The design, synthesis and properties of highly potent and selective inhibitors of herpes simplex virus types 1 and 2 thymidine kinase.

The rational design and synthesis of nucleotide analogues as inhibitors of herpes simplex virus (HSV) thymidine kinase is described. Starting from thymidine, product analogues which included phosphates, phosphonates, sulphonates, sulphonamides and carboxamides were prepared. The carboxamide series showed good structure-activity relationships and afforded a lead structure which inhibited the HSV-2 enzyme in the low micromolar range.