CS270597B2 - Method of tertiary alkylsubstituted naphthyridine and quinoline carboxylic acids production - Google Patents

Method of tertiary alkylsubstituted naphthyridine and quinoline carboxylic acids production Download PDF

Info

Publication number: CS270597B2
Authority: CS; Czechoslovakia
Prior art keywords: group; oxo; fluoro; dihydro; mmol
Prior art date: 1986-10-08

Application number

CS877295A

Other languages

Czech (cs)

English (en)

Other versions

CS729587A2 (en

Inventor

Abraham Weber

Daniel Bouzard

Munir Essiz

Cesare Pierre Di

Jean-Pierre Jacquet

Philippe Remuzon

Original Assignee

Bristol Myers Co

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

1986-10-08

Filing date

1987-10-08

Publication date

1990-07-12

1987-10-08 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1988-11-10 Priority to CS887400A priority Critical patent/CS270598B2/cs

1989-11-14 Publication of CS729587A2 publication Critical patent/CS729587A2/cs

1990-07-12 Publication of CS270597B2 publication Critical patent/CS270597B2/cs

Links

LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical class C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 title claims abstract description 6
238000000034 method Methods 0.000 title claims description 33
150000005054 naphthyridines Chemical class 0.000 title claims description 3
238000004519 manufacturing process Methods 0.000 title description 9
150000001412 amines Chemical class 0.000 claims abstract description 13
238000002360 preparation method Methods 0.000 claims abstract description 11
150000001875 compounds Chemical class 0.000 claims description 167
-1 C 1 -C 4 alkylamino Chemical group 0.000 claims description 133
125000000217 alkyl group Chemical group 0.000 claims description 30
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
150000003839 salts Chemical class 0.000 claims description 26
239000002253 acid Substances 0.000 claims description 24
229910052757 nitrogen Inorganic materials 0.000 claims description 24
229910052731 fluorine Inorganic materials 0.000 claims description 23
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
125000001424 substituent group Chemical group 0.000 claims description 22
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 17
239000011737 fluorine Substances 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 13
125000001153 fluoro group Chemical group F* 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
239000002585 base Substances 0.000 claims description 10
125000001309 chloro group Chemical group Cl* 0.000 claims description 9
125000003277 amino group Chemical group 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
150000007513 acids Chemical class 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
239000007858 starting material Substances 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
239000011593 sulfur Substances 0.000 claims description 4
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000004385 trihaloalkyl group Chemical group 0.000 claims description 3
229910052720 vanadium Inorganic materials 0.000 claims description 3
229910001420 alkaline earth metal ion Inorganic materials 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
229910001413 alkali metal ion Inorganic materials 0.000 claims 1
150000001340 alkali metals Chemical class 0.000 claims 1
125000000547 substituted alkyl group Chemical group 0.000 claims 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 58
241001465754 Metazoa Species 0.000 abstract description 5
239000000543 intermediate Substances 0.000 abstract description 5
208000035143 Bacterial infection Diseases 0.000 abstract description 4
