Simple synthesis and biological properties of flocoumafen 1 and its structural isomers are described. The key synthetic strategies involve Knoevenagel condensation, Grignard reaction, intramolecular ring cyclization and coupling reaction. Flocoumafen 1 was easily separated into cis and trans forms using flash column chromatography. They were then evaluated for suppression of LPS-induced NO generation and anti-excitotoxicity in vitro. It was found that the trans-flocoumafen was potent suppressor of NO generation with the concentration of 10 𝜇M in vitro, while no significant effect for neurotoxicity in cultured cortical neurons.