title: Design, synthesis, and biological evaluation of fluoronitrophenyl substituted folate analogues as potential inhibitors of GAR transformylase and AICAR transformylase.
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.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. boger@scripps.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Boger
authors.forename: T H
authors.initials: TH
authors.lastname: Marsilje
authors.forename: R A
authors.initials: RA
authors.lastname: Castro
authors.forename: M P
authors.initials: MP
authors.lastname: Hedrick
authors.forename: Q
authors.initials: Q
authors.lastname: Jin
authors.forename: S J
authors.initials: SJ
authors.lastname: Baker
authors.forename: J H
authors.initials: JH
authors.lastname: Shim
authors.forename: S J
authors.initials: SJ
authors.lastname: Benkovic
mesh_terms: D000818:Animals; D001681:Biological Assay; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005461:Fluorine / Q000737:chemistry; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019877:Hydroxymethyl and Formyl Transferases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009574:Nitro Compounds / Q000138:chemical synthesis*; D051026:Phosphoribosylglycinamide Formyltransferase; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011687:Purines / Q000096:biosynthesis; D012265:Ribonucleotides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D011687:Purines; D012265:Ribonucleotides; D005461:Fluorine; D005492:Folic Acid; D019877:Hydroxymethyl and Formyl Transferases; D051026:Phosphoribosylglycinamide Formyltransferase