Quinolones, process for their preparation and pharmaceutical com

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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Details

514314, 546156, A61K 3147, C07D21516

Patent

active

053327497

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to novel quinolones and more particularly to quinolones substituted with a piperidinyl ring.
More particularly it has a subject matter novel piperidinyl quinolone 3-carboxylic acids having the general formula I ##STR3## wherein Z represents an amino group and R.sub.1 represents a lower alkyl radical which may be substituted with a hydroxy, an acyl residue coming from a carboxylic organic acid, an alkylcarbonic acid, an alkyl sulphonic acid or an arylamino carbonyl group of the formula ##STR4## wherein Ar is an aromatic mono- or bicyclic radical which is optionally substituted by one, two or three substituents selected from the group consisting of a lower alkyl radical, a halogen, and a trifluoromethyl equal to 0 or 1
Among the compounds of this invention, it may distinguished three sub-groups.
a) The amino and alkylamino derivatives of formula I.sub.A ##STR5## wherein R.sub.1 represents hydrogen or a lower alkyl radical, which is straight or branched and which may be substituted by a hydroxy.
b) The acylamino derivatives of formula I.sub.B ##STR6## wherein Ac represents the residue of an aliphatic, aromatic or cyclanic carboxylic acid having from 1 to 10 carbon atoms, the residue of an alkylcarbonic acid or the residue of an alkyl sulphonic acid which may be substituted with a hydroxy or a trifluoromethyl radical.
The (uriedo) derivatives of formula I.sub.c ##STR7## wherein X represents oxygen or sulphur W is a group .gtoreq.CH or .gtoreq.N
Amoug the compounds of general formula I, the compounds for which Z, R.sub.1 is an ureido group are those which are presently preferred.
The compounds according to this invention may be salified by adding a mineral or organic base. The main salts which are useful, are those of alkali-metals, of alkaline metals, of iron, of ammonium, the alkylamine salts, the hydroxy alkyl amine salts, the phenylalkylamine salts, the pyridylalkylamine salts, the cyclanylamine salts, the dicyclanylamine salts.
Among these salts, the salts of sodium, lithium, ammonium, N-methyl glucamine and tromethanol are those presently preferred.
These compounds may also exist in the form of a N-oxide the solubility in water and in the biological media of which is improved.
These compounds may also be salified by a strong mineral or organic acid when R.sub.1 is hydrogen, a lower alkyl radical or a lower hydroxyalkyl radical.
The compounds according to the invention show very strong antibacterial properties, namely against Gram positive bacterias.
Moreover they have the properties to be very slightly resorbed through the digestive tract and consequently their elimination is essentially fecal.
They may be then efficiently be used as medicines of the bacterial infections of the digestive tract, for treating bacterial dysentery traveller's diarrhea, or intestinal infections. They may also be utilized topically for the treatment of the ocular infections or in conjunction the infections of the auditive tract.
For these purposes the compounds according to this invention are utilized in the form of pharmaceutical compositions wherein the active ingredient of general formula I or one of its salts is admixed with a carrier or vehicle, which is inert, non-toxic, pharmaceutical-acceptable.
The more appropriate pharmaceutical forms are those intended for the administration through the digestive tract such as the drinkable suspensions or solutions, the granules, the capsules, the uncoated or coated tablets, the dragees, the sachets of powders, which may be flavoured or not, sweetened or not, the pills or the cachets.
For the topic application as an external antibacterial-agent, they may be used in the form of solutions, creames, salves, and gels.
The daily dosage mainly depends on the severity of the infection and on the susceptibility of the microbial strain to the antibacterial-agent. The unitary dosology ranges from 100 to 600 mg per unit dosage. The daily dose ranges from 200 to 1200 mg divided in two intakes.
This invention also relates to a process for obtaining the compounds of g

REFERENCES:
patent: 4851418 (1989-07-01), Sanchez
patent: 4894458 (1990-01-01), Masuzawa et al.

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