Kick Ellen, Martin Richard, Xie Yinong, Flatt Brenton, Schweiger Edwin, Wang Tie-Lin, Busch Brett, Nyman Michael, Gu Xiao-Hui, Yan Grace, Wagner Brandee, Nanao Max, Nguyen Lam, Stout Thomas, Plonowski Artur, Schulman Ira, Ostrowski Jacek, Kirchgessner Todd, Wexler Ruth, Mohan Raju
Discovery Chemistry, Research & Development, Bristol-Myers Squibb, PO Box 5400, Princeton, NJ 08543-5400, United States.
Exelixis Inc, 210 East Grand Avenue, So. San Francisco, CA 94080, United States.
Bioorg Med Chem Lett. 2015 Jan 15;25(2):372-7. doi: 10.1016/j.bmcl.2014.11.029. Epub 2014 Nov 15.
A series of biaryl pyrazole and imidazole Liver X Receptor (LXR) partial agonists has been synthesized displaying LXRβ selectivity. The LXRβ selective partial agonist 18 was identified with potent induction of ATP binding transporters ABCA1 and ABCG1 in human whole blood (EC50=1.2μM, 55% efficacy). In mice 18 displayed peripheral induction of ABCA1 at 3 and 10mpk doses with no significant elevation of plasma or hepatic triglycerides at these doses, showing an improved profile compared to a full pan-agonist.
已合成了一系列具有肝脏X受体（LXR）β选择性的联芳基吡唑和咪唑LXR部分激动剂。LXRβ选择性部分激动剂18在人全血中对ATP结合转运蛋白ABCA1和ABCG1具有强效诱导作用（半数有效浓度=1.2μM，效能为55%）。在小鼠中，18在3和10mg/kg剂量下可诱导外周ABCA1表达，且在这些剂量下血浆或肝脏甘油三酯无显著升高，与全泛激动剂相比显示出更好的特性。
