Novel heterocycles as selective alpha1-adrenergic receptor antagonists.
A novel series of aryl piperazine substituted heterocycles has been synthesized and identified as antagonists of the alpha1a-adrenergic receptor (alpha1a-AR), which has been implicated in benign prostatic hyperplasia (BPH). These compounds selectively inhibit binding to the alpha1a-AR with K(i)s as low as 2.1 nM.
Li
X
X
The R. W. Johnson Pharmaceutical Research Institute, San Diego, CA 92121, USA. xli@prius.jnj.com
McCoy
K A
KA
Murray
W V
WV
Jolliffe
L
L
Pulito
V
V
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000502:physiology; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D011470:Prostatic Hyperplasia / Q000503:physiopathology; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014162:Transfection
C547713:ADRA1A protein, human; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D006571:Heterocyclic Compounds; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins