Synthesis and anti-human immunodeficiency virus type 1 activity of (E)-N-phenylstyryl-N-alkylacetamide derivatives.
A series of (E)-N-phenylstyryl-N-alkylacetamides, 5, were synthesized by direct reduction-acetylation of beta-arylnitroolefins, followed by N-alkylation. The title compounds were characterized by (1)H-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 R(1) in 5 was ortho-substituted, the resulting compounds showed better inhibitory activities against HIV-1 RT. Among the tested compounds, 5i (R(1) = 2-Br, R(2) = 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 EC(50) value of 4 microM in C8166 cells.
Cheng
Pi
P
School of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China. picheng55@126.com
Chen
Ji-Jun
JJ
Huang
Ning
N
Wang
Rui-Rui
RR
Zheng
Yong-Tang
YT
Liang
Yi-Zeng
YZ
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D013343:Styrenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000081:Acetamides; D019380:Anti-HIV Agents; D013343:Styrenes