Patent CA-1189508-A (CA)
Inventor: HAYES ROGER
IPC: C07D239/46
Filed: 1982-07-23
Granted: 1985-06-25
Abstract: ABSTRACT OF THE DISCLOSURE            The invention relates to compounds of the general formula (I)                    (I) and physiologically acceptable salts, hydrates and bioprecursors thereof, in which R1 represents hydrogens, C1-14 alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, trifluoroalkyl, heteroaralkyl or alkyl substituted by cycloalkyl, hydroxy, alkoxy, amino, alkylamino or dialkylamino; and R2 represents hydrogen or C1-4 alkyl group; or R1 and R2 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 or sulphur:        Alk represents a straight or branched alkylene chain of l to 3 carbon atoms;        Q represents a benzene ring in which incorporation into the rest of the molecule is through bonds at the 1-and 3- or 1- and 4- positions:        R5 represents hydrogen or acyl; n and m, which may be the same or different, are each 1 or 2;        R3 represents hydrogen, alkyl, alkenyl, aralkyl, hydroxy C2-6 alkyl, alkoxy C2-6 alkyl or C1-4 alkanoyloxy C2-6 alkyl; and R7 represents hydrogen, alkyl, alkenyl, aralkyl, acyloxyalkyl, alkylthioalkyl, arylthioalkyl, aryloxyalkyl, aralkyloxyalkyl, or the group (CH2)qR6 where q is zero, 1, 2, 3, 4, 5 or 6 and the alkylene chain (CH2)q may be straight or branched, and R6 is hydroxy, alkoxy, nitro, heteroaryl, tetra-hydropyranyloxy or CH2NHC(=X)NHR9 where X represents NCN, Abstract continued...          NSO2 Methyl, NSO2 Phenyl or CHNO2 and R9 is alkyl;        or R6 is the group NR10R11, where R10 is hydrogen or alkyl; and R11 is hydrogen, alkyl, alkenyl, aryl, aralkyl, or heteroaralkyl, or R11 is the group SO2R12 where R12 is alkyl or aryl; or R11 is the group COR13 where R13 is hydrogen, alkyl, aryl, aralkyl, alkoxy, halo-methyl, heteroaryl, heteroaralkyl or the group NHR14 where R14 is hydrogen, alkyl, cycloalkylr aryl or aralkyl; or R10 and R11 together represent the group =CR15R16 where R15 represents aryl or heteroaryl and R16 represents hydrogen or alkyl;        or R6 is the group SO2R17 in which R17 is hydroxy, alkyl, aryl or the group NR18R19 where R18 and R19, which may be the same or different, each represent hydrogen or alkyl;        or R6 is the group COR20 where R20 is hydrogen, hydroxy, alkoxy, aryloxy, aralkyloxy, alkyl, aryl, aralkyl or the group NR21R22 where R21 is hydrogen or alkyl optionally substituted by a hydroxy or alkoxy group; and R22 is hydrogen, alkyl (optionally substituted by a hydroxy or alkoxy group), alkenyl, aryl, aralkyl or cycloalkyl, or NR21R22 forms a 5 to 8 membered ring which may contain another heteroatom, e.g. oxygen, or a double bond and/or may be substituted by hydroxy or one or two C1-3 alkyl groups or R6 is the group CR23=NR24 where R23 is hydrogen, alkyl, aryl or aralkyl and R24 is hydroxy, alkoxy, aralkyl-oxy or -NHC(=Y)NH2 where Y is oxygen or sulphur;        or when A represents CR7 and B represents N, the groups R3 and R7 taken together represent   or -(CH2)4-;     with the proviso that when the group R6 contains a carbon atom through which it is linked to the alkylene group (CH2)q then the total number of carbon atoms in the resulting chain is not greater than 6 (i.e. q is not greater than 5).      The compounds show pharmacological activity as selective histamine H2-antagonists.