Fluorine-substitution in cholesteryl ester transfer protein inhibitors (CETP-inhibitors): Biology, chemistry, SAR, and properties

The inhibition of the cholesteryl ester transfer protein (CETP) provides a method for the elevation of the high density lipoprotein cholesterol (HDL-C) level, i.e. the 'good' cholesterol. The expected anti-atherogenic effect of this approach is independent of the proven benefits of lowering the low density lipoprotein cholesterol (LDL-C) level, i.e. the 'bad' cholesterol. A medicinal chemistry project is presented starting from the first screening hit to the second generation development candidate. The structure-activity relationship, the syntheses and the role of fluorine during optimization, as well as the biological activities are discussed.