JPS62228063A - Quinolinecarboxylic acid derivative - Google Patents

Abstract

NEW MATERIAL:The quinolinecaboxylic acid derivative of formula I [R1 is lower alkyl, lower halogenoalkyl or lower alkylamino; Y is group of formula II (R2 and R3 are H or lower alkyl; n is 2 or 3; m is 1 or 2) or formula III (R4, R5 and R6 are H or lower alkyl; n' is 0 or 1)] and its salt. EXAMPLE:6-Fluoro-1-(2-fluoroethyl)-8-methoxy-7-(4-methyl-1-piperazinyl )-1,4-dihy dro-4-oxoquinoline-3-carboxylic acid. USE:The compound has antibacterial activity and is useful as a medicine. For example, the compound exhibits strong antibacterial activity against various kinds of pathogenic bacteria such as Gram-positive bacteria (e.g. enterococci) and Gram-negative bacteria (e.g. E.coli, dysentery bacillus, pneumobacillus, etc.). PREPARATION:The compound of formula I can be produced e.g. by reacting the compound of formula IV with the diamine compound of formula V according to the reaction formula.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel quinoline carboxylic acid derivatives useful as pharmaceuticals exhibiting antibacterial activity.

Constitution of the Invention The object compound of the present invention is a quinolinecarboxylic acid derivative represented by the general formula and a pharmacologically acceptable salt thereof.

In the above formula, R1 is a lower alkyl group, a lower alkyl group, or a lower alkylamino group, Y is a hydrogen atom or a lower alkyl group depending on the formula, n is 2 or 3, and m is 1 or 2 R4, R5 and R6 are the same or different and represent a hydrogen atom or a lower alkyl group, and n' represents 0 or 1. ].

In the general formula (1), R1 preferably represents a 100-chain or branched alkyl group having 1 to 3 carbon atoms, such as methyl, ethyl, n-propyl, and isopropyl, such as difluoro. Methyl, trifluoromethyl,
Halogenoalkyl groups having 1 to 2 carbon atoms such as 2-fluoroethyl and 2-chloroethyl, or alkylamino having 1 to 3 carbon atoms such as methylamino, ethylamino, n-propylamino, and isopropylamino. All groups shown, R2 and R3 and R4, R5
and R6 are the same or different and represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, such as methyl, ethyl, n-propyl, and isopropyl.

The compound having the general formula (1) k can be converted into a pharmacologically acceptable salt if necessary.

Such salts include acid salts of mineral acids such as hydrochlorides, hydrobromides, hydroiodides, sulfates, phosphates, methanesulfonates, ethanesulfonates, and benzenesulfones. Acid addition salts of organic acids such as acid salts, oxalates, maleates, fumarates, tartrates, citrates or alkali metal or alkali salts of carboxylic acids such as sodium salts, potassium salts, calcium salts Examples include earth metal salts. The uninvented compound +Il also exists as a hydrate, and can be converted into a compound, such as a prodrug, that is absorbed in the living body and metabolically produces the target compound.

Examples of the compound having the general formula (1) of the present invention include the following compounds.

6-20 // CH6-Q-CH3 -訃- The novel compound of the present invention having the general formula (1) can be produced, for example, according to the reaction formula shown below.

(Method A) (II) (I) (Method B) In the above formula, R1 and Y have the same meanings as defined above, and R7 represents a hydrogen atom or a lower alkyl group such as methyl or ethyl.

That is, the novel compound (I) of the present invention is the compound (II
) or its boron fluoride chelate compound (V) and 1-
It is produced by reacting several moles of diamine compound (III) in the presence or absence of a deoxidizing agent and in the presence or absence of a solvent.

As the solvent used in this reaction, aprotic polar solvents such as dimethyl sulfoxide, dimethylformamide, hexamethylphosphoric triamide, and dimethylacetamide are suitable; however, acetone, ketones such as methyl ethyl ketone, diethyl ether, and tetrahydrofuran , ethers such as dioxane, esters such as ethyl acetate, alcohols such as methanol, ethanol, n-furonognol, impropatol, butanol, and nitriles such as acetonitrile.

Examples of the deoxidizer include tertiary amines such as triethylamine, tributylamine, pyridine, picoline, lutidine, and collidine, and inorganic bases such as sodium carbonate and potassium carbonate.

