EP0329719A1 - Process for the preparation of quinoline carboxylic acid derivatives - Google Patents
Process for the preparation of quinoline carboxylic acid derivativesInfo
- Publication number
- EP0329719A1 EP0329719A1 EP88904603A EP88904603A EP0329719A1 EP 0329719 A1 EP0329719 A1 EP 0329719A1 EP 88904603 A EP88904603 A EP 88904603A EP 88904603 A EP88904603 A EP 88904603A EP 0329719 A1 EP0329719 A1 EP 0329719A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- general formula
- compound
- hydrogen
- process according
- stands
- Prior art date
- 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.)
- Ceased
Links
Classifications
-
- 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
Definitions
- This invention rel ates to a new process for the preparation of 1-substituted-7-(optionally substituted piperazine )-6-f luoro-8-(optionally fl uoro-substituted)-4-oxo-1 , 4- dihydro-quinoline-3-carboxylic acid derivatives of the general Formula I
- R 1 stands for phenyl being optionally substituted by 1 or 2 halogen atoms, or a group of the general Formula - -CH 2 CR 6 R 7 R 8 (wherein R 6 , R 7 and R 8 stand for hydrogen or halogen);
- R 2 stands for piperazlnyl or 4-methyl-piperazinyl;
- R 3 stands for hydrogen or fluorine.
- These compounds can be prepared by reacting 1-substituted phenyl-6-fluoro-7-chloro-4- oxo-1,4-dihydro-quinoline-3-carboxylic acid and cyclic amines in the presence of a solvent at a temperature of 100 °C for 20 hours (European patent specification 131839, J . Med. Chem. 1985, 1558., J . Med. Chem. 1987. 504.).
- acetone methyl ethyl ketone
- an ether e.g. dioxane, tetrahydrofuran, diethyl ether
- an ester e.g. ethyl acetate, methyl acetate, ethyl propionate
- a sulfoxide e.g. dimethyl sulfoxide
- an alcohol e.g. methanol, ethanol, 1-decanol, butanol
- an organic or inorganic base may be used. From the group of organic bases trialkyl amines (e.g. triethyl amine, tributyl amine), cyclic amines (e.g. pyridine, 1,5-diazabicyclo/5,4,0/undec-5-ene, 1,5-diazabicyclo/4.3.0/- non-5-ene, 1,4-diazabicyclc/2.2.2/octane) can be mentioned, while as inorganic base preferably hydroxides or carbonates of alkali or alkaline earth metals can be applied.
- acid binding agent advantageously potassium carbonate, potassium hydrogen carbonate, sodium hydroxide, calcium hydroxide, etc. or an excess of the amine of the general Formula III can be used.
- the boron derivative of the general Formula II and the amine of the general Formula III can be reacted at a temperature between 0 and 200 °C, depending on the solvent used.
- the reaction time may vary between half an hour and 10 hours. The reaction time depends on the reaction temperature, too. If the reaction is carried out at higher temperature, the reaction time can be shortened.
- the above reaction conditions are preferable values and other conditions may be used as well.
- the compounds of the general Formula IV can be hydrolysed to the desired quinoline-3-carboxylic acids of the general Formula I, after or without isolation, under acidic or basic conditions.
- the compound of the general Formula IV pre verted into pharmaceu tically acceptable salts thereof in a known manner.
- acid addition salts can be formed, e.g. salts formed with hydrogen halides, sulfonic acids, sulfuric acid or organic acids.
- One may form preferably chlorides, bromides, aryl sulfonates, methane sulfonates, maleates, fumarates, benzoates, etc.
- the compounds of the general Formula I form salts with alkali or alkaline earth metals or other metal ions as well. Accordingly the sodium, potassium, magnesium, silver, copper salts, etc. may be prepared.
- the compounds of the general Formula I and pharmaceutically acceptable salts thereof can be converted into hydrates (e.g. hemihydrates, trihydrates, etc.) by methods known per se.
- the starting materials of the general Formula II can be prepared by reacting 1-phenyl-6-fluoro-7-chloro-4-oxo-1,4- dihydro-quinoline-3-carboxylic acid (European patent specification 131.839) or 1-ethyl-6,7,8-trifluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (GB patent specification 2.057.440) with a boron derivative (e.g. with a compound of the general Formula V
- R is halogen or an aliphatic acyloxy group containing 2 to 6 carbon atoms or an aromatic acyloxy group containing 7 to 11 carbon atoms
- fluoroborate in aqueous or in organic medium.
