2,4,5-Trisubstituted thiazole derivatives as HIV-1 NNRTIs effective on both wild-type and mutant HIV-1 reverse transcriptase: Optimization of the substitution of positions 4 and 5

European Journal of Medicinal Chemistry
2016.0

Abstract

In our previous work, novel 2,4,5-trisubstituted thiazole derivatives (TSTs) were synthesized, and their activities were evaluated against HIV-1 reverse transcriptase. Some interesting results were obtained, which led us to a new discovery regarding these TSTs. In the present study, 21 new 2,4,5-trisubstituted thiazole derivatives were rationally designed and synthesized as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) in accordance with our previous study. Among the synthesized target compounds, compounds 14, 16, 17, and 19 showed more potent inhibitory activities against HIV-1 with an IC50 value of 0.010 μM. Compounds 4, 9, 10, 11, 13 and 16 were further tested on nine NNRTI-resistant HIV-1 strains, and all of these compounds exhibited inhibitory effects. A molecular docking study was conducted, and the results showed a consistent and stable binding mode for the typical compounds. These results have provided deeper insights and SAR of these types of NNRTIs.

DOI： 10.1016/j.ejmech.2016.07.047

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