Abstract
A series of androgen receptor modulators based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones was synthesized and evaluated in an androgen receptor transcriptional activation assay. The most potent analogues from the series exhibited single-digit nanomolar potency in vitro. Compound 18h demonstrated full efficacy in the maintenance of muscle weight, at 10 mg/kg, with reduced activity in prostate weight in an in vivo model of androgen action.
MeSH terms
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Animals
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Cell Line
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Dose-Response Relationship, Drug
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Humans
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Indicators and Reagents
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Male
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Models, Molecular
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Orchiectomy
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Oxazines / chemical synthesis*
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Oxazines / pharmacology*
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Quinolones / chemical synthesis*
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Quinolones / pharmacology*
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Rats
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Receptors, Androgen / chemistry
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Receptors, Androgen / drug effects*
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Receptors, Progesterone / chemistry
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Receptors, Progesterone / drug effects
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Receptors, Somatotropin / chemistry
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Receptors, Somatotropin / drug effects
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Structure-Activity Relationship
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Testosterone / blood
Substances
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Indicators and Reagents
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Oxazines
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Quinolones
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Receptors, Androgen
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Receptors, Progesterone
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Receptors, Somatotropin
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Testosterone