208000022362 bacterial infectious disease Diseases 0.000 abstract description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 100
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
239000000243 solution Substances 0.000 description 87
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 78
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
239000000725 suspension Substances 0.000 description 42
238000010992 reflux Methods 0.000 description 35
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 35
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
238000002844 melting Methods 0.000 description 33
230000008018 melting Effects 0.000 description 33
230000003287 optical effect Effects 0.000 description 31
239000002244 precipitate Substances 0.000 description 28
239000000047 product Substances 0.000 description 28
238000006243 chemical reaction Methods 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 25
239000011541 reaction mixture Substances 0.000 description 25
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
229910052943 magnesium sulfate Inorganic materials 0.000 description 21
235000019341 magnesium sulphate Nutrition 0.000 description 21
239000002904 solvent Substances 0.000 description 21
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
230000002829 reductive effect Effects 0.000 description 17
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 16
150000003254 radicals Chemical class 0.000 description 16
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
239000000706 filtrate Substances 0.000 description 14
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 13
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
230000000844 anti-bacterial effect Effects 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
238000001816 cooling Methods 0.000 description 11
XOUHWIKPJVQHHS-AWKYBWMHSA-N ethyl (2r)-4-acetyloxy-1-(4-methylphenyl)sulfonylpyrrolidine-2-carboxylate Chemical compound CCOC(=O)[C@H]1CC(OC(C)=O)CN1S(=O)(=O)C1=CC=C(C)C=C1 XOUHWIKPJVQHHS-AWKYBWMHSA-N 0.000 description 11
239000003054 catalyst Substances 0.000 description 10
238000001914 filtration Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000007787 solid Substances 0.000 description 9
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
PMMYEEVYMWASQN-QWWZWVQMSA-N cis-4-hydroxy-D-proline Chemical compound O[C@H]1C[NH2+][C@@H](C([O-])=O)C1 PMMYEEVYMWASQN-QWWZWVQMSA-N 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
CZAUMAMCRWLIQO-GLGOKHISSA-N ethyl (2r)-4-hydroxy-1-(4-methylphenyl)sulfonylpyrrolidine-2-carboxylate Chemical compound CCOC(=O)[C@H]1CC(O)CN1S(=O)(=O)C1=CC=C(C)C=C1 CZAUMAMCRWLIQO-GLGOKHISSA-N 0.000 description 8
125000004494 ethyl ester group Chemical group 0.000 description 8
239000008194 pharmaceutical composition Substances 0.000 description 8
UJDJLZINFVKBBH-PKTZIBPZSA-N [(2r,4s)-1-(4-methylphenyl)sulfonyl-4-(4-methylphenyl)sulfonyloxypyrrolidin-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1N(S(=O)(=O)C=2C=CC(C)=CC=2)C[C@@H](OS(=O)(=O)C=2C=CC(C)=CC=2)C1 UJDJLZINFVKBBH-PKTZIBPZSA-N 0.000 description 7
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 7
239000003480 eluent Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
RBSLQBNFZCEBJT-NFJWQWPMSA-N (5r)-5-(hydroxymethyl)-1-(4-methylphenyl)sulfonylpyrrolidin-3-ol Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1[C@@H](CO)CC(O)C1 RBSLQBNFZCEBJT-NFJWQWPMSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
239000012043 crude product Substances 0.000 description 6
125000004433 nitrogen atom Chemical group N* 0.000 description 6
150000003248 quinolines Chemical class 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
