10.1021/jm00103a009
The research aimed to investigate the impact of structural modifications on the anti-HIV-1 activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), a potent and selective anti-HIV-1 agent. The study involved the synthesis of a series of deoxy analogs and related compounds of HEPT to understand the effects of substitution in the acyclic structure on its antiviral activity. Key chemicals used in the synthesis process included primary alkyl halides for alkylation, LDA (lithium diisopropylamide) for lithiation, diaryl disulfides for the introduction of arylthio groups, and various solvents and reagents for purification and crystallization steps. The conclusions drawn from the research indicated that certain substitutions, particularly with ethoxymethyl and (benzyloxy)methyl groups, significantly improved the original anti-HIV-1 activity of HEPT. Notably, the introduction of bulkier alkyl groups at the N-1 position and modifications at the 5-methyl group led to remarkable improvements in anti-HIV-1 activity without increasing cytotoxicity, suggesting that these compounds could be promising candidates for the chemotherapy of AIDS.
