Design and Synthesis of anα_1a‐Adrenergic Receptor Subtype‐Selective Antagonist from BE2254

Abstract

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.

α1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms

“…One of α 1a antagonists, silodosin, is now in clinical use [14]. These compounds have demonstrated the ability to relax prostate muscle without producing cardiovascular side effects [15][16][17][18]. Surprisingly, many of these α 1a -selective compounds have not been proven to be very effective in relieving LUTS, especially the symptom of irritation (silodosin is effective in reduction of storage symptom [19]).…”