title: (Phenylpiperidinyl)cyclohexylsulfonamides: development of alpha1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS).
abstract: Although alpha(1) 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 alpha(1a/1d) subtype selective antagonist would bring more benefit for the therapy of BPH/LUTS. In developing such selective alpha(1a/1d) ligands, a series of (phenylpiperidinyl)cyclohexylsulfonamides has been synthesized and evaluated for binding to three cloned human alpha(1)-adrenergic receptor subtypes. Many compounds showed equal affinity for both alpha(1a) and alpha(1d) subtypes with good selectivity versus the alpha(1b) subtype.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development L.L.C., PO Box 300, 1000 Route 202 South, Raritan, NJ 08869, USA. George.Chiu@sanofi-aventis.com
authors.forename: George
authors.initials: G
authors.lastname: Chiu
authors.forename: Shengjian
authors.initials: S
authors.lastname: Li
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Connolly
authors.forename: Virginia
authors.initials: V
authors.lastname: Pulito
authors.forename: Jingchun
authors.initials: J
authors.lastname: Liu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Middleton
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D013449:Sulfonamides