DK173057B1 - 5-Alkyl-6-fluor-1,4-dihydro-4-oxo-1,8-naphthyridinforbindelser, fremgangsmåder til fremstilling deraf, farmaceutisk præpara - Google Patents

5-Alkyl-6-fluor-1,4-dihydro-4-oxo-1,8-naphthyridinforbindelser, fremgangsmåder til fremstilling deraf, farmaceutisk præpara Download PDF

Info

Publication number: DK173057B1
Authority: DK; Denmark
Prior art keywords: methyl; mmol; compound; solution; ethyl
Prior art date: 1988-01-25

Application number

DK199001746A

Other languages

Danish (da)

English (en)

Other versions

DK174690D0 (da

DK174690A (da

Inventor

John Michael Domagala

John Steven Kiely

Susan Elizabeth Hagen

Original Assignee

Warner Lambert 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.)

1988-01-25

Filing date

1990-07-20

Publication date

1999-12-13

1990-07-20 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

1990-07-20 Publication of DK174690D0 publication Critical patent/DK174690D0/da

1990-07-20 Publication of DK174690A publication Critical patent/DK174690A/da

1999-12-13 Application granted granted Critical

1999-12-13 Publication of DK173057B1 publication Critical patent/DK173057B1/da

Links

238000000034 method Methods 0.000 title claims abstract description 22
238000002360 preparation method Methods 0.000 title claims description 16
239000000825 pharmaceutical preparation Substances 0.000 title description 2
238000004519 manufacturing process Methods 0.000 claims abstract 4
150000001875 compounds Chemical class 0.000 claims description 131
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 58
-1 3-amino-1-pyrrolidinyl Chemical group 0.000 claims description 48
229910052739 hydrogen Inorganic materials 0.000 claims description 36
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 28
239000000460 chlorine Substances 0.000 claims description 25
239000001257 hydrogen Substances 0.000 claims description 25
239000002253 acid Substances 0.000 claims description 22
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 20
125000004432 carbon atom Chemical group C* 0.000 claims description 19
125000000217 alkyl group Chemical group 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
230000000844 anti-bacterial effect Effects 0.000 claims description 10
150000002367 halogens Chemical group 0.000 claims description 10
150000001412 amines Chemical class 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 5
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
150000001768 cations Chemical class 0.000 claims description 3
125000001188 haloalkyl group Chemical group 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
229920002554 vinyl polymer Polymers 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 6
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
IMFWNULEIDMBGU-UHFFFAOYSA-N ethyl 1-cyclopropyl-6-fluoro-5-methyl-4-oxo-7-piperazin-1-yl-1,8-naphthyridine-3-carboxylate Chemical compound C12=NC(N3CCNCC3)=C(F)C(C)=C2C(=O)C(C(=O)OCC)=CN1C1CC1 IMFWNULEIDMBGU-UHFFFAOYSA-N 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 53
239000000543 intermediate Substances 0.000 abstract description 7
208000035143 Bacterial infection Diseases 0.000 abstract description 2
208000022362 bacterial infectious disease Diseases 0.000 abstract description 2
238000009472 formulation Methods 0.000 abstract description 2
239000003242 anti bacterial agent Substances 0.000 abstract 2
LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical class C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 abstract 1
239000000243 solution Substances 0.000 description 110
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 66
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 43
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
239000000047 product Substances 0.000 description 29
239000007787 solid Substances 0.000 description 28
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 24
