Synthesis of some 5'-amino-2',5'-dideoxy-5-iodouridine derivatives and their antiviral properties against herpes simplex virus.

In an attempt to improve the antiviral efficacy of 5'-amino-2',5'-dideoxy-5-iodouridine (AIdU) the N-acetyl and N,3'-O-diacetyl derivatives were prepared. N-Acetylation of AIdU increased its ability to inhibit the phosphorylation of thymidine by the deoxypyrimidine kinase of herpes simplex virus type 1 (HSV1) while diacetylation had the converse effect. The affinity of the corresponding compounds containing uracil or thymine for virus deoxypyrimidine kinase was also determined. A range of N-acyl-, N-sulphonyl- and N,3'-O-diacyl- derivatives of AIdU were synthesized; enhanced inhibition of deoxypyrimidine kinase by a number of these compounds was observed. The previous observation that 5'-azido-2',5'-dideoxy-5-iodouridine has antiherpetic activity in vivo led us to investigate its 3'-O-acetyl derivative as well as the corresponding compound containing uracil. None of the derivatives described showed antiviral activity in cell culture against HSV1; acylation failed to enhance the potency of AIdU against HSV1 in vivo.