NO881121L - 5-SUBSTITUTED QUINOLON AND NAFTYRIDON CARBOXYLIC ACID DERIVATIVES. - Google Patents

Abstract

6-Substituted quinolone and naphthyryldone carboxylic acid derivatives of formula (I). where. X means fluorine or chlorine. T can i.a. means aalno, possibly down amlno, bydroxy or methoxy substituted alkylalno down 1-4 carbon atoms, dlalkylalno with 1-4 carbon atoms per. alkyl group,. Rkan.a. mean methyl, ethyl, propyl, isopropyl,. cyclopropyl, vinyl,. Rkan.a. mean hydrogen, alkyl down 1-4 carbon atoms ,. R represents methyl or a cyclic amino group ,. A can i.a. The process for their preparation as well as antibacterial agents and excipients containing these compounds are discussed.

Description

The invention relates to 5-substituted quinolone and naphthyridone carboxylic acid derivatives, a process for their preparation as well as antibacterial agents and additives containing these.

A number of patent applications have already been announced in which

5-Aminoquinolone carboxylic acids are required to be protected as antibacterial agents. The Japanese patent application 57 149 296 relates to pyridobenzoxazine derivatives with the following structure (1),

in which

R<1> means an amino residue and

R<2> means hydrogen or alkyl.

The introduction of the amino group takes place by nitration of the pyrdiobenzoxazine and the nitro group is then reduced to the amino group.

Also the 5-aminoquinolone carboxylic acids included in the European application 172 651, the South African patent application 8 502 369, and the Japanese patent application 58 174 367 are prepared from 5-nitroquinolone carboxylic acids which must first of all be prepared from suitable nitroaromatics.

It has now been found that 5-substituted quinolone and naphthyridone carboxylic acid derivs. with formula (I)

in which

X means fluorine or chlorine,

Y means amino, possibly with amino, hydroxy or methoxy substituted alkylamino with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cycloalkylamino with 3-6 carbon atoms, alkoxyamino with 1-4 carbon atoms, hydrosky, alkoxy with 1-4 carbon atoms, mercapto possibly with ethoxycarbonyl, ethoxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydrazino, hydroxyamino, methoxyamino, chlorine,

R<1> means methyl, ethyl, propyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, methoxy, amino, dimethylamino, ethylamine, phenyl, 4-fluorophenyl or 2,4-difluorophenyl.

R<2> means hydrogen, alkyl with 1-4 carbon atoms or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl and

R^ means methyl or a cyclic amino group which

in which

R<4>means hydrogen, alkyl with 1-4 carbon atoms, 2-hydroxyethyl, allyl, propargyl, 2-oxopropyl, 3-oxobutyl, phenazyl, formyl, benzyl, 4-aminobenzyl or (5-methyl-2-oxo-1 ,3-dioxol-4-yl)-methyl,

R<5> means hydrogen or methyl,

R<k>means hydrogen, alkyl with 1-4 carbon atoms, possibly substituted in particular with fluorine-substituted phenyl or benzyloxymethyl,

R<7> represents hydrogen, amino, methylamino, ethylamino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylamionmethyl, isopropylaminomethyl, hydroxy or hydroxymethyl,

R<8> means hydrogen, methyl, ethyl, fluorine or chlorine,

Å means N or C-R^, wherein

R^ means hydrogen, halogen such as fluorine or chlorine, methyl, cyano or nitro, or also together with R-'- can form a bridge with the structure

-0-CH2-CH-Ch3, -S-CH2-CH-CH3 or -CH2-CH2-CH-CH3

I I I

and their pharmaceutically usable hydrates and acid addition salts, as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids have a high antibacterial effect, especially in the gram-positive range, except 8-amino-9-fluoro-3-methyl-10-( 4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-

carboxylic acid, l-ethyl-5-amino-6,8-difluoro-7-(1-piperazinyl)-4-oxo-1,4-dlhydro-3-chlorolinecarboxylic acid, l-ethyl-5-amino-6,8 -difluoro-7-(4-methyl-1-piperazinyl)-4-oxo-1,4-dihydro-3-chloroquinocarboxylic acid as well as excluding 8-amino-9-fluoro-3-methyl-10(heterodiclyl)-7-oxo -2,3-dihydro-7G-pyrido[1,2,3-de][1,4]-benzoxazln-6-carboxylic acids and 1-ethyl-5-amino-6,8-difluoro-7-(heterocyclyl) - 4-oxo-1,4-dihydroquinoline-3-carboxylic acid, in which heterocyclyl means 3-amino-1-pyrroldinyl, 3-(aminomethyl)-1-pyrroldinyl, 3-(ethylaminomethyl)-1-pyrroldinyl, 2,7- dlazaspro[4,4]non-2-yl and 7-methyl (resp. ethyl )-2,7-dlaza-spro[4,4]-non-2-yl and 5-amino-7-(3-amino -1-pyrrolidineyl)-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid.

They are therefore suitable as active substances for human and veterinary medicine, as veterinary medicine also includes the treatment of fish for therapy or prevention of bacterial infection.

Preferred are 5-substituted quinolone and naphthyridone carboxylic acid derivatives of formula (I)

in which

X means fluorine or chlorine,

Y means amino, possibly with amino, hydroxy or methoxy substituted alkylamino with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cycloalkylamino with 3-6 carbon atoms, alkoxyamino with 1-4 carbon atoms, hydroxy, alkoxy with 1-4 carbon atoms, mercapto, possibly with ethoxycarbonyl, carboxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydrazino, hydroxyamino, methoxyamino , chlorine,

R<1>means methyl, ethyl, propyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, methoxy, amino, dimethylamino, ethylamino, phenyl, 4-fluorophenyl or 2,4-difluorophenyl,

R<2> means hydrogen, alkyl with 1-4 carbon atoms or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl and

r<3>represents methyl or a cyclic amino group which

in which

R<4>means hydrogen, alkyl with 1-4 carbon atoms, 2-hydroxyethyl, allyl, propargyl, 2-oxopropyl, 3-oxobutyl, phenacayl, formyl, benzyl, 4-aminobenzyl or (5-methyl-2-oxo-1 ,3-dioxol-4-yl)-methyl,

r<5> represents hydrogen or methyl,

R<6> means hydrogen, alkyl with 1-4 carbon atoms, optionally substituted in particular with fluorine-substituted phenyl or benzyloxymethyl,

R<7>is hydrogen, amino, methylamino, ethylamino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, isopropylaminomethyl, hydroxy or hydroxymethyl,

R<8> means hydrogen, methyl, ethyl, fluorine or chlorine,

A means N or C-R<9>, wherein

R<9>means hydrogen, halogen such as fluorine or chlorine, methyl, cyano or nitro, or also together with R-^can form a bridge of structure

and their pharmaceutically usable hydrates and acid addition salts as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids, except 8-amino-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7- oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, 1 -ethyl-5-amino-6,8-difluoro-7-(1- piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, l-ethyl-5-amino-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4-oxo-1,4 -dihydro-3-quinolonecarboxylic acid as well as excluding 8-amino-9-fluoro-3-methyl-10-(heterocyclyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [-1, 4]benzoxazine-6-carboxylic acid and l-ethyl-5-amino-6,8-difluoro-7-(heterocyclyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acids, wherein heterocyclyl means 3 -amino-l-pyrrolidinyl, 3-(aminomethyl)-l-pyrrolidinyl, 3-(ethylaminomethyl)-l-pyrrolidinyl, 2,7-diaza-spiro[4,4]non-2-yl, and 7-methyl( respectively ethyl)-2,7-diazaspiro-[4,4]non-2-yl, and 5-amino-7-(3-amino-1-pyrrolidinyl)-1-ethyl-6-fluoro-1,4 -dihydro-4-oxo-1,8-naphthyridinecarboxylic acid, as well as u except compounds in which R<3> represents the residue

with R<4>, R5 and R<6>= h or <C>1-C4-alkyl, when R<1> means cyclopropyl, X means fluorine, Y means amino, hydroxy or C₁-C₄₄-alkyl, and A means N, R<9> means halogen or H,

R<2>means H and their acid addition salts and compounds, in which Y means amino or chlorine, R<1>means cyclopropyl and X means fluorine, A means CF, and R<3>means in which R' means H or CH3, R" means H, CH3 or C2H5, R'" means H or methyl, or R2 means H, CH3 or C2H5.

Also preferred are the compounds of formula I in which

X means fluorine,

Y means amino, possibly with amino, hydroxy or methoxy substituted alkylamino with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cyclopropylamino, alkoxyamino with 1-3 carbon atoms, hydroxy, alkoxy with 1-4 carbon atoms, mercapto, possibly with ethoxycarbonyl, carboxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydroxyamino,

R 1 means ethyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, phenyl, 4-fluorophenyl or 2,4-difluorophenyl,

R<2> means hydrogen, alkyl with 1-3 carbon atoms, (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl,

R<3> means a cyclic amino group which

in which

R<4>means hydrogen, alkyl of 1-3 carbon atoms, 2-hydroxyethyl, allyl, 2-oxopropyl, 3-oxobutyl, phenacyl, benzyl, 4-aminobenzyl, (5-methyl-2-oxo-1,3-oxol -4-yl)-methyl,

R<5> means hydrogen or methyl,

r<6> means hydrogen, alkyl with 1-2 carbon atoms, phenyl, 4-fluorophenyl,

R<7> represents hydrogen, amino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, hydroxy or hydroxymethyl,

R<8> means hydrogen or methyl,

A means N or C-R<9>, wherein

R<9> means hydrogen, halogen such as fluorine or chlorine, or together with R-'- can form a bridge with structure

and their pharmaceutically usable hydrates and acid addition salts, as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids, except 8-amino-7-fluoro-8-methyl-10-(4-methyl-1-piperazinyl) -7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, 1-ethyl-5-amino-6,8-difluoro-7- ( 1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, l-ethyl-5-amino-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4-oxo -1,4-dihydro-3-quinolinecarboxylic acid, as well as excluding 8-amino-9-fluoro-3-methyl-10-(heterocyclyl)-7-oxo-2,3-dihydro-7H-pyridio[1,2,3 ]-de[1,4]benzoxazine-6-carboxylic acids and 1-ethyl-5-amino-6,8-difluoro-7-(heterocyclyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acids, wherein heterocyclyl means 3-amino-l-pyrrolidinyl, 3-(aminomethyl)-l-pyrrolidinyl or 3-(ethylaminomethyl)-l-pyrrolidinyl and 5-amino-7-(3-amino-l-pyrrolidinyl)-l-ethyl-6 -fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid.

