Synthesis and evaluation of new α-methylene-γ-lactone carbamates with NO production inhibitory effects in lipopolysaccharide-induced RAW 264.7 macrophages

•32 new carbamate derivatives were synthesized.•All compounds showed better effect on inhibiting NO production than aminoguanidine.•Compound 4s-2 showed significant inhibition on NO production and low cytotoxicity.•The structure–activity relationships of title compounds have been discussed.

A series of new α-methylene-γ-lactone carbamates were synthesized by an asymmetric synthetic route. The activities on inhibiting nitric oxide (NO) release of these compounds were evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. The results indicated that most of the compounds except one exhibited potent NO inhibitory effect with IC50 value more than 2 μΜ. The cytotoxicities of these compounds were estimated via MTT assays. The results suggested that six compounds were accompanied by low cytotoxicity. The structure–activity relationships were also discussed. The S configuration of C3 on lactones ring would be more helpful to NO inhibitory effect.

Graphical abstractCompound 4s-2 exhibited significant inhibitory effects on NO production. IC50=0.33 μM.Figure optionsDownload full-size imageDownload as PowerPoint slide