Patent CA-1192190-A (CA)
Inventor: HAYES ROGER
IPC: C07D295/096
Filed: 1982-07-23
Granted: 1985-08-20
Abstract: ABSTRACT OF THE DISCLOSURE          The invention relates to compounds of the general formula (I)        (I) and physiclogically acceptable salts, hydrates and bioprecursors thereof, in which R1 represents hydrogen, 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 1 to 3 carbon atoms;          Q represents a benzene ring in which incorpor-ation 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;           Z represents one of the groups         or ?NHR8 Abstract continued where X represents NCN, NSO2Methyl, NSO2Phenyl or CHNO2;     R8 represents alkyl; R3 represents hydrogen, alkyl, alkenyl, aralkyl, hydroxy C2-6 alkyl, alkoxy C2-6 alkyl or C1-4 alkanoyl-oxy C2-6 alkyl;          R7 represents hydrogen, alkyl, alkenyl, aralkyl, acyloxyalkyl, alkylthioalkyl, arylthioalkyl, aryloxy-alkyl, aralkyloxyalkyl, or the group (CH2)qR5 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 is as defined above, and R9 is alkyl;          or R6 is the group NR10R11, where R10 is hydro-gen 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, halomethyl, heteroaryl, heteroaralkyl or the group NHR14 where R14 is hydrogen, alkyl, cycloalkyl, 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 Abstract continued 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, aralkyloxy or -NHC(=Y)NH2 where Y is oxygen or sulphur;          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. g is not greater than 5);          R4 represents phenyl, phenoxy or pyridinyl which may optionally be substituted by one or more halogen, alkyl, alkoxyalkyl or alkoxy groups or by a methylene-dioxy group;          p represents an integer which is 1, 2 or 3; the compounds show pharmacological activity as selective histamine H2-antagonists.