The amount of the deoxidizing agent to be used is preferably equivalent to 5 times the mole of compound (II), but in the case of the above amines, it can be used in large excess as a solvent. Also, excess diamine (I
Since II) acts as a deoxidizing agent, the reaction proceeds smoothly even when no deoxidizing agent is added. The reaction is carried out at a temperature ranging from room temperature to 200°C.

After completion of the reaction, the target compound of this reaction can be obtained by treating the reaction mixture according to a conventional method, and if necessary, it can be further purified using a conventional purification method such as a recrystallization method or column chromatography.

When applying method B, first the target chelate compound (V
l) is obtained, which can be treated with a hydrous alcohol or a basic aqueous alcohol to obtain (
1)・BF3 adduct or (1) can be derived. (I)・BF3 adduct can be easily converted to C by treatment with a base.
I).

Bases used in this treatment include alkali hydroxides such as sodium hydroxide and potassium hydroxide, alkali carbonates such as sodium carbonate and potassium carbonate, or tertiary amines such as triethylamine and dimethylaminopyridine. can be given.

The thus obtained (1) or (I).BF3 adduct is converted into a desired salt according to a conventional method, if necessary.

Note that 0. The conversion reaction of compound (II') or (IV) to boron fluoride chelate compound (V) can be carried out by reacting with fluoroboric acid, for example, according to the method described in JP-A-59-67290. The compound having the general formula (1) k produced in this manner may have optical isomers or stereoisomers based on the asymmetric carbon atom of the Y moiety in its structure. In such cases, the starting material compound YH (I
The corresponding optical isomer of the target compound (I) can be obtained by carrying out the above reaction using II), or the mixture of optical isomers of compound (1) can be separated into individual optical isomers according to a conventional optical resolution method. You can get fit.

Compound (■) or (IV) which is the starting material for the above production method
is a new compound, and when R1 is a lower alkyl group or a halogeno lower alkyl group, the reaction route shown below [
C] or (Dl, and when R1 is a lower alkylamino group, is produced by reaction route CEJ.

[Route C]

(Vll) (Vl) (
DC) -20- (X) (IV) (IIa) [Route D] (IX) (XI) (Xll)
(Xllll) (XIV)
(IV) (X)
(XV)CH3 (XVI) (XVl[) (IIb
) In the above formula, R8 represents a lower alkyl group or a halogeno-lower alkyl group, R9 represents a lower alkyl group, and X represents a halogen atom such as chlorine, bromine, or iodine.

The reaction conditions and post-treatment methods for each step are detailed in Reference Examples.

Effects of the Invention The object compound of the present invention having the general formula (1)'e and its pharmacologically acceptable salts have excellent antibacterial activity. show.

Its antibacterial activity was measured by the agar plate dilution method.
Against a wide range of pathogens, including Durham-positive bacteria such as Staphylococcus aureus and Enterococcus and Durham-negative bacteria such as Escherichia coli, Shigella, Klebsiella pneumoniae, Proteus, Serratia, Enterobacter, Salmonella and Pseudomonas aeruginosa. A friend that shows strong activity.

Therefore, the compound (11) of the present invention is useful as an antibacterial agent for treating bacterial infections caused by these pathogens. Dosage forms for this purpose include, for example, tablets, capsules, granules, powders, and syrups. Examples include oral administration, such as intravenous injection, intramuscular injection, and parenteral administration, such as by planing.The dosage varies depending on age, body weight, symptoms, administration form, and number of administrations, but is usually administered to adults. Approximately 100 to 1,000 doses per day may be administered in one dose or in divided doses.

Next, the present invention will be explained in more detail with reference to Reference Examples and Examples.

2.3-Difluoro-6-nitrophenol (b) (
Known compound) 20.01 (0,114 mol) of aceto7
Dissolved in 700 ml, 18.9 g of potassium carbonate (0.1
37 mol) and methyl iodide 34. IP (0.24 mol) was added and the mixture was heated under reflux for 20 hours with stirring. Then, the solvent was distilled off under reduced pressure, the residue was extracted with ethyl acetate, the ethyl acetate layer was completely washed with water, and after drying, the solvent was completely distilled off under reduced pressure, 3.4-
Difluoro-2-methoxynitrobenzene (■)23.
(obtained as a yellow oil.

MS spectrum: m/e 189 (M+), 159
(M+-C'E(20) obtained as above 7'C3
+4'-difluoro-2-methoxynitrobenzene (
■) 23. OS' (0,114 mol) in 80% methanol 1! Dissolved in ammonium chloride 22.6 f (
0,422 mol) was added to 38.2 f' of reduced iron, and the mixture was heated under reflux for 4 hours with stirring.