- Example 2 1.06 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-0 3 ,0 4 )-bis- (propionato-0)-boron are reacted with 0.64 g of piperazine in 4 ml of dimethyl sulfoxide. A 6 w /v% of aqueous solution of 6.3 ml of sodium hydroxide are added and the reaction mixture is refluxed for an hour. After filtration the pH value is adjusted to 7 with 96 w /v% acetic acid, 10 ml of water are added and the reaction mixture is cooled overnight. The precipitated crystals are filtered, washed with water and dried.
- Example 3 1.06 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-0 3 ,0 4 )-bis- (propionato-0)-boron are reacted with 0.75 g of 1-methyl-piperazine. Thus 0.79 g of 1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo- 7-(1-methyl-piperazino)-quinoline-3-carboxylic acid are obtained. M.p. is 239-240 °C.
Abstract
Nouveau procédé pour la préparation de composés de formule générale (I) (où R1 représente un phényle éventuellement substitué par 1 ou 2 atomes d'halogène, ou un groupe de formule générale CH2CR6R7R8 (dans laquelle R6, R7 et R8 représentent un hydrogène ou un halogène); R2 est pipérazinyle ou 4-méthyle-pipérazinyle; R3 est hydrogène ou fluor) et de leurs sels pharmaceutiquement acceptables. Ce procédé consiste à faire réagir un composé de formule générale (II) (dans laquelle R est un halogène ou groupe acyloxy aliphatique contenant de 2 à 6 atomes de carbone ou bien un groupe acyloxy aromatique contenant de 7 à 11 atomes de carbone, R4 est fluor ou chlore) avec un dérivé de pipérazine de formule générale (III) ( où R5 est hydrogène ou méthyle ou bien son sel et à soumettre le composé ainsi obtenu de formule générale (IV) (où R, R1, R2 et R3 ont les notations précitées) à une hydrolyse après ou sans isolation, et si on le désire, à convertir le composé de formule générale (I) ainsi obtenu en son sel ou à libérer ledit composé de son sel. Les composés de formule générale (I) sont des agents antibactériens connus. L'avantage du procédé décrit est qu'il permet d'obtenir les composés désirés de formule générale (I) de manière simple, avec des rendements élevés et un temps de réaction court.New process for the preparation of compounds of general formula (I) (where R1 represents a phenyl optionally substituted by 1 or 2 halogen atoms, or a group of general formula CH2CR6R7R8 (in which R6, R7 and R8 represent a hydrogen or a halogen); R2 is piperazinyl or 4-methyl-piperazinyl; R3 is hydrogen or fluorine) and their pharmaceutically acceptable salts. This process consists in reacting a compound of general formula (II) (in which R is a halogen or aliphatic acyloxy group containing from 2 to 6 carbon atoms or else an aromatic acyloxy group containing from 7 to 11 carbon atoms, R4 is fluorine or chlorine) with a piperazine derivative of general formula (III) (where R5 is hydrogen or methyl or else its salt and to subject the compound thus obtained of general formula (IV) (where R, R1, R2 and R3 have the aforementioned notations) to hydrolysis after or without isolation, and if desired, to convert the compound of general formula (I) thus obtained into its salt or to release said compound from its salt. The compounds of general formula (I) are known antibacterial agents The advantage of the process described is that it makes it possible to obtain the desired compounds of general formula (I) in a simple manner, with high yields and a short reaction time.
Description
PROCESS FOR THE PREPARATION OF QU INOL INE CARBOXYL IC ACID DERIVATIVES
This invention rel ates to a new process for the preparation of 1-substituted-7-(optionally substituted piperazine )-6-f luoro-8-(optionally fl uoro-substituted)-4-oxo-1 , 4- dihydro-quinoline-3-carboxylic acid derivatives of the general Formula I
and pharmaceutically acceptable salts thereof.
In the general Formula I R1 stands for phenyl being optionally substituted by 1 or 2 halogen atoms, or a group of the general Formula - -CH2CR6R7R8 (wherein R6, R7 and R8 stand for hydrogen or halogen); R2 stands for piperazlnyl or 4-methyl-piperazinyl; R3 stands for hydrogen or fluorine.
