DD275685A5

DD275685A5 - Verfahren zur herstellung neuer chinolinderivate

Verfahren zur herstellung neuer chinolinderivate Download PDF

Info

Publication number: DD275685A5
Authority: DD; German Democratic Republic
Prior art keywords: compound; cyclopropyl; dihydro; amino; oxoquinoline
Prior art date: 1987-10-16

Application number

DD32078088A

Other languages

German (de)

English (en)

Inventor

Jun-Ichi Matumoto

Akira Minamida

Masahiro Fujita

Tohru Hirose

Junji Nakano

Shinichi Nakamura

Original Assignee

Dainippon Pharmaceutical Co.,Ltd,Jp

Priority date

1987-10-16

Filing date

1988-10-14

Publication date

1990-01-31

1988-10-14 Application filed by Dainippon Pharmaceutical Co.,Ltd,Jp filed Critical Dainippon Pharmaceutical Co.,Ltd,Jp

1990-01-31 Publication of DD275685A5 publication Critical patent/DD275685A5/de

Links

238000002360 preparation method Methods 0.000 title claims description 14
238000000034 method Methods 0.000 title abstract description 29
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 132
150000003839 salts Chemical class 0.000 claims abstract description 37
150000002148 esters Chemical class 0.000 claims abstract description 25
125000000217 alkyl group Chemical group 0.000 claims abstract description 23
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 23
125000005843 halogen group Chemical group 0.000 claims abstract description 18
125000003277 amino group Chemical group 0.000 claims abstract description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
-1 difluoroboryl group Chemical group 0.000 claims description 36
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 29
125000006239 protecting group Chemical group 0.000 claims description 17
229910021529 ammonia Inorganic materials 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
150000004885 piperazines Chemical class 0.000 claims description 3
230000003301 hydrolyzing effect Effects 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
230000000844 anti-bacterial effect Effects 0.000 abstract description 10
239000003242 anti bacterial agent Substances 0.000 abstract description 7
229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 abstract description 5
125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 66
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
239000000203 mixture Substances 0.000 description 46
239000013078 crystal Substances 0.000 description 30
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
239000000243 solution Substances 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
239000007864 aqueous solution Substances 0.000 description 27
239000011541 reaction mixture Substances 0.000 description 26
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
229960000583 acetic acid Drugs 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 24
239000002253 acid Substances 0.000 description 23
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
235000011054 acetic acid Nutrition 0.000 description 19
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
238000001914 filtration Methods 0.000 description 18
238000010992 reflux Methods 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000007858 starting material Substances 0.000 description 15
210000004027 cell Anatomy 0.000 description 13
235000011167 hydrochloric acid Nutrition 0.000 description 13
239000002904 solvent Substances 0.000 description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
241000699670 Mus sp. Species 0.000 description 10
208000015181 infectious disease Diseases 0.000 description 10
239000003814 drug Substances 0.000 description 9
125000000896 monocarboxylic acid group Chemical group 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
229940079593 drug Drugs 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
GTFYODRYQGFYOH-UHFFFAOYSA-N 5-amino-1-cyclopropyl-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid Chemical compound C1CNC(C)CN1C(C(=C1N)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 GTFYODRYQGFYOH-UHFFFAOYSA-N 0.000 description 7
238000001816 cooling Methods 0.000 description 7
239000000825 pharmaceutical preparation Substances 0.000 description 7
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
239000013522 chelant Substances 0.000 description 6
230000000694 effects Effects 0.000 description 6
230000002401 inhibitory effect Effects 0.000 description 6
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
150000003248 quinolines Chemical class 0.000 description 6
YAEWDTRTAONWPF-UHFFFAOYSA-N 5-amino-1-cyclopropyl-6,7-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)C=2C(N)=C(F)C(F)=CC=2N1C1CC1 YAEWDTRTAONWPF-UHFFFAOYSA-N 0.000 description 5
229920001817 Agar Polymers 0.000 description 5
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
239000000370 acceptor Substances 0.000 description 5
239000008272 agar Substances 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
