1,6-naphthyridinone derivatives having angiotension II antagonist activity

A heterocyclic derivative of the formula I

• wherein R.sup.1 is hydrogen, (1-8C)alkyl, (3-8C)cycloalkyl, phenyl or substituted (1-4C)alkyl, the latter containing one or more fluoro substituents or bearing a (3-8C)cycloalkyl, (1-4C)alkoxy or phenyl substituent;
• R.sup.2 is hydrogen, (1-4C)alkyl, (1-4C)alkoxy, halogeno, trifluoromethyl, carboxy, (1-4C)alkoxycarbonyl, (3-6C)alkenyloxycarbonyl, cyano, nitro, carbamoyl, (1-4C)alkanoyl, N-alkylcarbamoyl and di-(N-alkyl)carbamoyl of up to 7 carbon atoms, amino, alkylamino and dialkylamino of up to 6 carbon atoms, 3-(1-4C)alkylureido and (1-4C)alkanoylamino;
• R.sup.3 is selected from halogeno, (1-4C)alkoxy, hydroxy, amino, alkylamino and dialkylamino of up to 6 carbon atoms, and any of the values defined for R.sup.1 ;
• A is a linking group of the formula --CH.dbd.CH--CO--, --CO--CH.dbd.CH--, --CO--CH.sub.2 --CH.sub.2 -- or --CH.sub.2 --CH.sub.2 --CO--;
• each of Ra and Rb is independently an indicated hydrogen or an optional substituent on linking group A independently selected from (1-4C)alkyl, substituted (1-4C)alkyl containing one or more fluoro substituents or bearing a (3-8C)cycloalkyl, (1-4C)alkoxy or phenyl substituent, (3-8C)cycloalkyl, phenyl, pyridyl, (1-4C)alkoxy, halogeno, carboxy, (1-4C)alkoxycarbonyl, (3-6C)alkenyloxycarbonyl, carbamoyl, N-alkylcarbamoyl and di-(N-alkyl)carbamoyl of up to 7 carbon atoms, cyano, nitro, (1-4C)alkanoyl, (1-4C)alkylthio, (1-4C)alkylsulphinyl, (1-4C)alkylsulphonyl, phenylthio, phenylsulphinyl or phenylsulphonyl;
• R.sup.4 is selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy, halogeno, trifluoromethyl, cyano and nitro;
• X is a direct bond between the adjacent phenyl and methylene groups;
• Z is 1H-tetrazol-5-yl, --CO.NH.(1H-tetrazol-5-yl), --NHSO.sub.2 CF.sub.3 or a group of the formula --CO.OR.sup.5, --CO.NH.SO.sub.2.R.sup.6 or --SO.sub.2.NHR.sup.7 in which R.sup.5 is hydrogen or a non-toxic, biodegradable residue of a physiologically acceptable alcohol or phenol, R.sup.6 is (1-6C)alkyl, (3-8C)cycloalkyl or phenyl, and R.sup.7 is hydrogen, (1-4C)alkyl, (1-4C)alkanoyl or --CO.NH.(1-4C)alkyl;
• or Z is a 2-carboxybenzamido, 2-sulfobenzamido or 2-carboxybenzyloxy group, the benzene ring of which last three groups may optionally bear 1 or 2 additional substituents independently selected from (1-4C)alkyl, (1-4C)alkoxy and halogeno;
• and wherein any of said phenyl moieties may be unsubstituted or bear one or two substituents independently selected from (1-4C)alkyl, (1-4C)alkoxy, halogeno, cyano and trifluoromethyl;
• or an N-oxide thereof;
• or a non-toxic salt thereof.