It is known that a group of the 7-sυbstituted- carboxylic derivatives of the general Formula I (wherein R2 stands for piperazinyl, 4-methyl-piperazinyl, R1 stands for a group of the general Formula -CH2CR6R7R8 (wherein R6, R7 and R8 stand for hydrogen or halogen) and R3 stands for fluorine) possesses high antibacterial activity (J.Med. Chem. 1986, 29 ,
445; Drugs of Fut. 1984, 9 , 246; 23rd Intersci. Conf. Antimicrob. Agents Chemother. 1983, Abst . 658, 7th Int. Symp. Fut. Trends Chemother. 1986, 86). These compounds can be prepared by reacting 6,7,8-trifluoro-4-cxo-1,4-dihydro-quinoline-3- carboxylic acid and cyclic amines (Belgian patent specification 887874, GB patent specification 2057444, Austrian patent specification 537813 and European patent specification 1064489).
Another group of the 7-substituted-quinoline-3- carboxylic acids of the general Formula I (wherein R1 stands for phenyl optionally substituted by 1 or 2 halogen atoms, R2 stands for piperazinyl or 4-methyl-piperazinyl and R3 stands for hydrogen) has also high antibacterial activity (24th Intersci. Conf. Antimicrob. Agents Chemother, 1984, Abst. 72- 78., Amtimicrob. Agents Chemother. 1987., 619, Antimicrob. Agents Chemother. 1906., 192-208). These compounds can be prepared by reacting 1-substituted phenyl-6-fluoro-7-chloro-4- oxo-1,4-dihydro-quinoline-3-carboxylic acid and cyclic amines in the presence of a solvent at a temperature of 100 °C for 20 hours (European patent specification 131839, J . Med. Chem. 1985, 1558., J . Med. Chem. 1987. 504.).
According to the present invention there is provided a new process for the preparation of quinoline-3-carboxylic acid derivatives of the general Formula I (wherein R1 stands for phenyl optionally substituted by 1 or 2 halogen atoms, or a group of the general Formula -CH2CR6R7R8 (wherein R6, R7 and R8 stand for hydrogen cr halogen), R2 stands for piperazinyl, 4-methyl-piperazinyl and R3 stands for hydrogen or fluorine)
and pharmaceutically acceptable salts thereof which comprises reacting a compound of the general Formula II
(wherein R stands for halogen, an aliphatic acyloxy group containing 2 to 6 carbon atoms or aromatic acyloxy group containing 7 to 11 carbon atoms, R4 stands for fluorine or chlorine, R1 and R2 are as stated above) with an amine of the general Formula III
(wherein R5 stands for hydrogen or methyl) or a salt thereof and subjecting the compound of the general Formula IV
acetone, methyl ethyl ketone), an ether (e.g. dioxane, tetrahydrofuran, diethyl ether), an ester (e.g. ethyl acetate, methyl acetate, ethyl propionate), a sulfoxide (e.g. dimethyl sulfoxide), an alcohol (e.g. methanol, ethanol, 1-decanol, butanol) may be used.
As acid binding agent an organic or inorganic base may be used. From the group of organic bases trialkyl amines (e.g. triethyl amine, tributyl amine), cyclic amines (e.g. pyridine, 1,5-diazabicyclo/5,4,0/undec-5-ene, 1,5-diazabicyclo/4.3.0/- non-5-ene, 1,4-diazabicyclc/2.2.2/octane) can be mentioned, while as inorganic base preferably hydroxides or carbonates of alkali or alkaline earth metals can be applied. Thus as acid binding agent advantageously potassium carbonate, potassium hydrogen carbonate, sodium hydroxide, calcium hydroxide, etc. or an excess of the amine of the general Formula III can be used.
The boron derivative of the general Formula II and the amine of the general Formula III can be reacted at a temperature between 0 and 200 °C, depending on the solvent used. The reaction time may vary between half an hour and 10 hours. The reaction time depends on the reaction temperature, too. If the reaction is carried out at higher temperature, the reaction time can be shortened. The above reaction conditions are preferable values and other conditions may be used as well.
