The present invention relates to new aromatic amides substituted by a ribose, their preparation process and their use as medicaments.
A subject of the invention is the compounds of formula (I): 
in which
R1 represents a linear, branched or cyclic alkyl, alkenyl or alkynyl, O-alkyl, O-alkenyl or O-alkynyl radical containing up to 8 carbon atoms optionally substituted by one or more halogen atoms, optionally interrupted by an oxygen, sulphur or nitrogen atom, an optionally substituted aryl or aralkyl radical containing up to 18 carbon atoms, an optionally substituted mono or polycyclic aromatic or non-aromatic heterocyclic radical, an NH2, NHalk1 or NHalk2, NHalk3 or NHOalk4 radical, alk1, alk2, alk3 and alk4 representing an alkyl radical containing up to 8 carbon atoms,
R2 represents a hydrogen atom or a halogen atom,
R3 represents a hydrogen atom, an alkyl radical containing up to 8 carbon atoms or a halogen atom,
R4 represents an NHRxe2x80x2 or NHORxe2x80x3 radical in which Rxe2x80x2 or Rxe2x80x3 identical or different represent a hydrogen atom, a linear, branched or cyclic alkyl, alkenyl or alkynyl radical containing up to 8 carbon atoms, an optionally substituted aryl radical containing up to 14 carbon atoms,
R5 represents a hydrogen atom or an O-alkyl radical containing up to 8 carbon atoms,
R6 an alkyl or CH2xe2x80x94O-alkyl radical, in which alkyl represents an alkyl radical containing up to 8 carbon atoms,
R7 represents a hydrogen atom or an alkyl radical containing up to 8 carbon atoms or R6 and R7 form together with the carbon which carries them a ring as well as their addition salts with bases.
As examples of bases there can be mentioned the salts formed with amines such as arginine, lysine, the Na+, K+, NH3+, N(alk)3+ions, alk3 representing an alkyl radical containing up to 8 carbon atoms.
In the definition of the substituents:
the alkyl, alkenyl or alkynyl radical is preferably a methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, terbutyl, decyl or dodecyl, vinyl, allyl, ethynyl, propynyl, cyclobutyl, cyclopentyl or cyclohexyl radical,
the halogen is preferably fluorine or chlorine, or bromine,
the aryl radical is preferably the phenyl radical.
A more particular subject of the invention is the compounds of formula (I) in which R1 represents an alkyl radical containing up to 4 carbon atoms, for example 
radical, the compounds of formula (I) in which R1 represents a phenyl radical, the compounds of formula (I) in which R2 represents a hydrogen atom, the compounds of formula (I) in which R3 represents a methyl radical, the compounds of formula (I) in which R5 is an OCH3 radical, the compounds of formula (I) in which R6 and R7 represents a methyl radical of an ethyl radical as well as those in which R6 and R7 together with the carbon which carry them form a cyclopentyl radical.
Among the preferred compounds of the invention, there can be mentioned the compounds of formula (I) in which R4 represents an NHxe2x80x94Oxe2x80x94CH2xe2x80x94Cxe2x89xa1CH radical.
A particular subject of the invention is the compounds the preparation of which is given hereafter in the experimental part and quite particularly the product of Examples 10 and 11. The products of general formula (I) have a very good antibiotic activity on anaerobic gram bacteria such as staphylococci, streptococci, pneumococci, enterococci, listeria.
The compounds of the invention can therefore be used as medicaments in the treatment of germ-sensitive infections and, in particular, in that of staphylococcia, such as staphylococcal septicemias, malignant facial or cutaneous staphylococcia, pyodermatitis, septic or suppurating wounds, boils, anthrax, phlegmons, erysipelas and acne, staphylococcias such as primative or post-influenzal acute angina, bronchopneumonia, pulmonary suppuration, streptococcia such as acute angina, otitis, sinusitis, scarlatina, pneumococcia such as pneumonia, bronchitis and diphtheria. The products of the present invention are also active against infections caused by germs such as Haemophilus influenzae.
A subject of the invention is therefore the compounds of formula (I) as well as their pharmaceutically acceptable salts as medicaments.
A more particular subject of the invention is as medicaments the compounds indicated above as preferred compounds.
A subject of the invention is also the pharmaceutical compositions containing as active ingredient at least one of the medicaments defined above.
These compositions can be administered by buccal, rectal, parenteral route or by local route as a topical application on the skin and the mucous membranes, but the preferred administration route is the buccal or injectable route.
They can be solids or liquids and be presented in the pharmaceutical forms commonly used in human medicine, such as for example, plain or sugar-coated tablets, gelatin capsules, granules, suppositories, injectable preparations, ointments, creams, gels; they are prepared according to the usual methods. The active ingredient(s) can be incorporated with the excipients usually used in these pharmaceutical compositions, such as talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous or non aqueous vehicles, fatty substances of animal or vegetable origin, paraffin derivatives, glycols, various wetting, dispersing or emulsifying agents, preservatives.
These compositions can also be presented in the form of a powder intended to be dissolved extemporaneously in an appropriate vehicle, for example apyrogenic sterile water.
The dose administered is variable according to the condition treated, the patient in question, the administration route and the product considered. It can be, for example, comprised between 50 mg and 3000 mg per day by oral or injectable route in adults for the preferred products.
A subject of the invention is a process for the preparation of the compounds of formula (I) characterized in that a compound of formula (II): 
is subjected to the action of a compound of formula 
in which R1 retains its previous meaning and Hal represents a halogen atom in order to obtain the compound of formula (III): 
which is subjected to the action of a compound of formula
R4Hxe2x80x83xe2x80x83(IV)
in order to obtain the compound of formula 
A subject of the invention is also as new chemical products, the compounds of formula (II) and (III). In a preferred embodiment, Hal is a chlorine atom.
The compounds of formula (II) used as starting products in the process according to the invention, can be prepared as indicated hereafter in the experimental part. The preparation of the compounds of formula (II) described in the experimental part can be illustrated as follows: 
A subject of the invention is also a process characterized in that a compound of formula (V): 
in which the substituents retain their previous meaning and OM represents a blocked hydroxyl radical, is subjected to the action of a compound of formula R1COHal in which R1 retains its previous meaning and Hal represents a halogen atom, then to the action of an agent which releases the OH function in order to obtain the corresponding compound of formula (I): 
The products of formula (V) used as starting products are new products and are in themselves a subject of the invention.
USPTO Backgrounds
USPTO Backgrounds