Novel arylpiperazines as selective alpha1-adrenergic receptor antagonists.
A novel series of arylpiperazines has been synthesized and identified as antagonists of alpha1a adrenergic receptor (alpha1a-AR) implicated in benign prostatic hyperplasia. These compounds selectively bind to membrane bound alpha1a-AR with K(i)s as low as 0.66 nM. As such, these potentially represent a viable treatment for BPH without the side effects associated with known alpha1-adrenergic antagonists.
Li
X
X
The R. W. Johnson Pharmaceutical Research Institute, San Diego, CA 92121, USA.
Murray
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WV
Jolliffe
L
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Pulito
V
V
D018674:Adrenergic Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D001671:Biochemistry / Q000379:methods; D019556:COS Cells / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
C413736:1-(2-isopropoxyphenyl)-4-((2-oxopiperidin-1-yl)acetamido)propylpiperazine; C547713:ADRA1A protein, human; C547716:ADRA1B protein, human; C547719:ADRA1D protein, human; D018674:Adrenergic Antagonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D010879:Piperazines; D010880:Piperidines; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D000077489:Piperazine