Pharmacological management of benign prostatic hyperplasia (BPH) is most successfully achieved by R1 adrenoceptor antagonists that relax prostatic smooth muscle. Currently approved agents (terazosin, doxazosin, alfuzosin), originally developed as antihypertensives, suffer from significant cardiovascular side effects when used for BPH. Tamsulosin is the first "uroselective" R1 antagonist for BPH. Three human R1 receptor subtypes (R1a, R1b, R1d) have been cloned, and affinity for the R1a subtype correlates with modulation of prostatic tone. The title compound (A-131701) was synthesized in enantiomerically pure form via a nine-step process from ethyl 2-methoxyphenylbutyrate. Radioligand binding studies revealed sub-nanomolar affinity for the R1a subtype (Ki = 0.22 nM) and moderate selectivity over R1b (6.95 nM) and R1d (0.97 nM) subtypes, as well as other receptors. Functional assays showed it to be 11-13-fold selective for R1A (dog prostate, rat vas deferens) versus R1B (rat spleen) responses, superior to terazosin and tamsulosin. In vivo models (canine challenge intraurethral pressure [cIUP] and spontaneously hypertensive rat [SHR]) demonstrated A-131701 to be ~20-fold more selective for prostatic versus vascular tone than tamsulosin and ~100-fold more selective than terazosin. As a novel structural type with high R1a affinity and uroselectivity, A-131701 may have clinical utility for the symptomatic treatment of BPH with significantly reduced cardiovascular side effects.