2-substituted-4-hydroxy-3-quinolinecarboxylic acids, their preparation, their use as medicaments, compositions containing them and intermediates

Claim 1

Process for preparing the compounds with the formula (1'): in which X in position 5, 6, 7 or 8 represents a hydrogen atom, a halogen atom, an alkyl radical, linear or branched, containing 1-5 carbon atoms, an alkoxy radical, linear or branched, containing 1-4 carbon atoms, a trifluoromethyl radical, a tri- fluoromethylthio radical, or a trifluoromethoxy radical, R 1 ' represents a hydrogen atom or an alkyl radical containing 1-4 carbon atoms, R 2 ' represents a hydrogen atom or a radical chosen from the following radicals: thiazolyl, 4,5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl, tetrazolyl, thienyl, benzothiazolyl and phenyl, possibly substituted by one or more radicals chosen from the group constituted by a) the halogens, b) the alkyl radicals containing 1-4 carbon atoms unsubstituted or substituted by an amino, alkylamino or dialkylamino radical, of which the alkyl radicals contain 1-3 carbon atoms, c) the phenyl radical, d) the alkoxy radicals containing 1-4 carbon atoms, e) the hydroxy radical, f) the trifluoromethyl, radical, and g) the nitro radical, or R 1 ' and R 2 ' together form any one of the saturated or unsaturated rings mentioned above for R z ', the said ring then being linked to the nitrogen atom by a double bond, R 3 represents a hydrogen atom, a halogen atom, an alkyl radical containing 1-4 carbon atoms, R 4 represents a hydrogen atom or a halogen atom, R 5 represents a halogen atom, providing that R 3 , R 4 and R 5 do not each represent, at the same time, a fluorine atom, and R 6 represents a hydrogen atom, an alkyl radical containing 1-8 carbon atoms or an acyl radical containing 2-8 carbon atoms, as well as their salts of addition with acids and bases, characterized in that - either a compound with the formula (II): in which X retains the same significance as previously, alk represents an alkyl radical containing 1-8 carbon atoms and R represents a hydrogen atom or an alkyl radical containing 1-4 carbon atoms, is submitted to the action of a halogenation agent, then if applicable, to the action of a second halogenation agent, different from the first, so as to obtain the compound with the formula (IIIA): in which R 3 ', R 4 ' and R 5 ' retain the same significance given for R 3 , R 4 , and R 5 previously, which is submitted, if desired, to the action of a compound with the formula Hall M, in which Hall represents a halogen atom and M an alkali metal atom, so as to obtain the compound with the formula (III B ): in which R3" represents a hydrogen atom, a Hall halogen atom, an alkyl radical containing 1-4 carbon atoms, R4" represents a hydrogen atom or a Hall halogen atom and R5" represents a Hall halogen atom, then the compound with the formula (IIIA) or the compound with the formula (III B ) is submitted to the action of a saponification agent, so as to obtain a corresponding acid with the formula (IV): in which R 3 , R 4 and R 5 retain their preceding significance, which is transformed, if desired, into a functional derivative of the acid, then the acid with the formula (IV) or a functional derivative of this acid, is submitted to the action of a compound with the formula (V): in which R 1 ' and R 2 ' retain their preceding significance, so as to obtain the corresponding compound with the formula (l A '): in which X, R 1 ', R 2 ', R 3 , R 4 and R 5 are defined as previously, corresponding to a product with the formula (I') in which R 6 represents a hydrogen atom, which product with the formula (l A ') is submitted, if desired, to the action of an etherification agent or an esterification agent, so as to obtain a product with the formula (l B '): in which X, R 1 ', R 2 ', R 3 , R 4 and R 5 are defined as previously, and R 6 has the previously indicated values for R s , with the exception of hydrogen, which product with the formula (IA') or (I B ') is submitted, if desired, to the action of an acid or a base so as to form its salt, or a compound with the formula (VI): in which X retains its significance given in Claim 1, is submitted to the action of an acid with the formula (VII): in which R 3 , R 4 , R 5 retain their significances given in Claim 1 or a functional derivative of the acid with the formula (VII), so as to obtain a compound with the formula (VIII): in which X retains its preceding significance, which is submitted to the action of a compound with the formula (IX): in which R 1 ' and R z ' retain the significances given in Claim 1, so as to obtain the compound with the formula (X): in which R 1 ', R 2 ', R 3 , R 4 and R 5 retain their preceding significances, which is cyclized in the presence of an alkaline agent, so as to obtain a compound with the formula (IA'), as previously defined, which compound with the formula (l A ') is submitted, if desired, to the action of an etherification agent or an esterification agent, so as to obtain a compound with the formula (I B '), as previously defined, which compound with the formula (l A ') or (l B '), if desired, is submitted to the action of an acid or a base so as to form its salt.