Design and SAR of new substituted purines bearing aryl groups at N9 position as HIV-1 Tat–TAR interaction inhibitors

Twenty-four purine derivatives bearing aryl groups at N9 position were designed and synthesized as HIV-1 Tat–TAR interaction inhibitors. All the compounds showed high antiviral activities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Ten of them with low cytotoxicities were evaluated by Tat dependent HIV-1 LTR-driven CAT gene expression colorimetric enzyme assay in human 293T cells at a concentration of 30 μM, indicating effective inhibitory activities of blocking the Tat–TAR interaction. The aryl groups at N9 position affected the binding affinities between compounds and TAR RNA, showing some specificities of aryl groups to TAR RNA.

Twenty-four purine derivatives were designed and synthesized as HIV-1 Tat–TAR interaction inhibitors. The aryl groups at N9 position could affect the binding specificity between compounds and TARFigure optionsDownload as PowerPoint slide