Abstract
In an effort to find new and safer treatments for osteoporosis and frailty, we describe a novel series of selective androgen receptor modulators (SARMs). Using a structure-based approach, we identified compound 7, a potent AR (ARE EC50 = 0.34 nM) and selective (N/C interaction EC50 = 1206 nM) modulator. In vivo data, an AR LBD X-ray structure of 7, and further insights from modeling studies of ligand receptor interactions are also presented.
MeSH terms
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Anabolic Agents / chemical synthesis
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Anabolic Agents / chemistry*
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Anabolic Agents / pharmacokinetics
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Anabolic Agents / pharmacology
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Androgens / chemical synthesis
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Androgens / chemistry*
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Androgens / pharmacokinetics
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Androgens / pharmacology
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Animals
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Crystallography, X-Ray
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Hypothalamo-Hypophyseal System / drug effects
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Male
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Molecular Docking Simulation
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / physiology
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Nitriles / chemical synthesis
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Nitriles / chemistry*
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Nitriles / pharmacology
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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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Prostate / physiology
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Pyrroles / chemical synthesis
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Pyrroles / chemistry*
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Pyrroles / pharmacokinetics
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Pyrroles / pharmacology
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Rats
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Receptors, Androgen / metabolism*
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Seminal Vesicles / drug effects
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Seminal Vesicles / physiology
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Structure-Activity Relationship
Substances
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5-(2-fluoro-4-hydroxyphenyl)-1-methyl-1H-pyrrole-2-carbonitrile
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Anabolic Agents
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Androgens
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Nitriles
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Pyrroles
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Receptors, Androgen