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.
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 mM. 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.
European journal of medicinal chemistry