Synthesis and biological evaluation of pyridinone analogues as novel potent HIV-1 NNRTIs.

A novel 2-pyridinone scaffold was rationally designed and synthesized based on the active anti-HIV agent 1 (LAM-trans) via an efficient method. The biological results revealed that some target compounds inhibited HIV-1 reverse transcriptase in the lower micromolar concentration range (IC50 0.089–0.68μm). Notably, the most promising compound 25b exhibited extremely potent inhibitory activity against HIV-1 replication with an EC50 value of 0.0563μM and the viral selectivity index amounted to 3466.8. Molecular modeling studies were performed, and some SARs were rationalized.