Nomura Sayaka, Endo-Umeda Kaori, Fujii Shinya, Makishima Makoto, Hashimoto Yuichi, Ishikawa Minoru
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
Bioorg Med Chem Lett. 2018 Feb 15;28(4):796-801. doi: 10.1016/j.bmcl.2017.12.024. Epub 2017 Dec 13.
LXRβ-selective agonists are promising candidates to improve atherosclerosis without increasing plasma or hepatic TG levels. We have reported a series of tetrachlorophthalimide analogs as an LXRβ-selective agonist. However, they exhibited poor aqueous solubility probably due to its high hydrophobicity and highly rigid and plane structure. In this report, we present further structural development of tetrachloro(styrylphenyl)phthalimides as the LXRβ-selective agonists with improved aqueous solubility.
LXRβ选择性激动剂是有望在不增加血浆或肝脏甘油三酯水平的情况下改善动脉粥样硬化的候选药物。我们已报道了一系列四氯邻苯二甲酰亚胺类似物作为LXRβ选择性激动剂。然而，它们表现出较差的水溶性，这可能是由于其高疏水性以及高度刚性和平坦的结构。在本报告中，我们展示了四氯（苯乙烯基苯基）邻苯二甲酰亚胺作为具有改善水溶性的LXRβ选择性激动剂的进一步结构开发。
