Design, synthesis and pharmacology of 1,1-bistrifluoromethylcarbinol derivatives as liver X receptor β-selective agonists

A novel series of 1,3-bistrifluoromethylcarbinol derivatives that act as liver X receptor (LXR) beta-selective agonists was discovered. Structure-activity relationship studies led to the identification of molecule 62, which was more effective (E-max) and selective toward LXR beta than T0901317 and GW3965. Furthermore, 62 decreased LDL-C without elevating the plasma TG level and significantly suppressed the lipid-accumulation area in the aortic arch in a Bio F1B hamster fed a diet high in fat and cholesterol. We demonstrated that our LXRb agonist would be potentially useful as a hypolipidemic and anti-atherosclerotic agent. In this manuscript, we report the design, synthesis and pharmacology of 1,3-bistrifluoromethylcarbinol derivatives. (C) 2015 Elsevier Ltd. All rights reserved.