Relationship Between Conformation and Antiviral Activity-III. 3′-Azidothymidine (AZT) and 3′-Azido-2′, 3′-dideoxy-5-hydroxymethyluridine

3′-Azido-2′,3′-dideoxy-5-hydroxymethyluridine (AZHMddUrd) was synthesized to improve the potency of 5-hydroxymethyl-2′-deoxyuridine (HMdUrd) against human immunodeficiency virus (HIV). AZHMddUrd was a very poor inhibitor of HIV replication (ED 50 >200 μM) and was also nontoxic up to 400 μM (highest concentration tested) to HT4-6C (HeLa CD 4 ) cells. AZT was phosphorylated by human cellular thymidine kinase. In contrast, AZHMddUrd and HMdUrd were poor substrates for the kinase. The relationship between molecular conformation and antiretroviral activity for 3′-azidothymidine (AZT), HMdUrd and AZHMddUrd is discussed.