Novel indolizine derivatives with unprecedented inhibitory activity on human farnesyltransferase

Abstract

The rational structural modification of new substituted indolizin-3-yl(phenyl)methanones 1a–i, 2a–i and 3a–i has greatly improved human farnesyltransferase inhibition. The para-bromophenyl analog 2f bearing an ester unit on the indolizine ring demonstrates the highest inhibition potential, with IC50 value of 1.3±0.2μM. The amidic series 1a–i proves to be the most promising for future modulations, particularly at the triple bond level.