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
241000588724 Escherichia coli Species 0.000 description 5
239000005909 Kieselgur Substances 0.000 description 5
229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 5
239000012267 brine Substances 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000002198 insoluble material Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
ISYQWKOXKGJREA-ALUAXPQUSA-N (1r,4r)-2,5-diazabicyclo[2.2.1]heptane;dihydrobromide Chemical compound Br.Br.C1N[C@@]2([H])CN[C@]1([H])C2 ISYQWKOXKGJREA-ALUAXPQUSA-N 0.000 description 4
SOMPEQIPSQFVMO-MBORUXJMSA-N (1r,4r)-2-benzyl-2,5-diazabicyclo[2.2.1]heptane;dihydrobromide Chemical compound Br.Br.C([C@@]1(NC[C@@]2([H])C1)[H])N2CC1=CC=CC=C1 SOMPEQIPSQFVMO-MBORUXJMSA-N 0.000 description 4
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 4
241000894006 Bacteria Species 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
238000009835 boiling Methods 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
239000012141 concentrate Substances 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
238000000354 decomposition reaction Methods 0.000 description 4
238000001035 drying Methods 0.000 description 4
239000012280 lithium aluminium hydride Substances 0.000 description 4
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 4
229960000210 nalidixic acid Drugs 0.000 description 4
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 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 3
QXNOSGDKQAIMRL-UHFFFAOYSA-N 1-tert-butyl-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C1CNC(C)CN1C(C(=C1)F)=NC2=C1C(=O)C(C(O)=O)=CN2C(C)(C)C QXNOSGDKQAIMRL-UHFFFAOYSA-N 0.000 description 3
ZFRUGZMCGCYBRC-UHFFFAOYSA-N 1h-1,8-naphthyridin-2-one Chemical class C1=CC=NC2=NC(O)=CC=C21 ZFRUGZMCGCYBRC-UHFFFAOYSA-N 0.000 description 3
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
QXMPIEOTDBYZDL-UHFFFAOYSA-N 3-benzyl-3,8-diazabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CN1CC1=CC=CC=C1 QXMPIEOTDBYZDL-UHFFFAOYSA-N 0.000 description 3
LAEFEQWBXJQNGP-UHFFFAOYSA-N 3-benzyl-8-methyl-3,8-diazabicyclo[3.2.1]octane-2,4-dione Chemical compound CN1C(C2=O)CCC1C(=O)N2CC1=CC=CC=C1 LAEFEQWBXJQNGP-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
239000000872 buffer Substances 0.000 description 3
150000001721 carbon Chemical class 0.000 description 3
150000001768 cations Chemical class 0.000 description 3
229960003405 ciprofloxacin Drugs 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
230000000694 effects Effects 0.000 description 3
239000000284 extract Substances 0.000 description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
229960001180 norfloxacin Drugs 0.000 description 3
125000004193 piperazinyl group Chemical group 0.000 description 3
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
238000005406 washing Methods 0.000 description 3
SDFTVHVPMKAQAE-UHFFFAOYSA-N (1,4-dibenzylpiperazin-2-yl)methanamine Chemical compound C1CN(CC=2C=CC=CC=2)C(CN)CN1CC1=CC=CC=C1 SDFTVHVPMKAQAE-UHFFFAOYSA-N 0.000 description 2
KPXBMEKTAFSEQX-LLVKDONJSA-N (3r)-3-azido-1-benzylpyrrolidine Chemical compound C1[C@H](N=[N+]=[N-])CCN1CC1=CC=CC=C1 KPXBMEKTAFSEQX-LLVKDONJSA-N 0.000 description 2
KPXBMEKTAFSEQX-NSHDSACASA-N (3s)-3-azido-1-benzylpyrrolidine Chemical compound C1[C@@H](N=[N+]=[N-])CCN1CC1=CC=CC=C1 KPXBMEKTAFSEQX-NSHDSACASA-N 0.000 description 2
CKZVBXBEDDAEFE-UHFFFAOYSA-N (4-benzylmorpholin-2-yl)methanamine Chemical compound C1COC(CN)CN1CC1=CC=CC=C1 CKZVBXBEDDAEFE-UHFFFAOYSA-N 0.000 description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
LPECDQDHFCOVSK-UHFFFAOYSA-N 1,4-dibenzyl-2-(chloromethyl)piperazine Chemical compound C1CN(CC=2C=CC=CC=2)C(CCl)CN1CC1=CC=CC=C1 LPECDQDHFCOVSK-UHFFFAOYSA-N 0.000 description 2