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 22
229910052943 magnesium sulfate Inorganic materials 0.000 description 22
235000019341 magnesium sulphate Nutrition 0.000 description 22
239000012074 organic phase Substances 0.000 description 22
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
239000000741 silica gel Substances 0.000 description 19
229910002027 silica gel Inorganic materials 0.000 description 19
239000003921 oil Substances 0.000 description 18
235000019198 oils Nutrition 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 18
239000002904 solvent Substances 0.000 description 17
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
238000010992 reflux Methods 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 15
235000002639 sodium chloride Nutrition 0.000 description 14
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
239000002585 base Substances 0.000 description 12
238000001914 filtration Methods 0.000 description 12
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 12
125000004435 hydrogen atom Chemical class [H]* 0.000 description 11
239000000725 suspension Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
238000004440 column chromatography Methods 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
239000002002 slurry Substances 0.000 description 10
229910052786 argon Inorganic materials 0.000 description 8
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
235000019502 Orange oil Nutrition 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
239000010502 orange oil Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000003826 tablet Substances 0.000 description 6
238000004458 analytical method Methods 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000012043 crude product Substances 0.000 description 5
239000013078 crystal Substances 0.000 description 5
229940043279 diisopropylamine Drugs 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000000843 powder Substances 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
241000191967 Staphylococcus aureus Species 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000012458 free base Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
239000012453 solvate Substances 0.000 description 4
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 4
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 3
QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical class N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 3
AIHYSSLMNNDQQS-UHFFFAOYSA-N 3-chloro-2,4,5-trifluoro-6-methylbenzoic acid Chemical compound CC1=C(F)C(F)=C(Cl)C(F)=C1C(O)=O AIHYSSLMNNDQQS-UHFFFAOYSA-N 0.000 description 3
QNTYWFRSDUCLRD-UHFFFAOYSA-N 4,4-dimethyl-2-(2,4,5-trifluorophenyl)-5h-1,3-oxazole Chemical compound CC1(C)COC(C=2C(=CC(F)=C(F)C=2)F)=N1 QNTYWFRSDUCLRD-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
HGINADPHJQTSKN-UHFFFAOYSA-N Monoethyl malonic acid Chemical compound CCOC(=O)CC(O)=O HGINADPHJQTSKN-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
244000309464 bull Species 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
150000003840 hydrochlorides Chemical class 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 3
WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 3
238000002156 mixing Methods 0.000 description 3
150000003141 primary amines Chemical group 0.000 description 3
XUWVIABDWDTJRZ-UHFFFAOYSA-N propan-2-ylazanide Chemical compound CC(C)[NH-] XUWVIABDWDTJRZ-UHFFFAOYSA-N 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
150000005058 1,8-naphthyridines Chemical class 0.000 description 2
SUUYTEUAWNNSEE-UHFFFAOYSA-N 2,4,5-trifluoro-3-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(C(F)(F)F)=C1F SUUYTEUAWNNSEE-UHFFFAOYSA-N 0.000 description 2
CACZOIOUVVFGLV-UHFFFAOYSA-N 2,6-dichloro-5-fluoro-4-methylpyridine-3-carboxylic acid Chemical compound CC1=C(F)C(Cl)=NC(Cl)=C1C(O)=O CACZOIOUVVFGLV-UHFFFAOYSA-N 0.000 description 2
