Nucleotides, Part LIX , Synthesis, Characterization, and Biological Activities of New Potential Antiviral Agents: (2′ – 5′)Adenylate Trimer Analogs Containing 3′-Deoxy-3′-(hexadecanoylamino)adenosine at the 2′-Terminus

Based upon 3′-amino-3′-deoxyadenosine (15), its protected 3′-hexadecanoylamino derivative 22 was chosen as starting material for the synthesis of a series of new modified 2′ – 5′-adenylate trimers 33 – 36 as potential antiviral agents. All (2′ – 5′)A trimer analogs 33 – 36 inhibit HIV-1 replication as measured by the inhibition of syncytia formation and inhibition of HIV-1 reverse transcriptase activity. Compound 34 inhibits HIV-1 reverse transcription by 100% and subsequently inhibits expression of HIV-1 p24. However, compound 35 acts differently, since it does not inhibit HIV-1 reverse transcription, HIV-1 integrase, or HIV-1 p24 expression. Therefore, 35 appears to exert its inhibitory effect at a later stage of HIV-1 replication, i.e., the budding process.