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Synthesis and Biological Evaluation of Isosteric Analogues of FK866, an Inhibitor of NAD Salvage
Author(s) -
Galli Ubaldina,
Ercolano Emanuela,
Carraro Lorenzo,
Blasi Roman Cintia R.,
Sorba Giovanni,
Caico Pier Luigi,
Genazzani Armando A.,
Tron Gian Cesare,
Billington Richard A.
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200700311
Subject(s) - nicotinamide phosphoribosyltransferase , nad+ kinase , enzyme , nicotinamide , biochemistry , nucleotide salvage , chemistry , pharmacology , biology , cancer research , stereochemistry , gene , nucleotide
One of the great challenges of medicinal chemistry is to create novel, effective, chemotherapeutic agents that show specificity for cancer cells combined with low systemic toxicity. A novel idea is to target the enzymes of the NAD biosynthesis and recycling pathways given that cancer cells display a higher NAD turnover rate than healthy cells. To this end, the compound FK866 (APO866; ( E )‐ N ‐[4‐(1‐benzoylpiperidin‐4‐yl) butyl]‐3‐(pyridin‐3‐yl) acrylamide), which blocks nicotinamide phosphoribosyltransferase (NMPRTase) has entered clinical trials as a potential chemotherapeutic agent. Here we report the synthesis of analogues of FK866 synthesized by click chemistry.