Novel indolizine derivatives with unprecedented inhibitory activity on human farnesyltransferase

作者：Dumea Carmen; Belei Dalila; Ghinet Alina; Dubois Joelle; Farce Amaury; Bicu Elena^*

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(24): 5777-5781.

DOI：10.1016/j.bmcl.2014.10.044

• Indolizine
• Farnesyltransferase inhibitor
• Activated ester
• Propargyl ester
• Butynyl ester
• Propargyl amide

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 mu M. The amidic series 1a-i proves to be the most promising for future modulations, particularly at the triple bond level.

• 出版日期2014-12-15