Abstract

The oral diuretic properties of formoguanamine and other s-triazines were studied in rats and dogs. By a comparison of minimal active doses, four compounds were found to be more active than formoguanamine in rats. Potency was increased four to five times in 2-amino-4-anilino-s-triazine. Its derivatives, 2-amino-4-p-chloroanilino-s-triazine, 2-amino-4-p-fluoroanilino-s-triazine, and 2-acetylamino-4-N-acetyl-p-chloroanilino-s-triazine, were approximately nine times as potent as formoguanamine. Substitutions at position 6 in active compounds caused a loss of activity. Compounds found active in the rat were then studied in dogs. Water diuresis was more strongly stimulated than sodium excretion with relatively large oral doses. The structure-activity relationships found in the rat were not manifest in dogs. Intravenously, a small dose of 2-amino-4-p-chloroanilino-s-triazine was strongly effective in causing water and sodium diuresis; poor absorption thus appears to be an important factor for the response in dogs.