CA1334592C - Composes pyridinyl-quinolone, leur preparation et leur utilisation - Google Patents

Composes pyridinyl-quinolone, leur preparation et leur utilisation

Info

Publication number: CA1334592C
Authority: CA; Canada
Prior art keywords: hydrogen; compound; fluoro; formula; alkyl
Prior art date: 1987-09-08
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA 576627

Other languages

English (en)

Inventor

Michael Reuman

Baldev Singh

George Yohe Lesher

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sanofi SA

Original Assignee

Sterling Drug Inc

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.)

1987-09-08

Filing date

1988-09-07

Publication date

1995-02-28

1988-09-07 Application filed by Sterling Drug Inc filed Critical Sterling Drug Inc

1995-02-28 Application granted granted Critical

1995-02-28 Publication of CA1334592C publication Critical patent/CA1334592C/fr

2012-02-28 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

238000002360 preparation method Methods 0.000 title description 10
XLDJFTWREGCIST-UHFFFAOYSA-N 3-pyridin-2-yl-1h-quinolin-2-one Chemical class O=C1NC2=CC=CC=C2C=C1C1=CC=CC=N1 XLDJFTWREGCIST-UHFFFAOYSA-N 0.000 title description 2
239000001257 hydrogen Substances 0.000 claims abstract description 58
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 58
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 31
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 25
125000000217 alkyl group Chemical group 0.000 claims abstract description 15
150000002148 esters Chemical class 0.000 claims abstract description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
150000001875 compounds Chemical class 0.000 claims description 89
239000000203 mixture Substances 0.000 claims description 35
238000000034 method Methods 0.000 claims description 26
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 24
-1 amine salt Chemical class 0.000 claims description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 17
150000002431 hydrogen Chemical group 0.000 claims description 15
239000003054 catalyst Substances 0.000 claims description 14
229910000104 sodium hydride Inorganic materials 0.000 claims description 12
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 11
239000012312 sodium hydride Substances 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 10
229910052763 palladium Inorganic materials 0.000 claims description 9
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 8
229910052783 alkali metal Inorganic materials 0.000 claims description 8
150000001340 alkali metals Chemical class 0.000 claims description 8
239000007868 Raney catalyst Substances 0.000 claims description 7
229910000564 Raney nickel Inorganic materials 0.000 claims description 7
238000010438 heat treatment Methods 0.000 claims description 6
241000894006 Bacteria Species 0.000 claims description 5
239000007858 starting material Substances 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 4
FNKLCGHPPNAPBJ-UHFFFAOYSA-N 1-cyclopropyl-7-(2,6-dimethylpyridin-4-yl)-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound CC1=NC(C)=CC(C=2C(=CC=3C(=O)C(C(O)=O)=CN(C=3C=2)C2CC2)F)=C1 FNKLCGHPPNAPBJ-UHFFFAOYSA-N 0.000 claims description 3
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims description 3
230000003301 hydrolyzing effect Effects 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims 2
125000001309 chloro group Chemical group Cl* 0.000 claims 2
125000002346 iodo group Chemical group I* 0.000 claims 2
QUYSIYPMTRHBAI-UHFFFAOYSA-N 1-cyclopropyl-7-(2,6-dimethylpyridin-4-yl)-5,6,8-trifluoro-4-oxoquinoline-3-carboxylic acid Chemical compound CC1=NC(C)=CC(C=2C(=C3C(C(C(C(O)=O)=CN3C3CC3)=O)=C(F)C=2F)F)=C1 QUYSIYPMTRHBAI-UHFFFAOYSA-N 0.000 claims 1
