Design, synthesis and evaluation of novel 2H-1, 4-benzodiazepine-2-ones as inhibitors of HIV-1 transcription

HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1 transcription.  Based on the β-turn motif present in HIV-1 Tat, a series of novel benzodiazepine analogs were designed as β-turn mimetics and prepared from p-chloro-nitrobenzene/2-phenylacetonitrile, p-toluidine/benzoyl chloride, or (Z)-7-nitro-5- phenyl-1H-benzoe1, 4diazepin-2(3H)-one (nitrazepam) through different synthetic routes.  Preliminary biological evaluation indicated that compound 30 exhibited inhibitory activity on HIV-1 tat-mediated LTR transcription with EC₅₀ of 25.0 μmol·L⁻¹ and showed no obvious cytotoxic effects on TZM-Bl cells under the concentration of 100 μmol·L⁻¹.