A series of 6- or 7-methylchroman-2-carboxylic acid N-(substituted) phenylamides (2a-s, 3a-s) were synthesized. Their abilities to inhibit nuclear factor-κB (NF-κB) activity were evaluated in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. Compounds with substituents such as -H, -CH3, and -CF3 on the phenyl ring were poor inhibitors of NF-κB. The most active NF-κB inhibitors contained 4-Cl (3s) and 4-OMe (3g) in the 7-methylchroman-2-carboxamide derivatives and 2-OH (2b) and 4-Cl (2s) in the 6-methylchroman-2-carboxamide derivatives (IC 50: 20.2-24.0 μM). These were slightly more potent than a reference compound, KL-1156 (1) (IC50: 43.9 μM).
Bibliographical noteFunding Information:
This work was supported by the research grant of the Chungbuk National University in 2007, the grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program / Chungbuk BIT Research-Oriented University Consortium), and the Korea Science and Engineering Foundation (KOSEF) Grant funded by the Korea Government (MOST) (R13-2008-001-00000-00).
- 7-Methylchroman-2- carboxamide
- NF-κB inhibitor