Research efforts in the α1 adrenergic receptor antagonist area have led to the discovery of some marketed antihypertensive drugs.1 These agents apparently function by relaxing vascular smooth muscle which contains high concentrations of α1 receptors. Researchers also found that α1 receptors are abundant in the human prostate, bladder neck, and urethra,2 and demonstrated that the use of nonselective α1 receptor antagonists could provide symptomatic relief from the dynamic component of urinary flow problems resulting from increased adrenergic tone in males with hyperplastic prostates.3 Subsequent to these findings, pharmacological and binding studies indicated there are three subclasses of α1 receptors. The existence of these receptor subtypes, the α1a, α1b, and α1d, has been confirmed through the use of molecular biological cloning techniques.4 The study of a variety of tissue preparations led to the discovery of a heterogeneous distribution of the three α1 receptors within animal and human tissues. Later, it was discovered that the α1a receptor was the putative target for the treatment of benign prostatic hyperplasia (BPH).5 The effort to synthesize agents selective for each of the three α1 receptor subtypes has been an active area of research. As a result, the structures of α1a selective antagonists,6 α1a selective agonists,7 the α1b selective antagonist, (+)-cyclazosin,8 and an α1d selective antagonist 1, BMY-7378,9 have been disclosed. Despite these advances, the physiological roles of the α1b and α1d receptors in blood pressure or other physiological functions remain undefined. Our goal at the outset of this research was to synthesize novel, potent, and subtype selective α1 antagonists. The strategy was to convert the subtype nonselective α1 receptor antagonist 2, prazosin, into a subtype selective antagonist. Our approach was to incorporate new structural elements into the prazosin piperazine subunit. Herein, we describe our preliminary results focusing on the synthesis and pharmacological evaluation of some novel, potent, and selective α1b receptor antagonists.