Next, the reaction solution K was filtered, the F solution was concentrated under reduced pressure, and the residue was extracted with toluene. After washing the toluene layer with water and drying, the solvent was completely distilled off under reduced pressure to obtain 3,4-difluoro2-methoxyaniline (
IXllo, 29i obtained as a reddish-brown oil.

MS spectrum: m/e 159 (M+), 144 (
M+-CH5) (Reference Example 2) 6,7-difluoro-
8-Methoquinoline-3-carboxylic acid ethyl ester (
IV.

3.4-difluoro-2-methoxyaniline ■1.74
5' (0,011 mol) Niethoxymethylene diethyl malonate 2.842 (0,013 mol) was added in total, 14
The mixture was stirred at 0 to 150°C for 3 hours. Next, 2omi2 of diphenyl ether was added to the reaction mixture at 240-250°C.
Stir for hours. After cooling to room temperature, add n-hexane 100
The precipitated crystals kF were collected to obtain 1.60 g of 6,7-difluoro-4-hydroxy-8-methoxyquinoline-3-carboxylic acid ethyl ester (X) as a colorless powder.

MS, 1. Pect/l/: mle 283 (M+
), 237 (M+-c2H5oH) 6,7-difluoro-4-hydroxy-8-methoxyquinoline-3-carzenic acid ethyl ester (3) obtained as above 1.6
Or (0,0057 mocarium 1.2 Or (0
,0085 mol) and methioiodide #2.40? (0,
017 mol) f, was added and stirred at 60-65°C for 17 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and the residue was extracted with dichloromethane, washed with dichloromethane layered with water, dried, and then distilled off under reduced pressure to give 6,7-difluoro-8-methoxy-1-methyl-1,4-dihydro-4- Oxoquinoline-3-carmenic acid ethyl ester (IV, R1; methyl) 1.60
1 was obtained as a light brown powder.

MS Spect/l/: mle 297 (M”
), 225 (M+-CH outside H2-Co2) 3.4-difluoro-2-methoxyani9f Figure 10.21 (060
64 mol) was dissolved in 100 ml of toluene, and 16.2 f (0,077 mol) of trifluoroacetic anhydride was added dropwise while cooling with water. After the addition was completed, the mixture was stirred at room temperature for 2 hours, and the reaction mixture was completely concentrated under reduced pressure to obtain 03113.5 g of 3,4-difluoro-2-methoxy-N-(trifluoroacetyl)aniline as light brown needle crystals.

MS spectrum: mle 255 (M+), 186
(M+-CF3), 158 (M+-COCF3) 3,4-difluoro-2-methoxy-N-(,)lifluoroacetyl)aniline (XD3) obtained as above
．． OOg (0,012 mol) -ii DMF 50
ml.

Dissolved in potassium carbonate 2.44 ? (0,018 mol), potassium iodide of catalyst t and 1.80 f (0,014 mol) of 2-fluoroethyl bromide,
The mixture was stirred at 65°C for 5 hours. Bath medium after reaction? Distillation under reduced pressure,
The residue was extracted with ethyl acetate and subjected to silica gel column chromatography (solvent: toluene) to give 3.4- ・difluoro-N-(2-fluoroethyl)-2-methoxy-
N-()IJfluoroacetyl)aniline (X[l,
R,; 2-fluoroethyl) 0.69fi obtained as a colorless oil.

MS Spect A/: mle 301 (M+), 26
8 (M+-CH2F), 232 (M-CF3) Next, this was mixed with potassium hydroxide 0.25 F (0,00
After standing at room temperature for 5 hours, the solvent was completely distilled off under reduced pressure, and the residue was extracted with toluene to obtain 3,4-nofluoro-N-(2-fluoroethyl)-.
2-Methoxyaniline (X[lI, Rg; 2-fur, t-oethyl #) 0.45 i-obtained as a light brown oil.

MS Spectrum IT] //e2o5(M+), 190
(M+-CH5), 172 (M+-CH2F) Then 1, the 3,4-nofluoro(N-2-fluoroethyl)-2-methoxyaniline (X[[I.

RFl'2-fluoroethyl)0.45y(0,00
22%) Toethoxymethylene malonic acid No. 5
7f (0,0026 mol) at 140-150
' Oxoquinoline-3-carginic acid ethyl ester (lV
, R,: 2-fluoroethyl) 0.185''i was obtained as a colorless powder.