WHXJSJBKDGZVDA-UHFFFAOYSA-N 1-cyclopropyl-7-(2,6-dimethylpyridin-4-yl)-6,8-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound CC1=NC(C)=CC(C=2C(=C3C(C(C(C(O)=O)=CN3C3CC3)=O)=CC=2F)F)=C1 WHXJSJBKDGZVDA-UHFFFAOYSA-N 0.000 claims 1
UNQUGKCGLRDDRV-UHFFFAOYSA-N 1-cyclopropyl-7-(2,6-dimethylpyridin-4-yl)-6,8-difluoro-5-phenylsulfanyl-4h-quinoline-3-carboxylic acid Chemical compound CC1=NC(C)=CC(C=2C(=C3N(C4CC4)C=C(CC3=C(SC=3C=CC=CC=3)C=2F)C(O)=O)F)=C1 UNQUGKCGLRDDRV-UHFFFAOYSA-N 0.000 claims 1
VVZIUBVSLQPQRL-UHFFFAOYSA-N 8-benzylsulfanyl-1-cyclopropyl-7-(2,6-dimethylpyridin-4-yl)-6-fluoro-4h-quinoline-3-carboxylic acid Chemical compound CC1=NC(C)=CC(C=2C(=C3N(C4CC4)C=C(CC3=CC=2F)C(O)=O)SCC=2C=CC=CC=2)=C1 VVZIUBVSLQPQRL-UHFFFAOYSA-N 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
239000002253 acid Substances 0.000 abstract description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 6
150000007513 acids Chemical class 0.000 abstract description 3
238000005859 coupling reaction Methods 0.000 abstract description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 3
239000003242 anti bacterial agent Substances 0.000 abstract description 2
125000005843 halogen group Chemical group 0.000 abstract description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 69
ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
239000000243 solution Substances 0.000 description 41
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 30
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
229910001868 water Inorganic materials 0.000 description 27
239000000047 product Substances 0.000 description 26
239000011541 reaction mixture Substances 0.000 description 26
239000007787 solid Substances 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 20
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
235000011167 hydrochloric acid Nutrition 0.000 description 14
238000010992 reflux Methods 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
239000012043 crude product Substances 0.000 description 13
229960000443 hydrochloric acid Drugs 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
229910052757 nitrogen Inorganic materials 0.000 description 9
229960005419 nitrogen Drugs 0.000 description 9
229910000027 potassium carbonate Inorganic materials 0.000 description 9
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
239000000463 material Substances 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
229940093956 potassium carbonate Drugs 0.000 description 8
239000002002 slurry Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
239000000460 chlorine Substances 0.000 description 7
239000008367 deionised water Substances 0.000 description 7
229910021641 deionized water Inorganic materials 0.000 description 7
239000000284 extract Substances 0.000 description 7
235000011181 potassium carbonates Nutrition 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
241000588724 Escherichia coli Species 0.000 description 6
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 6
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
230000000844 anti-bacterial effect Effects 0.000 description 6
238000001816 cooling Methods 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
HGINADPHJQTSKN-UHFFFAOYSA-M 3-ethoxy-3-oxopropanoate Chemical compound CCOC(=O)CC([O-])=O HGINADPHJQTSKN-UHFFFAOYSA-M 0.000 description 5
SXCXPXVEOPFPOH-UHFFFAOYSA-N 4-chloro-2,6-dimethylpyridine Chemical compound CC1=CC(Cl)=CC(C)=N1 SXCXPXVEOPFPOH-UHFFFAOYSA-N 0.000 description 5
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 5
241000191938 Micrococcus luteus Species 0.000 description 5
239000002585 base Substances 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
