Biphenyl-substituted guanidine derivatives useful as hypoglycaemic agents

A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a hypoglycaemically effective amount of a compound of formula I ##STR24## and pharmaceutically acceptable salts thereof, in which R.sub.1 is phenyl optionally substituted by halo, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, alkanoyl of 2 to 4 carbon atoms, or a group of formula S(O).sub.n R.sub.8 in which n=0 or 1 and R.sub.8 is an alkyl group of 1 to 3 carbon atoms;

• R.sub.2 is a group of formula II ##STR25## in which R.sub.6 and R.sub.7, which are the same or different, are H or an alkyl group containing 1 to 4 carbon atoms;
• R.sub.1 is H or a straight or branched aliphatic group of 1 to 4 carbon atoms;
• R.sub.4 is (a) H, (b) a straight or branched aliphatic group of 1 to 6 carbon atoms optionally substituted by hydroxy or an acylated derivative thereof, by an alkoxy group containing 1 to 3 carbon atoms, by an alkylthio group containing 1 to 3 carbon atoms, by an optionally alkylated amino group, by a carbocyclic group containing 3 to 7 carbon atoms, by pyridinyl or by cyano, (c) a carbocyclic ring containing 3 to 7 carbon atoms and optionally substituted by hydroxy with the proviso that R.sub.3, R.sub.4, R.sub.6 and R.sub.7 are not all methyl when R.sub.1 is phenyl;
• or
• the group R.sub.2 and the group R.sub.3 together with the carbon and nitrogen atoms to which they are attached form a heterocyclic ring of formula IV ##STR26## in which R.sub.4 is as hereinbefore described except that R.sub.4 cannot be H, in which R.sub.11 is H or an alkyl group containing 1 or 2 carbon atoms, and E is an alkylene group of 2 to 4 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms;
• or
• R.sub.3 and R.sub.4 together with the nitrogen atom to which they are attached form a heterocyclic ring of formula V ##STR27## in which G is an alkylene group of 4 to 6 carbon atoms optionally interrupted by oxygen, sulphur, sulphinyl, sulphonyl, or nitrogen optionally substituted by (a) a carbocyclic ring containing 3 to 7 carbon atoms (b) a methylsulphonyl group or (c) an alkyl group containing 1 to 3 carbon atoms and optionally substituted by hydroxy or an alkoxy group containing 1 to 3 carbon atoms, said alkylene group being optionally substituted by (a) one or more alkyl groups containing 1 to 3 carbon atoms and optionally substituted by hydroxy, (b) by one or more hydroxy groups or an ester thereof, (c) by one or more alkoxy groups, (d) by oxo or oxime or oxime ether or (e) by one or more groups of formula S(O).sub.m R.sub.8 in which m=0 or 1 and R.sub.8 is an alkyl group containing 1 to 3 carbon atoms and
• R.sub.5 represents H or one or more optional substituents selected from halo, alkyl groups containing 1 to 4 carbon atoms, alkoxy groups containing 1 to 3 carbon atoms, trifluoromethyl, or groups of formula S(O).sub.m R.sub.8 in which m is 0.1 or 2 and R.sub.8 is an alkyl group containing 1 to 3 carbon atoms.

A method of treating hyperglycaemia comprising administering to a subject in need thereof a hypoglycaemically effective amount of a compound of formula I ##STR28## and pharmaceutically acceptable salts thereof, in which R.sub.1 is phenyl optionally substituted by halo, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, alkanoyl of 2 to 4 carbon atoms, or a group of formula S(O).sub.n R.sub.8 in which n=0 or 1 and R.sub.8 is an alkyl group of 1 to 3 carbon atoms;

• R.sub.2 is a group of formula II ##STR29## in which R.sub.6 and R.sub.7, which are the same or different, are H or an alkyl group containing 1 to 4 carbon atoms;
• R.sub.3 is H or a straight or branched aliphatic group of 1 to 4 carbon atoms;
• R.sub.4 is (a) H, (b) a straight or branched aliphatic group of 1 to 6 carbon atoms optionally substituted by hydroxy or an acylated derivative thereof, by an alkoxy group containing 1 to 3 carbon atoms, by an alkylthio group containing 1 to 3 carbon atoms, by an optionally alkylated amino group, by a carbocyclic group containing 3 to 7 carbon atoms, by pyridyl or by cyano, (c) a carbocyclic ring containing 3 to 7 carbon atoms and optionally substituted by hydroxy with the proviso that R.sub.3, R.sub.4, R.sub.6 and R.sub.7 are not all methyl when R.sub.1 is phenyl;
• or
• the group R.sub.2 and the group R.sub.3 together with the carbon and nitrogen atoms to which they are attached from a heterocyclic ring of formula IV ##STR30## in which R.sub.4 is as hereinbefore described except that R.sub.4 cannot be H, in which R.sub.11 is H or an alkyl group containing 1 or 2 carbon atoms, and E is an alkylene group of 2 to 4 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms;
• or
• R.sub.3 and R.sub.4 together with the nitrogen atom to which they are attached form a heterocyclic ring of formula V ##STR31## in which G is an alkylene group of 4 to 6 carbon atoms optionally interrupted by oxygen, sulphur, sulphinyl, sulphonyl, or nitrogen optionally substituted by (a) a carbocyclic ring containing 3 to 7 carbon atoms (b) a methylsulphonyl group or (c) an alkyl group containing 1 to 3 carbon atoms and optionally substituted by hydroxy or an alkoxy group containing 1 to 3 carbon atoms, said alkylene group being optionally substituted by (a) one or more alkyl groups containing 1 to 3 carbon atoms and optionally substituted by hydroxy, (b) by one or more hydroxy groups or an ester thereof, (c) by one or more alkoxy groups, (d) by oxo or oxime or oxime ether or (e) by one or more groups of formula S(O).sub.m R.sub.8 in which m=0 or 1 and R.sub.8 is an alkyl group containing 1 to 3 carbon atoms and
• R.sub.5 represents H or one or more optional substituents selected from halo, alkyl groups containing 1 to 4 carbon atoms, alkoxy groups containing 1 to 3 carbon atoms, trifluoromethyl, or groups of formula S(O).sub.m R.sub.8 in which m is 0.1 or 2 and R.sub.8 is an alkyl group containing 1 to 3 carbon atoms.