Atrial natriuretic peptide receptor modulators: effects of disubstituted quinazolines on receptor binding and in vitro biological activity

Prazosin was found to increase 125 I-labeled rat atrial natriuretic peptide ([ 125 I]rANP) receptor binding by 50% (SC 50 ) in bovine adrenal zona glomerulosa membranes. A series of 2,4-disubstituted quinazolines was prepared in order to identify more potent analogues for additional in vitro testing. Compound 7 (N-[3-[[2-(diethylamino)-4-quinazolinyl] amino] propyl] guanidine dinitrate) from this series significantly decreased the EC 50 for rANP-mediated inhibition of ACTH-stimulated aldosterone synthesis in rat adrenal glomerulosa cells