Synthesis and biological activity of novel 1H,3H-thiazolo[3,4-a] benzimidazoles: non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors

Using a known human immunodeficiency virus type 1 (HIV-1) non-nucleoside re verse transcriptase inhibitor (NNRTI), 1-(2.6-difluorophenyl)-1H,3H-thiazol o[3,4-a]benzimidazole (TBZ NSC 625487) as the lead structure for drug desig n, a series of novel 1H,3H-thiazolo[3,4-a]benzimidazole derivatives substit uted on the benzene-fused ring was prepared. Their in vitro anti-HIV-1 acti vity, as well as their inhibitory effects on the viral reverse transcriptas e, were evaluated. The structure-activity relationships for these compounds are described and the results suggest that the apolar binding pocket of RT , into which the NNRTIs must fit, can accommodate only groups with a limite d size and shape.