The compounds of the general Formula IV can be hydrolysed to the desired quinoline-3-carboxylic acids of the general Formula I, after or without isolation, under acidic or basic conditions. The compound of the general Formula IV pre
verted into pharmaceu tically acceptable salts thereof in a known manner. Thus preferably acid addition salts can be formed, e.g. salts formed with hydrogen halides, sulfonic acids, sulfuric acid or organic acids. One may form preferably chlorides, bromides, aryl sulfonates, methane sulfonates, maleates, fumarates, benzoates, etc. The compounds of the general Formula I form salts with alkali or alkaline earth metals or other metal ions as well. Accordingly the sodium, potassium, magnesium, silver, copper salts, etc. may be prepared.
The compounds of the general Formula I and pharmaceutically acceptable salts thereof can be converted into hydrates (e.g. hemihydrates, trihydrates, etc.) by methods known per se.
According to a further aspect of the present invention there are provided new compounds of the general Formula IV (wherein R, R1, R2 and R3 are as stated above).
The starting materials of the general Formula II can be prepared by reacting 1-phenyl-6-fluoro-7-chloro-4-oxo-1,4- dihydro-quinoline-3-carboxylic acid (European patent specification 131.839) or 1-ethyl-6,7,8-trifluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (GB patent specification 2.057.440) with a boron derivative (e.g. with a compound of the general Formula V
(wherein R is halogen or an aliphatic acyloxy group containing
2 to 6 carbon atoms or an aromatic acyloxy group containing 7 to 11 carbon atoms) or with fluoroborate in aqueous or in organic medium.
Further details of the present invention are to be found in the following Examples without limiting the scope of protection to the said Examples.
Example 1
1.59 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo- quinoline-3-carboxylate-03,04)-difluoro-boron are reacted with 1.29 g of piperazine in 8 ml of dimethyl sulfoxide at 100 °C for 3 hours. A 6 w/v% aqueous solution of 12.6 ml of sodium hydroxide are added and hydrolysis is carried out by heating for 2 hours. The reaction mixture is filtered, the pH value is adjusted to 7 with 96 w/v% acetic acid and diluted with 15 ml of water. The crystalline reaction mixture is cooled overnight and the precipitated crystals are filtered, washed with water and dried. Thus 1.61 g of 1-ethyl-6,8-difluoro-1,4-dihydro-4- oxo-7-piperazino-quinoline-3-carboxylic acid are obtained. M.p. is 234-236 °C.
Analysis for the Formula C 16H 17F2N 3O3 : Calculated: C=56.90% H=5.07% N=12.45% Found: C=56.75% H=5.02% N=12.48%.
Example 2
1.95 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate-03,04)-bis(diacetate-0)-boron are reacted with 1.29 g of piperazine in 8 ml of dimethyl sulfoxide at 110 °C for 2 hours. A 3 w/v% aqueous solution of 20 ml of 3 w/v% sodium hydroxide are added. The reaction mixture is re- fluxed for an hour whereupon filtered and the pH value is adjusted to 7 with 96 w/v% acetic acid. After cooling and diluting with 10 ml of water the precipitated crystals are filtered and dried. Thus 1.59 g of ochre coloured 1-ethyl-6,8- difluoro-1,4-dihydro-4-oxo-7-piperazino-quinoline-3-carboxylic acid are obtained. M.p. is 234 °C.
Analysis for the Formula C 16H 17F2N 3O3 : Calculated: C=56.90% H=5.07% N=12.45% Found: C=57.03% H=5.11% N=12.51%.
Example 3
According to Example 2 1.06 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-03,04)-bis- (propionato-0)-boron are reacted with 0.64 g of piperazine in 4 ml of dimethyl sulfoxide. A 6 w/v% of aqueous solution of 6.3 ml of sodium hydroxide are added and the reaction mixture is refluxed for an hour. After filtration the pH value is adjusted to 7 with 96 w/v% acetic acid, 10 ml of water are added and the reaction mixture is cooled overnight. The precipitated crystals are filtered, washed with water and dried.
Example 6
According to Example 3 1.06 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-03,04)-bis- (propionato-0)-boron are reacted with 0.75 g of 1-methyl-piperazine. Thus 0.79 g of 1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo- 7-(1-methyl-piperazino)-quinoline-3-carboxylic acid are obtained. M.p. is 239-240 °C.
Analysis for the Formula C17H19F2N3O3 : Calculated: C=58.10% H=5.45% N=11.91% Found: C=57.95% H=5.37% N=11.90%.
