The class
Optimised benzylaminopropanamide derivative HL16 emerges as a sub-micromolar CETP inhibitor active in hamsters (Bioorg Med Chem 2015)
Original title: Design, synthesis and biological evaluation of N,N-3-phenyl-3-benzylaminopropanamide derivatives as novel cholesteryl ester transfer protein inhibitor
Building on lead compound L10 (IC50 8.06 micromolar), discovered by pharmacophore-based virtual screening, researchers identified compound HL6 (IC50 10.7 micromolar) through systematic structure variation, then optimised the structure-activity relationship to develop N,N-3-phenyl-3-benzylaminopropanamide derivatives as novel CETP inhibitors. Compounds were synthesised and evaluated using a BODIPY-CE fluorescence assay, identifying HL16 as a highly potent CETP inhibitor in vitro (IC50 0.69 micromolar). HL16 also showed favourable HDL-C-raising and LDL-C-lowering effects in vivo in hamsters, and molecular docking showed it occupies the CETP binding site with interactions at key amino acid residues.
Original abstract
A series of N,N-3-phenyl-3-benzylaminopropanamide derivatives were identified as novel CETP (cholesteryl ester transfer protein) inhibitors. In our previous study, lead compound L10 was discovered by pharmacophore-based virtual screening (Dong-Mei Zhao et al., 2014). Based on L10 (IC50 8.06 μM), compound HL6 (IC50 10.7 μM) was discovered following systematic structure variation and biological tests. Further optimization of the structure-activity relationship (SAR) resulted in N,N-3-phenyl-3-benzylaminopro panamides derivatives as novel CETP inhibitors. They were synthesized and evaluated against CETP by BODIPY-CE fluorescence assay. Among them, HL16 (IC50 0.69 μM) was a highly potent CETP inhibitor in vitro. In addition, HL16 exhibited favorable HDL-C enhancement and LDL-C reduction in vivo by hamster. The molecular docking of HL16 into the CETP was performed. The binding mode demonstrated that HL16 occupied the CETP binding site and formed interactions with the key amino acid residues.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.