1,2,4-TRIAZOLE DERIVATIVES, PROCESSES FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

摘要

The invention provides compounds of the general formula (I) and physiologically acceptable salts, hydrates and bioprecursors thereof, in which R1 and R2, which may be the same or different, each represent hydrogen, C1-10 alkyl, cycloalkyl, alkenyl, aralkyl, trifluoroalkyl, heteroaralkyl, or alkyl substituted by hydroxy, alkoxy, amino, alkylamino, dialkyamino or cycloalkyl, or R1 and R2 may together with the nitrogen atom to which they are attached form a 5 to 10 membered ring which may be saturated or may contain at least one double bond, may be unsubstituted or may be substituted by one or more C1-3 alkyl groups, or a hydroxy group and/or may contain another heteroatom selected from oxygen and sulphur; Alk represents a straight or branched alkylene chain of 1 to 6 carbon atoms and is attached to the cyclohexadiene ring at either the 4- or 5- position; X represents -CH2 or -O-; m represents 2, 3, 4 or 5 and when X is -O- the chain (CH2)m may be interrupted by an oxygen atom provided that there are at least two methylene groups between any two heteroatoms in the moiety -X(CH2)mNH-; R3 represents hydrogen, alkyl, alkenyl, aralkyl, or C2-6 alkyl substituted by hydroxy or alkoxy; and R4 represents hydrogen, alkyl, alkenyl, aralkyl, hydroxyalkyl, acyloxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkyloxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, hydroxy or alkoxy or the group NR5R6 where R5 represents hydrogen, alkyl, alkyl substituted by hydroxy or C1-3 alkoxy, alkenyl, aralkyl or heteroaralkyl and R6 represents any of the groups defined for R5 or may represent the group COR7 where R7 represents hydrogen, alkyl, aryl, aralkyl, alkoxy, heteroaryl or monocyclic heteroaralkyl or R6 represents the group SO2R8 where R8 represents alkyl or aryl, or R6 represents the group where Y is oxygen or sulphur and R9 represents hydrogen, alkyl, cycloalkyl, aryl or aralkyl, or R5 and R6 taken together may represent the group =CR10R11 where R10 represents aryl or heteroaryl and R11 represents hydrogen or alkyl. The compounds show activity as selective histamine H2-antagonists.