1-Arylpiperazinyl-4-cyclohexylamine derived isoindole-1,3-diones as potent and selective alpha-1a/1d adrenergic receptor ligands.
Subtype-selective alpha-1a and/or alpha-1d adrenergic receptor antagonists may be useful for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) with fewer adverse effects than non-selective drugs. A series of 1-arylpiperazinyl-4-cyclohexylamine derived isoindole-1,3-diones has been synthesized, displaying in vitro alpha(1a) and alpha(1d) binding affinity K(i) values in the range of 0.09-38nM with K(i)(alpha1b)/K(i)(alpha1a) and K(i)(alpha1b)/K(i)(alpha1d) selectivity ratios up to 3607-fold.
Li
Shengjian
S
Johnson & Johnson Pharmaceutical Research and Development LLC, Drug Discovery Research, PO Box 300, 1000 Route 202 South, Raritan, NJ 08869, USA. sli3@prdus.jnj.com
Chiu
George
G
Pulito
Virginia L
VL
Liu
Jingchun
J
Connolly
Peter J
PJ
Middleton
Steven A
SA
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D019275:Radiopharmaceuticals; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D044024:Tetralones
D000317:Adrenergic alpha-Antagonists; D007202:Indicators and Reagents; D007211:Indoles; D008024:Ligands; D010879:Piperazines; D019275:Radiopharmaceuticals; D018340:Receptors, Adrenergic, alpha-1; D044024:Tetralones; C048008:2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl)tetralone