Particularly preferred are those compounds of formula I in which

X means fluorine,

Y means amino, possibly with amino, hydroxy or methoxy substituted alkylamino, with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cyclopropylamino, methoxyamino, hydroxy, alkoxy" with 1-4 carbon atoms, mercapto, possibly with ethoxycarbonyl, carboxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenyltlo,

R<1>means ethyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, phenyl, 4-fluorophenyl or 2,4-difluorophenyl,

R<2> means hydrogen, alkyl with 1-2 carbon atoms, (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl,

R<3> means a cyclic amino group which

in which

R<4> means hydrogen, alkyl with 1-2 carbon atoms, 2-hydroxyethyl, 2-oxopropyl, 3-oxobutyl, phenacyl, 4-aminobenzyl, R<5> means hydrogen or methyl,

r<6> means hydrogen, methyl, phenyl, 4-fluorophenyl,

R<7> represents hydrogen, amino, aminomethyl, methylaminomethyl, ethylaminomethyl, hydroxy or hydroxymethyl,

R<8> means hydrogen,

A means N or C-R<9>, wherein

R<9> means hydrogen, halogen such as fluorine or chlorine, or also

-together—with R-^ can form- a bridge with the structure

and their pharmaceutically usable hydrates and acid addition salts, as well as alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids except 8-amino-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)- 7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, l-ethyl-5-amino-6,8-difluoro-7-( 1-piperazinyl)-4-oxo-1, 4-dihydro-3-quinolinecarboxylic acid, 1-ethyl-5-amino-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4-oxo-1 ,4-dihydro-3-quinolinecarboxylic acid as well as excluding 8-amino-9-fluoro-3-methyl-10-(heterocyclyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acids and l-ethyl-5-amino-6,8-difluoro-7-(heterocyclyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acids, wherein heterocyclyl means 3- amino-l-pyrrolidinyl, 3-(aminomethyl)-1-pyrrolidinyl or 3-(ethylaminomethyl)-l-pyrrolidinyl, and 5-amino-7-(3-amino-l-l-pyrrolidinyl)-l-ethyl-6-fluoro -1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid. Furthermore, it was found that the compounds of formula (I) are obtained when compounds of formula (II)

in which

X, R<1>, R<2>, R<3> and A have the above meaning, are reacted with compounds of formula (III)

in which

Y has the above meaning,

-possibly-; —in the presence of s-y-r-e-offpf regret .

If, for example, 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3-quino1incarboxylic acid and ammonia are used as starting materials, the reaction can -pet is represented by the following formula form:

The compounds of formula (II) used as starting materials are known or can be prepared by known methods (European patent application 202 763, German patent application 35 22 405). Examples include: 7-[3-(aminomethyl)-1-pyrrolidinyl)-1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-7 -[3-[(methylaminoÆmethyl]-1-pyrrolidinyl]-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-7-[3-[(ethylamino) methyl]-1-pyrrolidinyl]-5-6-8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 7-[3-amino-1-pyrrolidinyl]-1-cyclopropyl-5,6, 8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-7-[3-(ethylamino)-1-pyrrolidinyl]-5,6,8-trifluoro-1,4-dihydro -4-oxo-3-quinolinecarboxylic acid,

-1 -^^-o^^pylr--&^--6T-8-4^4^1-uo-r -1,4-dihydro --^7-^-^3^ [_[-( 1 -methyl -

ethyl ) aml no] methyl]-1-pyrroiidinyl]-4-oxo-3-quinolinecarboxylic acid , 7-[3-( amlnomethyl)-1-pyrrolidinyl]-1-cyclopropyl-1,4-dihydro-5,6-difluoro -4-oxo-1,8-naphthyridine-3-carboxylic acid, 1-cyclopropyl-7-[3-[(ethylamino)methyl]-1-pyrroidinyl]-1,4-dihydro-5,6-difluoro- 4-oxo-1,8-naphthyridine-3-carboxylic acid, 7-[3-amino-1-pyrroyldinyl]-1-cyclopropyl-1,4-dihydro-5,6-difluoro-4-oxo-1, 8-Naphthyridine-3-carboxylic acid, 7-[3-(-aminomethyl)-1-pyrroyl diny 1]-1-ethyl-5,6-difluoro-1,4-dihydro-4-oxo-1 . -[3-(aminomethyl)-1-pyrrolidinyl]-5,6,8-trifluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 7-[3-(aminomethyl )1-pyrrolidinyl)-5,6,8-trifluoro-l-ethenyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, l-ethyl-7-[3-[(ethyl amino ) methyl 1 ] -1-pyrrolidinyl]-5,6-difluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, l-ethyl-7-[3-[(ethylamino) m ethyl]-1-pyrrolidinyl]-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-5, 6,8-trifluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 1-ethenyl-7-[3-[(ethylamino)methyl-1-pyrroidinyl]- 5,6,8-trifluoro-1,4-4-oxo-3-quinolinecarboxylic acid, 1-ethyl-5,6-difluoro-1,4-dihydro-7-[3-[[ (1-methylethyl) -amino]-methyl]-1-pyrroiidinyl]-4-oxo-1,8-naphthyridine-3-carboxylic acid, 1-ethyl-7- [3-[(1-methylethyl)aminomethyl]-1-pyrrolidinyl]-5 ,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 1-ethyl-5,6-difluoro-1,4-dihydro-7-(7-methyl-2,7-diaza -spiro[4,4]non-2-yl)-4-oxo-1,8-naphthyridine-3-carboxylic acid, 1-ethyl-5,6,8-trifluoro-1,4-dihydro-7-(7 -ethyl-2,7-diazaspiro-[4,4]non-3-quinolinecarboxylic acid,

1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(7-methyl-2,7-diazaspiro[4,4]non-2-yl]-4-oxo-3-quinolinecarboxylic acid . e-j

1-cyclopropyl-5,6-difluoro-1,4-dihydro-7-(3-hydroxy-1-pyrrolidinyl)-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-5,6,8-trifluoro-1 ,4-Dihydro-7-(3-hydroxy-1-pyrrolidinyl)-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-5,6-difluoro-1,4-dihydro-7-(3-hydroxy-1 -pyrrolidinyl)-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-7-(1,4-diazabicyclo[3.2.1]oct-4-yl)-5,6,8-trifluoro-1,4-dihydro- 4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-7-(1,4-diazabicyclo[3.2.1.]oct-4-yl)-5,6-difluoro-1,4-dihydro-4-oxo-1 ,8-naphthyridine-3-carboxylic acid, 1-cyclopropyl-5,68-trifluoro-1,4-dihydro-7-(2-methyl-1,4-diazabicyclo[3.2.1]oct-4-yl)- 4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(8-methyl-3,8-diazabicyclo[3.2.1]oeth-3-yl) -4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid,

1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-(4-methyl-1-piperazinyl)-3-quinolinecarboxylic acid,

1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-(4-ethyl-1-piperazinyl)-3-quinolinecarboxylic acid,

1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-[4-(2-hydroxyethyl)-1-piperazinyl]-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-5,6, 8-trifluoro-1,4-dihydro-4-oxo-7-(3-methyl-1-piperazinyl)-3-quinolinecarboxylic acid,

l-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-(3,5-dimethyl-1-piperazinyl)-3-quinolinecarboxylic acid, l-cyclopropyl-5,6,8- trifluoro-1,4-dihydro-4-oxo-7-morpholino-3-quinolinecarboxylic acid,

1-cyclopropyl-5,6,87-trifluoro-1,4-dihydro-4-oxo-7-thiomoro-folino-3-quinolinecarboxylic acid,

1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-(4-isopropyl-1-piperazinyl)-3-quinolinecarboxylic acid, 7-(4-allyl-1-piperazinyl)- 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid,

1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-[4-(2-oxopropyl)-1-pyrroperaz-yn-y-1-] 3-quino -linkarbookGylGyr-e-r

1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-[4-(3-oxobutyl )-1-piperazinyl]-3-quinoline carboxylic acid, 1-cyclopropyl-5,6, 8-trifluoro-1,4-dihydro-4-oxo-7-(3-phenyl-1-piperazinyl)-3-quinolinecarboxylic acid,

1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(1-imidazolyl)-4-oxo-3-quinolinecarboxylic acid,

1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-(1-pyrrolyl)-3-quinolinecarboxylic acid,

S-8,9-difluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6- carboxylic acid.

The compounds of formula (III) used as starting compounds are known. Examples include: ammonia, methylamine, ethylamine, propylamine, isopropylamine, butylamine, dimethylamine, ethylmethylamine, diethylamine, 2-hydroxyethylamine, ethylenediamine, 2-(tert.-butoxycarbonylamino)ethylamine, 2-methoxyethylamine, cyclopropylamine, methoxyamine, butoxyamine , methanol, methyl mercaptan, thiophenol, mercaptoacetic acid ethyl ester, mercaptoacetic acid hydrazine.

The reaction of (II) with (III) is preferably carried out in a diluent such as dimethylsulfoxide, N,N-dimethylformamide, hexamethylphosphoric acid trisamide, sulfolane, water, an alcohol such as methanol, ethanol, n-propanol, isopropanol, glycol monomethyl ether, acetonitrile or pyridine. Likewise, mixtures of these diluents can be used.

All common inorganic and organic acid binders can be used as acid binders. These preferably include the alkali hydroxides, alkali carbonates, sodium hydride, organic amines and amidines. As particularly suitable, the following should be mentioned in detail: triethylamine, 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.3.0]undec-7-ene (DBU).

The reaction temperatures can be varied over a large range. ~Vanl igvi-s—arbeit—man— meilrotn— era.-.—7-6—og 2 (KP-C-;—f gt-t r i nn s v i s between 100 and 180°C. The conversion can be carried out at normal pressure , but also at elevated pressure. Usually, work is carried out at a pressure between about 1 and about 100 bar, preferably between 1 and 10 bar.

When carrying out the method according to the invention, 1 to 50 mol, preferably 1 to 30 mol, of the compound (III) is used for 1 mol of carboxylic acid (II).

In some cases, protecting groups can also be used which can be cleaved off after completion of the reaction of (II) with (III). Thus, for example, esters are cleaved by enrichment in the presence of sulfuric acid at 100 to 150°C, hydrolytically to carboxylic acids. The cleavage of the tert.-butoxycarbonyl residue as an amino protecting group takes place in the presence of acids such as hydrochloric acid, hydrobromic acid, (see Houben-Weyll, Methoden der organischen Chemie, Volume E4, page 144 (1983)).

Under the same acidic conditions, the cleavage of the tetrahydroxypyrronyl residue also takes place as a hydroxy protecting group (see J.F.W. McOmie, Protective Groups in Organic Chemistry

(1973), page 104).

To produce the esters according to the invention, the basic carboxylic acid can also be converted into excess alcohol in the presence of strong acids, such as sulfuric acid, anhydrous chlorohydrogenmethanesulfonic acid, p-toluenesulfonic acid or acidic ion exchangers, at temperatures of approx. 20 to 200°C, preferably approx. 60 - 120°C. The formed reaction band can also be removed by azeotropic distillation with chloroform, tetrachloromethane, benzene or toluene.

The (5-methyl-2-oxo-1,3-dioxol-4-yl-methyl)-esters used as prodrugs can also be obtained by reaction with an alkaline salt of the underlying carboxylic acid with 4-bromomethyl- or

-4-chlor orme-ty 1 - 5 - m e t y-Ir—I-r3—d-i-ok-s-o 1 2 o n—i—et—op plrø-s n-I-ng agent such as dimethylformamide, dimethylacetamide, dimethylsulfoxide or

tetramethylurea at temperatures of approx. 0°C to 100°C, preferably 0° to 50°C.

The introduction of aminobenzyl residue R<4> can also take place by reduction of a nitrobenzyl residue already introduced into the active substance of formula (I) by catalytically energized hydrogen, or chemically by reduction with iron or zinc.

The production of the acid addition salts of the compounds according to the invention takes place in the usual way, for example by dissolving the betaine in excess aqueous acid, and precipitation of the salt with a water-miscible organic solvent such as methanol, ethanol, acetone, acetonitrile. You can also heat equivalent quantities of betaine and acid in water or an alcohol such as glycol monomethyl ether, and then evaporate to dryness, or suck off the precipitated salt. Pharmaceutically applicable salts include, for example, the salts of hydrochloric acid, sulfuric acid, acetic acid, glycolic acid, lactic acid, succinic acid, citric acid, tartaric acid, methanesulfonic acid, galacturonic acid, gluconic acid, embonic acid, glutamic acid or aspartic acid.

