A series of acrylamide analogs of rimonabant, where the N ‐aminopiperidine moiety was replaced by various amines such as benzylamines or heterocyclic amines, were synthesized and their inhibition of nitric oxide (NO) production was evaluated in lipopolysaccharide (LPS)‐induced BV2 microglial cells. Among the synthesized compounds, the 3‐dimethylaminobenzyl analog 7n (IC 50 = 1.32 ± 0.01 μM) showed significantly higher inhibitory activity than rimonabant (IC 50 = 15.66 ± 0.14 μM) and suppressed NO production dose‐dependently without cytotoxicity. In addition, 7n inhibited the expression of iNOS, COX‐2, and proinflammatory cytokines and attenuated LPS‐induced activation of nuclear factor‐kappa B (NF‐κB) and MAPK phosphorylation in BV2 cells. These results demonstrated that 7n exerted anti‐inflammatory effects by NF‐κB and the JNK and p38 MAPK pathways in BV2 cells and could become a prospective candidate for treatment of neuroinflammation‐related disorders.
Yoon et al. (Sun,) studied this question.