VYXHWCUUIOIRAW-UHFFFAOYSA-N ethyl 3-(4-bromo-2,5-difluorophenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=CC(F)=C(Br)C=C1F VYXHWCUUIOIRAW-UHFFFAOYSA-N 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
UTFQNVUJDSLOGV-UHFFFAOYSA-N (2,6-dimethylpyridin-4-yl)-trimethylstannane Chemical compound CC1=CC([Sn](C)(C)C)=CC(C)=N1 UTFQNVUJDSLOGV-UHFFFAOYSA-N 0.000 description 4
QFTZULJNRAHOIY-UHFFFAOYSA-N 1,4-dibromo-2,3,5,6-tetrafluorobenzene Chemical compound FC1=C(F)C(Br)=C(F)C(F)=C1Br QFTZULJNRAHOIY-UHFFFAOYSA-N 0.000 description 4
MTZLICDXLGQWJV-UHFFFAOYSA-N 4-bromo-2,3,5,6-tetrafluorobenzoic acid Chemical compound OC(=O)C1=C(F)C(F)=C(Br)C(F)=C1F MTZLICDXLGQWJV-UHFFFAOYSA-N 0.000 description 4
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
235000011089 carbon dioxide Nutrition 0.000 description 4
239000003610 charcoal Substances 0.000 description 4
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 4
DEBQYFKGIMRBLZ-UHFFFAOYSA-N ethyl 3-(4-bromo-2,3,5,6-tetrafluorophenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=C(F)C(F)=C(Br)C(F)=C1F DEBQYFKGIMRBLZ-UHFFFAOYSA-N 0.000 description 4
229940093499 ethyl acetate Drugs 0.000 description 4
235000019439 ethyl acetate Nutrition 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
239000012265 solid product Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
JPTNTBSBJPCXGI-UHFFFAOYSA-N 1-(4-bromo-2,5-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=C(Br)C=C1F JPTNTBSBJPCXGI-UHFFFAOYSA-N 0.000 description 3
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 3
YWZSTHLOAZTDFJ-UHFFFAOYSA-N 4-bromo-2,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(Br)C=C1F YWZSTHLOAZTDFJ-UHFFFAOYSA-N 0.000 description 3
ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
229910021120 PdC12 Inorganic materials 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
239000012346 acetyl chloride Substances 0.000 description 3
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910002092 carbon dioxide Inorganic materials 0.000 description 3
230000000694 effects Effects 0.000 description 3
XUAAMQAWMYDUOO-UHFFFAOYSA-N ethyl 2-(4-bromo-2,3,5,6-tetrafluorobenzoyl)-3-(cyclopropylamino)prop-2-enoate Chemical compound FC=1C(F)=C(Br)C(F)=C(F)C=1C(=O)C(C(=O)OCC)=CNC1CC1 XUAAMQAWMYDUOO-UHFFFAOYSA-N 0.000 description 3
POKPUCWXUHWGMX-UHFFFAOYSA-N ethyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=CC(F)=C(Cl)C=C1Cl POKPUCWXUHWGMX-UHFFFAOYSA-N 0.000 description 3
DVCODOGPGKNXNM-UHFFFAOYSA-N ethyl 7-bromo-1-cyclopropyl-5,6,8-trifluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=C(F)C(Br)=C(F)C(F)=C2C(=O)C(C(=O)OCC)=CN1C1CC1 DVCODOGPGKNXNM-UHFFFAOYSA-N 0.000 description 3
GJYVCONENKJLIF-UHFFFAOYSA-N ethyl 7-bromo-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(Br)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1CC1 GJYVCONENKJLIF-UHFFFAOYSA-N 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
244000005700 microbiome Species 0.000 description 3
125000000896 monocarboxylic acid group Chemical group 0.000 description 3
230000036647 reaction Effects 0.000 description 3
239000012258 stirred mixture Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
OGBCTQYIZYZCIP-UHFFFAOYSA-N tributyl-(2,6-dimethylpyridin-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC(C)=NC(C)=C1 OGBCTQYIZYZCIP-UHFFFAOYSA-N 0.000 description 3
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
GLVMLJCMUBZVTJ-UHFFFAOYSA-N 1,4-dibromo-2,5-difluorobenzene Chemical compound FC1=CC(Br)=C(F)C=C1Br GLVMLJCMUBZVTJ-UHFFFAOYSA-N 0.000 description 2
FAKJFAMIABOKBW-UHFFFAOYSA-N 1-(2,4-dichloro-5-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=C(Cl)C=C1Cl FAKJFAMIABOKBW-UHFFFAOYSA-N 0.000 description 2
XVYIQLOULDERAO-UHFFFAOYSA-N 4-bromo-2,3,5,6-tetrafluorobenzoyl chloride Chemical compound FC1=C(F)C(C(Cl)=O)=C(F)C(F)=C1Br XVYIQLOULDERAO-UHFFFAOYSA-N 0.000 description 2
