A structure-based approach was used to optimize our newclass of quinoline LXR modulators leading to phenyl acetic acidsubstituted quinolines
15 and
16. Both compounds displayed goodbinding affinity for LXR
and LXR
and were potent activators inLBD transactivation assays. The compounds also increased expressionof ABCA1 and stimulated cholesterol efflux in THP-1 cells. Quinoline
16 showed good oral bioavailability and in vivo efficacy in a LDLrknockout mouse model for lesions.