Synthesis of 2-(alkylamino)-5,6- and -6,7-dihydroxy-3,4-dihydroquinazolines and evaluation as potential dopamine agonists

Abstract

Based upon the known dopaminergic properties of 2-aminodihydroxy-1,2,3,4-tetrahydronaphthalenes (ADTN's), heterocyclic congeners were prepared. Several 2-(alkylamino)-5,6- and -6,7-dihydroxy-3,4-dihydroquinazolines were synthesized and tested for a dopamine-like vasodilatory action in the canine renal artery. The 6,7-disubstituted series had a weak antagonist effect against dopamine. Neither 5,6- nor 6,7-dihydroxy substitution gave dopamine agonists. Measured pKa values confirmed the expectation that the dihydroquinazolines were more basic than dopamine, one possible reason for the lack of dopamine-like action.