Synthesis and biological evaluation of pentanedioic acid derivatives as farnesyltransferase inhibitors

Article abstract of DOI:10.1039/c4md00498a

Structure-based virtual screening of a commercial library identified pentanedioic acid derivatives (6 and 13b) as a kind of novel scaffold farnesyltransferase inhibitors (FTIs). Chemical modifications of the lead compounds, biological assays and analysis of the structure-activity relationships (SAR) were conducted to discover more potent FTIs. Some of them displayed excellent inhibition against FTase, and among them, the most active compound 13n with an IC₅₀ value of 0.0029 μM and SAR analysis might be helpful to the discovery of more potent FTIs. This journal is