(Arylpiperazinyl)cyclohexylsufonamides: Discovery of α1a/1d-selective adrenergic receptor antagonists for the treatment of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS)

Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS) can be effectively treated by α1-adrenergic receptor antagonists. Unfortunately, all currently marketed α1 blockers produced CV related side effects that are caused by the subtype non-selective nature of the drugs. To overcome this problem, it was postulated that a α1a/1d subtype selective antagonist would bring more benefit for the treatment of BPH/LUTS. In developing selective α1a/1d ligands, (arylpiperazinyl)cyclohexylsulfonamides were synthesized and their binding profiles against three cloned human α1-adrenergic receptor subtypes were evaluated. Many compounds show equal affinity for both α1a and α1d subtypes with good selectivity against the α1b subtype. They also overcome the problem of dopamine receptor affinity that previous analogues had exhibited.

A series of (arylpiperazinyl)cyclohexylsulfonamides that show selectivity to human α1a/1d-adrenergic receptors was developed. These compounds have potential for the treatment of BPH/LUTS.Figure optionsDownload as PowerPoint slide