MS spectrum 2 m7'e 329 (M+), 284
CM" 0C2H5), 257 (M+-CH, 7CH2
-Co2) 6,7-nofluoro-1-(2-fluoroethyl)-8-methoxy-1,4-dihydro-4-
Oxoquinoline-3-cardanoic acid ethyl ester #(IV
IRg; 2-fur40ethyl) 0.181i'(0,0
O05mol)'e meta/-#15ml disoluble%, 4ti(l
! /v) 5 ml of caustic soda aqueous solution was added and left at room temperature for 5 hours. Crystals kF precipitate when acidified with concentrated hydrochloric acid
and 6,7-nofluoro-1-(2-fluoroethyl)-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carfonic acid (U,, R,: 2-fluoroethyl )0.117 as a colorless powder.

MS spectrum: m/e 301 (M+), 257 (
M”-Co2)-8-methoxy-1,4-dihydro-4
-3,4-difluoro-2- obtained in Oxo Reference Example 3
Methoxy-N-()lifluoroacetyl)aniline@
7. Of (0,027 mol) k DMF 130
Dissolved in ml, potassium carbonate 5.66 f (0,04
1 mol) and 6.397 (0,041 mol) of ethyl iodide were added and stirred at 70°C for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, the residue was extracted with ethyl acetate, and subjected to silica gel column chromatography (solvent: Toluene 7) K! +),
3.4-yfluoro-N-ethyl-2-methoxy-N-
()lifluoroacetyl)aniso7 (X[[,Rg
MS spectrum: m/e 283 (M”), 214
(M+-CF'3) Next, this was mixed with potassium hydroxide 3.
4f (0,060 mol) was dissolved in 80% methanol, and after standing at room temperature for 5 hours, the solvent was completely distilled off under reduced pressure, and the residue was extracted with toluene to obtain 3.4-,'fluoro-N-ethyl-2-methoxyaniline. (X[[1,E(8:Ether)) Obtained as a 5.5ft reddish brown oil.

MS Spect/l/: m/e 187 (M”)
, 172 (M+-CR2) then this compound 4.0
f (0,021 mol) and 5.54 r (0,026 mol) of noethyl ethoxymethylene malonate at 150 to 1
Heat separately at 60°C for 9 hours, cool to room temperature, and add acetic anhydride 4
2 m/j and 18 mA of concentrated sulfuric acid were sequentially added, and the mixture was left at room temperature for 1 hour. The reaction mixture was pressurized into ice water, the precipitated crystals fF were collected, and 6,7-difluoro-1-ethyl-8-methoxy-
1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester (IVIR8; ethyl) 2.099'
i Obtained as a colorless powder.

MS Spect/l/: m/e 311 (M+),
239 (M -CH2=CH2-Co2)oxoquinoline-3-carboxylic acid (■b, ~: Me6.7-difluoro-4-hydroxy-8-methoxyquinoline-3-carboxylic acid ethyl ester (X) 1. 13 f (0,00
4 mol) dissolved in DMF 2 ON, potassium carbonate 1.
10 f (0,008 mol) was added and stirred at room temperature for 3 hours. Then 0-(2°4-dinitrophenyl)hydroxylamine 0,81? (0,0041 mol)
was added and stirred at room temperature for 6 hours. After the reaction was completed, the solvent was distilled off under reduced pressure, and the residue was washed with water and ethanol in that order. The entire solid obtained was extracted with chloroform, and the chloroform was distilled off under reduced pressure to obtain 1-amino-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester ( XV) 0.62 f'e
Obtained as an ocher powder book.

MS Spect/l/: m/e 298(M”)I
R spectrum (KBr, crn), 3380
,3200.172ONMR spectrum (CDCt,
, δ): 1.38 (3) 1, t, -0CH2
C5) -3 go 4.23 (3I (, d, -0CH3) 4.32 (2H, q, -0CH2CH5) 6.0
1 (2H, S, -NNH2) 7.88 (1) 1.
d, ci, H at 5th position) 8.48 (IH, s, H at 2nd position) Acetic anhydride 3.8ml. (0.04 mol) vc, 1.5 ml of formic acid (0.04 mol) was added dropwise under ice cooling, stirred for 15 minutes, and further stirred at 50°C for 15 minutes. To this solution was added 1-amino-6,7-tunluoro-8-methoxy-1,4-dihydro-4-oxoquinoline-3 obtained as described above.
-Carboxylic acid ethyl ester (XV) 0.6 r (
(J, 002 mol) dissolved in formic acid 4.2 ml (0,11 mol) #'? was added dropwise while cooling with water, and the mixture was stirred at room temperature for 9 hours.

