The D-1 and D-2 affinities, in vivo femoral and renal vasodilatory effects, oral antihypertensive and diuretic effects and syntheses of selected dopamine congeners are described.Several dopamine analogs have been reported2 to be selective peripheral D-2 dopamine receptor agonists, while the benzazepin, fenoldopam, is known to be a potent peripheral D-I receptor agonist. 3 A series of4-(2-aminoethyl)-2(3H) indolones has been reported to be highly active as peripheral DA-receptor agonists in the isolated perfused rabbit ear artery. 46 Dopamine receptor activity of some 5-(2-aminoethyl)carbostyril 7, 4-(2-aminoethyl)indole derivatives s'9 and a series of N,N-di-n-propyldopamine congeners containing phenolic bioisosteres ~° with activity at D-1 and D-2 receptors has been reported. However, to date, no reports of therapeutically useful peripherally acting dopamine analogs with combined D-I and D-2 receptor activity have appeared. I IA single chemical entity combining selective peripheral D-1 and D-2 dopamine receptor affinity 12 whose in vivo activity is consistent with peripheral D-I and D-2 stimulation might provide a useful treatment Ibr hypertension, acute and chronic renal failure, and congestive heart disease.~3'14 This is based upon findings that the stimulation of peripheral D-2 dopamine receptors prejunctionally inhibit release of norepinephrinc (NE) from postganglionic noradrenergic nerves, thereby reducing the postjunctional effects of NE on the vasculature and myocardium. This leads to passive systemic vasodilation, a decrease in blood pressure and a reduction in heart rate. Further, stimulation of peripheral D-1 dopamine receptors (located primarily in the renal and mesenteric vascular beds and on renal tubular cells) leads to renal vasodilation, increased renal blood flow and diuresis. 3Our goal was to identify such a chemical entity. The structure activity relationship of derivatives of dopamine (1) 2'3'11 and the dopamine receptor agonist activity of 2, N,N-dipropyl dopamine (DPDA) 12 and 3, NbutyI-N-propyl dopamine) ~3 prompted us to synthesize a number of analogs of I and evaluate their activity at D- 1 and D-2 receptors. Those compounds showing activity at D- 1 and D-2 receptors were then evaluated in vivo. 14