Patent EP-0048555-A1 (EP)
Inventor: CAREY LINDA
IPC: C07D295/096
Filed: 1981-08-27
Abstract: he invention provides compounds of the general formula (I) 
     and physiologically acceptable salts, hydrates and bioprecursors thereof, in which
     R, represents 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 a C 1-4 alkyl group;   or R 1  and R 2  together with the nitrogen atom to which they are attached form a 5-10 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, e.g. methyl, 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;   Q represents a furan or thiophen ring in which incorporation into the rest of the molecule is through bonds at the 2-and 5- positions, the furan or thiophen ring optionally bearing a further substituent R 5  adjacent to the group R 1 R 2 N-Alk, or 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 s  represents halogen or C 1-4  alkyl which may be substituted by hydroxy or C 1-4  alkoxy;   X and Y, which may be the same or different, each represent oxygen, sulphur, methylene or a bond;   n represents zero, 1, 2 or 3 and m represents an integer from 2 to 5 with the provisos that (a) the total number of atoms in the chain X(CH 2 ) n Y(CH 2 ) m  is an integer from 3 to 8 and (b) when X and Y represent oxygen or sulphur then n is 2 or 3.   R 3  represents alkyl, alkenyl, aralkyl, hydroxy-C 2-6  alkyl or alkoxy-C 2-6  alkyl; and   R 4  represents hydrogen, alkyl, alkenyl, aralkyl, acyloxyalkyl, alkylthioalkyl, arylthioalkyl, aryloxyalkyl, aralkyloxyalkyl, or the group (CH 2 ) q R 6  where q is zero, 1,2,3,4, 5 or 6 and the alkylene chain (CH 2 ) q  may be straight or branched, and   R 6  is hydroxy, alkoxy, nitro, heteroaryl or CH 2 NHC(=A)NHR 7  where A is NCN, NSO 2 Methyl, NSO z Phenyl, or CHNO z , and R 7  is alkyl;   or R 6  is the group NR 8 R 9  where R 8  is hydrogen or alkyl; and R 9  is hydrogen, alkyl, alkenyl, aryl, aralkyl, or heteroaralkyl, or R 9  is the group SO 2 R 10  where R 10  is alkyl or aryl; or R 9  is the group COR 11  where R 11  is hydrogen, alkyl, aryl, aralkyl, alkoxy, halomethyl, heteroaryl, heteroaralkyl, or the group NHR 12  where R 12  is hydrogen, alkyl, cycloalkyl, aryl or   aralkyl; or R 8  and R 9  together represent the group =CR 13 R 14  where R 13  represents aryl or heteroaryl and R 14  represents hydrogen or alkyl;   or R 6  is the group SO 2 R 15  in which R, 5  is hydroxy, alkyl, aryl or the group NR 16 R 17  where R 16  and R 17 , which may be the same or different, each represent hydrogen or alkyl;   or R 6  is the group COR 18  where R 18  is hydrogen, hydroxy, alkoxy, aryloxy, aralkyloxy, alkyl, aryl, aralkyl or the group NR 19 R 20  where R 19  is hydrogen or alkyl optionally substituted by a hydroxy or alkoxy group; and R 20  is hydrogen, alkyl (optionally substituted by a hydroxy or alkoxy group), alkenyl, aryl, aralkyl or cycloalkyl, or NR 19 R 20  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 (e.g. methyl) groups; or R 6  is the group CR 21 =NR 22  where R 21  is hydrogen, alkyl, aryl or aralkyl and R 22  is hydroxy, alkoxy, aralkyloxy or -NHC(=B)NH 2  where B is oxygen or sulphur;   
     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); or R 3  and R 4  together represent the group + CH=CH )̵ 2  or -(CH 2 ) 4 -. 
     The compounds show pharmacological activity as selective histamine H 2 -antagonists.