Abstract
The design and synthesis of 10-(2-benzoxazolcarbonyl)-DDACTHF (1) as an inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide transformylase (AICAR Tfase) are reported. Ketone 1 and the corresponding alcohol 13 were evaluated for inhibition of GAR Tfase and AICAR Tfase and the former was found to be a potent inhibitor of recombinant human (rh) GAR Tfase (Ki=600 nM).
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites
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Cell Line
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Cell Survival / drug effects
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Humans
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Hydroxymethyl and Formyl Transferases / antagonists & inhibitors*
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Inhibitory Concentration 50
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Phosphoribosylaminoimidazolecarboxamide Formyltransferase
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Phosphoribosylglycinamide Formyltransferase
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Purines / antagonists & inhibitors
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Purines / biosynthesis*
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Structure-Activity Relationship
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Tetrahydrofolates / chemistry*
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Tetrahydrofolates / pharmacology
Substances
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10-(2-benzoxazolcarbonyl)-5,10-dideaza-acyclic-5,6,7,8-tetrahydrofolic acid
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Enzyme Inhibitors
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Purines
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Tetrahydrofolates
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Hydroxymethyl and Formyl Transferases
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Phosphoribosylglycinamide Formyltransferase
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Phosphoribosylaminoimidazolecarboxamide Formyltransferase