METHOD OF OBTAINING DERIVATIVES OF 1,2,5-OXADIZOL-3,4-BIS-CARBONIC ACID OR THEIR PHARMACEUTICALLY ACCEPTABLE ACID-ADDITIVE SALTS

摘要

1,2,5-Oxadiazole-3,4-dicarboxylic acid derivatives of the formula I IMAGE in which R1 represents the group -OH, -OR3, -NH2, -NHR4 or -NR5R6, R2 represents the group -NHR4 or -NR5R6, R3 represents an alkyl group having 1 to 4 C atoms, R4 represents an alkyl group having 1 to 6 C atoms, a cycloalkyl group having 5 or 6 C atoms, an aralkyl group which can optionally be substituted by 1 or 2 methoxy groups, or a heteroarylalkyl group, a -CH2(CH2)m-OCH3 group in which m is 0 or 1, a 2-hydroxyethyl group or a base-substituted alkyl group and R5 and R6 independently of one another have one of the meanings of R4 or together with the nitrogen atom to which they are bonded form an optionally substituted heterocyclic ring, are prepared by reacting a 1,2,5-oxadiazole-3,4-bis-carboxylate of the formula II IMAGE with at least 2 moles of an amine R4NH2 or R5R6NH or with less than 2 moles, in particular 1 to 1.1 moles, of an amine R4NH2 or R5R6NH, if appropriate, the product is subsequently reacted with NH3 or with another amine R4NH2 or R5R6NH, or is hydrolysed to eliminate the R3O group, or by removing the oxide oxygen from a 2-oxy-1,2,5-oxadiazole- 3,4-bis(carboxamide) of the formula III IMAGE by reduction. They are used as pharmacologically active substances.