The title compound, 5, was prepared and found to be a potent diuretic in the rat. At 27 mg/kg, urine output was 250% of the saline control, and the excretion of electrolytes was similar to hydrochlorothiazide control. At 80 mg/kg, the potassium excretion was the same as the saline control, and the sodium and chloride excretions more than doubled. Several analogues were prepared and tested. Some show diuretic activity. This paper reports our efforts to synthesize a potassium-sparing diuretic using a pyrido[2,3-d]pyrimidine as the lead compound. Some potassium-sparing diuretics, such as triamterene, are derivatives of nitrogen-containing heterocyclic compounds. They usually are not of sufficient natriuretic potency when used alone and frequently must be delivered in conjunction with other diuretic agents in order to augment natriuresis and reduce potassium loss. Osselaere and Lepiere found that 2-(3-pyridyl)-3Hpyrido[2,3-d]pyrimidin-4-one (1) had high diuretic activity, but the potassium-sparing properties were not reported. We designed compounds to include derivatives of different fused heterocyclic rings and measured the effect these molecular modifications have on the electrolyte content of urine.