Patent EP-0071434-A2 (EP)
Inventor: HAYES ROGER
IPC: C07D239/46
Filed: 1982-07-23
Abstract: The invention relates to compounds of the general formula (I)
     and physiologically acceptable salts, hydrates and bioprecursors thereof, in which
     R 1  represents hydrogen, C 1-14  alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, trifluoroalkyl, heteroaralkyl or alkyl substituted by cycloalkyl, hydroxy, alkoxy, amino, alkylamino or dialkylamino; and   R 2  represents hydrogen or C 1-4  alkyl group;   or R 1  and R 2  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 C 1-3  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 incorporation into the rest of the molecule is through bonds at the 1- and 3- or 1-and 4- positions:   R 5  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
     where X represents NCN, NS0 2 Methyl, NS0 2 Phenyl or CHNO 2 ;   R 8  represents alkyl;   A represents N and B represents CR 7 ; or   A represents CR 7  and B represents N; or   A and B both represent N;   R 3  represents hydrogen, alkyl, alkenyl, aralkyl, hydroxy C 2-6  alkyl, alkoxy C 2-6  alkyl or C 1-4  alkanoyloxy C 2-6  alkyl;   R 7  represents hydrogen, alkyl, alkenyl, aralkyl, acyloxyalkyl, alkylthioalkyl, arylthioalkyl, aryloxyalkyl, aralkyloxyalkyl, or the group (CH 2 ) q R 8  where q is zero, 1, 2, 3, 4, or 6 and the alkylene chain (CH 2 ) q  may be straight or branched, and   R 6  is hydroxy, alkoxy, nitro, heteroaryl, tetrahydropyranyloxy or CH 2 NHC(=X)NHR 9  where X is as defined above, and R 9  is alkyl;   or R 6  is the group NR 10 R 11 , where R 10  is hydrogen or alkyl; and R 11  is hydrogen, alkyl, alkenyl, aryl, aralkyl, or heteroaralkyl, or R 11  is the group SO 2 R 12  where R 12  is alkyl or aryl; or R 11  is the group COR 13  where R, 3  is hydrogen, alkyl, aryl, aralkyl, alkoxy, halomethyl, heteroaryl, heteroaralkyl or the group NHR 14  where R 14  is hydrogen, alkyl, cycloalkyl, aryl or aralkyl; or R 10  and R 11  together represent the group =CR 15 R 16  where R 15  represents aryl or heteroaryl and R 16  represents hydrogen or alkyl;   or R 6  is the group SO 2 R 17  in which R 17  is hydroxy, alkyl, aryl or the group NR 18 R 19  where R, s  and R 19 , which may be the same or different, each represent hydrogen or alkyl;   or R 6  is the group COR20 where R 20  is hydrogen, hydroxy, alkoxy, aryloxy, aralkyloxy, alkyl, aryl, aralkyl or the group NRZ 21 R 22  where R 21  is hydrogen or alkyl optionally substituted by a hydroxy or alkoxy group; and R 22  is hydrogen, alkyl (optionally substituted by a hydroxy or alkoxy group), alkenyl, aryl, aralkyl or cycloalkyl, or NR 21 R 22  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 C 1-3  alkyl groups; or R 6  is the group CR 23 =NR 24  where R23 is hydrogen, alkyl, aryl or aralkyl and R 24  is hydroxy, alkoxy, aralkyloxy or -NHC(=Y)NH 2  where Y is oxygen or sulphur;   or when A represents CR 7  and B represents N, the groups R 3  and R 7  taken together represent (̵ CH=CH )̵ 2  or - (CH 2 ) 4 ;   with the proviso that when the group R 6  contains a carbon atom through which it is linked to the alkylene group (CH 2 )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);   R 4  represents phenyt, phenoxy or pyridinyl which may optionally be substituted by one or more halogen, alkyl, alkoxyalkyl or alkoxy groups or by a methylenedioxy group;   p represents an integer which is 1, 2 or 3;   The compounds show pharmacological activity as selective histamine H 2 -antagonists.