After the reaction was completed, the solvent was distilled off under reduced pressure, and the residue was washed with water and ether in order to obtain 6,7-nofluoro-1-(formylaminoco-8-methoxy-1°4-dihydro-4-oxoquinoline-3-carboxylic acid). Acid ethyl ester (XVI) 0.
6t2 Obtained as a pale yellow powder.

3S-R spectrum (KBr, cm-') 1700~
1725, 1614NMR,', Pect# CDMS
O-d6-CDCl3. δ):♀ 1.39 (3H, t, -COCI(20H3)7.
97 (IH, d4.5 position H) 8.38 (IH, bs, -NHCHO) 9.4
1 (2H, bs, -NHCHO+ 2-position H) 6,7-difluoro-1-(formylamino)-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carvone obtained as above Acid ethyl ester (Xvl)
0.6? (0,0018 mol) kDMF 8
m1vc dissolved, potassium carbonate 0.51 f (0,00
37 moles) and methyl iodide 0.78 f (0,005
2 mol) was added thereto and stirred at room temperature for 3 hours. After the reaction is complete,
The entire solvent was distilled off under reduced pressure, the residue was extracted with chloroform, the entire chloroform layer was washed with water, dried, and then distilled off under reduced pressure to give 6,7-nofluoro-1-(N-formylmethylamino)-8-methoxy-1,4-dihydro. -4-oxoquinoline-3-carboxylic acid ethyl ester (XJ, R2: methyl) 0.5
f ffi Obtained as a colorless powder.

MS spectrum: m/e 340 (M) 268
(M-CH2=CH2-Co2) Ethyl 6,7-nofluoro-1-(N-formylmethylamino)-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate obtained as above Ester (XVII, R2
: methyl) 0.505' (0,0015 mol) f ethanol-# Dissolved in 10 ml, IN NaOH4.5 ml (
0,0045 mol) was added and stirred at room temperature for 2 hours.

After the reaction is complete, collect the crystals KF that precipitates as acidic with acetic acid,
0.35 ml of 6.7-difluoro-8-methoxy-1-(methylamine)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (nb, R9: methylamino) was obtained as a colorless powder. .

MS Spect/L/: m/e 284 (M)2
40 (M-Co2) NMR spectrum (CDCl3.δ): 2.90 (3H
, d, -NHCH5) 4.30 (3H, d, -0CH3) 6.69 (IH
, q, -side 5H3) 8.10 (IH, d4, 5th position H) 8.83 (IH, s, 2nd position H) 14.33 (IH, s, -COOH) 6 obtained in Reference Example 3 , 7-difluoro-1-(2-fluoroethyl)-8-methoxy-1,4-dihydro-4
-oxoquinoline-3-carboxylic acid 0.117 (0,0
004 mol) and N-methylbiperazine 0.2C1 (0,
002 mol) Total trimethyl sulfoxide 3 ml. and stirred at 70°C for 6 hours.

After the reaction, the solvent and excess N-methylpiperazine were distilled off under reduced pressure at the same temperature, and the residue was washed with all ethyl acetate to obtain a pale yellow powder. This total ethanol is 2Qm/! and concentrated hydrochloric acid 1mB
After suspending it in a mixed solution, it was concentrated under reduced pressure and 20ml of water was added to the residue.
In addition, the insoluble matter was removed, the F solution was concentrated under reduced pressure, and the obtained crystals were washed with ethanol to obtain the desired 6-fluoro-1.
-(2-fluoroethyl)-8-methoxy-7-(4-
Methyl-1-piperazinyl)-1,4-dihydro-4
-Oxoquinoline-3-carboxylic acid hydrochloride 30 kg was obtained as a completely colorless powder.

