Design, synthesis, and biological evaluation of fluoronitrophenyl substituted folate analogues as potential inhibitors of GAR transformylase and AICAR transformylase

D L Boger; T H Marsilje; R A Castro; M P Hedrick; Q Jin; S J Baker; J H Shim; S J Benkovic

doi:10.1016/s0960-894x(00)00271-7

Design, synthesis, and biological evaluation of fluoronitrophenyl substituted folate analogues as potential inhibitors of GAR transformylase and AICAR transformylase

Bioorg Med Chem Lett. 2000 Jul 3;10(13):1471-5. doi: 10.1016/s0960-894x(00)00271-7.

Authors

D L Boger¹, T H Marsilje, R A Castro, M P Hedrick, Q Jin, S J Baker, J H Shim, S J Benkovic

Affiliation

¹ Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. boger@scripps.edu

PMID: 10888335
DOI: 10.1016/s0960-894x(00)00271-7

Abstract

The examination results of a novel series of potential inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide transformylase (AICAR Tfase) are reported. These agents incorporate an electrophilic fluoronitrophenyl group that can potentially react with an active site nucleophile or the substrate GAR/AICAR amine via nucleophilic aromatic substitution.

MeSH terms

Animals
Biological Assay
Combinatorial Chemistry Techniques
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Fluorine / chemistry
Folic Acid / analogs & derivatives*
Folic Acid / pharmacology
Hydroxymethyl and Formyl Transferases / antagonists & inhibitors*
Molecular Structure
Nitro Compounds / chemical synthesis*
Phosphoribosylglycinamide Formyltransferase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Purines / biosynthesis
Ribonucleotides / metabolism*
Tumor Cells, Cultured

Substances

Enzyme Inhibitors
Nitro Compounds
Purines
Ribonucleotides
Fluorine
Folic Acid
Hydroxymethyl and Formyl Transferases
Phosphoribosylglycinamide Formyltransferase