Example 7
0.46 g of 1-(4'-fluoro-phenyl)-6-fluoro-7-chloro-1,4- dihydro-4-oxo-quinoline-3-carboxylate-03,04)-bis(acetato-0)- boron are reacted with 0.6 g of N-methyl-piperazine in 5 ml of dimethyl sulfoxide at 110 °C for an hour. 10 ml of 5 w/v%. aqueous sodium hydrogen carbonate solution are added, the reaction mixture is refluxed for 2 hours whereupon the pH value is adjusted to 7 with 96 w/v% acetic acid. The reaction mixture is cooled and the precipitated crystals are filtered and washed with cold water. Thus 3.54 g of 1-(4'-fluorophenyl)-6-fluoro-7-(N-methyl-piperazinyl)-1,4-dihydro-4-oxo- quinoline-3-carboxylic acid are obtained. M.p. is 282-284 °C. The carboxylic acid thus obtained is dissolved in a weak solution of hydrochloride acid under heating, the solution is evaporated in vacuo and thus the hydrochloric salt of 1-(4'-
r
: 7
Claims
1. Process for the preparation of compounds of the general Formula I
(wherein
R1 stands for phenyl being optionally substituted by 1 or 2 halogen atoms, or a group of the general Formula - CH2CR6R7R8 (wherein R6, R7 and R8 stand for hydrogen or halogen);
R2 stands for piperazinyl or 4-methyl-piperazinyl;
R3 stands for hydrogen or fluorine) and pharmaceutically acceptable salts thereof which comprises reacting a compound of the general Formula II
thus obtained (wherein R, R1, R2 and R3 are as stated above) to hydrolysis after or without isolation and if desired converting the compound of the general Formula I thus obtained into a salt thereof or setting free the same from its salt.
2. Process according to Claim 1 which comprises reacting a compound of the general formula II with an amine of the general Formula III in the presence of an organic solvent, preferably an acid amide, sulfoxide, ketone, alcohol, ether or ester.
3. Process according to Claim 2 which comprises using dimethyl sulfoxide as organic solvent.
4. Process according to Claim 1 which comprises carrying out the reaction of the compounds of the general Formulae II and III in the presence of an acid binding agent.
5. Process according to Claim 4 which comprises using an amine or an excess of the compound of the general Formula VI as acid binding agent.
6. Process according to Claim 1 which comprises carrying out the hydrolysis in acidic medium.
7. Process according to Claim 6 which comprises carrying out the reaction by using an organic or inorganic acid, preferably hydrochloric acid, sulfuric acid or acetic a c i ci .
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU285887A HU200175B (en) | 1987-06-24 | 1987-06-24 | Process for producing quinolinecarboxylic acid derivatives |
| HU285887 | 1987-06-24 | ||
| HU873146A HU199822B (en) | 1987-07-10 | 1987-07-10 | Process for production of derivatives of quinoline carbonic acid |
| HU314687 | 1987-07-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0329719A1 true EP0329719A1 (en) | 1989-08-30 |
Family
ID=26317564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP88904603A Ceased EP0329719A1 (en) | 1987-06-24 | 1988-05-20 | Process for the preparation of quinoline carboxylic acid derivatives |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0329719A1 (en) |
| JP (1) | JP2693988B2 (en) |
| KR (1) | KR970005911B1 (en) |
| CN (1) | CN1025028C (en) |
| CA (1) | CA1325010C (en) |
| CS (1) | CS274677B2 (en) |
| DK (1) | DK84089D0 (en) |
| ES (1) | ES2006994A6 (en) |
| FI (1) | FI91400C (en) |
| WO (1) | WO1988010253A1 (en) |
| YU (1) | YU46570B (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4562852A (en) * | 1984-08-20 | 1986-01-07 | Britt Franklin J | Safety valve |