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
BOENESHSMHPTSG-UHFFFAOYSA-N 1-tert-butyl-6,7-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=C(F)C=C2N(C(C)(C)C)C=C(C(O)=O)C(=O)C2=C1 BOENESHSMHPTSG-UHFFFAOYSA-N 0.000 description 2
JLLJFRRJDWYHQW-UHFFFAOYSA-N 1-tert-butyl-6,8-difluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid Chemical compound FC1=C2N(C(C)(C)C)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 JLLJFRRJDWYHQW-UHFFFAOYSA-N 0.000 description 2
RVHUZUJEVPOKAR-UHFFFAOYSA-N 1-tert-butyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound FC1=CN=C2N(C(C)(C)C)C=C(C(O)=O)C(=O)C2=C1 RVHUZUJEVPOKAR-UHFFFAOYSA-N 0.000 description 2
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XRSXCUKNZCMZCH-UHFFFAOYSA-N 1-tert-butyl-7-(2,5-diazabicyclo[2.2.2]octan-2-yl)-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(NC2)CCC2N1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C(C)(C)C)C2=C1 XRSXCUKNZCMZCH-UHFFFAOYSA-N 0.000 description 2
QPYPHVIKUCZQIL-UHFFFAOYSA-N 1-tert-butyl-7-[3-(ethylaminomethyl)pyrrolidin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(CNCC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C(C)(C)C QPYPHVIKUCZQIL-UHFFFAOYSA-N 0.000 description 2
KJIOMULFEKIXRJ-UHFFFAOYSA-N 1-tert-butyl-7-[4-(dimethylamino)piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1CN(N(C)C)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C(C)(C)C KJIOMULFEKIXRJ-UHFFFAOYSA-N 0.000 description 2
CMZSIQCZAFAEDH-UHFFFAOYSA-N 2,2,2-trifluoro-n-pyrrolidin-3-ylacetamide;hydrochloride Chemical compound Cl.FC(F)(F)C(=O)NC1CCNC1 CMZSIQCZAFAEDH-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
FRMIQAALKHOOTQ-UHFFFAOYSA-N 2-[(1,4-dibenzylpiperazin-2-yl)methyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC(N(CC1)CC=2C=CC=CC=2)CN1CC1=CC=CC=C1 FRMIQAALKHOOTQ-UHFFFAOYSA-N 0.000 description 2
125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
OCLZWPZPBKEJDI-UHFFFAOYSA-N 3-(1,4-dibenzylpiperazin-2-yl)propanoic acid Chemical compound C1CN(CC=2C=CC=CC=2)C(CCC(=O)O)CN1CC1=CC=CC=C1 OCLZWPZPBKEJDI-UHFFFAOYSA-N 0.000 description 2
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FXPQRHKDEJUSLS-UHFFFAOYSA-N 4-(aminomethyl)-1-benzylpyrrolidin-3-ol Chemical compound C1C(O)C(CN)CN1CC1=CC=CC=C1 FXPQRHKDEJUSLS-UHFFFAOYSA-N 0.000 description 2
VVCVFAUQZAUJML-UHFFFAOYSA-N 6-fluoro-4-oxo-7-piperazin-1-yl-1-prop-1-en-2-yl-1,8-naphthyridine-2-carboxylic acid Chemical compound N1=C2N(C(=C)C)C(C(O)=O)=CC(=O)C2=CC(F)=C1N1CCNCC1 VVCVFAUQZAUJML-UHFFFAOYSA-N 0.000 description 2
XPXVAHSZDHKCBP-UHFFFAOYSA-N 7-(3-aminopyrrolidin-1-yl)-1-tert-butyl-6-fluoro-4-oxoquinoline-3-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2N(C(C)(C)C)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCC(N)C1 XPXVAHSZDHKCBP-UHFFFAOYSA-N 0.000 description 2
VBBKUEQDMFQGGA-UHFFFAOYSA-N 7-[2-(aminomethyl)morpholin-4-yl]-1-tert-butyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound N1=C2N(C(C)(C)C)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCOC(CN)C1 VBBKUEQDMFQGGA-UHFFFAOYSA-N 0.000 description 2
CLUTZARYOPKXOL-UHFFFAOYSA-N 7-chloro-6-fluoro-4-oxo-1-prop-1-en-2-ylquinoline-3-carboxylic acid Chemical compound FC1=C(Cl)C=C2N(C(=C)C)C=C(C(O)=O)C(=O)C2=C1 CLUTZARYOPKXOL-UHFFFAOYSA-N 0.000 description 2
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125000006414 CCl Chemical group ClC* 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
239000012448 Lithium borohydride Substances 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-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
