Synthesis and Biological Activity of Novel 1H,3H-Thiazolo[3,4-a]Benzimidazoles: Non-nucleoside Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitors

Abstract

Using a known human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI), 1-(2,6-difluorophenyl)-1 H,3 H-thiazolo[3,4- a]benzimidazole (TBZ NSC 625487) as the lead structure for drug design, a series of novel 1 H,3 H-thiazolo[3,4- a]benzimidazole derivatives substituted on the benzene-fused ring was prepared. Their in vitro anti-HIV-1 activity, as well as their inhibitory effects on the viral reverse transcriptase, 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 limited size and shape.