Synthesis and Evaluation of 2,2‐Dimethylchroman Derivatives as Inhibitors of ICAM‐1 Expression on Human Endothelial Cells

We herein report the synthesis of novel 2,2‐dimethylchroman analogs and their effect on the modulation of tumor necrosis factor‐α‐induced expression of intercellular adhesion molecule‐1 in human endothelial cells. These compounds were found to be potent inhibitors of tumor necrosis factor‐α‐induced expression of intercellular adhesion molecule‐1 on human endothelial cells at very low concentration. The structure–activity relationship of these compounds has been studied. The IC₅₀ and maximum tolerable dose value of the lead compound 7d (X═NH, R═4Cl) of this study was found to be 9.5 and 150 μM, respectively. The present results indicate that our novel compound is potentially effective and therefore could be useful for further pharmaceutical studies.