ZMDQWHCTODNNLT-UHFFFAOYSA-N 2h-1,2-benzoxazine-3-carboxylic acid Chemical class C1=CC=C2ONC(C(=O)O)=CC2=C1 ZMDQWHCTODNNLT-UHFFFAOYSA-N 0.000 description 2
IKADJZHHXKPMAH-UHFFFAOYSA-N 3-bromo-2,5,6-trifluorobenzoic acid Chemical compound OC(=O)C1=C(F)C(F)=CC(Br)=C1F IKADJZHHXKPMAH-UHFFFAOYSA-N 0.000 description 2
CONZWNKKCGOBBN-UHFFFAOYSA-N 3-chloro-2,4,5-trifluoro-6-methylbenzoyl chloride Chemical compound CC1=C(F)C(F)=C(Cl)C(F)=C1C(Cl)=O CONZWNKKCGOBBN-UHFFFAOYSA-N 0.000 description 2
VCAUNUFFGWTOBI-UHFFFAOYSA-N 4,4-dimethyl-2-(2,3,4,5-tetrafluoro-6-methylphenyl)-5h-1,3-oxazole Chemical compound CC1=C(F)C(F)=C(F)C(F)=C1C1=NC(C)(C)CO1 VCAUNUFFGWTOBI-UHFFFAOYSA-N 0.000 description 2
FGWOBIITFQTTDG-UHFFFAOYSA-N 4,4-dimethyl-2-(3,4,6-trifluoro-2-methylphenyl)-5h-1,3-oxazole Chemical compound CC1=C(F)C(F)=CC(F)=C1C1=NC(C)(C)CO1 FGWOBIITFQTTDG-UHFFFAOYSA-N 0.000 description 2
BBYVNRLCDGQARF-UHFFFAOYSA-N 7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)C=2C(C)=C(F)C(N3CC(N)CC3)=NC=2N1C1CC1 BBYVNRLCDGQARF-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
241000588697 Enterobacter cloacae Species 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
241000588747 Klebsiella pneumoniae Species 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
241000588769 Proteus <enterobacteria> Species 0.000 description 2
241000589517 Pseudomonas aeruginosa Species 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
241000194017 Streptococcus Species 0.000 description 2
241000193998 Streptococcus pneumoniae Species 0.000 description 2
241000193996 Streptococcus pyogenes Species 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
229940125898 compound 5 Drugs 0.000 description 2
239000013058 crude material Substances 0.000 description 2
PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 2
238000004821 distillation Methods 0.000 description 2
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GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
FLSIXVNZZOMAKK-UHFFFAOYSA-N [3-(4,4-dimethyl-5h-1,3-oxazol-2-yl)-2,5,6-trifluoro-4-methylphenyl]-trimethylsilane Chemical compound CC1=C(F)C(F)=C([Si](C)(C)C)C(F)=C1C1=NC(C)(C)CO1 FLSIXVNZZOMAKK-UHFFFAOYSA-N 0.000 description 1
IEZAANOMRBUEHI-UHFFFAOYSA-N [3-(4,4-dimethyl-5h-1,3-oxazol-2-yl)-2,5,6-trifluorophenyl]-trimethylsilane Chemical compound CC1(C)COC(C=2C(=C(C(F)=C(F)C=2)[Si](C)(C)C)F)=N1 IEZAANOMRBUEHI-UHFFFAOYSA-N 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
150000003973 alkyl amines Chemical group 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
125000004647 alkyl sulfenyl group Chemical group 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
OKTJSMMVPCPJKN-BJUDXGSMSA-N carbon-11 Chemical compound [11C] OKTJSMMVPCPJKN-BJUDXGSMSA-N 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
150000004985 diamines Chemical class 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000003113 dilution method Methods 0.000 description 1
229960001760 dimethyl sulfoxide Drugs 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
JFWURCREFDQUTD-UHFFFAOYSA-N ethyl 1,8-naphthyridine-3-carboxylate Chemical compound N1=CC=CC2=CC(C(=O)OCC)=CN=C21 JFWURCREFDQUTD-UHFFFAOYSA-N 0.000 description 1
QTYIWWXOSHKRFO-UHFFFAOYSA-N ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-5-methyl-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(F)=C(F)C(C)=C2C(=O)C(C(=O)OCC)=CN1C1=CC=C(F)C=C1F QTYIWWXOSHKRFO-UHFFFAOYSA-N 0.000 description 1
GLTTTXNKWRCTPH-UHFFFAOYSA-N ethyl 1-(2-bromoethyl)-6,7,8-trifluoro-5-methyl-4-oxoquinoline-3-carboxylate Chemical compound FC1=C(F)C(C)=C2C(=O)C(C(=O)OCC)=CN(CCBr)C2=C1F GLTTTXNKWRCTPH-UHFFFAOYSA-N 0.000 description 1
USDUZYISEFEACI-UHFFFAOYSA-N ethyl 1-ethyl-6,7-difluoro-5-methyl-4-oxoquinoline-3-carboxylate Chemical compound FC1=C(F)C(C)=C2C(=O)C(C(=O)OCC)=CN(CC)C2=C1 USDUZYISEFEACI-UHFFFAOYSA-N 0.000 description 1
