) * | 1981-10-29 | 1983-05-11 | Bayer Ag, 5090 Leverkusen | 1-cyclopropyl-6-fluor-1,4-dihydro-4-oxo-7-piperazino-chinolin-3-carbonsaeuren, verfahren zu ihrer herstellung sowie diese enthaltende antibakterielle mittel |
| DE3318145A1 (de) * | 1983-05-18 | 1984-11-22 | Bayer Ag, 5090 Leverkusen | 7-amino-1-cyclopropyl-6,8-difluor-1,4-dihydro-4-oxo-3-chinolincarbonsaeuren, verfahren zu ihrer herstellung sowie diese enthaltende antibakterielle mittel |
| AU553415B2 (en) * | 1983-09-19 | 1986-07-17 | Abbott Japan Co., Ltd. | 6-fluoro-1-4-dihydro-4-oxo-7-substituted piperazinyl- quinoline-3-carboxylic acids |
| IL74244A (en) * | 1984-02-17 | 1988-06-30 | Warner Lambert Co | Quinoline derivatives,their preparation and pharmaceutical compositions containing them |
| DE3420743A1 (de) * | 1984-06-04 | 1985-12-05 | Bayer Ag, 5090 Leverkusen | 7-amino-1-cyclopropyl-6,8-dihalogen-1,4-dihydro-4-oxo-3-chinolincarbonsaeuren, verfahren zu ihrer herstellung sowie diese enthaltende antibakterielle mittel |
| JPS61205258A (ja) * | 1985-03-08 | 1986-09-11 | Kyorin Pharmaceut Co Ltd | キノロンカルボン酸誘導体及びその製造方法 |
-
1986
- 1986-12-03 DE DE19863641312 patent/DE3641312A1/de not_active Withdrawn
-
1987
- 1987-11-17 NO NO874788A patent/NO174199C/no not_active IP Right Cessation
- 1987-11-20 ES ES198787117130T patent/ES2038156T3/es not_active Expired - Lifetime
- 1987-11-20 AT AT87117130T patent/ATE73446T1/de not_active IP Right Cessation
- 1987-11-20 EP EP87117130A patent/EP0274033B1/de not_active Expired - Lifetime
- 1987-11-20 DE DE8787117130T patent/DE3777370D1/de not_active Expired - Lifetime
- 1987-11-26 YU YU2156/87A patent/YU45049B/xx unknown
- 1987-11-27 IL IL84627A patent/IL84627A/xx not_active IP Right Cessation
- 1987-11-30 CS CS878688A patent/CS270577B2/cs not_active IP Right Cessation
- 1987-11-30 NZ NZ222736A patent/NZ222736A/en unknown
- 1987-12-01 FI FI875289A patent/FI875289A7/fi not_active Application Discontinuation
- 1987-12-01 DD DD87309727A patent/DD270904A5/de not_active IP Right Cessation
- 1987-12-01 JP JP62301624A patent/JPS63145268A/ja active Pending
- 1987-12-02 PL PL1987269185A patent/PL158614B1/pl unknown
- 1987-12-02 IE IE327987A patent/IE64261B1/en not_active IP Right Cessation
- 1987-12-02 KR KR1019870013716A patent/KR970005191B1/ko not_active Expired - Fee Related
- 1987-12-02 ZA ZA879040A patent/ZA879040B/xx unknown
- 1987-12-02 CN CN198787107230A patent/CN87107230A/zh active Pending
- 1987-12-02 HU HU875424A patent/HU199823B/hu unknown
- 1987-12-02 SU SU87A patent/SU1482526A3/ru active
- 1987-12-02 DK DK198706331A patent/DK174929B1/da not_active IP Right Cessation
- 1987-12-02 UA UA4203762A patent/UA8017A1/uk unknown
- 1987-12-02 PT PT86252A patent/PT86252B/pt unknown
- 1987-12-02 PH PH36159A patent/PH24489A/en unknown
- 1987-12-03 AU AU82177/87A patent/AU593961B2/en not_active Expired
-
1992
- 1992-04-08 GR GR920400663T patent/GR3004301T3/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| IF00 | In force as of 2000-06-30 in czech republic | ||
| MK4A | Patent expired |
Effective date: 20071130 |