Synthesis and Anti-Human Immunodeficiency Virus Type 1 Activity of (E)-N-Phenylstyryl-N-alkylacetamide Derivatives

Abstract

A series of (E)-N-phenylstyryl-N-alkylacetamides, 5, were synthesized by direct reduction-acetylation of β-arylnitroolefins, followed by N-alkylation. The title compounds were characterized by 1H-NMR, EIMS and IR analysis. All the synthesized compounds were assayed as HIV-1 non-nucleoside reverse transcriptase inhibitors. A SAR study revealed that when group R1 in 5 was ortho-substituted, the resulting compounds showed better inhibitory activities against HIV-1 RT. Among the tested compounds, 5i (R1 = 2-Br, R2 = 3,5-difluorobenzyl) exhibited the highest enzyme activity, with a 88.89% inhibitory ratio against HIV-1 reverse transcriptase at the tested concentration. Further cell-based anti-HIV-1 assays showed that compound 5i exhibited a SI value of 29 with an EC50 value of 4 μM in C8166 cells.

Keywords

• (E)-N-phenylstyryl-N-alkylacetamides
• synthesis
• reverse transcriptase
• anti-HIV-1 activity