PMID:15848772
| Citation |
Cheng, H, Hwang, I, Chong, Y, Tavassoli, A, Webb, ME, Zhang, Y, Wilson, IA, Benkovic, SJ and Boger, DL (2005) Synthesis and biological evaluation of N-[4-[5-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(2,2,2-trifluoroacetyl)pentyl]benzoyl]-L-glutamic acid as a potential inhibitor of GAR Tfase and the de novo purine biosynthetic pathway. Bioorg. Med. Chem. 13:3593-9 |
|---|---|
| Abstract |
The synthesis and evaluation of N-[4-[5-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(2,2,2-trifluoroacetyl)pentyl]benzoyl]-L-glutamic acid (2) as an inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) are reported. The inhibitor 2 was prepared in a convergent synthesis involving C-alkylation of methyl 4-(4,4,4-trifluoro-3-dimethylhydrazonobutyl)benzoate with 1-chloro-3-iodopropane followed by construction of the pyrimidinone ring. Compound 2 was found to be an effective inhibitor of recombinant human GAR Tfase (K(i) = 0.50 microM), whereas it was inactive (K(i) > 100 microM) against E. coli GAR Tfase as well as recombinant human AICAR Tfase. Compound 2 exhibited modest, purine-sensitive growth inhibitory activity against the CCRF-CEM cell line (IC50 = 6.0 microM). |
| Links |
PubMed Online version:10.1016/j.bmc.2004.11.049 |
| Keywords |
Antineoplastic Agents/chemical synthesis; Antineoplastic Agents/pharmacology; Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology; Glutamic Acid/analogs & derivatives; Glutamic Acid/chemical synthesis; Glutamic Acid/pharmacology; Humans; Hydroxymethyl and Formyl Transferases/antagonists & inhibitors; Molecular Structure; Phosphoribosylaminoimidazolecarboxamide Formyltransferase; Phosphoribosylglycinamide Formyltransferase; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology; Purines/antagonists & inhibitors; Purines/biosynthesis; Pyrimidines/chemical synthesis; Pyrimidines/pharmacology; Structure-Activity Relationship; Tumor Cells, Cultured |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.