PHABVASECVGBNQ-UHFFFAOYSA-N ethyl 3-(2,6-dichloro-5-fluoro-4-methylpyridin-3-yl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=C(C)C(F)=C(Cl)N=C1Cl PHABVASECVGBNQ-UHFFFAOYSA-N 0.000 description 1
LUBWVPQBPFZZEA-UHFFFAOYSA-N ethyl 3-(cyclopropylamino)-2-(3,4,5,6-tetrafluoro-3-methylcyclohexa-1,5-diene-1-carbonyl)prop-2-enoate Chemical compound C=1C(C)(F)C(F)C(F)=C(F)C=1C(=O)C(C(=O)OCC)=CNC1CC1 LUBWVPQBPFZZEA-UHFFFAOYSA-N 0.000 description 1
VMAWFFKOQKRHQH-UHFFFAOYSA-N ethyl 3-(cyclopropylamino)-2-(3,4,6-trifluoro-2-methylbenzoyl)prop-2-enoate Chemical compound FC=1C=C(F)C(F)=C(C)C=1C(=O)C(C(=O)OCC)=CNC1CC1 VMAWFFKOQKRHQH-UHFFFAOYSA-N 0.000 description 1
NDSHMZFAYDQXNP-UHFFFAOYSA-N ethyl 3-(ethylamino)-2-(2,3,4,5-tetrafluoro-6-methylbenzoyl)prop-2-enoate Chemical compound CCNC=C(C(=O)OCC)C(=O)C1=C(C)C(F)=C(F)C(F)=C1F NDSHMZFAYDQXNP-UHFFFAOYSA-N 0.000 description 1
RZAZFQQODFHNIO-UHFFFAOYSA-N ethyl 3-ethoxy-2-(2,3,4,5-tetrafluoro-6-methylbenzoyl)prop-2-enoate Chemical compound CCOC=C(C(=O)OCC)C(=O)C1=C(C)C(F)=C(F)C(F)=C1F RZAZFQQODFHNIO-UHFFFAOYSA-N 0.000 description 1
VTCVEQVLVZSWOS-UHFFFAOYSA-N ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2,3-dihydro-1,8-naphthyridine-3-carboxylate Chemical compound C12=NC(Cl)=C(F)C=C2C(=O)C(C(=O)OCC)CN1C1CC1 VTCVEQVLVZSWOS-UHFFFAOYSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
RBVLUTAXWVILBT-UHFFFAOYSA-N ethyl prop-2-eneperoxoate Chemical compound CCOOC(=O)C=C RBVLUTAXWVILBT-UHFFFAOYSA-N 0.000 description 1
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
239000000314 lubricant Substances 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
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
WTRWSSDZHQOPJI-UHFFFAOYSA-N methyl 1-benzyl-5-oxopyrrolidine-3-carboxylate Chemical compound O=C1CC(C(=O)OC)CN1CC1=CC=CC=C1 WTRWSSDZHQOPJI-UHFFFAOYSA-N 0.000 description 1
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
229960000316 methyprylon Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
AOTWIFLKURJQGE-UHFFFAOYSA-N n-cyclopropylaniline Chemical compound C1CC1NC1=CC=CC=C1 AOTWIFLKURJQGE-UHFFFAOYSA-N 0.000 description 1
150000005054 naphthyridines Chemical class 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
UWBHMRBRLOJJAA-UHFFFAOYSA-N oxaluric acid Chemical compound NC(=O)NC(=O)C(O)=O UWBHMRBRLOJJAA-UHFFFAOYSA-N 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
239000006201 parenteral dosage form Substances 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
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
235000014786 phosphorus Nutrition 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 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
150000003222 pyridines Chemical class 0.000 description 1
OQCUGPQOZNYIMV-UHFFFAOYSA-N pyrrolidin-3-ylmethanamine Chemical compound NCC1CCNC1 OQCUGPQOZNYIMV-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical class C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
MHOVAHRLVXNVSD-OIOBTWANSA-N rhodium-100 Chemical compound [100Rh] MHOVAHRLVXNVSD-OIOBTWANSA-N 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000000859 sublimation Methods 0.000 description 1
230000008022 sublimation Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
235000001508 sulfur Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000007885 tablet disintegrant Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
RETFQNLOTMGLAJ-UHFFFAOYSA-N tert-butyl 4-amino-2-methyl-1H-pyrrole-3-carboxylate Chemical compound C(C)(C)(C)OC(=O)C1=C(NC=C1N)C RETFQNLOTMGLAJ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- 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
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Communicable Diseases (AREA)
Animal Behavior & Ethology (AREA)
Oncology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Quinoline Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

