Electron-withdrawing substituents boost potency in a new propanethioate class of CETP inhibitors, reaching 50 percent inhibition at 2 micromolar (Bioorg Med Chem Lett 2004)

Researchers studied how the structure of the benzene moiety in S-(2-(acylamino)phenyl) 2,2-dimethylpropanethioates affects CETP inhibitory activity. Substituents on the benzene ring influenced potency in a type- and position-dependent manner, with electron-withdrawing groups at the 4- or 5-position increasing CETP inhibitory activity. The most potent compound in the series achieved 50% inhibition of CETP activity in human plasma at a concentration of 2 micromolar, establishing structure-activity relationships for this propanethioate-based CETP inhibitor class.