Abstract
We have designed the nitrophenylfurylacryl-substituted benzophenone 4f as a non-thiol farnesyltransferase inhibitor utilizing a novel aryl binding site of farnesyltransferase. Variation of the 2-acylamino substituent at the benzophenone core structure of our initial lead 4f yielded several non-thiol farnesyltransferase inhibitors with improved activity. These compounds display activity in the low nanomolar range.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkyl and Aryl Transferases / antagonists & inhibitors*
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Amides / chemical synthesis*
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Amides / pharmacology*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Farnesyltranstransferase
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Furans / chemical synthesis*
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Furans / pharmacology*
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Indicators and Reagents
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Nitro Compounds / chemical synthesis*
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Nitro Compounds / pharmacology*
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Protein Conformation
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Saccharomyces cerevisiae / enzymology
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Structure-Activity Relationship
Substances
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Amides
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Enzyme Inhibitors
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Furans
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Indicators and Reagents
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Nitro Compounds
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Alkyl and Aryl Transferases
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Farnesyltranstransferase