Verfahren zur Herstellung von Oxadiazol-Derivaten

摘要

The invention comprises compounds of the formula wherein R represents an unsubstituted aryl group, an alkoxy- and/or halogen-substituted aryl group, or a diphenylmethyl group which may be substituted by a halogen atom or an alkoxy group, A represents (i) an alkylene or aralkylene group where R represents an unsubstituted aryl group, (ii) an alkylene group where R represents a substituted aryl group, or (iii) an alkylene group or a valency bond where R represents a diphenylmethyl group, R1 represents the grouping -A1-B, wherein A1 represents a valency bond or an alkylene group and B represents an alkyl, amino, alkylamino or dialkylamino group, an aromatic group substituted by an amino group, or a heterocyclic group containing nitrogen; acid addition salts thereof; and processes for their preparation comprising (a) reacting an amidoxime of the formula with, as an acylating agent, an acid of the formula R2COOH, wherein R2 has the same meaning as R1, or represents a group which is capable of transformation into the group R1, or with an acylating derivative of such an acid, thereafter, if necessary, effecting ring closure as a separate reaction step by eliminating water, to obtain a compound of the formula the group R2, where different from R1 being converted into R1 either before or after ring closure, or (b) (for compounds wherein the group R-A- represents a b,b-diphenylethyl group) reacting a compound of the formula with benzene in the presence of a Lewis acid, or (c) (for compounds wherein R1 represents the group -CH2.CH2.NBD in which B and D each represents a hydrogen atom or an alkyl group, or B and D together with the nitrogen atom form a ring which may contain further hetero atoms) reacting an amidoxime of Formula III with acrylic acid or beta-alkoxy-propionic acids or acylating derivatives thereof to yield compounds of the formula wherein R4 represents a vinyl group or the group of the formula -CH2-CH2-OR5, wherein R5 represents an alkyl group, and reacting the compounds thus obtained with amines of the formula HNBD before or after ring closure and, if necessary, effecting ring closure. Pharmaceutical compositions having spasmolytic, anti-tussive, local anaesthetic, anti-inflammatory, anti-pyretic and vasodilator activity, for oral or parenteral administration, comprise a compound of the invention together with a pharmaceutical carrier or diluent.