DK199001746A 1988-01-25 1990-07-20 5-Alkyl-6-fluor-1,4-dihydro-4-oxo-1,8-naphthyridinforbindelser, fremgangsmåder til fremstilling deraf, farmaceutisk præpara DK173057B1 (da)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US14746288A	1988-01-25	1988-01-25
US14746288		1988-01-25
US07/280,924 US4920120A (en)	1988-01-25	1988-12-09	Antibacterial agents
US28092488		1988-12-09
US8900278		1989-01-23
PCT/US1989/000278 WO1989006649A2 (en)	1988-01-25	1989-01-23	Antibacterial agents

Publications (3)

Publication Number	Publication Date
DK174690D0 DK174690D0 (da)	1990-07-20
DK174690A DK174690A (da)	1990-07-20
DK173057B1 true DK173057B1 (da)	1999-12-13

Family

ID=26844956

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
DK199001746A DK173057B1 (da)	1988-01-25	1990-07-20	5-Alkyl-6-fluor-1,4-dihydro-4-oxo-1,8-naphthyridinforbindelser, fremgangsmåder til fremstilling deraf, farmaceutisk præpara
DK140996A DK140996A (da)	1988-01-25	1996-12-09	Fremgangsmåde til fremstilling af 2,3,4,5-tetraflour-6-alkyl-benzoesyreforbindelser

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
DK140996A DK140996A (da)	1988-01-25	1996-12-09	Fremgangsmåde til fremstilling af 2,3,4,5-tetraflour-6-alkyl-benzoesyreforbindelser

Country Status (16)

Country	Link
US (1)	US4920120A (no)
EP (2)	EP0398967A1 (no)
JP (2)	JP2815119B2 (no)
KR (3)	KR0130931B1 (no)
AT (1)	ATE109471T1 (no)
AU (4)	AU624118B2 (no)
CA (1)	CA1340492C (no)
DE (1)	DE68917163T2 (no)
DK (2)	DK173057B1 (no)
ES (1)	ES2056963T3 (no)
FI (1)	FI93360C (no)
IE (1)	IE65350B1 (no)
NO (2)	NO178194C (no)
NZ (1)	NZ227680A (no)
PT (1)	PT89520B (no)
WO (1)	WO1989006649A2 (no)

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1988
- 1988-12-09 US US07/280,924 patent/US4920120A/en not_active Expired - Lifetime
- 1988-12-30 IE IE390088A patent/IE65350B1/en not_active IP Right Cessation
1989
- 1989-01-03 CA CA000587421A patent/CA1340492C/en not_active Expired - Fee Related
- 1989-01-20 NZ NZ227680A patent/NZ227680A/xx unknown
- 1989-01-23 KR KR1019890701774A patent/KR0130931B1/ko not_active IP Right Cessation
- 1989-01-23 ES ES89101085T patent/ES2056963T3/es not_active Expired - Lifetime
- 1989-01-23 JP JP1502150A patent/JP2815119B2/ja not_active Expired - Fee Related
- 1989-01-23 DE DE68917163T patent/DE68917163T2/de not_active Expired - Fee Related
- 1989-01-23 AT AT89101085T patent/ATE109471T1/de not_active IP Right Cessation
- 1989-01-23 WO PCT/US1989/000278 patent/WO1989006649A2/en active IP Right Grant
- 1989-01-23 EP EP89902326A patent/EP0398967A1/en active Pending
- 1989-01-23 AU AU30483/89A patent/AU624118B2/en not_active Ceased
- 1989-01-23 EP EP89101085A patent/EP0326891B1/en not_active Expired - Lifetime
- 1989-01-24 PT PT89520A patent/PT89520B/pt not_active IP Right Cessation
1990
- 1990-07-20 DK DK199001746A patent/DK173057B1/da not_active IP Right Cessation
- 1990-07-23 FI FI903696A patent/FI93360C/fi not_active IP Right Cessation
- 1990-07-24 NO NO903286A patent/NO178194C/no not_active IP Right Cessation
1992
- 1992-03-27 AU AU13888/92A patent/AU659444B2/en not_active Ceased
1994
- 1994-06-30 NO NO942468A patent/NO300263B1/no not_active IP Right Cessation
1995
- 1995-07-27 AU AU27223/95A patent/AU674272B2/en not_active Ceased
- 1995-07-27 AU AU27224/95A patent/AU671575B2/en not_active Ceased
1996
- 1996-12-09 DK DK140996A patent/DK140996A/da not_active Application Discontinuation
1997
- 1997-09-18 KR KR1019970706494A patent/KR0182275B1/ko not_active IP Right Cessation
- 1997-09-18 KR KR97706493A patent/KR0145958B1/ko not_active Application Discontinuation
1998
- 1998-04-01 JP JP10104208A patent/JP2986154B2/ja not_active Expired - Fee Related

