Acyclic analogues of 3'-azido-3'-deoxythymidine as potential antiviral agents. Nucleoside synthesis by Michael addition.

An acyclic derivative of 3'-azido-3'-deoxythymidine, (R,S)-1-[1-(2-hydroxyethoxy)-3-azidopropyl]thymine (2), has been synthesized by a path involving Michael-type addition. Related thymidine analogues lacking the C(3')-C(4') bond were similarly obtained. The method provides a versatile new route to nucleoside analogues. The new compounds were found to be essentially inactive against human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro when tested up to 100 microM.