Abstract
Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clinical trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered a series of aryl tetrahydropyridines that incorporate substituted glycine, phenylalanine and histidine residues. The design, synthesis, SAR and biological properties of these compounds will be discussed.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Alkyl and Aryl Transferases / antagonists & inhibitors*
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Biological Availability
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Crystallography, X-Ray
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Farnesyltranstransferase
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Genes, ras / drug effects
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Glycine / analogs & derivatives*
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Glycine / pharmacology
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Histidine / analogs & derivatives*
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Histidine / pharmacology
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Models, Molecular
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Molecular Conformation
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Phenylalanine / analogs & derivatives*
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Phenylalanine / pharmacology
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Pyridines / chemical synthesis*
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Pyridines / pharmacology*
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Pyridines
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Phenylalanine
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Histidine
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Alkyl and Aryl Transferases
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geranylgeranyltransferase type-I
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Farnesyltranstransferase
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Glycine