Abstract
A series of selective androgen receptor modulators (SARMs) with a wide spectrum of receptor modulating activities was developed based on optimization of the 4-substituted 6-bisalkylamino-2-quinolinones (3). Significance of the trifluoromethyl group on the side chains and its interactions with amino acid residues within the androgen receptor (AR) ligand binding domain are discussed. A representative analog (9) was tested orally in a rodent model of hypogonadism and demonstrated desirable tissue selectivity.
MeSH terms
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Androgen Antagonists / chemical synthesis
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Androgen Antagonists / pharmacology
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Androgen Receptor Antagonists
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Androgens
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Animals
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Binding, Competitive / drug effects
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Dihydrotestosterone / antagonists & inhibitors
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Dihydrotestosterone / pharmacology
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Genitalia, Male / drug effects
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Hypogonadism / drug therapy
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Indicators and Reagents
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Magnetic Resonance Spectroscopy
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Male
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Models, Molecular
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Molecular Conformation
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Orchiectomy
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Organ Size / drug effects
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Organ Specificity
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Prostate / drug effects
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Quinolines / chemical synthesis*
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Quinolines / chemistry*
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Rats
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Receptors, Androgen / drug effects*
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Structure-Activity Relationship
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Transfection
Substances
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Androgen Antagonists
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Androgen Receptor Antagonists
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Androgens
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Indicators and Reagents
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Quinolines
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Receptors, Androgen
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Dihydrotestosterone