Design and synthesis of an alpha1a-adrenergic receptor subtype-selective antagonist from BE2254

An alpha1a-adrenoceptor-selective antagonist has the potential to be a new benign prostatic hyperplasia drug with reduced side-effects. Modification of the non-selective antagonist BE2254 led to the development of a series of tetralin analogs. Evaluation of these compounds in cloned human alpha1-adrenoceptors resulted in the discovery of an analog that showed selectivity toward the human alpha1a-adrenergic receptor subtype. The compound also showed moderate potency to block human prostate muscle contraction.