10.1016/j.bmcl.2010.03.031
The purpose was to develop compounds with high affinity for LXRβ, a nuclear hormone receptor that plays a role in lipid metabolism and reverse cholesterol transport (RCT), which could potentially complement existing therapies for atherosclerosis by increasing levels of circulating high-density lipoprotein (HDL), often referred to as 'good cholesterol'. The study identified several compounds with LXRβ binding IC50 values below 10 nM and EC50 values below 1.0 nM in an ABCA1 mRNA induction assay in J774 mouse cells, showing efficacy comparable to T0901317, a known LXR agonist. Notably, compound 8a demonstrated a significant reduction in atherosclerotic lesion progression in LDL receptor knockout mice but also increased triglyceride levels, indicating potential side effects.