(Phenylpiperidinyl)cyclohexylsulfonamides: development of alpha1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS).
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.
Chiu
George
G
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
Li
Shengjian
S
Connolly
Peter J
PJ
Pulito
Virginia
V
Liu
Jingchun
J
Middleton
Steven A
SA
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*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D013449:Sulfonamides