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±0.2 μM. The amidic series 1a-i proves to be the most promising for future modulations, particularly at the triple bond level.
Keywords: Activated ester; Butynyl ester; Farnesyltransferase inhibitor; Indolizine; Propargyl amide; Propargyl ester.
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