Synthesis of analogues of the benzodiazepine Ro 5-3335, antagonist of Tat HIV-1. Biological evaluation by luciferase transactivation and anti-viral assay

Article abstract of DOI:10.1016/0223-5234(96)85171-3

Ro 5-3335 is a benzodiazepine which is an antagonist of the Tat protein of HIV-1. A series of Ro 5-3335-derived compounds have been synthesized in order to evaluate whether opened analogues of the benzodiazepine tricyclic structure possess biological activity. The analogues are constituted by two aromatic rings variously substituted, linked by an amino acid. The activity of these compounds has been determined by the quantification of both inhibition of Tat activity using a cell-based transfection assay and inhibition of HIV replication in acutely infected cells. No analogue provided a notable inhibition of Tat-dependent transactivation or any anti-HIV activity.