Abstract
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.
MeSH terms
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Adrenergic Antagonists / chemistry*
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Adrenergic Antagonists / metabolism
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Adrenergic Antagonists / pharmacology*
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Adrenergic alpha-1 Receptor Antagonists*
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Animals
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Biochemistry / methods
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COS Cells / metabolism
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Cell Membrane / metabolism
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Drug Evaluation, Preclinical / methods
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Humans
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In Vitro Techniques
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Male
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Piperazine
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Piperazines / chemistry*
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Piperazines / metabolism
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Piperazines / pharmacology*
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Piperidines / chemistry*
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Piperidines / metabolism
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Piperidines / pharmacology*
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Prostate / drug effects
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Rats
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Receptors, Adrenergic, alpha-1 / genetics
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Receptors, Adrenergic, alpha-1 / metabolism
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Recombinant Proteins / drug effects
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
Substances
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1-(2-isopropoxyphenyl)-4-((2-oxopiperidin-1-yl)acetamido)propylpiperazine
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ADRA1A protein, human
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ADRA1B protein, human
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ADRA1D protein, human
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Adrenergic Antagonists
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Adrenergic alpha-1 Receptor Antagonists
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Piperazines
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Piperidines
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Receptors, Adrenergic, alpha-1
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Recombinant Proteins
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Piperazine