CS273048B1 - Derivative of bis 4-quinolone-6-fluoro-3-carboxylic acid and method of its preparation - Google Patents
Derivative of bis 4-quinolone-6-fluoro-3-carboxylic acid and method of its preparation Download PDFInfo
- Publication number
- CS273048B1 CS273048B1 CS535389A CS535389A CS273048B1 CS 273048 B1 CS273048 B1 CS 273048B1 CS 535389 A CS535389 A CS 535389A CS 535389 A CS535389 A CS 535389A CS 273048 B1 CS273048 B1 CS 273048B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- fluoro
- carboxylic acid
- dihydro
- ethyl
- oxo
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- WNNSMMJBBOPPOT-UHFFFAOYSA-N 7-chloro-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=C(Cl)C=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 WNNSMMJBBOPPOT-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims abstract description 3
- 238000009835 boiling Methods 0.000 claims abstract 2
- 239000011541 reaction mixture Substances 0.000 claims abstract 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 abstract description 4
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 241000894006 Bacteria Species 0.000 abstract description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- -1 alkaline earth metal salts Chemical class 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- ILNJBIQQAIIMEY-UHFFFAOYSA-N 4-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CN=C21 ILNJBIQQAIIMEY-UHFFFAOYSA-N 0.000 description 1
- KKORZNPFZXORNH-UHFFFAOYSA-N 4-oxo-3h-quinoline-2-carboxylic acid Chemical class C1=CC=C2C(=O)CC(C(=O)O)=NC2=C1 KKORZNPFZXORNH-UHFFFAOYSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108010054814 DNA Gyrase Proteins 0.000 description 1
- 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 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229960001180 norfloxacin Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Vynález se týká derivátu bis 4-chinolon-S-fluor-3-karboxyIové kyseliny, v němž dvě molekuly jsou spojeny v poloze 7 piperazinem a který má antibakteríálni účinek.The present invention relates to a bis 4-quinolone-5-fluoro-3-carboxylic acid derivative in which the two molecules are linked at the 7-position by piperazine and which has an antibacterial effect.
Deriváty 4-chinolon-2-karboxylových kyselin se používají v lékařství jako antibakteriálni sloučeniny. Oejich účinek Je založen na zásahu do syntézy deoxyribonukleové kyseliny tim způsobem, že inhibuji DNK-gyrázu, která Je odpovědná za tvorbu suparstruktury chromozomů.4-Quinolone-2-carboxylic acid derivatives are used in medicine as antibacterial compounds. Their effect is based on interfering with the synthesis of deoxyribonucleic acid in such a way that it inhibits DNA-gyrase, which is responsible for the formation of chromosome superstructure.
□ednou z velmi účinných sloučenin této struktury Je norfloxacin, l-ethyl-6-fluor-l,4-dihydro-4-oxo-7-(l-piperazinyl)-3-chinolinkarboxylová kyselina, který vzhledem k rychlé resorpci se používá především při léčeni:.infekci urogenitálního traktu.One of the most potent compounds of this structure is norfloxacin, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -3-quinolinecarboxylic acid, which is mainly used due to its rapid resorption in the treatment of: an urogenital tract infection.
Podstatou vynálezu je nový derivát 4-chinolo-6-fluor-3-karboxylové kyseliny vzorce IThe present invention provides a novel 4-quinolo-6-fluoro-3-carboxylic acid derivative of the formula I
Vynález se dále týká způsobu přípravy sloučeniny vzorce I, jehož podstata spočívá v tom, že na l-athyl-6-fluor-l,4-dihydro-4-oxo-7-(l-piperazinyl)-3-chinolinkarboxYlovou kyselinu se působí l-ethyl-7-chlor-6-fluor-l,4-dihydro-4-oxo-3-chinolinkarboxylovou kyselinou v prostředí výšsvroucího rozpouštědla, 3 výhodou dimethylformamidu nebo difenyletheru, při teplotách 90 až 240 °C. Reakce se katalyzuje bázickými sloučeninami, s výhodou triethylaminem. Při reakci sa používá molárnl poměr obou komponent 1 : 1 až 1 s 5.The invention further relates to a process for the preparation of a compound of the formula I which comprises treating 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -3-quinolinecarboxylic acid. 1-ethyl-7-chloro-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid in an environment of a rising solvent, preferably dimethylformamide or diphenyl ether, at temperatures of 90 to 240 ° C. The reaction is catalyzed by basic compounds, preferably triethylamine. In the reaction, a molar ratio of both components of 1: 1 to 1 s 5 is used.
Sloučenina vzorce I inhibuje růet grampozitivnlch i gramnegativních bakterií:The compound of formula I inhibits a variety of Gram positive and Gram negative bacteria:
Escharichia coli 0,75 ^ug/mlEscharichia coli 0.75 µg / ml
Staphllococeus aureus 30 yug/mlStaphllococeus aureus 30 yug / ml
Pseudomonas aeruginosa 30 y.ug/ralPseudomonas aeruginosa 30 y.ug/ral
Sloučenina vzorce I se vyznačuje velmi nepatrnou rozpustnosti a tim i malou reeorbovatelnosti a je proto vhodná pro použiti Jak v humánní tak i veterinární medicíně k léčeni infekci gestrointestinálniho traktu.The compound of formula I is characterized by very low solubility and thus low re-absorbability and is therefore suitable for use in both human and veterinary medicine for the treatment of gestrointestinal tract infections.
Může se používat též v různých farmaceuticky použitelných formách. Jako Jsou soli alkalických kovů nebo kovů alkalických zemin.·It can also be used in various pharmaceutically usable forms. Such as alkali metal or alkaline earth metal salts.
Příklad 1 l,4-bis(l-ethYl-6-fluor-l,4-dihydro-4-oxo-3-karboxY-7-chinolyl)-piperazinExample 1 1,4-bis (1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3-carboxyl-7-quinolyl) -piperazine
4,8 g l-ethyl-6-fluor-l,4-dihydro-4-oxa-7-(l-piperazinyl)-3-chinalinkarboxylové kyseliny a 7;1 g l-athyl-7-chlor-6-fluor-l,4-dihydro-4-oxo-3-chinolinkarboxylové kyseliny se zahřívá v prostředí 70 ml dimethylformamidu a 3 g triethylaminu na 120 až 140 °C. Po 10 hodinách sa vzniklý l,4-bi8(l-ethyl-6-fluor-l,4-dihydro-4-oxo-3-karboxy-7-chinolyl)piparazin za horka odfiltruje a promyje vodou. Přečisti se rozpuštěním ve vodném roztoku louhu sodného nebo draselného a vysrážením kyselinou chlorovodíkovou. Získá se sloučenina rozkládající se nad 310 °C s výtěžkem 3,9 g.4.8 g of 1-ethyl-6-fluoro-1,4-dihydro-4-oxa-7- (1-piperazinyl) -3-quinalinecarboxylic acid and 7,1 g of 1-ethyl-7-chloro-6-fluoro The 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid is heated in an atmosphere of 70 ml of dimethylformamide and 3 g of triethylamine to 120-140 ° C. After 10 hours, the 1,4-b8 (1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3-carboxy-7-quinolyl) piparazine formed is filtered hot and washed with water. Purify by dissolution in aqueous sodium or potassium hydroxide solution and precipitation with hydrochloric acid. The product is decomposed above 310 ° C in a yield of 3.9 g.