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
CJLYDGCQKXYZAA-SFHVURJKSA-N [(2S)-1-benzylpyrrolidin-2-yl] 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)O[C@@H]1N(CC=2C=CC=CC=2)CCC1 CJLYDGCQKXYZAA-SFHVURJKSA-N 0.000 description 2
UJDJLZINFVKBBH-UHFFFAOYSA-N [1-(4-methylphenyl)sulfonyl-4-(4-methylphenyl)sulfonyloxypyrrolidin-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1N(S(=O)(=O)C=2C=CC(C)=CC=2)CC(OS(=O)(=O)C=2C=CC(C)=CC=2)C1 UJDJLZINFVKBBH-UHFFFAOYSA-N 0.000 description 2
VQRFXOBYURQTDE-UHFFFAOYSA-N [5-(hydroxymethyl)-1-(4-methylphenyl)sulfonylpyrrolidin-3-yl] 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1CN(S(=O)(=O)C=2C=CC(C)=CC=2)C(CO)C1 VQRFXOBYURQTDE-UHFFFAOYSA-N 0.000 description 2
CBWUNQZJGJFJLZ-UHFFFAOYSA-N [Cl].Cl Chemical compound [Cl].Cl CBWUNQZJGJFJLZ-UHFFFAOYSA-N 0.000 description 2
150000001339 alkali metal compounds Chemical class 0.000 description 2
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WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
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230000005494 condensation Effects 0.000 description 2
239000013058 crude material Substances 0.000 description 2
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238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
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ANVYTUWEYPVUNT-UUSAFJCLSA-N ethyl (2r)-1-(4-methylphenyl)sulfonyl-4-(4-methylphenyl)sulfonyloxypyrrolidine-2-carboxylate Chemical compound C([C@@H]1C(=O)OCC)C(OS(=O)(=O)C=2C=CC(C)=CC=2)CN1S(=O)(=O)C1=CC=C(C)C=C1 ANVYTUWEYPVUNT-UUSAFJCLSA-N 0.000 description 2
GXEWFQHRTCLCLP-UHFFFAOYSA-N ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-[1-(dimethylamino)propan-2-ylamino]prop-2-enoate Chemical compound CN(C)CC(C)NC=C(C(=O)OCC)C(=O)C1=CC(F)=C(Cl)C=C1Cl GXEWFQHRTCLCLP-UHFFFAOYSA-N 0.000 description 2
PIAXTYMIBWHNJS-UHFFFAOYSA-N ethyl 7-chloro-1-[1-(dimethylamino)propan-2-yl]-6-fluoro-4-oxoquinoline-3-carboxylate Chemical compound ClC1=C(F)C=C2C(=O)C(C(=O)OCC)=CN(C(C)CN(C)C)C2=C1 PIAXTYMIBWHNJS-UHFFFAOYSA-N 0.000 description 2
230000001747 exhibiting effect Effects 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
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125000001188 haloalkyl group Chemical group 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
125000002768 hydroxyalkyl group Chemical group 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000155 melt Substances 0.000 description 2
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239000011707 mineral Substances 0.000 description 2
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QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
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238000007911 parenteral administration Methods 0.000 description 2
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229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
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239000000843 powder Substances 0.000 description 2
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239000011734 sodium Substances 0.000 description 2
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235000017557 sodium bicarbonate Nutrition 0.000 description 2
239000012265 solid product Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
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125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
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ZKXANRKOHXSTKC-UHFFFAOYSA-N 1-tert-butyl-7-(3,5-dimethylpiperazin-1-yl)-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)NC(C)CN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C(C)(C)C ZKXANRKOHXSTKC-UHFFFAOYSA-N 0.000 description 1
