Diphenylpyridylethanamine-based aminoheterocycles optimised as CETP inhibitors with better metabolic stability (Bioorg Med Chem Lett 2014)

Researchers explored a series of diphenylpyridylethanamine (DPPE)-based cholesteryl ester transfer protein (CETP) inhibitors, appending aminoheterocycles onto the N-terminus of the chemotype as urea mimetics. Potent compounds against CETP were discovered within this series and were further optimised to improve their metabolic stability and their pregnane X receptor (PXR) transactivation profile, a common liability in CETP inhibitor drug discovery. The work adds a new structural class of aminoheterocycle-appended CETP inhibitors to the medicinal chemistry toolkit for further optimisation.