Abstract
The 5alpha-reductase type 1 isozyme is a key enzyme in the metabolism of the androgen steroid hormones and inhibitors of this enzyme represent a new pharmacological treatment for several androgen dependent diseases. We developed a radiosubstrate in vitro incubation method for the determination of 5alpha-reductase type 1 activity using rat liver microsomes as an enzyme source. With this method we have studied the inhibiting activity of novel (5' S)-17beta-(4,5-dihydrooxazol-5-yl)androst-5-en-3-one compounds containing various derivatized phenyl substituents coupled to the exo -heterocyclic moiety. Tests revealed moderate inhibitory actions compared to finasteride, nevertheless, results provide interesting structure-activity relationship data.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase / analysis*
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
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5-alpha Reductase Inhibitors*
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Androstenes / chemistry
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Androstenes / pharmacology
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Animals
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Azasteroids / chemistry
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Azasteroids / pharmacology
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Female
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Finasteride / pharmacology
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In Vitro Techniques
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Isoenzymes / analysis
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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Microsomes, Liver / drug effects
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Microsomes, Liver / enzymology*
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Oxazoles / chemistry
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Oxazoles / pharmacology
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Rats
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Structure-Activity Relationship
Substances
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5-alpha Reductase Inhibitors
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Androstenes
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Azasteroids
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Enzyme Inhibitors
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Isoenzymes
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Oxazoles
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Finasteride
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase