Key result
Novel quinoxaline N-oxide ARB analogs boost potency and oral activity over nonoxidized counterparts.
Why the study?
Novel quinoxaline heterocycle-containing angiotensin II receptor antagonists were synthesized to explore their potency, duration, and oral activity improvements.
Novel quinoxaline ARBs show preclinical potency; leaves open clinical translation and oral bioavailability gains.
A series of novel quinoxaline heterocycle containing angiotensin II receptor antagonist analogs were prepared. This heterocycle was coupled to the biphenyl moiety via an oxygen atom linker instead of a carbon atom. Many of these analogs exhibit very potent activity and long duration of effect. Interestingly, the N-oxide quinoxaline analog was more potent than the nonoxidized quinoxaline as in the comparison of compounds 5 vs 30. In order to improve oral activity, the carboxylic acid function of these compounds was converted to the double ester. This change did result in an improvement in oral activity as represented by compound 44.
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Kim et al. (1993) studied this question. Quinoxaline N-oxide angiotensin II receptor antagonist analogs vs. Nonoxidized quinoxaline analogs was evaluated on Potency and oral activity. Quinoxaline N-oxide angiotensin II receptor antagonist analogs showed higher potency than nonoxidized analogs, and conversion to a double ester improved oral activity.
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