Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-11-19
2000-09-05
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546153, A01N 4342, C07D21516
Patent
active
061143510
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new antibacterial compositions, in particular orally administrable compositions, based on N-oxides of saturated nitrogen-containing heterocycles which are substituted by quinolonecarboxylic acids or naphthyridonecarboxylic acids, and to new active compounds and their preparation.
N-oxides of saturated nitrogen-containing heterocycles which are substituted by quinolonecarboxylic acids are known as metabolites of the active compounds on which they are based. However, it is also known that these metabolites have no antibacterial action (J. Guibert et. al. Pathol. Biol. 1989, 37(5), 406-10; Venezia et. al. Antimicrob. Agents. Chemot. 1989, 33(5), 762-6).
It was further known that the oral administration of antibacterial compositions based on quinolone- or naphthyridonecarboxylic acids via the feed or drinking water of animals is often problematical. Refusal of drinking water or feed and thus an inadequate dose of the medicament often occurs. As medication via the feed or the drinking water is a very simple and stress-free type of administration for veterinary surgeon, animal keeper and animal to be treated, there is a high need for orally administrable compositions. It is desirable to be able to administer precisely the highly active antibacterial compositions of the quinolonecarboxylic acid series, such as enrofloxacin, reliably via the feed.
There have been found:
1. Antibacterial compositions based on N-oxides of saturated nitrogen-containing heterocycles which are substituted by quinolone- or naphthyridonecarboxylic acids of the formula (I) or (II): ##STR1## in which X represents hydrogen, halogen, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, NH.sub.2, ##STR2## in which R.sup.4 represents straight-chain or branched C.sub.1 -C.sub.4 -alkyl which is optionally substituted by hydroxyl or methoxy, cyclopropyl, acyl having 1 to 3 C atoms, cyclopropyl, 2-fluoroethyl, methoxy, 4-fluorophenyl, 2,4-difluorophenyl or methylamino, optionally substituted by methoxy or 2-methoxyethoxy, and cyclohexyl, benzyl, 2-oxopropyl, phenacyl, ethoxycarbonylmethyl, pivaloyloxymethyl, .dbd.C(CH.sub.3)--, phenyl, and .dbd.CH.sub.2, salts with bases. The compounds of the formulae I and II can be present in the form of their racemates or in enantiomeric forms.
2. Compositions administrable via the feed or drinking water of animals, based on N-oxides of saturated nitrogen-containing heterocycles which are substituted by quinolone- or naphthyridonecarboxylic acids, of the formulae (I) or (II): ##STR3## in which Z and X have the meaning indicated above, ##STR4## in which R.sup.4 represents straight-chain or branched C.sub.1 -C.sub.4 -alkyl which is optionally substituted by hydroxyl or methoxy, cyclopropyl, acyl having 1 to 3 C atoms, cyclopropyl, 2-fluoroethyl, methoxy, 4-fluorophenyl, 2,4-difluorophenyl or methylamino, optionally substituted by methoxy or 2-methoxyethoxy, and cyclohexyl, benzyl, 2-oxopropyl, phenacyl, ethoxycarbonylmethyl, pivaloyloxymethyl, .dbd.C(OCH.sub.3), methyl or phenyl, salts with bases.
3. New N-oxides of saturated nitrogen-containing heterocycles which are substituted by quinolonecarboxylic acids, of the formula (Ia): ##STR5## in which Y represents radicals of the structures: ##STR6## in which R.sup.4 represents straight-chain or branched C.sub.1 -C.sub.4 -alkyl which is optionally substituted by hydroxyl or methoxy, cyclopropyl, acyl having 1 to 3 C atoms, optionally substituted by methoxy, and benzyl, 2-oxopropyl, phenacyl and also ethoxycarbonylmethyl, salts with bases.
It has furthermore been found that the compounds of the formula (Ia) are obtained when ##STR7## in which Y' represents the saturated nitrogen-containing heterocycle on which the N-oxide radicals Z are based, oxygen-donating agents, or when ##STR8## in which Z, A, R.sup.1, R.sup.2 have the meaning indicated above and N-oxides of saturated nitrogen-containing heterocycles of the formula (V): binders.
Preferred compounds of the formula (I) are those in which by halogen, or cyclopropyl, ##STR9## in which R.sup.4 represe
REFERENCES:
patent: 5152984 (1992-10-01), Lange et al.
Venezia et al., "In Vitro Activities of Amifloxacin . . . ", Antimicrobial Agents and Chemotherapy, vol. 33, No. 5, pp. 762-766, May 1989.
Journal of Medicinal Chemistry, vol. 27, No. 9, 1984, pp. 1103-1108, XP002012275, M.P. Wentland, et al.: "Novel amino-substituted 3-quinolinecarboxylic acid antibacterial agents".
Antimicrob. Agents Chemoth., vol. 33, No. 5, 1989, pp. 762-766, XP000600481, R.A. Venezia, et al.: "In vitro activities of amifloxaciin and two of its metabolites".
Chemical Abstracts, vol. 114, No. 13, 1991, Abstract No. 114663w, Y. Niwata, et al. "In vitro and in vivo antibacterial activity of urinary metabolites of fleroxacin" p. 22.
Chemical Abstracts Registry Handbook, XP002012276, Abstract No. 221823s, F. Collignon, et al. "In vitro models" p. 8, vol. 109, 1988.
Chemical Abstracts Registry Handbook, XP002012277, RN=106100-88-3, No. 413, 1987, pp. 199-206, G.R. Granneman, et al. "HPLC procedures for the determination of difloxacin and it metabolites".
Pathol. Biol. vol. 37, No. 5, 1989, pp. 406-410, XP000600482, J. Guibert, et al.: "Antibacterial activity of pefloxacin in urine".
Hallenbach Werner
Rast Hubert
Scheer Martin
Akorli Godfried R.
Bayer Aktiengesellschaft
Gil Joseph C.
Shah Mukund J.
Truong Tamthom N.
LandOfFree
N-oxides as antibacterial agents does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with N-oxides as antibacterial agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and N-oxides as antibacterial agents will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2212456