OHDBFYOULUGQKS-UHFFFAOYSA-N 4-bromo-2,5-difluorobenzoyl chloride Chemical compound FC1=CC(C(Cl)=O)=C(F)C=C1Br OHDBFYOULUGQKS-UHFFFAOYSA-N 0.000 description 2
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
241000606124 Bacteroides fragilis Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
229910021590 Copper(II) bromide Inorganic materials 0.000 description 2
OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-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
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
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KWTSZCJMWHGPOS-UHFFFAOYSA-M chloro(trimethyl)stannane Chemical compound C[Sn](C)(C)Cl KWTSZCJMWHGPOS-UHFFFAOYSA-M 0.000 description 1
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OYFJQPXVCSSHAI-QFPUQLAESA-N enalapril maleate Chemical compound OC(=O)\C=C/C(O)=O.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 OYFJQPXVCSSHAI-QFPUQLAESA-N 0.000 description 1
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PQNFPAQWXMCBEC-UHFFFAOYSA-N ethyl 2-(4-bromo-2,5-difluorobenzoyl)-3-(cyclopropylamino)prop-2-enoate Chemical compound C=1C(F)=C(Br)C=C(F)C=1C(=O)C(C(=O)OCC)=CNC1CC1 PQNFPAQWXMCBEC-UHFFFAOYSA-N 0.000 description 1
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CBYGICOUOXMVKV-UHFFFAOYSA-N ethyl 3-amino-3-cyclopropyl-2-(2,4-dichloro-5-fluorobenzoyl)prop-2-enoate Chemical compound C=1C(F)=C(Cl)C=C(Cl)C=1C(=O)C(C(=O)OCC)=C(N)C1CC1 CBYGICOUOXMVKV-UHFFFAOYSA-N 0.000 description 1
RXOVIGAFIIOPLE-UHFFFAOYSA-N ethyl 7-azido-1-cyclopropyl-6,8-difluoro-4-oxoquinoline-2-carboxylate Chemical compound CCOC(=O)C1=CC(=O)C2=CC(F)=C(N=[N+]=[N-])C(F)=C2N1C1CC1 RXOVIGAFIIOPLE-UHFFFAOYSA-N 0.000 description 1
ISARIJLPDHNOHI-UHFFFAOYSA-N ethyl 7-azido-1-cyclopropyl-6,8-difluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=C(F)C(N=[N+]=[N-])=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1CC1 ISARIJLPDHNOHI-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
BTIJJDXEELBZFS-QDUVMHSLSA-K hemin Chemical compound CC1=C(CCC(O)=O)C(C=C2C(CCC(O)=O)=C(C)\C(N2[Fe](Cl)N23)=C\4)=N\C1=C/C2=C(C)C(C=C)=C3\C=C/1C(C)=C(C=C)C/4=N\1 BTIJJDXEELBZFS-QDUVMHSLSA-K 0.000 description 1
229940025294 hemin Drugs 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
229940011051 isopropyl acetate Drugs 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 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
238000001819 mass spectrum Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
238000006263 metalation reaction Methods 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
244000052769 pathogen Species 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000007686 potassium Nutrition 0.000 description 1
229960003975 potassium Drugs 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000013014 purified material Substances 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
229940031000 streptococcus pneumoniae Drugs 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 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
238000012546 transfer Methods 0.000 description 1
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
235000019168 vitamin K Nutrition 0.000 description 1
239000011712 vitamin K Substances 0.000 description 1
150000003721 vitamin K derivatives Chemical class 0.000 description 1
229940046010 vitamin k Drugs 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000002569 water oil cream Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA 576627 1987-09-08 1988-09-07 Composes pyridinyl-quinolone, leur preparation et leur utilisation Expired - Fee Related CA1334592C (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US9435987A	1987-09-08	1987-09-08
US094,359		1987-09-08
US21912488A	1988-07-15	1988-07-15
US219,124		1988-07-15

