(Phenylpiperidinyl)cyclohexylsulfonamides: Development of α1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS)

Although α1 adrenergic receptor blockers can be very effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), their usage is limited by CV-related side-effects that are caused by the subtype non-selective nature of the current drugs. To overcome this problem, it was hypothesized that a α1a/1d subtype selective antagonist would bring more benefit for the therapy of BPH/LUTS. In developing such selective α1a/1d ligands, a series of (phenylpiperidinyl)cyclohexylsulfonamides has been synthesized and evaluated for binding to three cloned human α1-adrenergic receptor subtypes. Many compounds showed equal affinity for both α1a and α1d subtypes with good selectivity versus the α1b subtype.

Graphical abstractA series of (phenylpiperidinyl)cyclohexylsulfonamides that show selectivity to human α1a/1d adrenergic receptors were developed. These compounds have potential for the treatment of BPH/LUTS.Figure optionsDownload full-size imageDownload as PowerPoint slide