QUINOXALINE N-OXIDE CONTAINING POTENT ANGIOTENSIN-II RECEPTOR ANTAGONISTS - SYNTHESIS, BIOLOGICAL PROPERTIES, AND STRUCTURE-ACTIVITY-RELATIONSHIPS

A series of novel quinoxaline heterocycle containing angiotensin II re ceptor antagonist analogs were prepared. This heterocycle was coupled to the biphenyl moiety via an oxygen atom linker instead of a carbon a tom. Many of these analogs exhibit very potent activity and long durat ion of effect. Interestingly, the N-oxide quinoxaline analog was more potent than the nonoxidized quinoxaline as in the comparison of compou nds 5 vs 30. In order to improve oral activity, the carboxylic acid fu nction of these compounds was converted to the double ester. This chan ge did result in an improvement in oral activity as represented by com pound 44.