Three new 5-arylethynyl-2′-deoxyuridines containing bulky aryls have been prepared and tested against HSV-1 in Vero cells. The introduction of a substituent in the phenyl group of an inactive compound, 5-phenylethynyl- 2′-deoxyuridine, leads to the appearance of anti-HSV properties. The most active compounds are those containing a polycyclic aromatic hydrocarbon residue attached to the 5 position of 2′-deoxyuridine through a rigid triple bond. © The Royal Society of Chemistry 2006.