The alkali or alkaline earth salts of the carboxylic acids according to the invention are obtained, for example, by dissolving betaine in deficit alkali or alkaline earth solution, filtering from undissolved betaine and evaporating the filtrate to dryness. Pharmaceutically suitable are sodium, potassium or calcium salts. By reacting an alkali or alkaline earth salt with a suitable silver salt such as silver nitrate, the corresponding silver salts are obtained.

The active substances according to the invention with an asymmetric carbon atom in the residue R<3> can exist both as racemates and also as enantiomerically pure compounds.

In addition to the connections listed in the examples, it should as

-nye-"v^k-s-emme stof-f-er—ir- detail is mentioned: 5-amino-7-[3-(aminomethyl)-1-pyrroyldlnyl]-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl -7 - [3-[ (methyl amino )methyl] -1-pyrr ol idinyl] -6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl - 7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-7- [3-amino-1-pyrrolidinyl]-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid,

5-amino-1-cyclopropyl-7-[3-(ethylamino)-1-pyrroidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino- 1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-[3-[[(1-methylethyl)amino]methyl]-1-pyrrolidinyl]-4-oxo-3-quinolinecarboxylic acid,

5-amino-7-[3-(aminomethyl)-1-pyrrolidinyl]-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-1,n8-naphthyridine-3-carboxylic acid, 5-amino -1-cyclopropyl-7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3- carboxylic acid,

5-amino-7-[3-amino-1-pyrrolidinyl]-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 5-amino-7- [3-(Amlnomethyl)-1-pyrrolidinyl]-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 5-amino-7-[3-( aminomethyl)-1-pyrrolidinyl]-1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid,

5-amino-7-[3-(aminomethyl)-1-pyrroidinyl]-6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-7-[3-(aminomethyl)-1-pyrroiidinyl]-6,8-difluoro-1-ethenyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-ethyl- 7-[3-[(ethylamino)methyl]-1-pyrroiidinyl]-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 5-amino-1-ethyl-7 -[3-[(ethylamino)methyl]-1-pyrroiidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-7-[3-[(ethylamino) methyl]-1-pyrrolidinyl]-6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-ethenyl-7-[3-[ (ethylamino)methyl-1-pyrrolidinyl]-6,8-- d i fl nor —1-t4—é-jrh-yd r o-4 -ok-&o - 3- quinolln carboxylic acid- r -

5-amino-1-ethyl-6-fluoro-1,4-dihydro-7-[3-[[(1-methylethyl)-amino]methyl]-1-pyrrolidinyl]-4-oxo-1,8-naphthyridine -3-carboxylic acid,

5-Amino-1-ethyl-7-[3-[(1-methylethyl)aminomethyl]-1-pyrroidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3- quinoline carboxylic acid, 5-amino-1-ethyl-6-fluoro-1,4-dihydro-7-(7-methyl-2,7-diaza-spiro[4.4]non-2-yl)-4-oxo-1, 8-naphthyridine-3-carboxylic acid, 5-amino-1-ethyl-6,8-difluoro-1,4-dihydro-7-(7-ethyl-2,7-diazaspiro[4.4]non-2-yl)- 4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(7-methyl-2,7-diazaspiro[4.4]non-2-yl)- 4-oxo-3-quinolinecarboxylic acid, 5-amino-7-(3-amino-1-pyrro idinyl)-1-ethy 1-6,8-difluoro-1,4-dihydro-4-oxo-3 -quinoline carboxylic acid,

5-amino-1-cyclopropyl-6-fluoro-1,4-dihydro-7-(3-hydroxy-1-pyrrolidinyo)-4-oxo-3-quinolinecarboxylic acid,

5-amino-1-cyclopropyl-6-fluoro-1,4-dihydro-7-(3-hydroxy-1-pyrrolidinyl)-4-oxo-3-quinolinecarboxylic acid,

5 - am i no-1-cyclopropyl-7-(1,4-diazabicyclo[3.2.1]oeth-4-yl)-6-flour-1,4-dihydro-4-oxo-1,8-naphthyridine- 3-carboxylic acid, 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(2-methyl-1,4-diazabicyclo[3.2.1]oeth-4-yl)-4- oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(8-methyl-3,8-diazabicyclo[3.2.l]oct-3-yl)- 4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-difluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 5-amino-l -cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-thymorpholino-3-quinolinecarboxylic acid, 5 - amino-1 -cyclopropyl 1 - 6 ,8-diflour-1 , 4-dihydr o- 4-oxo-7-(4-isopropyl-1-piperazinyl)-3-quinolinecarboxylic acid, 5-amino-7-(4-allyl-1-piperazinyl)-1-cyclopropyl-6,8-difluoro-1,4- dihydro-4-oxo-3-quinolinecarboxylic acid, 5 - amino-1 - cyclopropyl 1 - 6 , 8-di fluoro-1,4-dihydro-4-oxo-7 - [4-(2-oxopropyl)-1- piperazinyl]-3-quinlinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-fluoro-1,4-dihydro-4-oxo-7-[4-(3-oxobutyl)-1-piperazinyl]-3- quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-fluoro-1,4-dihydro-4-oxo-7-(1-pyrrolyl)-3-quinolinecarboxylic acid,

5-amino-7-[4-(4-arainobenzy 1 )-1-piperazinyl]-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1 -cyclopropyl 1-6,8-difluoro-1,4-dihydro-4-oxo-7-(4-phenacyl-1-piperazinyl)-3-quinolinecarboxylic acid, S-8-amino-9-fluoro-3-methyl -10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, 5-(2-aminoethylamino)-1- cyclopropyl-6,8-difluoro-1,4-chloro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid.

^ Example of a tablet According to the invention.

The lacquer sleeve contains:

The compounds according to the invention, with low toxicity, show a broad antibacterial spectrum against gram-positive and gram-negative germs, especially against enterobacteriaceae, above all also against those that are resistant to various antibiotics, such as e.g. penicillins, cephalosporins, aminoglucosides, sulfonamides, tetracyclines.

These valuable properties enable their use as chemotherapeutically active substances in medicine, as well as substances for the preservation of inorganic and organic materials, especially organic materials of any type, e.g. polymers, lubricants, paints, fibres, leather, paper and wood, of foodstuffs and water.

The compounds according to the invention are effective against a very broad spectrum of microorganisms. With their help, gram-negative and gram-positive bacteria and bacteria-like microorganisms can be fought, as well as prevent, improve and/or cure the diseases caused by these organisms.

Compounds according to the invention are particularly effective against bacteria and bacteria-like microorganisms. They are therefore particularly well suited for prophylaxis and chemotherapy of local and systemic infections in human and animal medicine, which are produced by these producers.

For example, local and/or systemic diseases caused by the following agents or by mixtures of the following agents can be treated and/or prevented: Gram-positive cocci, e.g. staphylococci (Staph. aureus, Staph. epidermidis) and streptococci (Strept. agalactiae, Strept. faecalis, Strept. pneumoniae, Strept. pyogenes); gram-nevative cocci (Neisseria gonorrhoeae) as well as gram-negative rods such as enterobacteriaceae, e.g. Escherichia coli, Haemophilus influenzae, citrobacter (Citrob. frundii , Citrob. divernis), salmonella and shigella; further klebsiels (Klebs. pneumoniae, Klebs. oxytoca), enterobacter (Ent. aerogenes, Ent. agglomerans), hafnia, serratia (Serr. marcescens), proteus (Pr. mirabilis, Pr. rettgeri, Pr. vulgaris), providencia, yersinia , as well as the genus acinetobacter. In addition, the antibacterial spectrum includes the genus pseudomonas (Ps. aeroginosa, Ps. maltofila) as well as strictly anaerobic bacteria such as e.g. Bacteroides fragilis, representatives of the genus Peptococcus, peptostreptococcus and the genus Clostridium; further mycoplasmas (M. pneumoniae, M. hominis, M. urealyticum) as well as mycobacteria, e.g. Mycobacterium tuberculosis.

The above list of producers is only to be taken as an example and in no way limiting. As diseases which are caused by the aforementioned agents or mixed infections and which are prevented, improved or can be cured by the compounds according to the invention, the following should be mentioned, for example: infectious diseases in humans such as otitis, pharyngitis, pneumoniae, pertonitis, pyelonephritis, cystitis, endocarditis, systemic infections, bronchitis (acute, chronic), septic infections, diseases of the upper respiratory tract, diffuse panbrochiolitis, pulmonary emphysema, dysentery, enteritis, liver abscesses, urethritis, prostatitis, epididymitis, gastrointestinal infections, bone and joint infections, cystic fibrosis, skin infections, postoperative wound infections, abscesses, phlegmons, wound infections, infected burns, burns, infections in the mouth area, infections after dental surgery, osteomyelitis, septic arthritis, cholecystitis, peritonitis with appendicitis, choclangitis, intra-abdominal abscesses, pancreatitis, sinusitis, mastoiditis, mastitis, tonsillitis , typhus, meningitis and infectious tions in the nervous system, salpingitis, endometritis, genital infections, pelvic peritonitis and eye infections.

Besides in humans, bacterial infections can also be treated in other types. Examples include: Pigs: coli diarrhoea, enterotoxemia, sepsis, dysentery, salmonellosis, mastitis-metritis-agalactia syndrome, mastitis; Ruminants (cattle, sheep, shepherds): diarrhoea, sepsis, broncho-pneumonia, salmonellosis, pasteurellosis, mycoplasmosis, genital infections;

Horse: bronchopneumonias, foal paralysis, purpural and postpurpural infections, salmonellosis;

Dog and cat: bronchopneumonia, diarrhoea, dermatitis, otitis, urinary tract infections, prostatitis;

Poultry (hen, turkey, quail, pigeon, migratory birds and others): mycoplasmosis, E.coil infections, chronic respiratory diseases, salmonellosis, pasteurellosis, psittacosis.

Likewise, bacterial diseases can be treated by breeding and keeping commercial and ornamental fish, as the antibacterial spectrum extends to further pathogens such as, for example, pasteurella, brucella, campylobacter, listeria, erysipelo-thrix, cornye bacteria, borrelia, treponema, nocardia, rickettsiae, yersinia.

The invention includes pharmaceutical preparations which, in addition to non-toxic inert pharmaceutically suitable carriers, contain one or more compounds according to the invention, or which consist of one or more active substances according to the invention, as well as methods for producing these preparations.

The invention also includes pharmaceutical preparations in dosage units. This means that the preparations are in the form of individual parts, e.g. tablets, dragees, capsules, pills, suppositories and ampoules, whose active substance content corresponds to a fraction or a multiple of a single dose. These dosage units can e.g. contain 1, 2, 3 or 4 single doses, or 1/2, 1/3 or 1/4 of a single dose. A single dose preferably contains the amount of active substance that is administered in one application and which usually corresponds to a whole, 1/2, 1/3 or 1/4 of a daily dose.

Non-toxic inert pharmaceutically suitable carriers are understood to mean solid, semi-solid or liquid diluents, fillers and formulation aids of any type.

