Chemical Sciences, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, PA 19426, USA.
Bioorg Med Chem Lett. 2010 Jan 15;20(2):526-30. doi: 10.1016/j.bmcl.2009.11.099. Epub 2009 Nov 23.
A series of 1-(3-aryloxyaryl)benzimidazoles incorporating a sulfone substituent (6) was prepared. High affinity LXR ligands were identified (LXRbeta binding IC(50) values <10nM), some with excellent agonist potency and efficacy in a functional assay of LXR activity measuring ABCA1 mRNA increases in human macrophage THP1 cells. The compounds were typically stable in liver microsome preparations and had good oral exposure in mice.
合成了一系列含有砜取代基的 1-(3-芳氧基苯基)苯并咪唑（6）。鉴定了具有高亲和力的 LXR 配体（LXRβ结合 IC50 值 <10nM），其中一些在测量人巨噬细胞 THP1 细胞 ABCA1 mRNA 增加的 LXR 活性功能测定中具有优异的激动剂效力和功效。这些化合物在肝微粒体制剂中通常稳定，并且在小鼠中具有良好的口服暴露量。
