The class
Optimised DPPE-derivative CETP inhibitor shows robust efficacy without raising blood pressure in telemetered rats (J Med Chem 2012)
Original title: Diphenylpyridylethanamine (DPPE) derivatives as cholesteryl ester transfer protein (CETP) inhibitors
Researchers identified a series of diphenylpyridylethanamine (DPPE) derivatives with potent CETP inhibitory activity, replacing the labile ester of initial lead compound 7 with amides and ureas. Further optimisation produced cyclopentylurea 15d, which reduced cholesteryl ester transfer activity to 48 percent of predose levels in hCETP/apoB-100 dual transgenic mice, though its pharmacokinetic profile was suboptimal. Optimising the N-terminus led to amide 20, with an improved pharmacokinetic profile and robust efficacy in both transgenic mice and hamsters. Unlike earlier CETP inhibitors linked to hypertension, compound 20 showed no significant change in mean arterial blood pressure or heart rate in telemetered rats despite sustained high drug exposure.
Original abstract
A series of diphenylpyridylethanamine (DPPE) derivatives was identified exhibiting potent CETP inhibition. Replacing the labile ester functionality in the initial lead 7 generated a series of amides and ureas. Further optimization of the DPPE series for potency resulted in the discovery of cyclopentylurea 15d, which demonstrated a reduction in cholesterol ester transfer activity (48% of predose level) in hCETP/apoB-100 dual transgenic mice. The PK profile of 15d was suboptimal, and further optimization of the N-terminus resulted in the discovery of amide 20 with an improved PK profile and robust efficacy in transgenic hCETP/apoB-100 mice and in hamsters. Compound 20 demonstrated no significant changes in either mean arterial blood pressure or heart rate in telemeterized rats despite sustained high exposures.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.