As preferred pharmaceutical preparations it should be mentioned

tablets, dragees, capsules, pills, granules, suppositories, solutions, suspensions, emulsions, pastes, ointments, gels, creams and lotions, powders and sprays. Tablets, dragees, capsules, pills and granules may contain the active substance(s) in addition to the usual carriers such as (a) fillers and thickeners, e.g. starches, milk sugars, cane sugar, glucose, mannitol and silicic acid, (b) binders, e.g. carboxymethylcellulose, alginates, gelatins, polyvinylpyrrolidone, (c) humectants, e.g. glycerol, (d) explosives, e.g. agar-agar, calcium carbonate and sodium carbonate, (e) dissolution retarders e.g. paraffin and (f) resorption accelerators, e.g. quaternary ammonium compounds, (g) wetting agents, e.g. cetyl alcohol, glycerol monostearate, (h) adsorbents, e.g. kaolin and bentonite and (i) lubricants, e.g. talc, calcium and magnesium stearate, and solid polyethylene glycols or mixtures of the substances listed under points (a) to (i). The tablets, dragees, capsules, pills and granules can be equipped with the usual opacifying agents containing coatings and sleeves, and also be composed in such a way that they possibly delay, release the virulent substance or substances only or preferentially in a specific part of the digestive tract, as iniile clay ing masses, e.g. polymer substances and wax can be used.

The active substance(s) may possibly be present in one or more of the carrier substances, also in micro-encapsulated form.

Suppositories can, in addition to the active substance(s), contain ordinary water-soluble or water-insoluble carriers, e.g. polyethylene glycols, fats, e.g. cocoa butter and higher esters, e.g. (C-j^-alcohol with C]^-fatty acid) or mixtures of these substances.

Ointments, pastes, creams and gels can contain the usual carrier substances, e.g. animal and vegetable fats, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, talc and zinc oxide or mixtures of these substances.

Powders and sprays can contain the usual carrier substances in addition to the active substance(s), e.g. milk sugar, talc, silicic acid, aluminum hydroxide, calcium silicate, and polyamide powders or mixtures of these substances. Sprays can, in addition to the usual propellant, e.g. contain chlorine, fluorine, hydrocarbon.

Solutions and emulsions can contain, in addition to the active substance(s), the usual carriers such as solvents, dissolution mediators and emulsifiers, e.g. water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils especially cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol, glycerol formal, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, or mixtures of these substances.

For parenteral application, the solutions and emulsions can also be available in sterile and blood isotonic form.

In addition to the active substance(s), suspensions may contain the usual carriers such as liquid diluents, e.g. water, ethyl alcohol, propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum ethhydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.

The aforementioned formulation forms can also contain coloring agents, preservatives as well as odor and taste improving additives, e.g. peppermint oil, eucalyptus oil and sweeteners, e.g. saccharin.

The therapeutically active compounds must be present in the pharmaceutical preparations listed above, preferably in a concentration of approx. 0.1 to 99.5, preferably of approx. 0.5 to 95% by weight of the total mixture.

The pharmaceutical preparations listed above may, in addition to the compounds according to the invention, also contain further pharmaceutically active substances.

Preparation of the above-mentioned pharmaceutical preparations takes place in the usual way according to known methods, e.g. by mixing the active substance(s) with the carrier oil or carrier substances.

The aforementioned preparations can be used on humans and animals, either orally, rectally, parenterally (intravenous, intramuscular, subcutaneous), intracisternal, intravaginal, intraperitoneal, local (powders, ointments, drops) and for the therapy of infections in cavities, body cavities. Suitable preparations include injection solutions, solutions and suspensions for oral therapy, gels, pour-on formulations, emulsions, ointments and drops. Ophthalmological and dermatological formulations, silver and other salts, ear drops, eye ointments, powders or solutions can be used for local therapy. In animals, intake can also take place over feed or drinking water in suitable formulations. Furthermore, gels, powders, powders, tablets, retard tablets, premixes, concentrates, granules, pellets, boli, capsules, aerosols, sprays, inhalers can be used in humans and animals. Furthermore, the compounds according to the invention can be incorporated into other carrier materials such as, for example, plastics (plastic chains for local therapy), collagen or bone cement.

In general, both in human and veterinary medicine it has proven to be advantageous to administer the active substances according to the invention, in total amounts of approx. 0.5 to approx. 500, preferably 50 to 100 mg/kg body weight per 24 hours, possibly in the form of several individual submissions, to achieve the desired results. A single dose contains the active substance(s) according to the invention, preferably in amounts of approx. 1 to approx. 80, especially 3 to 30 mg/kg body weight. However, it may be necessary to deviate from the aforementioned dosages, namely depending on the type of body weight and the object to be treated, the type and severity of the disease, the type of preparation and application of the medicine, as well as the time or interval within which the administration takes place.

Thus, in some cases it may be sufficient to come out with less than the above-mentioned amount of active substance, while in other cases the above-mentioned amount of active substance must be exceeded. The determination of the respective required optimal dosage of application type of the active substance can easily be carried out by any expert on the basis of his professional knowledge.

The new compounds can be given in the usual concentrations and preparations together with the feed or with preparations or with the drinking water. In this way, an infection with gram-negative or gram-positive bacteria can be prevented, improved and/or cured, thereby achieving a promotion of growth and an improvement in utilization of the forage.

o

Example A

11.1 g magnesium shavings are suspended in 1 25 ml anhydrous ethanol. It is mixed with 2.5 g of carbon tetrachloride and, when the reaction has started, a mixture of 79 g of malonic acid diethyl ester, 50 ml of absolute ethanol and 200 ml of anhydrous diethyl ether is added dropwise under reflux. It is then heated for another 2 hours under reflux temperature, cooled with ice/methanol to 0°C, and at this temperature a solution of 106.3 g (0.5 mol) pentafluorobenzoyl fluoride in 135 ml of diethyl ether is slowly added dropwise. It is stirred for 1 hour at 0°C, allowed to come to room temperature overnight, and allowed to turn under ice cooling into a mixture of 200 ml of ice water and 12.4 ml of concentrated sulfuric acid. The phases are separated, then extracted twice with ether. The combined ether solutions are washed with water, dried with NaCl, and the solvent is removed in vacuo. 170.8 g of pentafluorobenzoylmalonic acid diethyl ester is obtained as crude product.

An emulsion of 170 g of crude pentafluorobenzoylmalonic acid diethyl ester in 335 ml of water is mixed with 0.7 g of p-toluenesulfonic acid. The mixture is heated with good stirring for 3.5 hours until boiling, the cooled emulsion is extracted several times with methylene chloride, the combined CHgClg solutions are washed once with water, dried with Na2SO4 and the solvent is distilled off in a vacuum. Fractionation of the residue (125.3 g) in vacuo gives 79.5 g (56$ of the theoretical) pentafluorobenzoylacetic acid ethyl ester of boiling point 77-79'C/0.13 mbar, n<20>D: 1.4608.

With pentafluorobenzoyl chloride, the turnover proceeds similarly.

Example B.

246 g (0.87 mol) pentafluorobenzoyl-acetic acid ethyl ester are heated with 189 g (1.25 mol) triethyl orthoformic acid and 214 g (2.1 mol) acetic anhydride for 2 hours under reflux. It is then evaporated to 140°C bath temperature in vacuum, and 196 g (67% of the theoretical) of 3-ethoxy-2-(pentafluorobenzoyl)-acrylic acid ethyl ester are obtained as an oil.

Example C.

196 g (0.58 mol) of 3-ethoxy-2-(pentafluorobenzoyl)-acrylic acid ethyl ester are dissolved in 750 ml of ethanol, 34.2 g (0.6 mol) of cyclopropylamine are added dropwise while cooling. It is left to stir for 2 hours, left to stand overnight, the precipitated crystallisate is filtered off with suction, washed with cold ethanol and dried (123.2 g, m.p. 87-88°C). The mother liquor is evaporated to half, and a further fraction (37.4 g, m.p. 87-88°C) is isolated. Total yield: 160.6 g (7956 of theory) 3-cyclopropylamino-2-(pentafluorobenzoyl)-acrylic acid ethyl ester.

Example D.

160.6 g (0.46 mol) of 3-cyclopropylamino-2-(pentafluorobenzoyl)-acrylic acid ethyl ester are mixed in 700 ml of dimethylformamide with 33.4 g (0.8 mol) of sodium fluoride and heated for 3 hours under reflux. The mixture is poured into 3 liters of ice water, the precipitate is suctioned off and washed with water and dried.

Yield: 144.6 g (96$ of the theoretical) 1-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quino-1incarboxyl-acid ethyl ester of melting point 169-173°C.

Example E.

144.6 g (0.44 mol) of 1-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid ethyl ester are heated in a mixture of 854 ml of acetic acid, 612 ml of water and 97 ml concentrated sulfuric acid 1 3 hours under reflux. After cooling, pour in 3 liters of ice water, suck off the precipitate, wash with water and dry.

Yield: 117.9 g (89% of theoretical) 1-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with melting point 176-178°C, after recrystallization from ethanol: melting point 178-180°C.

Example F.

3-Ethoxy-2-(pentafluorobenzoyl)-acrylic acid ethyl ester is reacted analogously to example C with 50 µg of aqueous ethyl alcohol solution and 3-ethylamino-2-(pentafluorobenzoyl)-acrylic acid ethyl ester (cis-trans mixture) with melting point 87-88 is obtained °C, which is cyclized analogously to example D with sodium fluoride to 1-ethyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid ethyl ester with melting point 216-221°C (under decomposition) . This is hydrolysed analogously to example E to 1-ethyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with a melting point of 223-225°C (under decomposition).

Example G.

If the sequence of reactions mentioned in example F is carried out analogously with 2-amino-ethanol, amn over 3-(2-hydroxyethyl-amino)-2-(pentafluorobenzoyl)-acrylic acid ethyl ester (oil, which crystallizes very slowly, Rf value: 0.7 [elution medium: dichloromethane/methanol/17% aqueous ammonia solution 150:20:1, silica gel]) and 5,6,7,8-tetrafluoro-1,4-dihydro-1-(2-hydroxyethyl)-4 -oxo-3-quinolinecarboxylic acid ethyl ester (melting point: 200-203°C during decomposition) obtain 5-6-7-8-tetra-fluoro-1,4-dihydro-1-(2-hydroxyethyl)-4-oxo-3- quinoline carboxylic acid with melting point 192-194°C (under decomposition).

Example H.

10.1 g (0.032 mol) 3-ethoxy-2-(pentafluorobenzoyl)-acrylic acid ethyl ester has 1 12 ml of ethanol. A solution of 2.5 g (0.033 mol) 2-amino-1-propanol in 12 ml of ethanol is added dropwise under ice-cooling. It is then allowed to stir for 2 hours at room temperature and then evaporated in a vacuum. 11.0 g of 2-(pentafluorobenzoyl)-3-(1-hydroxy-2-propylamino)-acrylic acid ethyl ester are obtained as crude product (oil).

This crude product is heated with 5.8 g of potassium carbonate in 50 ml of dimethylformamide for 4 hours at 140°C. After cooling to room temperature, mix with water.

The precipitate is filtered off, dried, stirred with acetonitrile and

<recrystallized from glycol monomethyl ether acetate.

Yield: 2.4 g (24.356) 8,9,10-trifluoro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid ethyl ester with melting point 251-2°C (under decomposition).

2.0 g of this ester is heated together with 7 ml of acetic acid, 5 ml of water and 0.6 ml of sulfuric acid for 4 hours at 140° C. After cooling, it is mixed with water, the solid is isolated and dried.

Yield: 1.5 g (91*) 8 , 9 ,10-trifluoro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid with m.p. 300°C (during decomposition).

Recrystallization from dimethylformamide does not change the cleavage point.