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LYOAKSDOTROZEF-UHFFFAOYSA-N ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxyprop-2-enoate Chemical compound CCOC=C(C(=O)OCC)C(=O)C1=CC(F)=C(Cl)C=C1Cl LYOAKSDOTROZEF-UHFFFAOYSA-N 0.000 description 1
KEWGATABSZMVER-UHFFFAOYSA-N ethyl 6-chloro-7-fluoro-4-oxo-1-(1-phenylsulfanylpropan-2-yl)-1,8-naphthyridine-3-carboxylate Chemical compound C12=NC(F)=C(Cl)C=C2C(=O)C(C(=O)OCC)=CN1C(C)CSC1=CC=CC=C1 KEWGATABSZMVER-UHFFFAOYSA-N 0.000 description 1
CLPOCCWWVCRQFK-UHFFFAOYSA-N ethyl 6-fluoro-4-oxo-7-piperazin-1-yl-1-prop-1-en-2-yl-1,8-naphthyridine-2-carboxylate;hydrochloride Chemical compound Cl.N1=C2N(C(C)=C)C(C(=O)OCC)=CC(=O)C2=CC(F)=C1N1CCNCC1 CLPOCCWWVCRQFK-UHFFFAOYSA-N 0.000 description 1
FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
MDQRDWAGHRLBPA-UHFFFAOYSA-N fluoroamine Chemical compound FN MDQRDWAGHRLBPA-UHFFFAOYSA-N 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical group 0.000 description 1
XFRRWLGPLRIBTH-UHFFFAOYSA-N heptane;dihydrobromide Chemical compound Br.Br.CCCCCCC XFRRWLGPLRIBTH-UHFFFAOYSA-N 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
239000008101 lactose Substances 0.000 description 1
YPJRHEKCFKOVRT-UHFFFAOYSA-N lerociclib Chemical compound C1CN(C(C)C)CCN1C(C=N1)=CC=C1NC1=NC=C(C=C2N3C4(CCCCC4)CNC2=O)C3=N1 YPJRHEKCFKOVRT-UHFFFAOYSA-N 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
229960003646 lysine Drugs 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 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
229910052748 manganese Inorganic materials 0.000 description 1
239000011572 manganese Substances 0.000 description 1
VBLRSYYEAVUPMF-UHFFFAOYSA-N methyl 7-chloro-6-fluoro-4-oxo-1-prop-1-en-2-ylquinoline-3-carboxylate Chemical compound ClC1=C(F)C=C2C(=O)C(C(=O)OC)=CN(C(C)=C)C2=C1 VBLRSYYEAVUPMF-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
BTJGUJIKEABZDW-UHFFFAOYSA-N n-[(1,4-dibenzylpiperazin-2-yl)methyl]-2,2,2-trifluoroacetamide;dihydrochloride Chemical compound Cl.Cl.C1CN(CC=2C=CC=CC=2)C(CNC(=O)C(F)(F)F)CN1CC1=CC=CC=C1 BTJGUJIKEABZDW-UHFFFAOYSA-N 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
HVFSJXUIRWUHRG-UHFFFAOYSA-N oic acid Natural products C1CC2C3CC=C4CC(OC5C(C(O)C(O)C(CO)O5)O)CC(O)C4(C)C3CCC2(C)C1C(C)C(O)CC(C)=C(C)C(=O)OC1OC(COC(C)=O)C(O)C(O)C1OC(C(C1O)O)OC(COC(C)=O)C1OC1OC(CO)C(O)C(O)C1O HVFSJXUIRWUHRG-UHFFFAOYSA-N 0.000 description 1
238000010979 pH adjustment Methods 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
150000002960 penicillins Chemical class 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
150000007660 quinolones Chemical class 0.000 description 1
150000004053 quinones Chemical class 0.000 description 1
238000011160 research Methods 0.000 description 1
238000012552 review Methods 0.000 description 1
238000006748 scratching Methods 0.000 description 1
230000002393 scratching effect Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
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 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
MRYQZMHVZZSQRT-UHFFFAOYSA-M tetramethylazanium;acetate Chemical compound CC([O-])=O.C[N+](C)(C)C MRYQZMHVZZSQRT-UHFFFAOYSA-M 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000017105 transposition Effects 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CS877295A 1986-10-08 1987-10-08 Method of tertiary alkylsubstituted naphthyridine and quinoline carboxylic acids production CS270597B2 (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CS887400A CS270598B2 (en)	1986-10-08	1988-11-10	Method of 1-tertiary alkylsubstituted naphthyridine and quinoline carboxylic acids preparation

