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'-hexadecanoylam ino derivative 22 was chosen as starting material for the synthesis of a se ries of new modified 2'-5'-adenylate trimers 33-36 as potential antiviral a gents. All (2'-5')A trimer analogs 33-36 inhibit HIV-1 replication as measu red by the inhibition of syncytia formation and inhibition of HIV-1 reverse transcriptase activity. Compound 34 inhibits HIV-1 reverse transcription b y 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 budd ing process.