Also Published As

Publication number	Publication date
JP2815119B2 (ja)	1998-10-27
NO300263B1 (no)	1997-05-05
PT89520B (pt)	1994-02-28
PT89520A (pt)	1989-10-04
ES2056963T3 (es)	1994-10-16
KR0145958B1 (en)	1998-08-17
KR19980703084A (ko)	1998-09-05
FI93360C (fi)	1995-03-27
ATE109471T1 (de)	1994-08-15
WO1989006649A3 (en)	1989-12-28
AU2722395A (en)	1995-10-19
JPH03502452A (ja)	1991-06-06
KR900700475A (ko)	1990-08-13
EP0326891A3 (en)	1990-04-25
AU3048389A (en)	1989-08-11
DE68917163D1 (de)	1994-09-08
NO178194B (no)	1995-10-30
JP2986154B2 (ja)	1999-12-06
CA1340492C (en)	1999-04-13
EP0326891B1 (en)	1994-08-03
FI903696A0 (fi)	1990-07-23
IE883900L (en)	1989-07-25
AU674272B2 (en)	1996-12-12
AU624118B2 (en)	1992-06-04
AU671575B2 (en)	1996-08-29
NO178194C (no)	1996-02-07
AU659444B2 (en)	1995-05-18
DK140996A (da)	1996-12-09
US4920120A (en)	1990-04-24
DK174690D0 (da)	1990-07-20
KR0182275B1 (ko)	1999-05-01
JPH10291959A (ja)	1998-11-04
WO1989006649A2 (en)	1989-07-27
NO942468D0 (no)	1994-06-30
NO942468L (no)	1990-07-24
NZ227680A (en)	1991-11-26
FI93360B (fi)	1994-12-15
IE65350B1 (en)	1995-10-18
NO903286L (no)	1990-07-24
AU2722495A (en)	1995-10-05
AU1388892A (en)	1992-07-09
DK174690A (da)	1990-07-20
EP0398967A1 (en)	1990-11-28
DE68917163T2 (de)	1994-12-01
KR0130931B1 (ko)	1998-04-16
NO903286D0 (no)	1990-07-24
EP0326891A2 (en)	1989-08-09

Legal Events

Date	Code	Title	Description
1990-07-20	A0	Application filed
1999-12-13	B1	Patent granted (law 1993)
2004-09-06	PBP	Patent lapsed	Country of ref document: DK

Publication	Publication Date	Title
DK173057B1 (da)	1999-12-13	5-Alkyl-6-fluor-1,4-dihydro-4-oxo-1,8-naphthyridinforbindelser, fremgangsmåder til fremstilling deraf, farmaceutisk præpara
DK171098B1 (da)	1996-06-03	Analogifremgangsmåde til fremstilling af antibakterielle 1-cyclopropryl-8-chlor- eller 1-cyclopropyl-8-alkoxyquinoliner
DK171820B1 (da)	1997-06-23	Quinolinderivater
US4780468A (en)	1988-10-25	8-trifluoromethyl quinolones as antibacterial agents
KR950010325B1 (ko)	1995-09-14	4-옥소퀴놀린-3-카르복실산 유도체, 그의 제조방법
US6232313B1 (en)	2001-05-15	Pyridazino quinoline compounds
US4753953A (en)	1988-06-28	Pyridonecarboxylic acid derivatives and antibacterial pharmaceutical compositions thereof
IE850255L (en)	1985-08-17	Antibacterial quinoline and naphthyridine derivatives
RU2056411C1 (ru)	1996-03-20	Производные хинолон- или нафтиридонкарбоновой кислоты или их гидраты, или соли, способ их получения и антимикробная композиция
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