Arylazolyl(azinyl)thioacetanilides: Part 19.

With the continuation of our unremitting efforts toward the discovery of potent HIV-1 NNRTIs, a series of novel imidazo[4,5-b]pyridin-2-ylthioacetanilides were designed, synthesized, and evaluated for their antiviral activities through combining bioisosteric replacement and structure-based drug design. Almost all of the title compounds displayed moderate to good activities against wild-type (wt) HIV-1 strain with EC₅₀ values ranging from 0.059 to 1.41 μ m in a cell-based antiviral assay. Thereinto, compounds 12 and 13 were the most active two analogues possessing an EC₅₀ value of 0.059 and 0.073 μ m against wt HIV-1, respectively, which was much more effective than the control drug nevirapine (EC₅₀ = 0.26 μ m) and comparable to delavirdine (EC₅₀ = 0.038 μ m). In addition, one selected compound showed a remarkable reverse transcriptase inhibitory activity compared to nevirapine and etravirine. In the end of this manuscript, preliminary structure-activity relationships (SARs) and molecular modeling studies were detailedly discussed, which may provide valuable insights for further optimization. [ABSTRACT FROM AUTHOR]