Example 1. 30 g (0.1 mol) of 1-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are mixed with a mixture of 200 ml of acetonitrile and 100 ml of dimethylformamide with 15 g (0.15 mol) N-methylpiperazine and 16.5 g (0.165 mol) 1,4-diazabicyclo-[2.2.2]octane and heated for 3 hours under reflux. The suspension is evaporated, the residue is stirred with water, the undissolved precipitate is suctioned off, washed with water, methanol and dried at 80°C/12 mbar.

Yield: 20.3 g (53.5* of theoretical) 1-cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo -3-quinoline carboxylic acid with melting point 210-220°C (under cleavage); after recrystallization from glycol monomethyl ether: melting point 239-242°C (under decomposition).

Analogous to example 1, the compounds according to examples 2-14 are obtained: Example 2.

1-Cyclopropyl-7-(4-ethyl-1-piperazinyl)-5,6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with melting point 220-222°C (under decomposition) (from glycol monomethyl ether).

Example 3.

1-Cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-7-[4-(2-hydroxyethyl)-1-piperazinyl]-4-oxo-3-quinolinecarboxylic acid with melting point 244-247°C (under cleavage) (from glycol monomethyl ether).

Example 4.

1-Cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid with melting point 235-236°C (under decomposition) (from glycol monomethyl ether).

Example 5.

1-Cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid with melting point 257-258° C (under cleavage) (from glycol monomethyl ether).

Example 6.

1-Cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid.

Example 7.

1-Cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-4-oxo-7-(3-phenyl-1-piperazinyl)-3-quinolinecarboxylic acid with melting point 198-199°C (under decomposition) (after purification by flash chromatography on silica gel with dichloromethane/methanol/17* ammonia [30:8:1] as eluent; Rf value: 0.7).

Example 8.

1-cyclopropyl-5,6,7,8-trifluoro-7-[3-(4-fluorophenyl)-1-piperazinyl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with melting point 205-206°C (under cleavage) (from glycol monomethyl ether).

Example 9.

1-cyclopropyl 1-7 - (1 , 4-diazabicyclo[3 . 2 . l]oct-4-yl )-5 ,6 ,7 ,8-trifluoro-1 ,4-dihydro-4-oxo-3-quinolinecarboxylic acid with melting point 319-321°C (under decomposition).

Example 10.

1-cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-7-morpholino-4-oxo-3-quinolinecarboxylic acid with melting point 296-300°C (below

cleavage) (purification by stirring with dichloromethane/methanol/20* ammonia [2:4:1].

Example 11. - -,

1-Cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-4-oxo-7-(1-pyrrolidinyl)-3-quinolinecarboxylic acid with melting point 314-316°C (under decomposition) (from dimethylformamide) .

Example 12.

1-Cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-7-(3-hydroxy-1-pyrrolidinyl)-4-oxo-3-quinolinecarboxylic acid with melting point 281-282°C (under decomposition) (from glycol monomethyl ether).

Example 13. 1-cyclopropyl 1-7-(3-ethylaminomethyl-1-pyrrolidinyl)-5,6,7,8-trifluoro-1,4-dihydro-4-oxo-3 -quinoline carboxylic acid with a melting point from approx. 260°C (during decomposition).

Example 14.

1-Cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-7-(1-imidazolyl )-4-oxo-3-quinolIncarboxylic acid with melting point 207-208°C (under decomposition) (from glycol monomethyl ether) .

Example 15.

1.6 g (4.2 mmol) of the compound from Example 4 is dissolved in 5 ml of semi-concentrated hydrochloric acid and the solution is filtered, and the filtrate is mixed with ethanol to precipitate the hydrochloride. The salt is sucked off, washed with ethanol and dried at 100°C/12 mb ar.

Yield: 1.1 g (63* of theory) 1-cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3 -quinoline carboxylic acid hydrochloride with melting point 295°C (under decomposition).

Example 16.

Analogous to example 15, the compound from example 13 is transferred to 1-cyclopropyl-7-(3-ethylaminomethyl-1-pyrrolidinyl)-5,6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinol incarboxyl sy re-hydrochloride with melting point 298°C (under decomposition).

Example 17.

13.2 g (34.6 mmol) 1-cyclopropyl-5,6,7,8-trifluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3- quinoline carboxylic acid is mixed with 112 ml of pyridine with 56 ml of saturated ethanolic ammonia solution, and heated for 8 hours at 120° in an autoclave. After cooling, the precipitated yellow crystallisate is suctioned off, washed with water and ethanol and dried.

Yield: 9.3 g (71% of theory) 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4- oxo-3-quinolinecarboxylic acid with melting point 231-232°C (under decomposition); after recrystallization from glycol monomethyl ether: melting point 239-242°C (under decomposition).

If the reaction is carried out during 12 hours at 155°C in an autoclave, the reaction product with a melting point of 231-233°C (during cleavage) is isolated in 32* yield.

Mass spectrum: m/e 378 (M<+>), 358, 343, 322 (100*. M-C3H6N), 278, 235, 180, 129, 70, 56, 41.

Example 18a.

300 mg (0.8 mmol) of the compound from example 17 are suspended at 70°C in 7 ml of ethanol and mixed with 0.1 g of methanesulfonic acid. Stirring continues without heating and allowing it to cool overnight. The precipitate is suctioned off, washed with ethanol and dried at 80°C/0.1 mbar.

Yield: 260 mg (68.6 G of the theoretical) 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo- 3-quinoline carboxylic acid methanesulfonate with a melting point of 290°C (under decomposition).

<C>18H2oF2N403x CH3SO3H (474)

calculated: C 48.1 H 5.1 N 11.8 S 6.6

found : C 47.7 H5.1 N 11.8 S6.6.

Example 18b.

29.5 g (78 mmol) of the compound from example 17 are dissolved hot in approx. 700 ml semi-concentrated hydrochloric acid and filter. The filtrate is cooled, the precipitated crystallisate is filtered off with suction, washed with ethanol and dried.

Yield: 26.9 g (83% of theory) 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3 -quinoline carboxylic acid hydrochloride with a melting point from 330°C (under decomposition).

Analogous to example 17, the compound according to examples 19-29 is obtained.

Example 19.

5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid with melting point 239-241°C (under decomposition) (from glycol monomethyl ether).

Example 20. 5-amino-1-cyclopropyl 1-7-(4-ethyl-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with melting point 220-222 °C (during decomposition) (from glycol monomethyl ether).

Example 21.

( from glycol monomethyl ether).

Example 22.

5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid, with melting point 250-253° C (under cleavage) (from glycol monomethyl ester).

Example 23.

( during cleavage) (from glycol monomethyl ether).

Example 24.

5-amino-o—1-cyklepT-ep-y-^r—6-, 8 diflour 7—( [ 3 ( 4 - f luor f eny 1) -1 - piperazinyl]-1,4-dihydro-4- oxo-3-quinolinecarboxylic acid with

melting point 252-255°C (under decomposition) (from glycol monomethyl ether):"

Example 25.

5-amino-1-cyclopropyl 1-7-(1,4-dilazabl cyclo[3.2.1]oct-4-yl)-6,8-diflouro-1,4-dihydro-4-oxo-3 -quinoline carboxylic acid with melting point 282-285°C (under decomposition).

Example 26.

5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-morpholino-4-oxo-3-quinolinecarboxylic acid with melting point 287-290°C (under decomposition) (from glycol monomethyl ether).

Example 27.

5-amino-1-cyclopropyl 1-6,8-diflouro-1,4-dihydro-4-oxo-7-(1-pyrrolidinyl)-3-quinolinecarboxylic acid with melting point 241-244°C (under decomposition) (from glycol monomethyl ether).

Example 28.

5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(3-hydroxy-1-pyrrolidinyl)-4-oxo-3-quinolinecarboxylic acid with melting point 258-259°C (under decomposition ) (from glycol monomethyl ether).

Example 29.

5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(1-imidazolyl)-4-oxo-3-quinolinecarboxylic acid with melting point 268-270°C (under decomposition) (from glycol monomethyl ether).

Example 30.

0.9 g (2.5 mmol) of the compound from example 29 is suspended in 10 ml of water and mixed slowly with 0.6 g (6.2 mmol) of methanesulfonic acid. After adding approx. 5/6 of the amount, the product is strongly dissolved, then spontaneous crystallization occurs. The compact crystallisate is mixed with a further 5 ml of water, dissolved by heating. It is allowed to crystallize slowly, stirred with 10 ml of ethanol, the solid methanol is sucked off and dried at 100°C/0.1 mbar.

Yield: 0.87 g (75.7* of theory) 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(1-imidazolyl)-4-oxo-3-quinolinecarboxylic acid -methanesulfonate with melting point 274-276°C (under decomposition).

Example 31.

0.3 g (0.76 mmol) of the product from example 20 is suspended at 70°C in 7 ml of ethanol and mixed with 0.1 g of methanesulfonic acid. Stir again without heating and let it stand for 2 days. The crystallisate is suctioned off and dried at 80°C/l mbar.

Yield: 0.38 g (97* of theory) 5-amino-1-cyclo-,lopropyl-7-(4-ethyl--piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxo -3-quinolinecarboxylic acid methanesulfonate hydrate with melting point 271-273°C (under decomposition).

Example 32.

11.1 g (27 mmol) of the compound from example 13 are mixed in 70 ml of pyridine with 35 ml of the ethanolic ammonia solution and heated in an autoclave for 12 hours at 155°C. After cooling, the formed precipitate is suctioned off, washed with water, dissolved in 150 ml of semi-concentrated hydrochloric acid. The solution is filtered, evaporated and the residue is expelled with ethanol. The undissolved hydrochloride is suctioned off, washed with ethanol and dried.

Yield: 5 g (39* of theory) 5-amino-1-cyclopropyl-7-(3-ethylaminomethyl)-1-pyrroidinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3 -quinoline carboxylic acid hydrochloride hydrate with melting point 225-229°C (under decomposition); after recrystallization from glycol monomethyl ether: melting point 245-250°C with decomposition.

C20<H>24<F>2<N>4°3x HC1 x 1.5 H2<0>

calculated: C 51.1 H 5.9 N 11.9 Cl 7.6

found : C 51.1 H 5.9 N 11.8 Cl 7.6.

Example 33.

2.5 g (65.5 mmol) of 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid are mixed in 15 ml of pyridine with 7.5 ml of saturated ethanolic dimethylamine solution and heated in an autoclave for 6 hours at 120°C. After cooling, evaporate, stir with approx. 25 ml of water, and the precipitated product is suctioned off, washed with water and dried.

Yield: 0.8 g (30* of theoretical) 1-cyclopropyl-5-dimethylamino-6,8-difluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3 -quinoline carboxylic acid with melting point 221-223"C (under decomposition).

Example 34.

If the reaction is carried out analogously to example 33 with methylamine, 1-cyclopropyl-6,8-difluoro-1,4-dihydro-5-methylamine is obtained in no -7-(4-methyl-1-piperazinyl)-4-oxo-3 -quinoline carboxylic acid with melting point 226-229°C (under decomposition) (from glycol monomethyl ether).

Example 35.

1.9 g (5 mmol) of 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid are mixed in 20 ml of dimethyl sulfoxide with 0.6 g of 1,4-diazabicyclo[2.2.2]octane and 370 mg (5.7 mmol) of 2-aminoethanol and heated for 2 hours at 130-140°C. The mixture is evaporated, the residue is stirred with 20 ml of water, the precipitate is filtered off with suction and recrystallized from glycol monomethyl ether.

