Structure-activity relationships of the diuretic activity of triaza- and tetraaza-naphthalene compounds.
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The diuretic activity of 219 nitrogen containing heterocyclic compounds, classified into 13 groups based on the structural features, was studied on the saline loaded rats. One hundred and four out of the 219 compounds were active at the oral doses of 10 to 30 mg/kg. Several of pyrimidopyridazines, pyridazinopyridazines and pyridopyridazines produced as potent diuresis and natriuresis as hydrochlorothiazide at the oral dose of 0.1 mg/kg, in which 2-phenyl-5, 8-dimorpholinopyrimido [4, 5-d]-pyridazine (DS-210) and 1, 4-dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) were selected for more extensive evaluation as diuretic agents. Structure-activity relationships of the tested compounds are discussed.