Design and discovery of 2-oxochromene derivatives as liver X receptor β-selective agonists
Design and discovery of 2-oxochromene derivatives as liver X receptor β-selective agonists
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DOI：
10.1016/j.bmcl.2015.01.047
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发表时间：
2015-03-15
影响因子：
2.7
通讯作者：
Shibuya, Kimiyuki
中科院分区：
文献类型：
--
作者：
Matsuda, Takayuki;Okuda, Ayumu;Shibuya, Kimiyuki
In an attempt to molecularly design liver X receptor (LXR) beta-selective agonists, we discovered that the combination of the 2-oxochromene moiety (head) and the imidazoline-2,4-dione moiety (tail) plays an important role in the expression potency and selectivity toward LXR beta. We synthesized a series of 2-oxochromene derivatives and identified 43 as a LXR beta-selective agonist that increased the HDL-C level without significantly elevating the TG level and resulted in a decreased lipid-accumulation area in the aortic arch in a high-fat-and-cholesterol-fed Bio F1B hamster. In this manuscript, we report the design, synthesis and pharmacology of these 2-oxochromene derivatives. (C) 2015 Elsevier Ltd. All rights reserved.
