Nonnucleoside inhibitors of HIV-1 reverse transcriptase: from the biology of reverse transcription to molecular design.

Replication of human immunodeficiency virus 1 (HIV-1) uses a viral reverse transcriptase (RT) to convert its positive-strand RNA into double stranded DNA, which is then integrated into host genome. Reverse transcription is a complex event involving p66 and p51 RT subunits but also several viral proteins including Nef, Tat, Vif, IN, NCp7 and p55gag. Viral RNA itself forms a primer/template complex by association with a cellular tRNA(Lys3) which is already present in mature virions.

Synthesis and in vitro cytotoxic and antiviral activities of 1-(2,5,6-trideoxy-6-halogenohept-5-enofuranurononitrile)thymine and derivatives.

All 1-(2,5,6-trideoxy-6-halogenohept-5-enofuranurononitrile)thymine and their 3'-O-TBDMS derivatives have been prepared and their configuration established. Some of these compounds are endowed with a cytotoxic or cytostatic activity in cell culture. The single most important factor affecting the cytotoxicity of these compounds is the presence on the molecule of a soft (electrofugal) halogen atom.