Publications (1)

Publication Number	Publication Date
CA1334592C true CA1334592C (fr)	1995-02-28

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ID=26788765

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 576627 Expired - Fee Related CA1334592C (fr)	1987-09-08	1988-09-07	Composes pyridinyl-quinolone, leur preparation et leur utilisation

Country Status (1)

Country	Link
CA (1)	CA1334592C (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN120382671A (zh) *	2025-06-26	2025-07-29	明光瑞智电子科技有限公司	一种含磷阻燃无卤覆铜板的制备方法

1988
- 1988-09-07 CA CA 576627 patent/CA1334592C/fr not_active Expired - Fee Related

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN120382671A (zh) *	2025-06-26	2025-07-29	明光瑞智电子科技有限公司	一种含磷阻燃无卤覆铜板的制备方法
CN120382671B (zh) *	2025-06-26	2025-09-12	明光瑞智电子科技有限公司	一种含磷阻燃无卤覆铜板的制备方法

Legal Events

Date	Code	Title	Description
1998-03-02	MKLA	Lapsed

Publication	Publication Date	Title
EP0230295B1 (fr)	1994-05-25	Acide 8-alkoxyquinoléine et ses sels avec une toxicité sélective excellente et un procédé pour leur préparation
US4959363A (en)	1990-09-25	Quinolonecarboxamide compounds, their preparation and use as antivirals.
US4874764A (en)	1989-10-17	Benzoheterocyclic compounds
US4753953A (en)	1988-06-28	Pyridonecarboxylic acid derivatives and antibacterial pharmaceutical compositions thereof
US4977154A (en)	1990-12-11	5-amino and 5-hydroxy-6-fluoroquinolones as antibacterial agents
US5075319A (en)	1991-12-24	Pyridinyl-quinolone compounds, their preparation and use
KR920006236B1 (ko)	1992-08-01	퀴놀론카복실산 유도체의 제조방법
AU598394B2 (en)	1990-06-21	4-oxo-3-quinolinecarboxylic acids useful as antibacterial agents and preparation thereof
US4839355A (en)	1989-06-13	Tricyclic-pyridinylquinoline compounds, their preparation and use
HU195495B (en)	1988-05-30	Process for the production of new derivatives of kynolincarbonic acid and medical preparatives containing them
JPH0768219B2 (ja)	1995-07-26	キノリンカルボン酸の製造法
CA1334592C (fr)	1995-02-28	Composes pyridinyl-quinolone, leur preparation et leur utilisation
JPS61186379A (ja)	1986-08-20	１‐シクロプロピル‐１，４‐ジヒドロ‐４‐オキソ‐７‐［４‐（２‐オキソ‐１，３‐ジオキソル‐４‐イル‐メチル）‐１‐ピペラジニル］‐３‐キノリンカルボン酸
US5169853A (en)	1992-12-08	Pyridinyl-quinolone compounds, their preparation and use
JPS6237628B2 (fr)	1987-08-13
JPH0717608B2 (ja)	1995-03-01	６−アルコキシキノロンカルボン酸誘導体
US4826982A (en)	1989-05-02	Quinolonecarboxylic acid derivatives
KR950005201B1 (ko)	1995-05-19	8-알콕시퀴놀론카복실산 유도체
JPH0720940B2 (ja)	1995-03-08	キノリン誘導体の製造法
JPWO1991016311A1 (ja)	1992-06-04	７―置換ヒドラジノ―４―オキソ―キノリン―３―カルボン酸誘導体、その塩及びそのエステル
JPH0430396B2 (fr)	1992-05-21