HMYSKRVVGCRJKO-UHFFFAOYSA-N 1-cyclopropyl-5,6,7-trifluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(F)=C(F)C(F)=C2C(=O)C(C(=O)O)=CN1C1CC1 HMYSKRVVGCRJKO-UHFFFAOYSA-N 0.000 description 4
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-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
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000003610 charcoal Substances 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000012458 free base Substances 0.000 description 4
150000004677 hydrates Chemical class 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
239000000725 suspension Substances 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
210000002700 urine Anatomy 0.000 description 4
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 3
YDCDVKGBYXKGGH-UHFFFAOYSA-N 5-amino-1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)C=2C(N)=C(F)C(N3CCNCC3)=CC=2N1C1CC1 YDCDVKGBYXKGGH-UHFFFAOYSA-N 0.000 description 3
FJKKQUMMLOQJPY-AOOOYVTPSA-N 5-amino-1-cyclopropyl-7-[(3r,5s)-3,5-dimethylpiperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1[C@@H](C)N[C@@H](C)CN1C(C(=C1N)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 FJKKQUMMLOQJPY-AOOOYVTPSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
241000894006 Bacteria Species 0.000 description 3
241000606161 Chlamydia Species 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
241000204031 Mycoplasma Species 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
241000191967 Staphylococcus aureus Species 0.000 description 3
241000193998 Streptococcus pneumoniae Species 0.000 description 3
241000193996 Streptococcus pyogenes Species 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
230000001580 bacterial effect Effects 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
239000008103 glucose Substances 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
238000011534 incubation Methods 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
239000004310 lactic acid Substances 0.000 description 3
235000014655 lactic acid Nutrition 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
235000011007 phosphoric acid Nutrition 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
238000003797 solvolysis reaction Methods 0.000 description 3
229940031000 streptococcus pneumoniae Drugs 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
230000009885 systemic effect Effects 0.000 description 3
IFNWESYYDINUHV-OLQVQODUSA-N (2s,6r)-2,6-dimethylpiperazine Chemical compound C[C@H]1CNC[C@@H](C)N1 IFNWESYYDINUHV-OLQVQODUSA-N 0.000 description 2
WRVQFYLHOZQHFY-UHFFFAOYSA-N 1-(2-methylpiperazin-1-yl)ethanone Chemical compound CC1CNCCN1C(C)=O WRVQFYLHOZQHFY-UHFFFAOYSA-N 0.000 description 2
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
IQKLQBAJQTYSBW-UHFFFAOYSA-N 1-cyclopropyl-5,6-difluoro-7-(4-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid Chemical compound C1CN(C)CCN1C(C(=C1F)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 IQKLQBAJQTYSBW-UHFFFAOYSA-N 0.000 description 2
JMVKZWLEXQRABZ-UHFFFAOYSA-N 2,3,4,6-tetrafluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=C(F)C(F)=C1F JMVKZWLEXQRABZ-UHFFFAOYSA-N 0.000 description 2
JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 2
239000004475 Arginine Substances 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 2
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
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JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
241000589517 Pseudomonas aeruginosa Species 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
239000003929 acidic solution Substances 0.000 description 2
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239000004480 active ingredient Substances 0.000 description 2
238000002814 agar dilution Methods 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
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ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
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YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 2
RDAJVZBPGYEKAQ-UHFFFAOYSA-N ethyl 1-cyclopropyl-5,6,7-trifluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(F)=C(F)C(F)=C2C(=O)C(C(=O)OCC)=CN1C1CC1 RDAJVZBPGYEKAQ-UHFFFAOYSA-N 0.000 description 2
SIXXBMOWQJMYIE-UHFFFAOYSA-N ethyl 5-[acetyl(benzyl)amino]-1-cyclopropyl-6,7-difluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(F)=C(F)C(N(CC=3C=CC=CC=3)C(C)=O)=C2C(=O)C(C(=O)OCC)=CN1C1CC1 SIXXBMOWQJMYIE-UHFFFAOYSA-N 0.000 description 2
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235000013922 glutamic acid Nutrition 0.000 description 2
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229940093915 gynecological organic acid Drugs 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
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238000001802 infusion Methods 0.000 description 2
239000002198 insoluble material Substances 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
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