Separation of α-glucosidase-inhibitory and liver X receptor-antagonistic activities of phenethylphenyl phthalimide analogs and generation of LXRα-selective antagonists
Separation of α-glucosidase-inhibitory and liver X receptor-antagonistic activities of phenethylphenyl phthalimide analogs and generation of LXRα-selective antagonists
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DOI：
10.1016/j.bmc.2009.05.066
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发表时间：
2009-07-15
影响因子：
3.5
通讯作者：
Ishikawa, Minoru
中科院分区：
文献类型：
--
作者：
Motoshima, Kazunori;Noguchi-Yachide, Tomomi;Ishikawa, Minoru
肝X受体(LXR) α / β双激动剂是治疗代谢综合征的候选药物，因为它们的生物学作用包括增加由LXR β介导的胆固醇外排。然而，其临床应用目前受到LXR α介导的对甘油三酯（TG）合成的增强作用的限制。LXR α选择性拮抗剂与LXR α / β双激动剂联合使用可能克服这一缺点。本研究通过对具有LXR α / β双拮抗活性和α -葡萄糖苷酶抑制活性的苯乙基苯基酞酰亚胺9的结构发育研究，得到LXR α选择性拮抗剂23f。还获得了特异性α -葡萄糖苷酶抑制剂。2009爱思唯尔有限公司版权所有。
Liver X receptor (LXR) alpha/beta dual agonists are candidate medicaments for the treatment of metabolic syndrome, because their biological actions include increasing cholesterol efflux mediated by LXR beta. However, their clinical application is currently limited by their enhancing effect on triglyceride (TG) synthesis mediated by LXR alpha. Combination of an LXR alpha-selective antagonist with an LXR alpha/beta dual agonist may overcome this disadvantage. In the present work, structural development studies of phenethylphenyl phthalimide 9, which possesses LXR alpha/beta dual-antagonistic activity and alpha-glucosidase-inhibitory activity, led to the LXR alpha-selective antagonist 23f. Specific alpha-glucosidase inhibitors were also obtained. (C) 2009 Elsevier Ltd. All rights reserved.