Structural Development of Silicon‐Containing Retinoids: Structure?Activity Relationship Study of the Hydrophobic Pharmacophore of Retinobenzoic Acids Using Silyl Functionalities
Structural Development of Silicon‐Containing Retinoids: Structure?Activity Relationship Study of the Hydrophobic Pharmacophore of Retinobenzoic Acids Using Silyl Functionalities
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含硅类视黄醇的结构发展：利用甲硅烷基官能团研究视黄苯甲酸疏水药效团的结构-活性关系
DOI：
10.1002/cmdc.202200176
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发表时间：
2022
期刊：
影响因子：
3.4
通讯作者：
Kagechika Hiroyuki
中科院分区：
文献类型：
--
作者：
Oikawa Tsuyoshi;Fujii Shinya;Mori Shuichi;Masuno Hiroyuki;Kawachi Emiko;Kagechika Hiroyuki
我们设计并合成了一系列具有不同硅基官能团的维甲酸，以详细探讨维甲酸类化合物疏水部分的构效关系。在合成的化合物中，24Am55S(4)具有与先导化合物 相当的类维甲酸活性。化合物24 对视黄酸受体的三个亚型均有转录促进活性，但对视黄酸受体γ的活性最高，而AM80(3)和AM555S(4)对视黄酸受体α有较高的选择性。文中提出的非典型肺炎将有助于开发具有亚型选择性的维甲酸类化合物，特别是24 C可能是一种很有前途的新型RARγ配体的先导化合物。
We designed and synthesized a series of retinobenzoic acids bearing various silyl functionalities in order to explore in detail the structure‐activity relationship (SAR) at the hydrophobic moiety of retinoids. Among the synthesized compounds,24 cbearing at‐butyldimethylsilyl (TBS) group at the hydrophobic site exhibited potent retinoid activity comparable to that of the lead compound Am555S (4). Compound24 cexhibited transcription‐promoting activity towards all three subtypes of retinoic acid receptor (RAR), but showed the highest activity towards RARγ, in contrast to the high RARα‐selectivity of Am80 (3) and Am555S (4). The SARs presented here should be helpful in the development of subtype‐selective retinoids, and in particular24 cmight be a promising lead compound for new RARγ ligands.