| US4606367A (en) * | 1985-04-04 | 1986-08-19 | Britt Franklin J | Apparatus and method for relieving pressure within a high pressure tank |
| HU198709B (en) * | 1987-04-08 | 1989-11-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing quinoline-carboxylic acid derivatives |
| IL119476A (en) * | 1990-09-11 | 1999-10-28 | Schering Corp | Process for preparing acetals and hemi-acetals |
| US5869661A (en) * | 1991-07-16 | 1999-02-09 | Chugai Seiyaku Kabushiki Kaisha | Method of producing a quinolonecarboxylic acid derivative |
| JP3165742B2 (en) * | 1991-07-16 | 2001-05-14 | 中外製薬株式会社 | Method for producing quinolone carboxylic acid derivative |
| ES2049636B1 (en) * | 1992-04-15 | 1994-12-16 | Genesis Para La Investigacion | PROCEDURE FOR THE PREPARATION OF QUINOLINCARBOXILIC ACID DERIVATIVES. |
| ES2077490B1 (en) * | 1992-11-18 | 1996-10-16 | Marga Investigacion | TRIMETILSILILIC ESTERS AND SOLVATES OF CHELATES OF QUINOLIN-3-CARBOXYL ACIDS. PREPARATION AND APPLICATION TO THE QUINOLON PROCESS. |
| ES2092963B1 (en) * | 1995-04-12 | 1997-12-16 | Sint Quimica Sa | PROCEDURE FOR THE PREPARATION OF ACID 1-CICLOPROPIL-6-FLUORO-1, 4-DIHIDRO-7- (1S, 4S) -5-METHYL-2,5-DIAZABICICLO (2.2.1) HEPT-2-IL) -4 -OXO-3-QUINOLINCARBOXILICO AND ITS SALTS. |
| ES2095809B1 (en) * | 1995-07-27 | 1997-12-16 | Sint Quimica Sa | PROCEDURE FOR THE PREPARATION OF NAFTIRIDIN CARBOXYLIC ACIDS AND THEIR SALTS. |
| FR2916446B1 (en) | 2007-05-24 | 2009-08-21 | Biocodex Sa | NOVEL PROCESS FOR SYNTHESIZING FLUOROQUINOLONES |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59122470A (en) * | 1982-12-27 | 1984-07-14 | Dai Ichi Seiyaku Co Ltd | Preparation of quinoline-3-carboxylic acid derivative |
| NZ208470A (en) * | 1983-07-18 | 1988-06-30 | Abbott Lab | 6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid derivatives and antibacterial compositions containing such |
-
1988
- 1988-05-20 EP EP88904603A patent/EP0329719A1/en not_active Ceased
- 1988-05-20 WO PCT/HU1988/000036 patent/WO1988010253A1/en not_active Application Discontinuation
- 1988-05-20 KR KR1019890700325A patent/KR970005911B1/en not_active IP Right Cessation
- 1988-05-20 JP JP63504328A patent/JP2693988B2/en not_active Expired - Lifetime
- 1988-06-14 CS CS412388A patent/CS274677B2/en unknown
- 1988-06-21 ES ES8801926A patent/ES2006994A6/en not_active Expired
- 1988-06-23 YU YU121788A patent/YU46570B/en unknown
- 1988-06-23 CA CA000570183A patent/CA1325010C/en not_active Expired - Fee Related
- 1988-06-24 CN CN88103892A patent/CN1025028C/en not_active Expired - Fee Related
-
1989
- 1989-02-15 FI FI890723A patent/FI91400C/en not_active IP Right Cessation
- 1989-02-23 DK DK084089A patent/DK84089D0/en not_active Application Discontinuation
Non-Patent Citations (1)
| Title |
|---|
| See references of WO8810253A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CS412388A2 (en) | 1990-11-14 |
| KR970005911B1 (en) | 1997-04-22 |
| FI91400C (en) | 1994-06-27 |
| YU121788A (en) | 1989-12-31 |
| JPH02500366A (en) | 1990-02-08 |
| ES2006994A6 (en) | 1989-05-16 |
| JP2693988B2 (en) | 1997-12-24 |
| CA1325010C (en) | 1993-12-07 |
| CN1025028C (en) | 1994-06-15 |
| DK84089A (en) | 1989-02-23 |
| FI890723A (en) | 1989-02-15 |
| DK84089D0 (en) | 1989-02-23 |
| CS274677B2 (en) | 1991-09-15 |
| CN1032166A (en) | 1989-04-05 |
| KR890701564A (en) | 1989-12-21 |
| FI91400B (en) | 1994-03-15 |
| WO1988010253A1 (en) | 1988-12-29 |
| FI890723A0 (en) | 1989-02-15 |
| YU46570B (en) | 1993-11-16 |
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