(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.