Altered activity profile of a tertiary silanol analog of multi-targeting nuclear receptor modulator T0901317
Altered activity profile of a tertiary silanol analog of multi-targeting nuclear receptor modulator T0901317
复制标题
DOI：
10.1016/j.bmcl.2016.02.031
复制
发表时间：
2016-04-01
影响因子：
2.7
通讯作者：
Fujii, Shinya
中科院分区：
文献类型：
--
作者：
Toyama, Hirozumi;Sato, Shoko;Fujii, Shinya
我们报道了新型硅醇衍生物6(SIRA-T)的设计、合成和理化/生物学评价，该化合物是多靶点核受体调节剂T0901317(5)的硅醇类似物。化合物6的疏水性介于相应的醇13和全氟醇5之间。化合物5对肝X受体α和β、法尼醇X受体、孕烷X受体(PXR)和视黄酸受体相关孤儿受体(ROR)具有较强的活性，而硅醇6只对PXR和RORS具有活性。硅醇取代全氟醇是开发新型靶标选择性、生物活性化合物的一种很有前途的选择。(C)2016爱思唯尔有限公司。保留所有权利。
We report the design, synthesis, and physicochemical/biological evaluation of novel silanol derivative 6 (sila-T) as a silanol analog of multi-target nuclear receptor modulator T0901317 (5). Compound 6 showed intermediate hydrophobicity between the corresponding alcohol 13 and perfluoroalcohol 5. While 5 exhibited potent activities toward liver X receptor alpha and beta, farnesoid X receptor, pregnane X receptor (PXR) and retinoic acid receptor-related orphan receptor (ROR)gamma, silanol 6 exhibited activity only toward PXR and RORs. Incorporation of silanol instead of perfluoroalcohol is a promising option for developing novel target-selective, biologically active compounds. (C) 2016 Elsevier Ltd. All rights reserved.