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US91675286A	1986-10-08	1986-10-08
US9923187A	1987-09-25	1987-09-25

Publications (2)

Publication Number	Publication Date
CS729587A2 CS729587A2 (en)	1989-11-14
CS270597B2 true CS270597B2 (en)	1990-07-12

Family

ID=26795810

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS877295A CS270597B2 (en)	1986-10-08	1987-10-08	Method of tertiary alkylsubstituted naphthyridine and quinoline carboxylic acids production

Country Status (10)

Country	Link
EP (1)	EP0266576A3 (fr)
CN (1)	CN87106925A (fr)
CS (1)	CS270597B2 (fr)
IE (1)	IE872696L (fr)
IL (1)	IL84105A0 (fr)
NZ (1)	NZ222047A (fr)
OA (1)	OA08688A (fr)
PL (2)	PL154473B1 (fr)
PT (1)	PT85886B (fr)
YU (2)	YU46079B (fr)

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AU5123690A (en) *	1989-03-13	1990-09-13	Bristol-Myers Squibb Company	5-substituted-1,4-dihydro-4-oxo-nephthyridine-3-carboxylate antibacterial agents
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EP0571400A1 (fr) *	1991-01-14	1993-12-01	Hanmi Pharmaceutical Co.,Ltd.	Nouveaux composes de quinoleine et leurs procedes de preparation
JPH06509792A (ja) *	1991-01-14	1994-11-02	ハンミ藥品工業株式會社	新規なキノロン化合物及びその製造方法
KR940014395A (ko) *	1992-12-09	1994-07-18	강박광	신규한 퀴놀론 유도체 및 그의 제조방법
KR0148277B1 (ko) *	1993-01-18	1998-11-02	채영복	신규한 플루오르퀴놀론계 유도체 및 그의 제조방법
AU4272793A (en) *	1993-04-24	1994-11-21	Korea Research Institute Of Chemical Technology	Novel quinolone carboxylic acid derivatives and process for preparing the same
DE69509442T2 (de) *	1994-06-16	1999-09-02	Lg Chemical Ltd.	Chinolincarbonsäurederivate mit 7-(4-Amino-methyl-3-oxim)-pyrrolidin-Substituenten und Verfahren zu ihrer Herstellung
US20020032216A1 (en)	1997-03-21	2002-03-14	Lg Chemical Ltd.	Salt of naphthyridine carboxylic acid derivative
MA24500A1 (fr)	1997-03-21	1998-10-01	Lg Life Sciences Ltd	Derive du sel d'acide carboxylique de naphthyridine .
US6316488B1 (en) *	1999-06-17	2001-11-13	Merck & Co., Inc.	Antibiotic compound
GB9920919D0 (en)	1999-09-03	1999-11-10	Sb Pharmco Inc	Novel compound
GB9920917D0 (en)	1999-09-03	1999-11-10	Sb Pharmco Inc	Novel process
SE0003795D0 (sv)	2000-10-20	2000-10-20	Astrazeneca Ab	Pharmaceutically useful compounds
WO2003031443A1 (fr)	2001-10-04	2003-04-17	Morphochem Aktiengesellschaft für kombinatorische Chemie	Antibiotiques a action duale renfermant une oxazolidinone et une quinolone ou une fraction de naphthyridinone
WO2003031441A1 (fr) *	2001-10-04	2003-04-17	Morphochen Aktiengesellschaft Für Kombinatorische Chemie	Composes a actions multiples
KR100517638B1 (ko)	2002-04-08	2005-09-28	주식회사 엘지생명과학	게미플록사신 산염의 새로운 제조방법
KR101101982B1 (ko)	2003-04-30	2012-01-02	모르포켐 악티엥게셀샤프트 퓌르 콤비나토리셰 케미	옥사졸리디논-퀴놀린 하이브리드 항생제의 탄저병 및 기타감염증의 치료용의 용도
DE10340485B4 (de)	2003-09-03	2015-05-13	Morphochem AG Aktiengesellschaft für kombinatorische Chemie	Verfahren zur Herstellung von Oxazolidinon-Chinolon Hybriden
ATE401326T1 (de)	2003-12-18	2008-08-15	Morphochem Ag Komb Chemie	Oxazolidinon-chinolon hybrid antibiotika
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US4578473A (en) *	1985-04-15	1986-03-25	Warner-Lambert Company	Process for quinoline-3-carboxylic acid antibacterial agents

1987
- 1987-10-05 NZ NZ222047A patent/NZ222047A/xx unknown
- 1987-10-06 IL IL84105A patent/IL84105A0/xx unknown
- 1987-10-07 PL PL1987268098A patent/PL154473B1/pl unknown
- 1987-10-07 PL PL1987287459A patent/PL156484B1/pl unknown
- 1987-10-08 YU YU186887A patent/YU46079B/sh unknown
- 1987-10-08 PT PT85886A patent/PT85886B/pt not_active IP Right Cessation
- 1987-10-08 CS CS877295A patent/CS270597B2/cs unknown
- 1987-10-08 CN CN198787106925A patent/CN87106925A/zh active Pending
- 1987-10-08 EP EP87114686A patent/EP0266576A3/fr not_active Withdrawn
- 1987-10-08 OA OA59206A patent/OA08688A/fr unknown
- 1987-10-08 IE IE872696A patent/IE872696L/xx unknown
1988
- 1988-07-05 YU YU131088A patent/YU46112B/sh unknown

Also Published As

Publication number	Publication date
PL268098A1 (en)	1988-09-01
YU46112B (sh)	1992-12-21
OA08688A (fr)	1989-03-31
YU46079B (sh)	1992-12-21
CS729587A2 (en)	1989-11-14
YU131088A (en)	1988-12-31
PT85886A (en)	1987-11-01
YU186887A (en)	1988-12-31
IL84105A0 (en)	1988-03-31
CN87106925A (zh)	1988-09-14
EP0266576A3 (fr)	1989-03-22
PT85886B (pt)	1990-07-31
NZ222047A (en)	1991-01-29
IE872696L (en)	1988-04-08
PL154473B1 (en)	1991-08-30
EP0266576A2 (fr)	1988-05-11
PL156484B1 (en)	1992-03-31