Yield: 0.79 g (37.4* of the theoretical) 1-cyclopropyl-6,8--difluoro 1,4 d jrky-d^o-5—(--£—hydroxyctylamino )—7— (- 4-methyl 1-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid with melting point 189-190°C.

Example 36.

If cyclopropylamine is used analogously to example 35, 1-cyclopropyl-5-cyclopropylamino-6,8-difluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid is obtained with a melting point of 202 -204°C (during decomposition).

Example 37.

If you use analogous example 35 as starting compounds butylamine, you get 5-butylamino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid with melting point 148-149"C (under decomposition).

Example 38.

2.9 g (7.6 mmol) of 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid are mixed in 30 ml dimethylsulfoxide with 1.7 g (15 mmol) 1,4-diazabicyclo[2.2.2]octane and, under ice cooling, condense approx. 450 mg methyl mercaptan. After stirring without cooling, heat for 6 hours at 110°C. After cooling, the suspension is introduced into water, the precipitate is suctioned off, washed with water and dried at 80°C/12 mbar. Yield: 1.9 g (68% of theory) 1-cyclopropyl-6,8-difluoro-1,4-dihydro-5-methyl Imer capt o-7-(4-methyl-1-piperazi - —nyl) 4 oxo 3 quinol incarboxylic acid with—melting point—t—225-235 ° C

during cleavage; after recrystallization from dimethylformamide: melting point 232-241°C (under decomposition).

Example 39.

1.9 g (5 mmol) of 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid are mixed in 15 ml of dimethyl sulfoxide with 1.1 g (10 mmol) 1,4-diazabicyclo-[2.2.2]octane and 660 mg (6 mmol) thiophenol and heated for 2 hours at 110°C. The suspension is introduced into water, the precipitate is suctioned off, washed with water and recrystallized from dimethylformamide.

Yield: 1.1 g (46.7* of the theoretical) 1-cyclopropyl-6,8-. difluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-5-phenylthio-3-quinolinecarboxylic acid with melting point 234-236°C (under decomposition).

Example 40.

One works similarly to example 39 with mercaptoacetic acid methyl ester as starting compound, and obtains 1-cyclopropyl-6,8-difluoro-1,4-dihydro-5-(methoxycarbonylmethyl)-7-(4-methyl-1-piperazinyl)-4- oxo-3-quinoline carboxylic acid with melting point 180-183°C (under decomposition).

Example 41..

0.4 g (0.86 mmol) 1-cyclopropyl-6,8-difluoro-1,4-dihydro-5-(methoxycarbonylmethylthio)-7-(4-methyl-1-piperazinyl)-4-oxo-3- quinoline carboxylic acid is mixed in 2.7 ml of acetic acid and 1.5 ml of water with 0.3 ml of concentrated sulfuric acid and heated for 2 hours

at 150°C. The solution is introduced into ice water, the formed precipitate is suctioned off, washed with water and dried at 80°C/12 mbar.

Yield: 390 mg (100* of the theoretical) 5-carboxymethylthio-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(4-methio1-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid with melting point from approx. 265°C (during decomposition).

Example 42.

N-methylpiperazine is reacted with 1-ethyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and 1-ethyl-5,6,7,8-trifluoro-l ,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinoline carboxylic acid with melting point 214-216°C (under decomposition).

Example 43.

Analogously to example 17, the compound from example 42 is reacted with ammonia to 5-amino-1-ethyl-6,8-difluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid with melting point 246-248°C (under decomposition).

Example 44.

Analogous to example 1, N-methylpiperazine is reacted with 5,6,7,8-tetrafluoro-1,4-dihydro-1-(2-hydroxyethyl)-4-oxo-3-quinolinecarboxylic acid and 5,6,8-trifluoro -1,4-dihydro-1-(2-hydroxyethyl)-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid with melting point 210-211°C (under decomposition).

Example 45.

Analogously to example 17, the compound from example 44 is reacted with ammonia to 5-amino-6,8-difluoro-1,4-dihydro-1-(2-hydrocytyl)-7-(4-methyl-1-piperazinyl)-4 -oxo-3-quinolinecarboxylic acid.

Example 46.

Analogous to example 1, one reacts N-methylpiperazine with the compound from example 4 and obtains 8,9-difluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2 ,3-de] [1,4]benzoxazine-6-carboxylic acid.

Example 47.

The product from example 46 is reacted analogously to example 17 with ammonia to 8-amirio-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de ][1,4]benzoxazine-6-carboxylic acid with melting point 289-290°C (under decomposition).

Claims (11)