mp, 270-272℃ (decomposition) MS spectrum/
l/: m/e 381 (M"), 337 CM"
-Co2) NMR spectrum (DMSO-d6.δ):
285 (3H1S, N-CF2) 4, 65-5.10 (4H9m, N-CH2CH2
-F) 7.90 (LH, d, H at 5th position) 8.90 (IH, s, H at 2nd position) Elemental analysis: Cl8H21F2N304・HCl・2H2
CHN as 0 Theoretical value 47.63 5.77 9.26 Width measurement value 47.95 5.26 9.28 %
-methoxy-7-(4-methyl-1-pipera') 6,7-difluoro-1-ethyl-8-methoxy-1,4-dihydro-4-oxoquinoline-3- obtained in Reference Example 4
Carzenic acid ethyl ester 0.40 f (0,001
Crystals of 42% borofluoride (3 mol) were collected and washed with water. This was photo-dried, then dissolved in 4 ml of dimethyl sulfoxide, and 0.7 r of N-methylbiperazine (
0,007 mol) was added to the chelate compound (yellow crystals f
f1F was collected, suspended in 100 mJ of 80-thimethanol, and heated under reflux for 4 hours with stirring. The reaction solution was filtered while hot to remove insoluble materials, and the solution F was concentrated under reduced pressure. The resulting crystals were washed with ethanol to obtain the desired 1-ethyl-6-)luoro 8.
-methoxy-7-(4-methyl-1-piperazinyl)
50 μ of a boron trifluoride adduct of -1,4-dihydro-4-oxoquinoline-3-caldic acid was obtained as a colorless powder.

mp, 186-192℃ (decomposition) MS spec) k: m/e 363 (M”), 3
19(M”-Co2) NMR spectrum (DMSO-d
6. δ): 1.34(3I(,t,N-CHζ3)2
-80 (3H, s, N-CH5)3.85 (3H
,s --OCH3)4.69(2H,q,N-tsuCH
3) 7.86 (IH, d, H at 5th position) 8.90 (IH, s, H at 2nd position) Elemental analysis: CH as Cl8H22FN604・BF3
N Theoretical value 50.14 5.14 9.75 % Measured value 49.84 5.44 9.60 %-Methoxy-7-(4-methyl-T1-biperazini/L/)-1
14-dihydro-4-oxoquinoline-3-carzenic acid 1-ethyl-6-fluoro-8-methoxy-7-(4-methyl-1-piperazinyl)-1, obtained by the method described in Example 2. 4-dihyP-low 4-oxoquinoline-
3-Cardinic acid boron trifluoride adduct 130η (0,0
003 mol) in 30 ml of water, IN NaOHO
, 36ml K was added, and the reaction solution was concentrated under 41 pressures to obtain a crystal of total ethanol. After concentrating, the desired l-ethyl-6-fluoro-8-methoxy-7-(4-methyl-
70 μl of 1-piper')-1,4-dihydro-4-oxoquinoline-3-carginic acid was obtained as a light brown powder.

mp, 207-209°C (decomposed) MS spectrum: m/e 363 (M”), 319 (
M''-Co2) NMR spectrum (DMSO-d6-C
DC43, δ) = 1.34 (3H, t, N-CH
2CH5)2-47 (3HIs, N-CH5)3-
85 (3H, s -0-CH3)4.69 (2E(
, q, N-CH2CH5)'7.86(
IH, a, H at 5th position) 8.86 (IH, s, H at 2nd position) Elemental analysis: C as Cl8H22FN304/3H20
HN Theoretical value 51.79 6.76 10.07 % Measured value 51,89 6,58 9.93 [Example 4] The chelate compound obtained in Example 2 (Vll (yellow crystal) 200 mm (0, 00046 mol) to triethylamine y
Q, 5ml 2 containing 80cmeta/#501+
The mixture was stirred and heated under reflux for 6 hours. The reaction solution was filtered while hot to remove insoluble matter, and the filtrate was concentrated under reduced pressure. The resulting crystals were washed with ethanol to obtain the desired l-ethyl-6-fluoro-8-meth)oxy-7-(4 -Methyl-1-piperazinyl) -1,4-dihydro-4-oxoquinoline-
901 ng' of 3-calgenic acid was obtained as a light brown powder.

This compound was confirmed to be the same as the compound obtained in Example 3 by mp, MS spectrum, NMR spectral and elemental analysis.

[Examples 5 to 26] The following compounds were synthesized by the method of Example 1, 2.3 or 4.

Claims (1)

[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R_1 represents a lower alkyl group, halogeno lower alkyl group, or lower alkylamino group, Y is the formula ▲ Numerical formula, chemical formula, table, etc. There is a ▼ group (in the formula, R_2 and R_3 are the same or different and represent a hydrogen atom or a lower alkyl group, n represents 2 or 3, and m represents 1 or 2) or a formula ▲ Numerical formula, chemical formula, table ▼ group (wherein R_4, R_5 and R_6 are the same or different and represent a hydrogen atom or a lower alkyl group, and n' represents 0 or 1). ] A quinoline carboxylic acid derivative and a pharmacologically acceptable salt thereof.