Pro c28H2SN406F2 (552,5) vypočteno; 80,87 % C, 4,74 % H, 10,14 % N, 6,44 % Fj nalezeno: 60,4 % C, 4,7 % H, 9,7 % N, 6,6 % F.For c 28 H 26 N 4 O 6 F 2 (552.5) calculated; % C, 80.47;% H, 4.74;% N, 10.14;% F, 6.44. Found:% C, 60.4%;% H; 4.7%;
'H NMR spektrum (rozp. CFgCOOD) standard TMS)1 H NMR spectrum (CFgCOOD) (TMS standard)
3-j 1,81 (total 6H, t H-H > 7,4 Hz, CHg)3-j 1.81 (total 6H, tH-H > 7.4 Hz, CHg)
CS 273 048 BlCS 273 048 Bl
PŘEDMĚT VYNÁLEZUSUBJECT OF THE INVENTION
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS535389A CS273048B1 (en) | 1989-09-19 | 1989-09-19 | Derivative of bis 4-quinolone-6-fluoro-3-carboxylic acid and method of its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS535389A CS273048B1 (en) | 1989-09-19 | 1989-09-19 | Derivative of bis 4-quinolone-6-fluoro-3-carboxylic acid and method of its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS535389A1 CS535389A1 (en) | 1990-06-13 |
| CS273048B1 true CS273048B1 (en) | 1991-02-12 |
Family
ID=5398280
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS535389A CS273048B1 (en) | 1989-09-19 | 1989-09-19 | Derivative of bis 4-quinolone-6-fluoro-3-carboxylic acid and method of its preparation |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS273048B1 (en) |
-
1989
- 1989-09-19 CS CS535389A patent/CS273048B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CS535389A1 (en) | 1990-06-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1340285C (en) | Novel quinolonecarboxylic acid derivatives having at 7-position a piperidin-1-yl substituent | |
| SU1015827A3 (en) | Process for preparing derivatives of quinoline carboxylic acid or their hydrates | |
| JP3510955B2 (en) | Improved antiviral compounds | |
| US4292317A (en) | 1,4-Dihydro-quinoline-3-carboxylic acid derivatives, process for their preparation and compositions containing them | |
| HU186561B (en) | Process for preparing new quinoline derivatives and salts thereof | |
| DK172077B1 (en) | 6-Fluoro-7- (4- (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl-1-piperazinyl) -4-oxo-4H- (1,3) thiaceto (3, 2-a) Quinoline-3-carboxylic acid derivatives, process for their preparation and pharmaceutical preparations containing these compounds | |
| JPS6331465B2 (en) | ||
| EP0109284B1 (en) | 6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1h,5h-benzo(ij)quinolizine-2-carboxylic acid and derivatives | |
| JP3493692B2 (en) | Bisbiguanide compound and fungicide containing the same | |
| HU177657B (en) | Process for producing substituted piperasinyl-quinoline-carboxylic acid | |
| CS273048B1 (en) | Derivative of bis 4-quinolone-6-fluoro-3-carboxylic acid and method of its preparation | |
| JPS591489A (en) | Pyridobenzoxazine derivative | |
| US3900476A (en) | 2(2'-pyrimidylamino)quinazolines and their preparation | |
| US3647808A (en) | N-substituted diaminopyridines | |
| EP0339406A1 (en) | Quinoline-3-carboxylic acid derivatives, process for preparing the same, and composition exhibiting excellent antibacterial effect containing the same | |
| WO1987003586A1 (en) | Process for the preparation of 1-methylamino-quinoline-carboxylic acid derivatives | |
| JPH05112554A (en) | New quinolonecarboxylic acid derivative | |
| US4179509A (en) | (Substituted 2-carboxyanilino)nicotinic acids as inhibitors of allergic reactions | |
| RU2127270C1 (en) | Method of synthesis of 1-substituted-6-fluoro-4-oxo-7-(1- -piperazinyl)-1,4-dihydroquinoline-3-carboxylic acid, 1-substituted-6-fluoro-4-oxo-7-(4-substituted-1-piperazinyl)- -1,4-dihydroquinoline-3-carboxylate-boron-diacetate and a method of its synthesis | |
| JPS5929685A (en) | 7-substituted phenylpiperazino-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivative | |
| SU1041031A3 (en) | Process for preparing substituted benzonitriles | |
| US2428355A (en) | Amino-substituted acridines and method of making the same | |
| KR970003501B1 (en) | Quinolone derivatives and preparation method thereof | |
| JPH05331057A (en) | Fungicide | |
| KR840000522B1 (en) | Process for preparation of quinoline derivatives |