A series of chroman-2-carboxylic acid N-(substituted)phenylamides (2a-s, 3a-j) were synthesized. Their ability to inhibit nuclear factor-kappaB (NF-kappaB) activity was evaluated in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells and their antioxidant activity was examined. NF-kappaB inhibition by chroman compounds was not related to their antioxidant activity. Compounds with -H, -NO2 monosubstituents and -OCH3, -CF3 disubstituents on the phenyl ring were poor inhibitors of NF-kB activity. Compounds with -CH3, -CF3, -CI monosubstituents or -CI, -CH3 disubstituents exhibited moderate to good NF-kappaB activity inhibition (IC50: 18.2-95.8 microM). The most active NF-kappaB inhibitor, 2s, contained a 4-CI (IC50: 18.2 microM) substituent on the phenyl ring and was slightly more potent than the compound KL-1156 (1) (IC50: 43.9 microM).