Publication	Publication Date	Title
CS270597B2 (en)	1990-07-12	Method of tertiary alkylsubstituted naphthyridine and quinoline carboxylic acids production
DK170404B1 (da)	1995-08-21	7-(1-Pyrrolidinyl)-3-quinoloncarboxylsyrederivater, fremgangsmåder og mellemprodukter til deres fremstilling, lægemidler, dyrefoder, dyrefodertilsætningsmidler og forblandinger indeholdende derivaterne og anvendelse af derivaterne til fremstilling af lægemidler og som dyrefodertilsætningsmidler
DK173057B1 (da)	1999-12-13	5-Alkyl-6-fluor-1,4-dihydro-4-oxo-1,8-naphthyridinforbindelser, fremgangsmåder til fremstilling deraf, farmaceutisk præpara
DK172152B1 (da)	1997-12-01	Quinolon- og naphthyridinderivater
US5091384A (en)	1992-02-25	Anti-bacterial quinolone- and naphthyridone-carboxylic acid compounds
CZ667886A3 (en)	1993-02-17	Substituted bridged diazabicycloalkyl quinolonecarboxylic acids, process of their preparation and pharmaceutical compositions in which they are contained
Bouzard et al.	1990	Fluoronaphthyridines and quinolones as antibacterial agents. 2. Synthesis and structure-activity relationships of new 1-tert-butyl 7-substituted derivatives
US4954507A (en)	1990-09-04	1-tertiary-alkyl-substituted naphthyridine carboxylic acid antibacterial agents
SK285223B6 (sk)	2006-09-07	Deriváty kyseliny chinolónkarboxylovej a naftyridónkarboxylovej, spôsob ich výroby, liečivá tieto látky obsahujúce a ich použitie
CS246065B2 (en)	1986-10-16	Method of new 7-substituted cyclic aminonaphthyridine-,quinoline-and benzoxazinecarboxylic acids production
AU611400B2 (en)	1991-06-13	1-tertiary-alkyl-substituted naphthyridine-and quinoline-carboxylic acid antibacterial agents
JPS62169789A (ja)	1987-07-25	７−（アザビシクロアルキル）−キノロンカルボン酸及び−ナフチリドンカルボン酸誘導体
KR0136792B1 (ko)	1998-04-25	퀴놀론 카르복실산 유도체, 그 제조 방법, 이 화합물을 함유하는 향균제
US4965273A (en)	1990-10-23	Certain 1-tertiary-butyl-naphthyridone carboxylic acid derivatives anti-bacterial agents
JPH04502317A (ja)	1992-04-23	抗菌性キノロン化合物
US4923879A (en)	1990-05-08	1,8-Naphthyridines and their use as antibacterial agents
EP0424852A1 (fr)	1991-05-02	Composés de diazabicycloamine et leur procédé de préparation
SK280877B6 (sk)	2000-08-14	Deriváty kyseliny chinolónkarboxylovej a naftyridónkarboxylovej, spôsob ich výroby, liečivá tieto látky obsahujúce a ich použitie
US4962108A (en)	1990-10-09	Antibacterial quinoline compounds
AU668286B2 (en)	1996-04-26	Diazabicyclo(4.3.0)nonane and (3.3.0)octane heterocycles
JPH07300472A (ja)	1995-11-14	新規キノロンカルボン酸誘導体およびその製造方法
US4992546A (en)	1991-02-12	Process for preparing 6,8-diazabicyclo[3.2.2]nonane derivatives
US4968799A (en)	1990-11-06	Antibacterial agents
IE84193B1 (en)	2006-04-19	7-(1-Pyrrolidinyl)-3-quinolone and naphthyridone carboxylic acid derivatives, method for their preparation and for substituted mono- and bicyclic pyrrolidine intermediates, and their antibacterial and feed additive compositions
IE19970856A1 (en)	2000-02-23	7-(1-Pyrrolidinyl)-3-quinolone and naphthyridone carboxylic acid derivatives, method for their preparation and for substituted mono- and bicyclic pyrrolidine intermediates, and their antibacterial and feed additive compositions