Synthesis and Anti-Herpes Activity of a Series of Indolizines

Abstract

A systematic screening study identified 2-phenyl-indolizine [1] as having significant human cytomegalovirus (HCMV) activity (IC50 = 7-19 μM). Preliminary mode of action studies on infected cells treated with [1] indicated supression of HCMV-related polypeptides with little effect on the host cells. A series of analogues were synthesized, some of which showed improved HCMV activity although with lower therapeutic indices than [1]. Several analogues demonstrated significant varicella zoster virus activity, with 2-(4-cyanophenyl)indolizine [5] having an IC50 of 5 μM and a therapeutic index of 20 over cell toxicity in the MRC 5 cell line.