Synthesis of a series of 2-aryl-3-pyrimidyl-imidazo[1,2-a]pyridines with potent activity against herpes simplex viruses is described. Synthetic approaches allowing for variation of the 2-aryl, 3-heteroaryl as well as other imidazopyridine substituents are outlined and resulting effects on antiviral activity are highlighted. Several compounds with in vitro antiviral activity similar or better than acyclovir are described.