5-Alkynyl-2′-deoxyuridines, containing bulky aryl groups: evaluation of structure–anti-HSV-1 activity relationship

Four 5-alkynyl-2′-deoxyuridines containing different bulky substituents and flexible linkers between the triple bond and the aromatic residue have been prepared and tested against HSV-1 in Vero cells. Two nucleosides containing carbonyl groups, 5-(4-benzoylphenoxypropyn-1-yl)-2′-deoxyuridine () and 5-(estron-3-yloxypropyn-1-yl)-2′-deoxyuridine (), showed low cytotoxicity and moderate antiviral activity. The flexible linker appears not to be favorable for antiviral properties of 5-alkynyl-2′deoxyuridines: 5-[(perylen-3-yl)methoxypropyn-1-yl]-2′-deoxyuridine () showed considerable cytotoxicity and no antiviral activity in contrast to the active and nontoxic 5-(perylen-3-ylethynyl)-2′-deoxyuridine (), a nucleoside with a rigid triple-bond-connection of the aromatic system to the nucleobase.