1. Substituted quinolone and naphthyridone carboxylic acid derivatives of formula (I) in which X means fluorine or chlorine, Y means amlno, possibly with amlno, hydroxy, or methoxy substituted alkylamino with 1-4 carbon atoms, dialkylamlno with 1-4 carbon atoms per alkyl group, cycloalkylamino with 3-6 carbon atoms, alkoxyamino with 1-4 carbon atoms, hydroxy, alkoxy with 1-4 carbon atoms, mercapto, possibly with ethoxycarbonylcarboxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydrazino, hydroxyamino, methoxyamino , chlorine, R <1> means methyl, ethyl, propyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, methoxy, amino, diethylamino, ethylamino, phenyl, 4-fluorophenyl or 2,4-difluorophenyl, R <2> means hydrogen, alkyl with 1-4 carbon atoms or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl and R <3> means methyl or a cyclic amino group which in which R <4> means hydrogen, alkyl with 1-4 carbon atoms, 2-hydroxyethyl, allyl, propargyl, 2-oxopropyl, 3-oxobutyl, phenacyl, formyl, benzyl, 4-aminobenzyl or (5-methyl-2-oxo-13 -dioxol-4-yl)-methyl, r <5> means hydrogen or methyl, R^ means hydrogen, alkyl with 1-4 carbon atoms, optionally substituted, especially fluorine-substituted phenyl or benzyloxymethyl, R <7> means hydrogen, aminomethyl, amino, methylamino, ethylamino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, isopropylaminomethyl, hydroxy or hydroxymethyl, R <8> means hydrogen, methyl, ethyl, fluorine or chlorine, A means N or C-R <9> wherein R <9> means hydrogen, halogen, such as fluorine or chlorine, methyl, cyano or nitro or also together with R^ can form a bridge of the structure and their pharmaceutically usable hydrates and acid addition salts, as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids, except 8-amino-7-fluoro-8-methyl-10-(4-methyl-1-piperazinyl) -7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, 1-ethyl-5-amino-6,8-difluoro-7- (1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, l-ethyl-5-amino-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4-oxo- 1,4-dihydro-3-quinoincarboxylic acid, as well as excluding 8-amino-9-fluoro-3-methyl-10-(heterocyclyl)-7-oxo-2,3-dihydro-7H-pyridlo[1,2,3] -de[1,4]benzoxazine-6-carboxylic acids and 1-ethyl-5-amino-6,8-difluoro-7-(heterocyclyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acids, wherein heterocyclyl means 3-amino-l-pyrrolidinyl, 3-(aminomethyl)-l-pyrrolidinyl or 3-(ethylaminomethyl)-l-pyrrolidinyl and 5-amino-7-(3-amino-l-pyrrolidinyl)-l-ethyl-6- fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid. 2. Substituted quinoline and natyridone carboxylic acid derivatives of formula (I) in which X means fluorine or chlorine, Y means amlno, optionally with amino, hydroxy or methoxy substituted alkylamino with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cycloalkylamino with 3-6 carbon atoms, alkoxyamino with 1-4 carbon atoms, hydrosky, alkoxy with 1-4 carbon atoms, mercapto possibly with ethoxycarbonyl, carboxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydrazino, hydroxyamino, methoxyamino, chlorine, R <1> means methyl, ethyl, propyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, methoxy, amino, dimethylamino, ethylamine, phenyl, 4-fluorophenyl or 2,4-difluorophenyl. R <2> means hydrogen, alkyl with 1-4 carbon atoms or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl and R <3> means methyl or a cyclic amino group such as wherein R <4> means hydrogen, alkyl having 1-4 carbon atoms, 2-hydroxyethyl, allyl, propargyl, 2-oxopropyl, 3-oxobutyl, phenazyl, formyl, benzyl, 4-aminobenzyl or (5-methyl-2-oxo- 1,3-dioxol-4-yl)-methyl, R <5> means hydrogen or methyl, R <6> means hydrogen, alkyl with 1-4 carbon atoms, optionally substituted in particular with fluorine-substituted phenyl or benzyloxymethyl, R <7> means hydrogen, amino, methylamino, ethylamino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylamionmethyl, isopropylaminomethyl, hydroxy or hydroxymethyl, R <8> means hydrogen, methyl, ethyl, fluorine or chlorine, A means N or C-R <9> wherein, R<9> means hydrogen, halogen, such as fluorine or chlorine, methyl, cyano or nitro, or also together with R^ can form a bridge with the structure and their pharmaceutically usable hydrates and acid addition salts, as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids have a high antibacterial effect, especially in the gram-positive range, except 8-amino-9-fluoro-3-methyl-10-( 4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, l-ethyl-5-amino- 6,8-difluoro-7-(1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, 1-ethyl-5-amino-6,8-difluoro-7-(4-methyl- 1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid as well as excluding 8-amino-9-fluoro-3-methyl- . 10(heter6cyclyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [1'"4]-^benzoxazine-6-carboxylic acids and 1-ethyl-5-amino-6 . 3-(Ethylaminomethyl)-1-pyrrolidinyl, 2,7-diazaspiro[4,4]non-2-yl and 7-methyl (resp. ethyl)-2,7-diaza-spiro[4,4]-non- 2-yl and 5-amino-7-(3-amino-1-pyrrolidinyl)-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridinecarboxylic acid and excluding compounds in which R < 3> means the rest with R 4 , R 5 and R<6> = H or <C>1 -C4 -alkyl, when R<1> means cyclopropyl, X means fluorine, Y means amino, hydroxy or C 1 -C 8 -alkyl, and A means N, R <9> means halogen or H, R <2> means H, and their acid addition salts and compounds, wherein Y means amino or chlorine, R <1> means cyclopropyl and X means fluorine, A means CF, and R <3> means in which R' means H or CH3 , R" means H, CH3 or C2 H5 , R'" and R"" means H or methyl, and R<2> means H, CH3 or C2 H5 . 3. = . • Compound of formula I according to claim 1, wherein X-j.be ty r flour, Y means amino, possibly with amino, hydroxy or methoxy substituted alkylamino, with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cyclopropylamino, methoxyamino, hydroxy, alkoxyamino with 1-3 carbon atoms, hydroxy, alkoxy with 1-4 carbon atoms, mercapto, possibly with ethoxycarbonyl, carboxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydroxyamino, R <1> means ethyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, phenyl, 4-fluorophenyl or 2,4-difluorophenyl, R^ means hydrogen, alkyl of 1-3 carbon atoms, (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl, R <3> means a cyclic amino group in which R <4> means hydrogen, alkyl of 1-3 carbon atoms, 2-hydroxyethyl, allyl, 2-oxopropyl, 3-oxobutyl, phenacyl, benzyl, 4-aminobenzyl, (5-methyl-2-oxo-1,3-dioxole -4-yl)-methyl, R^ means hydrogen or methyl, R^ means hydrogen, alkyl with 1-2 carbon atoms, phenyl, 4-fluorophenyl, R <7> means hydrogen, amino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, hydroxy or hydroxymethyl, R» b means hydrogen or methyl, A means N or C-R <9> , wherein R<9> means hydrogen, halogen such as fluorine or chlorine, or together with R^ can form a bridge with the structure and their pharmaceutically usable hydrates and acid addition salts, as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids, except 8-amino-7-fluoro-8-methyl-10-(4-methyl-1-piperazinyl) -7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, 1-ethyl-5-amino-6,8-difluoro-7- (1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, l-ethyl-5-amino-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4-oxo -1,4-dihydro-3-quinolinecarboxylic acid, as well as excluding 8-amino-9-fluoro-3-methyl-10-(heterocyclyl)-7-oxo-2,3-dihydro-7H-pyr idio[1, 2,3]-de[1,4]benzoxazine-6-carboxylic acids and 1-ethyl-5-amino-6,8-difluoro-7-(heterocyclyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acids , wherein heterocyclyl means 3-amino-1-pyrrolidinyl, 3-(aminomethyl)-1-pyrrolidinyl or 3-(ethylaminomethyl)-1-pyrrolidinyl and 5-amino-7-(3-amino-1-pyrrolidinyl)- 1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid. 4. Compounds of formula (I) according to claim 1, in which X means fluorine, Y means" amino, possibly with amino, hydroxy or methoxy substituted alkylamino, with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cyclopropylamino, methoxyamino, hydroxy, alkoxy with 1-4 carbon atoms, mercapto, possibly with ethoxycarbonyl, carboxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, R <1> means ethyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, phenyl, 4-fluorophenyl or 2,4-difluorophenyl, R <2> means hydrogen, alkyl with 1-2 carbon atoms, (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl, R <3> means a cyclic amino group which in which R <4> means hydrogen, alkyl with 1-2 carbon atoms, 2-hydroxyethyl, 2-oxopropyl, 3-oxobutyl; phenacyl, 4-aminobenzyl, r <5> means hydrogen or methyl, R <6> means hydrogen, methyl, phenyl, 4-fluorophenyl, R <7> means hydrogen, amino, aminomethyl, methylaminomethyl, ethylaminomethyl, hydroxy or hydroxymethyl, R<8> means hydrogen, A means N or C-R <9> , wherein R <9> means hydrogen, halogen such as fluorine or chlorine, or together with R-*- can form a bridge with the structure -O -CH2 -CH-C H3 and their pharmaceutically usable hydrates and acid addition salts, as well as alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids except 8-amino-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)- 7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, l-ethyl-5-amino-6,8-difluoro-7 -(1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, l-ethyl-5-amino-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4-oxo -1,4-dihydro-3-quinolinecarboxylic acid as well as excluding 8-amino-9-fluoro-3-methyl-10-(heterocyclyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3- de][1,4]benzoxazine-6-carboxylic acids and l-ethyl-5-amino-6,8-difluoro-7-(heterocyclyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acids, wherein heterocyclyl means 3-amino-l-pyrrolidinyl, 3-(aminomethyl)-l-pyrrolidinyl or 3-(ethylaminomethyl)-l-pyrrolidinyl, and 5-amino-7-(3-amino-l-l-pyrrolidinyl)-l-ethyl-6 -fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid. 5. Compounds from the group consisting of l-cyclopropyl-5,6-difluoro-1,4-dihydro-7-(3-hydroxy-1-pyrrolidinyl)-4-oxo-3-quinolinecarboxylic acid, l-cyclopropyl-5 ,6,7,8-trifluoro-1,4-dihydro-7-(8-methyl-3,8-diazabicyclo[3.2.1]oeth-3-yl)-4-oxo-3-quinolinecarboxylic acid, l- cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinlinecarboxylic acid, 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro- 4-oxo-7-(4-methyl-1-piperazinyl)-3-quinolinecarboxylic acid, l-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-(4-ethyl-1 -piperazinyl)-3-quinolinecarboxylic acid, 1 - cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-[4-(2-hydroxyethyl)-1-piperazinyl]-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-5,6, 8-trifluoro-1,4-dihydro-4-oxo-7-(3-methyl-1-piperazinyl)-3-quinolinecarboxylic acid, 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4- oxo-7-(3,5-dimethyl-1-piperazinyl)-3-quinolinecarboxylic acid, l-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-morpholino-3-quinolinecarboxylic acid, l-Cyclopropyl-5,6,8-triflour-1,4-dihydro-4-oxo-7-thiomor-folino-3-quinolinecarboxylic acid, l-Cyclopropyl-5,6,8-triflour-1,4-dihydro- 4-oxo-7-(4-isopropyl-1-piperazinyl)-3-quinolinecarboxylic acid, 7-(4-allyl-1-piperazinyl)-1-cyclopropyl-5,6,8-trifluoro-1,4-di-hytyrcr=4-oxo-3-kt-n^ lri^^ rb^ k^ sylrsy -re^ 1 -cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-[4-(2-oxopropyl)-1-piperazinyl]-3-quinolinecarboxylic acid, 1 -cyclopropyl-5 ,6,8-trifluoro-1,4-dihydro-4-oxo-7-[4-(3-oxobutyl)-1-piperazinyl]-3-quinolinecarboxylic acid, l-cyclopropyl-5,6,8-trifluoro-l ,4-dihydro-4-oxo-7-(3-phenyl-1-.piperazinyl)-3-quinolinecarboxylic acid, 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(1-imidazolyl )-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-7-(1-pyrrolyl)-3-quinolinecarboxylic acid. 6. Compounds from the group consisting of 5-amino-7-[3-(aminomethyl)-1-pyrro1idinyl]-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5- amino -1 - cyclopropyl - 7- [3- [ (methyl amino ) methyl] -1-pyr rol idinyl] -6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino -1 - cyclopropyl 1 - 7- [3-[(ethylamino )methyl] -1-pyrrol idT-nyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5 -amino-7-[3-amino-1-pyrrolidinyl]-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1 - cyclopropyl 1-7 - [3-(ethylamino)-1-pyrrolidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-difluoro-1,4 -dihydro-7-[3-[[(1-methylethyl)amino]methyl]-1-pyrrolidinyl]-4-oxo-3-quinolinecarboxylic acid, 5-amino-7-[3-(aminomethyl)-1-pyrrolidinyl ]-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-1,m8-naphthyridine-3-carboxylic acid, 5 - amino-1 - cyclopropyl - 7- [3 - [( ethylamino )methyl] - 1-pyrroidinyl]-1,4-dihydro-6-fluoro-4-oxo-1,8-n of tyrin-3-carboxylic acid, 5-amino-7-[3-amino-1-pyrrolidinyl]-1-cyclopropyl-1,4-dihydro- 6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 5-amino-7-[3-(aminomethyl)-1-pyrrolidinyl]-1-ethyl-6-fluoro-1,4-dihydro- 4-oxo-1,8-naphthyridine-3-carboxylic acid, 5-amino-7-[3-(aminomethyl)-1-pyrrolidinyl]-1-ethyl-6,8-difluoro-1,-4-^ dihydrO" 4-oxo-3-quino-M-n c a r b e x-y 1 s y r c , 5-amino-7 - [3-( aminomethyl )-1-pyrrolidinyl]-6,8-difluoro-1-(2-fluoroethyl)- 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-7-[3-(aminomethyl)-1-pyrrolidinyl]-6,8-difluoro-1-ethenyl-1,4-dihydro-4- oxo-3-quinolinecarboxylic acid, 5-amino-1-ethyl-7-[3-[(ethylamino) methyl]-1-pyrroiidinyl]-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine -3-carboxylic acid, 5-amino-1-ethyl-7-[3 — [(ethylamino)methyl]-1-pyrroiidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolIncarboxylic acid , 5-amino-7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid , 5-amino-1-ethenyl-7-[3-[(ethylamino)methyl-1-pyrrolidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1 -ethyl-6-fluoro-1,4-dihydro-7- [3-[[(1-methylethyl)-amino]methyl]-l-pyrrolidinyl]-4-oxo-1,8-naphthyridine-3-carboxylic acid, 5-amino-l-ethyl-7-[3-[( 1-methylethyl )aminomethyl]-1-pyr rol idinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-ethyl-6-fluoro-1,4 -dihydro-7-(7-methyl-2,7-diaza-spiro[4.4]non-2-yl)-4-oxo-1,8-naphthyridine-3-carboxylic acid, 5-amino-1-ethyl-6 ,8-dlfluoro-1,4-dihydro-7-(7-ethyl-2,7-diazaspiro[4.4]non-2-yl)-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6 ,8-dlfluoro-1,4-dihydro-7-(7-methyl-2,7-diazaspiro[4.4]non-2-yl]-4-oxo-3-quinolinecarboxylic acid, 5 -amino-7 - ( 3- amino-1-pyrro idinyl)-1-ethyl 1-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6-fluoro-1 , 4-dihydro-7-(3-hydroxy-1-pyrrolidinyo)-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6-fluoro-1 , 4-dihydro-7-(3-hydroxy -1-pyrrolidinyl)-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-7-(1,4-dlazabicyclo[3.2.1]oct^4-yl)-6-flour-1,4- dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 5-ami no-1-cyclopropyl-6,8-dlfluoro-1,4-dihydro-7-(2-methyl-1,4-diazabicyclo[3.2.l]oct-4-yl)-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(8-methyl-3,8-dlazabicyclo[3.2.1]oeth-3-yl)-4-oxo-3- quinoline carboxylic acid, -§—aÆjrlf-o— 1 -cyclo p^epy-l— 6-,-8 -dif Iruo r -1,4- d4-hyd r-o-~4 -ok s o - 7 - (1 - piperazinyl)-3-quinolinecarboxylic acid, 5-amiho-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7- thimorpholino-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-dichloro-1,4-dihydro-4-oxo-7-(4-isopropyl-1-piperazinyl)-3-quinolinecarboxylic acid, 5-amino -7-(4-allyl-1-piperazinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-difluoro -1,4-dihydrodo-4-oxo-7-[4-(2-oxopropyl)-1-piperazinyl]-3-quinlinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-fluoro-1,4-dihydro -4-oxo-7-[4-(3-oxobutyl)-1-piperazinyl]-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl-6,8-fluoro-1,4-dihydro -4-oxo-7-(1-pyrrolyl)-3-quinolinecarboxylic acid, 5-amino-7-[4-(4-aminobenzyl)-1-piperazinyl]-1-cyclopropyl-6,8-diflouro-1,4 -dihydro-4-oxo-3-quinolinecarboxylic acid, 5-amino-1-cyclopropyl 1-6,8-diflour-1, 4-dihydro-4-oxo-7-(4-phenacyl-1-piperazinyl)-3 -quinolinecarboxylic acid, S-8-amino-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid, 7. 5-substituted quinolone and natyridone carboxylic acid derivatives of formula (I) in which X means fluorine or chlorine, Y means amino, possibly with amino, hydroxy or methoxy substituted alkylamino with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cycloalkylamino with 3-6 -carbonatofie^ -i—alcok s <y> aml^io- with—-1—4—carbon atoms-, —h yd r o sky, alkoxy with 1-4 carbon atoms, mercapto possibly with ethoxycarbonyl, ethoxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydrazino, hydroxyamino, methoxyamino, chlorine, R <*> means methyl, ethyl, propyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, methoxy, amino, dimethylamino, ethylamine, phenyl, 4-fluorophenyl or 2,4-difluorophenyl. R <2> means hydrogen, alkyl with 1-4 carbon atoms or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl and R <3> means methyl or a cyclic amino group which in which R <4> means hydrogen, alkyl with 1-4 carbon atoms, 2-hydroxyethyl, allyl, propargyl, 2-oxopropyl, 3-oxobutyl, phenazyl, formyl, benzyl, 4-aminobenzyl or (5-methyl-2-oxo-1 ,3-dioxol-4-yl)-methyl, r5 bcty^-^iydrogen—e-1-1 er-4iv&ty^, R^ means hydrogen, alkyl with 1-4 carbon atoms, optionally substituted in particular with fluorine-substituted phenyl or benzyloxymethyl, R <7> means hydrogen, amino, .methylamino, ethylamino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, isopropylaminomethyl, hydroxy or hydroxymethyl, R» b is hydrogen, methyl, ethyl, fluorine or chlorine, A means N or C-R9, wherein R <9> means hydrogen, halogen such as fluorine or chlorine, methyl, cyano or nitro, or together with can form a bridge with the structure and their pharmaceutically usable e%?hy d r a t e r and acid addition salts, as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids have a high antibacterial effect, especially in the gram-positive range, except 8-amino-9-fluoro-3-methyl -10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, l-ethyl- 5-Amino-6,8-difluoro-7-(1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, 1-ethyl-5-amino-6,8-difluoro-7- (4-methyl-1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid and except 8-amino-9-fluoro-3-methyl-10(heterodiclyl)-7-oxo-2,3 -dihydro-7G-pyrido[1,2,3-de][1,4]-benzoxazine-6-carboxylic acids and l-ethyl-5-amino-6,8-difluoro- 7-(Heterocyclyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, wherein heterocyclyl means 3-amino-1-pyrrolidinyl, 3-(aminomethyl)-1-pyrrolidinyl, 3-(ethylaminomethyl)-1-pyrrolidinyl , 2,7-diazaspiro[4,4]non-2-yl and 7-methyl (resp. ethyl)-2,7-diaza-spiro[4,4]-non-2-yl and 5-amino-7 -(3-amino-1-pyrrolidinyl)-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid for use in a method for the therapeutic treatment of the human and animal body. 8. Process for the preparation of 5-substituted quinolone and naphthyridine carboxyl-1-acid derivatives -with formula-(-14- in which X means fluorine or chlorine, Y means amino, possibly with amino, hydroxy or methoxy substituted alkylamino with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cycloalkylamino with 3-6 carbon atoms, alkoxyamino with 1-4 carbon atoms, hydroxy, alkoxy with 1-4 carbon atoms, mercapto, possibly with ethoxycarbonyl, carboxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydrazino, hydroxyamino, methoxyamino , chlorine, R <1> means methyl, ethyl, propyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, methoxy, amino, dimethylamino, ethylamino, phenyl, 4-fluorophenyl or 2,4-difluorophenyl, R2 means hydrogen, alkyl with 1-4 carbon atoms or (5-methyl-2-oxo-1, 3-dioxol-4-yl)-methyl and R <3> means methyl or a cyclic amino group which in which R <4> means hydrogen, alkyl with 1-4 carbon atoms, 2-hydroxyethyl, allyl, propargyl, 2-oxopropyl, 3-oxobutyl, phenacayl, formyl, benzyl, 4-aminobenzyl or (5-methyl-2-oxo-1 ,3-dioxol-4-yl)-methyl, R <5> means hydrogen or methyl, R^ means hydrogen, alkyl with 1-4 carbon atoms, optionally substituted in particular with fluorine-substituted phenyl or benzyloxymethyl, R <7> means hydrogen, amino, methylamino, ethylamino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, isopropylaminomethyl, hydroxy or hydroxymethyl, R <8> means hydrogen, methyl, ethyl, fluorine or chlorine, A means N or C-R <9> , wherein R <9> means hydrogen, halogen such as fluorine or chlorine, methyl, cyano or nitro, or also together with R^can form a bridge of structure and their pharmaceutically usable hydrates and acid addition salts as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids, except 8-amino-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7- oxo-2,3-di hy dr o-7H-pyrido[l,2,3-de][1,4]benzoxazine-6-carboxylic acid, l-ethyl-5-amino-6,8-difluoro-7 -(l-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, l-ethyl-5-amino-6,8-difluoro-7-(4-methyl-l-piperazinyl)-4-oxo -1,4-dihydro-3-quinolone carboxylic acid as well as excluding 8-amino-9-fluoro-3-methyl-10-(heterocyclyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2, 3-de][-1,4]benzoxazine- —6-Carboxy 1 acid—and—1-eth-yl-5-am-lno-6,8-di^-1-eur-7-(-heterocyclyl)-4-oxo-1,4-dihydro-3 -quinoline carboxylic acids, wherein heterocyclyl means 3-amino-l-pyrrolidinyl, 3-(aminomethyl)-l-pyrrolidinyl, 3-(ethylaminomethyl)-l-pyrrolidinyl, 2,7-diaza-spiro[4,4]non-2- yl, and 7-methyl(resp. ethyl)-2,7-diazaspiro-[4,4]non-2-yl, and 5-amino-7-(3-amino-1-pyrrolidinyl)-1-ethyl- 6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridinecarboxylic acid, characterized in that compounds with formula (II) in which X,R<1> ,R<2> ,R<3> and A have the above meaning, possibly reacted in the presence of acid scavengers with compounds of formula (III), in which Y has the above meaning. 9. Medicines containing 5-substituted quinolone and naphthyridone carboxylic acid derivatives of formula (I) in which X means fluorine or chlorine, Y means amino, optionally with amino, hydroxy or methoxy substituted alkylamino with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cycloalkylamino with 3-6 carbon atoms, alkoxyamino with 1-4 carbon atoms, hydrosky, alkoxy with 1-4 carbon atoms, mercapto possibly with ethoxycarbonyl, ethoxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydrazino, hydroxyamino, methoxyamino, chlorine, R<1> means methyl, ethyl, propyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, methoxy, amino, dimethylamino, ethylamine, phenyl, 4-fluorophenyl or 2,4-difluorophenyl. R <2> means hydrogen, alkyl with 1-4 carbon atoms or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl and R <3> means methyl or a cyclic amino group which wherein R <4> means hydrogen, alkyl of 1-4 carbon atoms, 2-hydroxyethyl, allyl, propargyl, 2-oxopropyl, 3-oxobutyl, phenazyl, formyl, benzyl, 4-aminobenzyl or (5-methyl-2-oxo- 1,3-dioxol-4-yl)-methyl, R^ means hydrogen or methyl, r <6> means hydrogen, alkyl with 1-4 carbon atoms, optionally substituted in particular with fluorine-substituted phenyl or benzyloxymethyl, R <7> means hydrogen, amino, methylamino, ethylamino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, isopropylaminomethyl, hydroxy or hydroxymethyl, R <8> means hydrogen, methyl, ethyl, fluorine or chlorine, A means N or C-R <9> , wherein R <9> means hydrogen, halogen such as fluorine or chlorine, methyl, cyano or nltro, or also together with R <*> can form a bridge with the structure and their pharmaceutically usable hydrates and acid addition salts, as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids have a high antibacterial effect, especially in the gram-positive range, except for 8-amino-9-fluoro-3-methyl-10-( 4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrldo[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, l-ethyl-5-amino- 6,8-difluoro-7-(1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, 1-ethyl-5-amino-6,8-difluoro-7-(4-methyl-1 -piperazinyl)-4-oxo-1,4-dlhydro-3-chlorolinecarboxylic acid as well as excluding 8-amino-9-fluoro-3-methyl-10(heterodecyl)-7-oxo-2,3-dihydro-7G-pyrido[ 1,2,3-de][1,4]-benzoxazine-6-carboxylic acids and 1-ethyl-5-amino-6,8-difluoro-7-(heterocyclyl)-4-oxo-1,4-dihydroquinoline- 3-carboxylic acid, wherein heterocyclyl means 3-amino-l-pyrrolidinyl, 3-(aminomethyl)-l-pyrrolidinyl, 3-(ethylaminomethyl)-l-pyrrolidinyl, 2,7-dlazaspiro[4,4]non-2-yl and 7-methyl (resp. ethyl)-2,7-dlaza-spiro[4,4]-non-2-yl and 5-amino-7-(3-amino-1-pyrrolidinyl) )-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid.. 10. Use of 5-substituted quinolone and naphthyridone carboxyl acid derivatives of formula (I) in which - :.. X means fluorine or chlorine, Y means amino, possibly with amino, hydroxy or methoxy substituted alkylamino with 1-4 carbon atoms, dialkylamino with 1-4 carbon atoms per alkyl group, cycloalkylamino with 3-6 carbon atoms, alkoxyamino with 1-4 carbon atoms, hydrosky, alkoxy with 1-4 carbon atoms, mercapto possibly with ethoxycarbonyl, ethoxy or hydroxy substituted alkylthio with 1-4 carbon atoms, phenylthio, hydrazino, hydroxyamino, methoxyamino, chlorine, R <1> means methyl, ethyl, propyl, isopropyl, cyclopropyl, vinyl, 2-hydroxyethyl, 2-fluoroethyl, methoxy, amino, dimethylamino, ethylamine, phenyl, 4-fluorophenyl or 2,4-difluorophenyl. R <2> means hydrogen, alkyl with 1-4 carbon atoms or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl and R <3> means methyl or a cyclic amino group such as wherein R <4> means hydrogen, alkyl with 1-4 carbon atoms, 2-hydroxyethyl, allyl, propargyl, 2-oxopropyl, 3-oxobutyl, phenazyl, formyl, benzyl, 4-aminobenzyl or (5-methyl-2-oxo-1 ,3-dioxol-4-yl)-methyl, R <5> means hydrogen or methyl, R <6> means hydrogen, alkyl with 1-4 carbon atoms, optionally substituted in particular with fluorine-substituted phenyl or benzyloxymethyl, R <7> means hydrogen, amino, methylamino, ethylamino, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, isopropylaminomethyl, hydroxy or hydroxymethyl, R <8> means hydrogen, methyl, ethyl, fluorine or chlorine, A means N or C-R <9> , wherein R <9> means hydrogen, halogen such as fluorine or chlorine, methyl, cyano or nitro, or also together with R <*> can form a bridge with the structure and their pharmaceutically usable hydrates and acid addition salts, as well as the alkali, alkaline earth, silver and guanidinium salts of the underlying carboxylic acids have a high antibacterial effect, especially in the gram-positive range, except 8-amino-9-fluoro-3-methyl-10-( 4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, l-ethyl-5-amino- 6,8-difluoro-7-(1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, l-ethyl-5-amino-6,8-difluoro-7-(4-methyl-1 -piperazinyl )-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid as well as excluding 8-amino-9-fluoro-3-methyl-10(heterodiclyl)-7-oxo-2,3-dihydro-7G-pyrido[ 1,2,3-de][1,4]-benzoxazine-6-carboxylic acids and 1-ethyl-5-amino-rf,8-di:^^fluoro-7-(heterocyclyl)-4-oxo-1, 4-dihydroquinoline-3-c.carboxylic acid, wherein heterocyclyl means 3-amino-l-pyrrolidinyl, 3-(aminomethyl)-l-pyrrolidinyl, 3-(ethylaminomethyl)-l-pyrrolidinyl, 2,7-diazaspiro[4,4 ]non-2-yl and 7-methyl (resp. ethyl)-2,7-diaza-spiro[4,4]-non-2-yl and 5-amino-7-(3-amino-1-pyrrole idinyl)-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid for the production of pharmaceuticals. 11. v The use of the compounds according to claim (I) for the production of veterinary medicinal products and animal feed products